New quinilone dosing guidlines ???

Hello, Summarians!

Exciting research that might really impact the way that pets are treated. The new recommendations for quinolones will be distributed to reference labs and then find their way into our C/S results.

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Updated quinolone dosing

The fluoroquinolones enrofloxacin (Baytril) and marbofloxacin (Zeniquin) were approved for use in dogs by the US Food and Drug Administration (FDA) in December 1988 and June 1999, respectively. The initial approvals were for treating dermal infections, respiratory infections, and urinary cystitis caused by specific bacteria. The recommended dosage for enrofloxacin was later expanded. The Clinical and Laboratory Standards Institute (CLSI) established methods and breakpoints for testing bacterial susceptibility to these drugs in dogs in 1999 and 2004. However, these breakpoints were determined before the importance of pharmacokinetic-pharmacodynamic (PK-PD) criteria in antimicrobial resistance became clear. There is concern that inappropriate use of fluoroquinolones in pets could lead to resistant bacteria emergence. If PK-PD targets are not met due to inadequate dosing, resistant strains may proliferate. Some evidence suggests that prior fluoroquinolone use in small animals may have contributed to the spread of resistant strains. To address these concerns, the CLSI-VAST subcommittee has revised the antimicrobial susceptibility testing (AST) breakpoints for enrofloxacin and marbofloxacin. The new breakpoints will be included in the upcoming 7th edition of the CLSI standard. The revised breakpoints differ significantly from the old ones, with many bacteria previously classified as "susceptible" now classified as "resistant." Three interpretive categories are introduced: Susceptible (S), Susceptible-dose dependent (SDD), and Resistant (R). The S category implies that bacteria can be effectively inhibited at recommended dosages. The SDD category indicates that susceptibility depends on higher doses than initially recommended. The R category suggests that bacteria are not inhibited at achievable concentrations with normal dosages. The analysis focused on Staphylococcus pseudintermedius, Escherichia coli, and Proteus mirabilis isolates from dogs. For each drug and bacterium, the CLSI considered both the wild-type cutoff (COWT) and the PK-PD cutoff (COPD) to establish the breakpoints. It's important to note that susceptibility testing should be performed before selecting a drug and dose. While Pseudomonas aeruginosa was not extensively analyzed due to data limitations, the revised breakpoints should also apply to it based on similar PK-PD targets. Most P. aeruginosa isolates are expected to fall in the R category. In conclusion, the CLSI-VAST subcommittee has revised interpretive categories and breakpoints for enrofloxacin and marbofloxacin in dogs to reflect current understanding of PK-PD and antimicrobial resistance. The new breakpoints will be published in the 7th edition of CLSI Vet01(S). This revision is significant, with some previously "susceptible" bacteria now considered "resistant," and the introduction of the SDD category, which may require higher doses. The aim is to promote responsible antimicrobial stewardship and reduce inappropriate use, which could lead to multi-drug resistance in animals, posing a risk to both animal and human health. The same principles will be applied to other fluoroquinolones and cat isolates in the future. 

Papich, M. G., Gunnett, L. A., & Lubbers, B. V. (2023). Revision of fluoroquinolone breakpoints used for interpretation of antimicrobial susceptibility testing of canine bacterial isolates. American Journal of Veterinary Research https://doi.org/10.2460/ajvr.23.07.0159 

Bottom line — New info about the pharmacokinetics of resistance

Commensal bacterial lung populations

Traditional methods for identifying bacteria in the lower respiratory tract have limitations, as they can only culture a small portion of all bacteria. Newer molecular sequencing techniques have revealed diverse microbial communities in the lower respiratory tract, even though it has a low biomass. These communities are important for respiratory health, and changes in their composition can lead to respiratory diseases. Studying the respiratory microbiota in dogs and cats, which share similarities with humans, has potential for insights into respiratory diseases. However, many questions remain, such as the existence of a healthy airway microbiota, the role of specific bacteria in diseases, mechanisms of host-microbiome interactions, and the possibility of modulating the microbiota for therapeutic purposes. Addressing these questions could improve our understanding of respiratory diseases in various species. 

Vientós-Plotts, AI, Ericsson, AC, Reinero, CR. The respiratory microbiota and its impact on health and disease in dogs and cats: A One Health perspective. J Vet Intern Med. 2023; 37(5): 1641-1655. doi:10.1111/jvim.16824 

Bottom line — Maybe lungs weren't designed to be sterile

Biologic age in dogs vs chronologic age in dogs

This research focuses on using domestic dogs as a model species for antiaging studies due to their similarities with humans in terms of size, genetic diversity, and aging trajectory. The study involves over 340 dog breeds, each with distinct genetic traits, making them ideal for investigating the relationship between genetics and aging. The researchers develop epigenetic clocks based on DNA methylation patterns to estimate the age of dogs and humans, demonstrating common aging mechanisms between the species. Despite the chronological age clocks not directly correlating with breed characteristics like lifespan and weight, the study introduces an epigenetic predictor of average time to death, offering insights into mortality risk based on blood methylation profiles. This predictor reveals associations between breed lifespan, weight, and specific DNA methylation patterns, shedding light on the molecular aspects of the inverse relationship between breed size and lifespan in dogs. Overall, the research highlights the potential of dogs as a model for antiaging research, underscores the shared aging mechanisms between dogs and humans, and provides valuable insights into the molecular basis of breed-specific aging characteristics. 

Horvath S, Lu AT, Haghani A, Zoller JA, Li CZ, Lim AR, Brooke RT, Raj K, Serres-Armero A, Dreger DL, Hogan AN, Plassais J, Ostrander EA. DNA methylation clocks for dogs and humans. Proc Natl Acad Sci U S A. 2022 May 24;119(21):e2120887119.  

Bottom line — May help develop interventions to help increase longevity

Just putting things in perspective …