Abstract：
Antimicrobial resistance within Staphylococcus pseudintermedius poses a significant risk for the treatment of canine pyoderma and as a reservoir for resistance and potential zoonoses, but few studies examine long-term temporal trends of resistance. This study assesses the antimicrobial resistance prevalence and minimum inhibitory concentration (MIC) trends in S. pseudintermedius (n=1804) isolated from canine skin samples at the Cornell University Animal Health Diagnostic Center (AHDC) between 2007 and 2020. Not susceptible (NS) prevalence, Cochran-Armitage tests, logrank tests, MIC50 and MIC90 quantiles, and survival analysis models were used to evaluate resistance prevalence and temporal trends to 23 antimicrobials. We use splines as predictors in accelerated failure time (AFT) models to model non-linear temporal trends in MICs. Multidrug resistance was common among isolates (47%), and isolates had moderate to high NS prevalence to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, the macrolides/lincosamides, the tetracyclines, and trimethoprim-sulfamethoxazole. However, low levels of NS to amikacin, rifampin, and vancomycin were observed. Around one third of isolates (38%) were found to be methicillin resistant S. pseudintermedius (MRSP), and these isolates had a higher prevalence of NS to all tested antimicrobials than methicillin susceptible isolates. Amongst the MRSP isolates, one phenotypically vancomycin resistant isolate (MIC >16 µg/mL) was identified, but genomic sequence data was unavailable. AFT models showed increasing MICs across time to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, and the macrolides/lincosamides, and decreasing temporal resistance (decreasing MICs) to doxycycline was observed amongst isolates. Notably, ATF modeling showed changes in MIC distributions that were not identified using Cochran-Armitage tests on prevalence, MIC quantiles, and logrank tests. Increasing resistance amongst these S. pseudintermedius isolates highlights the need for rational, empirical prescribing practices and increased antimicrobial resistance (AMR) surveillance to maintain the efficacy of current therapeutic agents. AFT models with non-linear predictors may be a useful, breakpoint-independent, surveillance tool alongside other modeling methods and antibiograms.
摘要：
假中介葡萄球菌的抗菌素耐药性对治疗犬脓皮病和作为耐药性和潜在人畜共患病的储库构成了重大风险。但是很少有研究研究抵抗的长期时间趋势。这项研究评估了2007年至2020年在康奈尔大学动物健康诊断中心（AHDC）从犬皮肤样品中分离出的假中介链球菌（n=1804）的抗菌素耐药性流行和最低抑菌浓度（MIC）趋势。不敏感（NS）患病率，Cochran-Armitage测试,logrank测试,MIC50和MIC90分位数，和生存分析模型用于评估23种抗菌药物的耐药患病率和时间趋势。我们在加速故障时间（AFT）模型中使用样条作为预测因子，以对MIC的非线性时间趋势进行建模。多药耐药在分离株中很常见(47%)，分离株对β-内酰胺类药物有中等至高的NS患病率，氯霉素,氟喹诺酮类药物,庆大霉素,大环内酯类/lincosamides，四环素类药物,和甲氧苄啶-磺胺甲恶唑.然而,低水平的NS到阿米卡星，利福平,观察万古霉素。大约三分之一的分离株（38％）被发现是耐甲氧西林的假中介链球菌（MRSP），这些分离株在所有受试抗菌药物中的NS患病率高于甲氧西林敏感分离株。在MRSP分离物中,鉴定出一种表型上耐万古霉素的分离株（MIC>16µg/mL），但基因组序列数据不可用。AFT模型显示，随着时间的推移，对β-内酰胺的MIC增加，氯霉素,氟喹诺酮类药物,庆大霉素,和大环内酯类/林可沙酰胺，在分离株中观察到对多西环素的时间抗性降低(MIC降低)。值得注意的是,ATF模型显示MIC分布的变化，使用Cochran-Armitage测试对患病率没有确定，MIC分位数,和logrank测试。这些假中介链球菌分离株的耐药性不断增加，凸显了对理性的需求，经验处方实践和增加抗菌素耐药性（AMR）监测，以维持当前治疗药物的疗效。具有非线性预测因子的AFT模型可能是有用的，断点独立，监测工具以及其他建模方法和抗菌图。
