Braspenning Anouk J M M, Rajakani Sahaya Glingston, Sey Adwoa, El Bounja Mariem, Lammens Christine, Glupczynski Youri, Malhotra-Kumar Surbhi
Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Universiteit Antwerpen, 2610 Antwerp, Belgium.
Antibiotics (Basel). 2024 Mar 20;13(3):281. doi: 10.3390/antibiotics13030281.
Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug-resistant (MDR) are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) ( = 676) isolated from patients hospitalized in 13 intensive care units (ICUs) in six European countries in a clinical trial assessing the impact of decolonization strategies. All isolates were whole-genome-sequenced and studied for in vitro colistin susceptibility. The majority were colistin-susceptible (CS) ( = 597, MIC ≤ 2 µg/mL), and 79 were fully colistin-resistant (CR) (MIC > 2 µg/mL). A total of 288 CS isolates were randomly selected for population analysis profiling (PAP) to assess CHR prevalence. CHR was detected in 108/288 CS . No significant association was found between the occurrence of CHR and country, MIC-value, K-antigen type, and O-antigen type. Overall, 92% (617/671) of the were MDR with high prevalence among CS (91%, 539/592) and CR (98.7%, 78/79) isolates. In contrast, the proportion of carbapenemase-producing (CP-Kpn) was higher among CR (72.2%, 57/79) than CS isolates (29.3%, 174/594). The proportions of MDR and CP-Kpn were similar among CHR (MDR: 85%, 91/107; CP-Kpn: 29.9%, 32/107) and selected CS isolates (MDR: 84.7%, 244/288; CP-Kpn: 28.1%, 80/285). WGS analysis of PAP isolates showed diverse insertion elements in or even among technical replicates underscoring the stochasticity of the CHR phenotype. CHR isolates showed high sequence type (ST) diversity (Simpson's diversity index, SDI: 0.97, in 52 of the 85 STs tested). CR (SDI: 0.85) isolates were highly associated with specific STs (ST101, ST147, ST258/ST512, ≤ 0.003). The widespread nature of CHR among MDR in our study urge the development of rapid HR detection methods to inform on the need for combination regimens.
在多重耐药菌（MDR）普遍存在且经验性使用黏菌素可能导致治疗失败的情况下，对黏菌素的异质性耐药（HR）尤其令人担忧。本研究旨在评估在一项评估去定植策略影响的临床试验中，从6个欧洲国家13个重症监护病房（ICU）住院患者中分离出的MDR肺炎克雷伯菌（n = 676）中黏菌素HR（CHR）的发生频率。所有分离株均进行全基因组测序，并研究其体外对黏菌素的敏感性。大多数分离株对黏菌素敏感（CS）（n = 597，MIC≤2μg/mL），79株对黏菌素完全耐药（CR）（MIC>2μg/mL）。总共随机选择288株CS分离株进行群体分析谱（PAP）以评估CHR的流行率。在108/288株CS分离株中检测到CHR。未发现CHR的发生与国家、MIC值、K抗原类型和O抗原类型之间存在显著关联。总体而言，671株分离株中有92%（617/671）为MDR，在CS（91%，539/592）和CR（98.7%，78/79）分离株中流行率较高。相比之下，产碳青霉烯酶肺炎克雷伯菌（CP-Kpn）在CR分离株（72.2%，57/79）中的比例高于CS分离株（29.3%，174/594）。CHR（MDR：85%，91/107；CP-Kpn：29.9%，32/107）和选定的CS分离株（MDR：84.7%，244/288；CP-Kpn：28.1%，80/285）中MDR和CP-Kpn的比例相似。对PAP分离株的全基因组测序分析显示，在分离株内甚至技术重复之间存在多种插入元件，突出了CHR表型的随机性。CHR分离株表现出高度的序列类型（ST）多样性（辛普森多样性指数，SDI：0.97，在测试的85种ST中的52种）。CR分离株（SDI：0.85）与特定的STs（ST101、ST147、ST258/ST512，P≤0.003）高度相关。我们研究中CHR在MDR肺炎克雷伯菌中的广泛存在促使开发快速HR检测方法，以确定联合治疗方案的必要性。
