Unmasking a Silent Threat: New Insights into Carbapenem-Resistant Enterobacter Species
- Ray Sullivan
- Aug 9
- 3 min read
Carbapenem-resistant bacteria are a major global health concern, and Enterobacter species are increasingly problematic, especially those producing carbapenemases. These infections are particularly concerning due to their high mortality rates. Historically, understanding these infections has been challenging due to complex bacterial taxonomy and a scarcity of comprehensive international clinical and molecular data.
Barry Kreiswirth, Center for Discovery & Innovation, led an international group of researchers that shed light on this global threat. Conducted as part of the international multicenter CRACKLE-2 study, researchers enrolled 136 hospitalized patients with carbapenemase-producing Enterobacter species (CP-Enterobacter spp.) from 30 hospitals in 7 countries between 2016 and 2018. By collecting detailed clinical and microbiologic data and performing whole genome sequencing, the study aimed to deepen our understanding of these resistant pathogens.
Jiang et al. identified 11 different Enterobacter species among the isolates. The findings highlight that two species, E. xiangfangensis (60%) and E. hoffmannii (13%), are the most common culprits among international CP-Enterobacter spp. This is significant because previous taxonomic challenges often led to these being broadly reported as E. cloacae complex, limiting detailed understanding.
In terms of resistance mechanisms, the most prevalent carbapenemase gene family was blaKPC, found in 78% of isolates, followed by blaNDM in 9%. The distribution of these genes varied geographically: blaKPC was predominantly identified in the US, Colombia, and Argentina, while blaNDM was found in China, the US, and Colombia. The study also observed high resistance rates to common antibiotics like aztreonam, cefepime, and ceftriaxone, but lower rates to amikacin, colistin, polymyxin B, and tigecycline.
The clinical outcomes for patients with these infections are serious. The study reported an overall 30-day mortality rate of 20% and a 90-day mortality rate of 27%. Notably, older age at enrollment was significantly associated with increased 30-day mortality. Despite the different Enterobacter species identified, the study found no significant differences in clinical characteristics or outcomes, including mortality, among patients infected with E. xiangfangensis, E. hoffmannii, or other Enterobacter species. This suggests that regardless of the specific Enterobacter species, the presence of carbapenemase production poses a consistent severe threat.
One of the insights from this research concerns the molecular epidemiology of these resistant bacteria. The whole genome sequencing analysis revealed that the widespread global emergence of CP-Enterobacter spp is largely driven by the clonal spread of a few predominant clones. The three major clones identified were ST171 E. xiangfangensis, ST78 E. hoffmannii, and ST93 E. xiangfangensis.
The study suggests that a key factor contributing to the formation and global dissemination of these predominant clones is their acquisition of fluoroquinolone resistance–associated mutations (in genes like gyrA and parC) and carbapenemase-encoding plasmids. For instance, within ST171 E. xiangfangensis, different clades were identified, each showing unique gyrA genotypes and harboring different carbapenemase genes like blaKPC-4, blaKPC-3, blaNDM, and blaOXA-48. Similarly, ST78 E. hoffmannii and ST93 E. xiangfangensis also acquired a diverse array of carbapenemase-carrying plasmids, facilitating their spread. This suggests a pattern of independent acquisition of resistance mechanisms within these successful bacterial lineages.
This comprehensive international study confirms the critical role of E. xiangfangensis and E. hoffmannii as common carbapenemase-producing Enterobacter species globally. The findings underscore the importance of detailed genomic analysis to understand how these bacteria evolve and spread, emphasizing that the ability to acquire both resistance to common antibiotics and genes for carbapenemase production is a key driver of their epidemic success.
While the study offers invaluable insights, it acknowledges some limitations, such as limited patient enrollment from Asia-Pacific countries and no sites from Europe or Africa, meaning the results may not fully capture the global epidemiology. Nonetheless, this research highlights the urgent public health threat posed by CP-Enterobacter spp and emphasizes the continuous need for molecular epidemiology to inform effective strategies against antimicrobial resistance.
Jiang J, Komarow L, Hill C, Boutzoukas AE, Hanson B, Arias CA, Bonomo RA, Evans S, Doi Y, Satlin MJ, Weston G, Cober E, Valderrama-Beltran SL, Mendoza SS, Liu Z, Fries BC, Tambyah PA, Chambers HF, Fowler VG Jr, van Duin D, Kreiswirth BN, Chen L. Molecular Epidemiology and Clinical Characterization of Carbapenemase-Producing Enterobacter Species From an International Cohort. J Infect Dis. 2025 Jul 11;231(6):1489-1501. doi: 10.1093/infdis/jiae616. PMID: 39667036; PMCID: PMC12247830.
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