78. Aerobactin Gene iuc as a Virulence Marker Associated with Increased Mortality in Carbapenem-Resistant Klebsiella pneumoniae infections: A Multicenter Observational Cohort Study from China

TL;DR

This study shows that the iuc gene in drug-resistant Klebsiella pneumoniae is linked to higher patient death rates, suggesting it should be monitored in hospitals.

Contribution

The study identifies the iuc gene as a novel virulence marker associated with increased mortality in CRKP infections.

Findings

iuc-positive CRKP infections were linked to a 4.10-fold higher risk of 30-day mortality after adjusting for confounders.

Kaplan-Meier analysis showed significantly poorer survival for patients with iuc-positive CRKP infections.

iuc was detected in 63% of CRKP isolates and was associated with worse clinical outcomes.

Abstract

Despite growing reports of virulence gene acquisition in carbapenem-resistant Klebsiella pneumoniae (CRKP) strains, the clinical implications of these infections remain poorly understood.

In this study, 246 hospitalized patients with clinical CRKP infections were enrolled from six hospitals across China between 2017 and 2019 (CRACKLE-2 China Cohort). All CRKP isolates underwent whole-genome sequencing to determine sequence types and the presence of virulence genes, including iuc (aerobactin), iro (salmochelin), and mucoid phenotype regulators (rmpADC and rmpA2). Clinical, microbiological, and outcome data were compared by iuc status, and multivariable logistic regression was used to assess factors associated with 30-day mortality. Kaplan-Meier analysis was performed to evaluate 30-day survival.

Among the 246 CRKP isolates, ST11 (78%, 192/246) and ST15 (14%, 34/246) were predominant. iuc was detected in 63% (154/246) of the isolates. rmpA2 (Pearson coefficient r=0.9; P< 0.01) and rmpA (r=0.7; P< 0.01) were highly correlated with iuc. In only 6/246 isolates (2%) iro was detected, five of which were iuc-positive. Demographics and clinical characteristics did not differ between patients infected with iuc-positive and iuc-negative isolates (Table 1). Clinical outcomes were worse in iuc-positive CRKP infections; unadjusted 30-day mortality was higher in the iuc-positive group compared to the iuc-negative group (16% vs. 5%, 24/154 vs. 5/92; P< 0.05). Additionally, the 30-day DOOR outcomes were significantly different, and the presence of iuc was associated with less desirable outcomes (DOOR probability 37.8%; 95% Halperin confidence interval: 31.3%-44.7%, Table 2). After adjusting for potential confounders, iuc-positive CRKP infections remained independently predictive of increased 30-day all-cause mortality (adjusted odds ratio [aOR], 4.10; 95% CI, 1.31-12.86; P=0.016) (Table 3). Kaplan-Meier survival analysis further demonstrated significantly poorer survival among patients with iuc-positive infections (log-rank p=0.018) (Figure 1).

These findings suggest that the presence of iuc contributes to increased mortality in CRKP infections and highlight the need for its surveillance in clinical settings.

Angelique E. Boutzoukas, MD, MPH, Elion Therapeutics: Advisor/Consultant|Entasis Therapeutics Inc., an affiliate of Innoviva Specialty Therapeutics, Inc.: Board Member David van Duin, MD, PhD, AbbVie Inc: Advisor/Consultant|Merck & Co., Inc.: Advisor/Consultant|Merck & Co., Inc.: Grant/Research Support|Parexel International: DSMB|Pfizer, Inc.: Advisor/Consultant|Pfizer, Inc.: Honoraria|Roche Pharmaceuticals: Advisor/Consultant|TEVA: Advisor/Consultant

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