Dataset Information

Prediction of Prognosis in Adult Patients With Carbapenem-Resistant Klebsiella pneumoniae Infection.

ABSTRACT:

Objective

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with poor patient outcomes. We aimed to analyze the clinical information of adult patients with CRKP infection in order to establish a nomogram for mortality risk as well as to determine the treatment effectiveness of different antimicrobial regimens.

Methods

Adult patients diagnosed with CRKP infection in a tertiary hospital in Shanghai between September 2019 and March 2021 were included. The clinical characteristics and clinical outcomes of these patients were analyzed.

Results

A total of 199 cases of CRKP infection were examined. Five factors, namely age ≥65 years, respiratory failure, Sequential Organ Failure Assessment score, serum procalcitonin ≥5 ng/mL, and appropriate treatments in 3 days, were found to be associated with 30-day mortality. Upon incorporating these factors, the nomogram achieved good concordance indexes of 0.85 (95% confidence interval [CI]: 0.80-0.90) and well-fitted calibration curves. Receiver-operating characteristic curves for 7-, 15-, and 30-day survival had areas under the curve of 0.90, 0.87, and 0.88, respectively. Three-drug combination therapy was observed to be associated with lower mortality in the high-risk group (adjusted hazard ratio = 0.24, 95% CI: 0.06-0.99) but not in the low-risk group. Ceftazidime-avibactam, fosfomycin, and amikacin were effective against infections caused by CRKP. Tigecycline improved the treatment efficiency in 7 days, but a trend toward increased mortality was seen (HR, 1.69; 95% CI: 0.98-2.94; P = 0.061).

Conclusion

The antimicrobial regimen efficacy data and the predictive nomogram established in this study can help clinicians in identifying high-risk adult patients with CRKP infection, improving the therapeutic effect, and reducing mortality.

SUBMITTER: Chen J

PROVIDER: S-EPMC8787092 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Carbapenem-resistantKlebsiella pneumoniae(CR-Kp) is significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract, where the bacterium is usually present at low density, but can bloom following antibiotic treatment, mostly in hospital settings. The impact of disturbances in the intestinal environment on the fitness, survival, expansion, and drug susceptibility of this pathogen is not well-understood. Nevertheless, gaining such knowledge could lead to innovative intervention strategies for addressing colonization and infection. Here, we adopted anin vivomodel to examine the transcriptional adaptation of a CR-Kp clinical isolate to immune activation in the intestine. We report that as early as 6 hours following host treatment with anti-CD3 antibody, CR-Kp underwent rapid transcriptional changes including downregulation of genes involved in sugar utilization and amino acid biosynthesis, and upregulation of genes involved in amino acid uptake and catabolism, antibiotic resistance, and stress response. In agreement with these findings, the concentration of oxidative species and amino acids was increased in the mouse intestine following treatment. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were particularly upregulated, however their deletion did not impair CR-Kp fitness in vivoupon immune activation. Transcription factor enrichment analysis identified the global regulator cAMP-Receptor Protein CRP as a potential orchestrator of the observed transcriptional signature. In keeping with the recognized role of CRP in regulating utilization of alternative carbon sources, CRP deletion in CR-Kp resulted in strongly impaired gut colonization, but this effect was not amplified by immune activation. Thus, following intestinal colonization, which occurs in a CRP-dependent manner, CR-Kp can rapidly respond to immune cues by implementing a well-defined and complex transcriptional program whose direct relevance towards bacterial fitness remains cryptic. Further analyses utilizing this model may identify key factors to tackle the intestinal stage of CR-Kp colonization.