Prognostic Significance of the Relative Load of KPC-Producing Klebsiella pneumoniae within the Intestinal Microbiota in a Prospective Cohort of Colonized Patients
Increased relative bacterial load of KPC-producing Klebsiella pneumoniae (KPC-KP) within the intestinal microbiota has been associated with KPC-KP bacteremia. Prospective observational study of KPC-KP adult carriers with a hospital admission at recruitment or within the three prior months (January 2018 to February 2019). A qPCR-based assay was developed to measure the relative load of KPC-KP in rectal swabs (RLKPC, proportion of blaKPC relative to 16S rRNA gene copy number). We generated Fine-Gray competing risk and Cox regression models for survival analysis of all-site KPC-KP infection and all-cause mortality, respectively, at 90 and 30 days. The median RLKPC at baseline among 80 KPC-KP adult carriers was 0.28% (range 0.001% to 2.70%). Giannella Risk Score (GRS) was independently associated with 90-day and 30-day all-site infection (adjusted subdistribution hazard ratio [aHR] 1.23, 95% CI = 1.15 to 1.32, P < 0.001). RLKPC (adjusted hazard ratio [aHR] 1.04, 95% CI = 1.01 to 1.07, P = 0.008) and age (aHR 1.05, 95% CI = 1.01 to 1.10, P = 0.008) were independent predictors of 90-day all-cause mortality in a Cox model stratified by length of hospital stay (LOHS) ≥20 days. An adjusted Cox model for 30-day all-cause mortality, stratified by LOHS ≥14 days, included RLKPC (aHR 1.03, 95% CI = 1.00 to 1.06, P = 0.027), age (aHR 1.10, 95% CI = 1.03 to 1.18, P = 0.004), and severe KPC-KP infection (INCREMENT-CPE score >7, aHR 2.96, 95% CI = 0.97 to 9.07, P = 0.057). KPC-KP relative intestinal load was independently associated with all-cause mortality in our clinical setting, after adjusting for age and severe KPC-KP infection. Our study confirms the utility of GRS to predict infection risk in patients colonized by KPC-KP. IMPORTANCE The rapid dissemination of carbapenemase-producing Enterobacterales represents a global public health threat. Increased relative load of KPC-producing Klebsiella pneumoniae (KPC-KP) within the intestinal microbiota has been associated with an increased risk of bloodstream infection by KPC-KP. We developed a qPCR assay for quantification of the relative KPC-KP intestinal load (RLKPC) in 80 colonized patients and examined its association with subsequent all-site KPC-KP infection and all-cause mortality within 90 days. Giannella Risk Score, which predicts infection risk in colonized patients, was independently associated with the development of all-site KPC-KP infection. RLKPC was not associated with all-site KPC-KP infection, possibly reflecting the large heterogeneity in patient clinical conditions and infection types. RLKPC was an independent predictor of all-cause mortality within 90 and 30 days in our clinical setting. We hypothesize that KPC-KP load may behave as a surrogate marker for the severity of the patient's clinical condition.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Microbiology spectrum - 10(2022), 4 vom: 31. Aug., Seite e0272821 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pérez-Nadales, Elena [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.09.2022 Date Revised 20.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1128/spectrum.02728-21 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM342873814 |
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| 100 | 1 | |a Pérez-Nadales, Elena |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Prognostic Significance of the Relative Load of KPC-Producing Klebsiella pneumoniae within the Intestinal Microbiota in a Prospective Cohort of Colonized Patients |
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| 500 | |a Date Revised 20.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Increased relative bacterial load of KPC-producing Klebsiella pneumoniae (KPC-KP) within the intestinal microbiota has been associated with KPC-KP bacteremia. Prospective observational study of KPC-KP adult carriers with a hospital admission at recruitment or within the three prior months (January 2018 to February 2019). A qPCR-based assay was developed to measure the relative load of KPC-KP in rectal swabs (RLKPC, proportion of blaKPC relative to 16S rRNA gene copy number). We generated Fine-Gray competing risk and Cox regression models for survival analysis of all-site KPC-KP infection and all-cause mortality, respectively, at 90 and 30 days. The median RLKPC at baseline among 80 KPC-KP adult carriers was 0.28% (range 0.001% to 2.70%). Giannella Risk Score (GRS) was independently associated with 90-day and 30-day all-site infection (adjusted subdistribution hazard ratio [aHR] 1.23, 95% CI = 1.15 to 1.32, P < 0.001). RLKPC (adjusted hazard ratio [aHR] 1.04, 95% CI = 1.01 to 1.07, P = 0.008) and age (aHR 1.05, 95% CI = 1.01 to 1.10, P = 0.008) were independent predictors of 90-day all-cause mortality in a Cox model stratified by length of hospital stay (LOHS) ≥20 days. An adjusted Cox model for 30-day all-cause mortality, stratified by LOHS ≥14 days, included RLKPC (aHR 1.03, 95% CI = 1.00 to 1.06, P = 0.027), age (aHR 1.10, 95% CI = 1.03 to 1.18, P = 0.004), and severe KPC-KP infection (INCREMENT-CPE score >7, aHR 2.96, 95% CI = 0.97 to 9.07, P = 0.057). KPC-KP relative intestinal load was independently associated with all-cause mortality in our clinical setting, after adjusting for age and severe KPC-KP infection. Our study confirms the utility of GRS to predict infection risk in patients colonized by KPC-KP. IMPORTANCE The rapid dissemination of carbapenemase-producing Enterobacterales represents a global public health threat. Increased relative load of KPC-producing Klebsiella pneumoniae (KPC-KP) within the intestinal microbiota has been associated with an increased risk of bloodstream infection by KPC-KP. We developed a qPCR assay for quantification of the relative KPC-KP intestinal load (RLKPC) in 80 colonized patients and examined its association with subsequent all-site KPC-KP infection and all-cause mortality within 90 days. Giannella Risk Score, which predicts infection risk in colonized patients, was independently associated with the development of all-site KPC-KP infection. RLKPC was not associated with all-site KPC-KP infection, possibly reflecting the large heterogeneity in patient clinical conditions and infection types. RLKPC was an independent predictor of all-cause mortality within 90 and 30 days in our clinical setting. We hypothesize that KPC-KP load may behave as a surrogate marker for the severity of the patient's clinical condition | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a KPC-producing Klebsiella pneumoniae | |
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| 650 | 4 | |a mortality | |
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| 650 | 7 | |a Bacterial Proteins |2 NLM | |
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| 650 | 7 | |a EC 3.5.2.6 |2 NLM | |
| 700 | 1 | |a M Natera, Alejandra |e verfasserin |4 aut | |
| 700 | 1 | |a Recio-Rufián, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Guzmán-Puche, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Marín-Sanz, Juan Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Martín-Pérez, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Cano, Ángela |e verfasserin |4 aut | |
| 700 | 1 | |a Castón, Juan José |e verfasserin |4 aut | |
| 700 | 1 | |a Elías-López, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Machuca, Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Gutiérrez-Gutiérrez, Belén |e verfasserin |4 aut | |
| 700 | 1 | |a Martínez-Martínez, Luis |e verfasserin |4 aut | |
| 700 | 1 | |a Torre-Cisneros, Julián |e verfasserin |4 aut | |
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