Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing  Klebsiella pneumoniae

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Abstract

Background

Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU).

Methods

An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated.

Results

A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intra-abdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5 h [IQR 1–36]) versus those who died (48 h [IQR 5–108], p = 0.014). A propensity score matching showed that receipt of an in vitro active therapy within 24 h from BC collection was associated with lower 30-day mortality (HR = 0.36, 95% CI: 0.188–0.690, p = 0.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118–6.336], p = 0.027), cardiovascular disease (HR 2.196 [95% CI 1.082–4.457], p = 0.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132–1.687], p = 0.001), SOFA score (HR 1.122 [95% CI 1.036–1.216], p = 0.005), and age (HR 1.030 [95% CI 1.006–1.054], p = 0.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071–0.745], p = 0.014) compared to colistin-containing regimens.

Conclusions

Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24 h from the collection of BC.

Electronic supplementary material

The online version of this article (10.1186/s13054-020-2742-9) contains supplementary material, which is available to authorized users.

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Most cited references 26

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Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.

Christopher W Seymour, Foster C Gesten, Hallie C Prescott … (2017)

Background In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. Methods We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. Results Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). Conclusions More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).

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Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections.

N. Friedman, Keith S. Kaye, Jason Stout … (2002)

Bloodstream infections occurring in persons residing in the community, regardless of whether those persons have been receiving health care in an outpatient facility, have traditionally been categorized as community-acquired infections. To develop a new classification scheme for bloodstream infections that distinguishes among community-acquired, health care-associated, and nosocomial infections. Prospective observational study. One academic medical center and two community hospitals. All adult patients admitted to the hospital with bloodstream infection. Demographic characteristics, living arrangements before hospitalization, comorbid medical conditions, factors predisposing to bloodstream infection, date of hospitalization, dates and number of positive blood cultures, results of microbiological susceptibility testing, dates of hospital discharge or death, and mortality rates at 3 to 6 months of follow-up. 504 patients with bloodstream infections were enrolled; 143 (28%) had community-acquired bloodstream infections, 186 (37%) had health care-associated bloodstream infections, and 175 (35%) had nosocomial bloodstream infections. Of the 186 patients with health care-associated bloodstream infection, 29 resided in a nursing home, 64 were receiving home health care, 78 were receiving intravenous or intravascular therapy at home or in a clinic, and 117 had been hospitalized in the 90 days before their bloodstream infection. Cancer was more common in patients with health care-associated or nosocomial bloodstream infection than in patients with community-acquired bloodstream infection. Intravascular devices were the most common source of health care-associated and nosocomial infections, and Staphylococcus aureus was the most frequent pathogen in these types of infections. Methicillin-resistant S. aureus occurred with similar frequency in the groups with health care-associated infection (52%) and nosocomial infection (61%) but was uncommon in the group with community-acquired bloodstream infection (14%) (P = 0.001). Mortality rate at follow-up was greater in patients with health care-associated infection (29% versus 16%; P = 0.019) or nosocomial infection (37% versus 16%; P < 0.001) than in patients with community-acquired infection. Health care-associated bloodstream infections are similar to nosocomial infections in terms of frequency of various comorbid conditions, source of infection, pathogens and their susceptibility patterns, and mortality rate at follow-up. A separate category for health care-associated bloodstream infections is justified, and this new category will have obvious implications for choices about empirical therapy and infection-control surveillance.

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Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies.

Gopi Patel, Shirish Huprikar, Stephanie H. Factor … (2008)

Carbapenem-resistant Klebsiella pneumoniae is an emerging healthcare-associated pathogen. To describe the epidemiology of and clinical outcomes associated with carbapenem-resistant K. pneumoniae infection and to identify risk factors associated with mortality among patients with this type of infection. Mount Sinai Hospital, a 1,171-bed tertiary care teaching hospital in New York City. Two matched case-control studies. In the first matched case-control study, case patients with carbapenem-resistant K. pneumoniae infection were compared with control patients with carbapenem-susceptible K. pneumoniae infection. In the second case-control study, patients who survived carbapenem-resistant K. pneumoniae infection were compared with those who did not survive, to identify risk factors associated with mortality among patients with carbapenem-resistant K. pneumoniae infection. There were 99 case patients and 99 control patients identified. Carbapenem-resistant K. pneumoniae infection was independently associated with recent organ or stem-cell transplantation (P=.008), receipt of mechanical ventilation (P=.04), longer length of stay before infection (P=.01), and exposure to cephalosporins (P=.02) and carbapenems (P<.001). Case patients were more likely than control patients to die during hospitalization (48% vs 20%; P<.001) and to die from infection (38% vs 12%; P<.001). Removal of the focus of infection (ie, debridement) was independently associated with patient survival (P=.002). The timely administration of antibiotics with in vitro activity against carbapenem-resistant K. pneumoniae was not associated with patient survival. Carbapenem-resistant K. pneumoniae infection is associated with numerous healthcare-related risk factors and with high mortality. The mortality rate associated with carbapenem-resistant K. pneumoniae infection and the limited antimicrobial options for treatment of carbapenem-resistant K. pneumoniae infection highlight the need for improved detection of carbapenem-resistant K. pneumoniae infection, identification of effective preventive measures, and development of novel agents with reliable clinical efficacy against carbapenem-resistant K. pneumoniae.

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Author and article information

Contributors

Marco Falcone: marco.falcone@unipi.it

Journal

Journal ID (nlm-ta): Crit Care

Title: Critical Care

Publisher: BioMed Central (London )

ISSN (Print): 1364-8535

ISSN (Electronic): 1466-609X

Publication date (Electronic): 30 January 2020

Publication date PMC-release: 30 January 2020

Publication date Collection: 2020

Volume: 24

Electronic Location Identifier: 29

Affiliations

[1 ]Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa, 2, 56124 Pisa, PI Italy

[2 ]ISNI 0000 0001 2151 3065, GRID grid.5606.5, Infectious Diseases Clinic Department of Health Science, , University of Genoa and Hospital Policlinico San Martino – IRCCS, ; Genoa, Italy

[3 ]ISNI 0000 0004 1756 8209, GRID grid.144189.1, Microbiology Unit, , Azienda Ospedaliera Universitaria Pisana, ; Pisa, Italy

[4 ]ISNI 0000 0004 1757 3729, GRID grid.5395.a, Emergency Medicine Department, , University of Pisa, ; Pisa, Italy

[5 ]GRID grid.411492.b, Infectious Diseases Division, Department of Medicine, , University of Udine and Azienda Sanitaria Universitaria Integrata di Udine, ; Udine, Italy

[6 ]ISNI 0000 0001 2300 0941, GRID grid.6530.0, Department of Economics and Finance, , University of Rome “Tor Vergata”, ; Rome, Italy

Article

Publisher ID: 2742

DOI: 10.1186/s13054-020-2742-9

PMC ID: 6993311

PubMed ID: 32000834

SO-VID: e129437a-22d5-4f56-8609-dcfa1348bbe4

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 1 November 2019

Date accepted : 14 January 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100005612, Shionogi;

Award ID: only for writing

Custom metadata

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: bloodstream infections,bacteremia,antibiotic resistance,carbapenem-resistant,carbapenemases,kpc,klebsiella pneumoniae,mortality,time to appropriate antibiotic therapy

Data availability:

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: bloodstream infections, bacteremia, antibiotic resistance, carbapenem-resistant, carbapenemases, kpc, klebsiella pneumoniae, mortality, time to appropriate antibiotic therapy

Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae

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Abstract

Background

Methods

Results

Conclusions

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Irish Journal of Paramedicine

Most cited references 26

Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.

Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections.

Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies.

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