Safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an ESBL-endemic setting

Lew, Kaung Yuan; Ng, Tat Ming; Tan, Michelle W.; Tan, Si Hui; Lew, Ee Ling; L, Li; Ang, Brenda; Lye, David C.; Teng, Christine B

doi:10.1093/jac/dku479

Cited by 78 publications

(71 citation statements)

References 24 publications

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“…However, their utilization favours the emergence of resistant microorganisms, even when administered for less than 3 days (Armand-Lefèvre et al, 2013), including highly resistant bacteria such as Acinetobacter baumannii . In the present study, de-escalation achieved a significant reduction in carbapenem treatment duration of up to 4 days, similar to previously published findings (Alvarez-Lerma et al, 2006;Apisarnthanarak et al, 2013a;Lew et al, 2014). This reduction in exposure to broad-spectrum antibiotics such as carbapenems has been found to lead to a reduced emergence of microorganisms p = 0.014; b p = 0.003; c p = 0.006; d p = 0.001; e p = 0.730; f p = 0.564.…”

Section: Discussionsupporting

confidence: 93%

“…Normally, 48-72 h are considered from microbiological isolation and susceptibility results are available. The time taken varies between studies (Eachempati et al, 2009;Apisarnthanarak et al, 2013b;Lew et al, 2014;Viasus et al, 2017). It was decided to use an average of four until microbiological results and issue of the definitive susceptibility report.…”

Section: Discussionmentioning

confidence: 99%

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Clinical outcomes of carbapenem de-escalation regardless of microbiological results: A propensity score analysis

Sadyrbaeva-Dolgova

Aznarte-Padial

Pasquau-Liaño

et al. 2019

International Journal of Infectious Diseases

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Objective: The aim of this study was to evaluate the safety and efficacy of de-escalation in patients under treatment with carbapenems and its impact on clinical outcomes. Methods: A prospective observational study was conducted for 1 year. Patients administered active carbapenems for at least 24 h were included. Primary outcomes were in-hospital mortality, mortality at 30 days after carbapenem prescription, and infection-related readmission within 30 days. De-escalation was defined as the substitution of carbapenem with narrower spectrum antimicrobial agents or its discontinuation during the first 96 h of treatment. Results: The study included 1161 patients, and de-escalation was performed in 667 (57.5%) of these. In the de-escalation group, 54.9% of cultures were positive. After propensity score matching, 30-day mortality was lower (17.4% vs. 25.7%, p = 0.036), carbapenem treatment was 4 days shorter (4 vs. 8 days, p < 0.001), total antibiotic therapy duration was 2 days longer (12 vs. 10 days, p = 0.003), and length of hospital stay was 5 days shorter (8 vs. 13 days, p = 0.008) in the de-escalated versus non-de-escalated patients. Inhospital mortality and 30-day readmission rates did not differ significantly between these groups. Conclusion: Carbapenem de-escalation is a safe strategy that does not compromise the clinical status of patients.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of carbapenem de-escalation regardless of microbiological results: A propensity score analysis

Sadyrbaeva-Dolgova

Aznarte-Padial

Pasquau-Liaño

et al. 2019

International Journal of Infectious Diseases

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“…Use of the spectrum score method provided an objective definition that was used to identify de-escalation events. Lastly, we controlled for potentially confounding variables, which is in contrast to many prior investigations of de-escalation on clinical outcomes [13, 14]. …”

Section: Discussionmentioning

confidence: 99%

Outcomes Associated With Antimicrobial De-escalation of Treatment for Pneumonia Within the Veterans Healthcare Administration

Bohan¹,

Remington

Jones

et al. 2016

Open Forum Infectious Diseases

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De-escalation, an antimicrobial stewardship concept, involves narrowing broad-spectrum empiric antimicrobial therapy based on clinical data. Current health outcomes evidence is lacking to support de-escalation. Studying Veterans Healthcare Administration pneumonia patients, de-escalation was associated with improved length of stay without affecting 30-day readmission or 30-day Clostridium difficile infection rates.

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“…The choice of any β-lactam should be maximized, by a PK/PD point of view, with high dosages and by infusion strategies maximizing the time above the MIC (t9MIC); a loading dose followed by maintenance doses with extended or continuous infusion is recommended [12]. Accordingly, the use of carbapenems, either empiric or targeted, should be reserved for patients with severe infections caused by ESBLproducing bacteria with a complex resistance pattern, and de-escalation therapy from carbapenems should be always performed if feasible [23]. However, there are a number of unsolved issues especially for the use of BLBLIs which often are perceived as inferior in the treatment of infections by ESBL producers, with data not strongly supported by clinical evidence [24].…”

Section: Epidemiology Of Multi-drug Resistant (Mdr) Enterobacteriaceamentioning

confidence: 99%

Epidemiology and Treatment of MDR Enterobacteriaceae

Bassetti

Pecori

Sibani

et al. 2015

Curr Treat Options Infect Dis

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Opinion statementThe major progress in the history of medicine represented by the discovery of antibiotics is nowadays compromised by the universal spread of antibiotic resistance. World Health Organization (WHO) lists third-generation cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae and carbapenem-resistant K. pneumoniae in a group of seven bacteria of international concern, responsible for both healthcare-associated and community-acquired infections. Patients infected by these pathogens have limited therapeutic options, worse clinical outcomes, increased mortality rates, and a higher healthcare resources consumption. In infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, appropriate monotherapy is effective and carbapenems are the drugs of choice; however, β-lactams/β-lactamase inhibitors (BLBLIs) are regarded as an alternative mainly in patients without severe infections, with E. coli bacteremia with urinary source or with low minimum inhibitory concentrations (MICs). For infections caused by carbapenem-resistant Enterobacteriaceae (CRE), where the predicted mortality rate of patients is high, a combination antimicrobial treatment should be preferred. Many important variables in the treatment such as the role of high dosages and loading doses, the variable degrees of dosage reduction for impaired renal function, and the inclusion of carbapenems or tigecycline are a matter of debate. Despite the obscure vision provided by a notable number of meta-analyses, tigecycline is an effective and safe option for the treatment of MDR Enterobacteriaceae, as part of a combination regimen in case of infections caused by CRE, where a higher dosage (200 mg/daily) should be preferred. Colistin is the most active in vitro agent against CRE. Despite clinical data about the efficacy of fosfomycin against MDR Enterobacteriaceae are limited, this molecule represents an interesting option for the treatment of lower urinary tract and even systemic infections caused by difficult-to-treat Gram-negative pathogens. Based on in vitro studies, ceftolozane-tazobactam and ceftazidime-avibactam will represent very interesting new drugs for the treatment of ESBL-producing and CRE infections, respectively.

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Safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an ESBL-endemic setting

Abstract: This study suggests that the ASP-guided de-escalation of carbapenems led to comparable clinical success, fewer adverse effects and a lower incidence of the development of resistance. This approach is safe and practicable, and should be a key component of an ASP.

Cited by 78 publications

References 24 publications

Clinical outcomes of carbapenem de-escalation regardless of microbiological results: A propensity score analysis

Clinical outcomes of carbapenem de-escalation regardless of microbiological results: A propensity score analysis

Outcomes Associated With Antimicrobial De-escalation of Treatment for Pneumonia Within the Veterans Healthcare Administration

Epidemiology and Treatment of MDR Enterobacteriaceae

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