Carbapenem-Resistant Enterobacteriaceae Infections in Patients on Renal Replacement Therapy

Eilertson, Brandon; Cober, Eric; Richter, Sandra; Pérez, Federico; Salata, Robert A.; Kalayjian, Robert C.; Watkins, Richard R.; Doi, Yohei; Kaye, Keith S.; Evans, Scott; Fowler, Vance G.; DeHovitz, Jack; Kreiswirth, Barry N.; Duin, David van

doi:10.1093/ofid/ofx216

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…Other meta-analyses also demonstrated significant positive associations between CRE and mortality when CSE-infected patients were used as a baseline. [6][7][8] We also revealed the association between the primary outcomes and these factors including CCI score, 9,11,16,29 number of days with an invasive device or indwelling line, 13,15,21 septic shock, 30,31 acute respiratory failure, 13 site of severe infection, 13,32 and moderate to severe renal impairment 33,34 ; such associations were well supported by multiple studies. 10,35 For the secondary outcomes, we found that a 90-day readmission rate was associated with CRE infections, agreeing with a study by Zilberberg et al 22 In addition, the mean of LOS and the cost of treatment in the CRE-infected patients were considerably higher than those in the CSE-infected patients, which agrees with several other studies.…”

Section: Discussionsupporting

confidence: 68%

Factors Affecting Clinical Outcomes of Carbapenem-Resistant Enterobacteriaceae and Carbapenem-Susceptible Enterobacteriaceae Infections

Soontaros

Leelakanok

Tantipong³

et al. 2021

Infect Dis Clin Pract

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Background: Carbapenem-resistant Enterobacteriaceae (CRE) is currently an emerging global public health problem and has significant negative impacts in many countries. This study aimed to identify risk factors associated with the mortality and readmission of CRE-and carbapenem-susceptible Enterobacteriaceae (CSE)-infected patients in Thailand. Length of stay (LOS) and the cost of treatment for the infections were also investigated.Method: A retrospective cohort study was conducted in patients with CRE-and CSE-positive cultures from January 2016 to June 2019 in an advanced-level government hospital in Thailand. Risk factors for mortality and readmission were analyzed by logistic regression analysis. The differences in LOS and cost of treatment between CRE-and CSE-infected patients were analyzed by the independent t test.Results: A total of 316 and 329 of the patients that were CRE and CSE culture positive, respectively, were included. Carbapenem-resistant Enterobacteriaceae was significantly associated with 30-day mortality [adjusted odds ratio (aOR), 2.86; 95% confidence interval (CI), 1.84-4.44; P < 0.001] and with 90-day mortality (aOR, 3.11; 95% CI, 2.01-4.83; P < 0.001). Factors that increased the risk of 30-day mortality and 90-day mortality were the Charlson Comorbidity Index score, the number of days with an invasive device or indwelling line, septic shock, acute respiratory failure, site of severe infection, and moderate to severe renal impairment. Carbapenem-resistant Enterobacteriaceae was also associated with 90-day readmission rate (aOR, 3.24; 95% CI, 1.85-5.70; P < 0.001). The LOS of CRE-infected patients and CSE-infected patients was significantly different and was 29.18 ± 36.44 and 9.78 ± 12.77 days, respectively ( P < 0.001). The cost of treatment in CRE-and CSE-infected patients was significantly different ( P < 0.001). The cost in CRE-infected patients was 181,183.65 ± 281,325.26 baht, whereas the cost in CSE-infected patients was 53,296.75 ± 79,316.67 baht ( P < 0.001). Antibiotics for CRE-specific therapy including colistin, fosfomycin, tigecycline, or aminoglycosides, that were prescribed in combination were the mainstay treatments.Conclusions: Carbapenem-resistant Enterobacteriaceae was an independent predictor for mortality and readmission. Length of stay and cost of treatment in CRE-infected patients were significantly higher than in CSE-infected patients.

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Section: Discussionsupporting

confidence: 68%

Factors Affecting Clinical Outcomes of Carbapenem-Resistant Enterobacteriaceae and Carbapenem-Susceptible Enterobacteriaceae Infections

Soontaros

Leelakanok

Tantipong³

et al. 2021

Infect Dis Clin Pract

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“…(ESBL)-producing and CR Enterobacterales demonstrate that approximately 20% of patients require RRT at baseline and that the need for RRT is independently associated with clinical failure, development of resistance, and mortality [8][9][10][11][12]. Although mortality in this population is likely multifactorial in etiology, pharmacokinetic (PK) alterations in patients receiving continuous RRT (CRRT) have been shown to lead to suboptimal antimicrobial exposures and worse clinical outcomes, especially for highly renally eliminated agents with time-dependent pharmacodynamic (PD) properties such as the β-lactams [13].…”

Section: Key Pointsmentioning

confidence: 99%

Pharmacokinetics, Pharmacodynamics, and Dose Optimization of Cefiderocol during Continuous Renal Replacement Therapy

et al. 2021

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Background The need for continuous renal replacement therapy (CRRT) in critically ill patients with serious infections is associated with clinical failure, emergence of resistance, and excess mortality. These poor outcomes are attributable in large part to subtherapeutic antimicrobial exposure and failure to achieve target pharmacokinetic/pharmacodynamic (PK/ PD) thresholds during CRRT. Cefiderocol is a novel siderophore cephalosporin with broad in vitro activity against resistant pathogens and is often used to treat critically ill patients, including those receiving CRRT, despite the lack of data to guide dosing in this population. Objective The aim of this study was to evaluate the PK and PD of cefiderocol during in vitro and in vivo CRRT and provide optimal dosing recommendations. Methods The PK and dialytic clearance of cefiderocol was evaluated via an established in vitro CRRT model across various modes, filter types, and effluent flow rates. These data were combined with in vivo PK data from nine patients receiving cefiderocol while receiving CRRT from phase III clinical trials. Optimal dosing regimens and their respective probability of target attainment (PTA) were assessed via an established population PK model with Bayesian estimation and 1000-subject Monte Carlo simulations at each effluent flow rate. ResultsThe overall mean sieving/saturation coefficient during in vitro CRRT was 0.90 across all modes, filter types, effluent flow rates, and points of replacement fluid dilution tested. Adsorption was negligible at 10.9%. Three-way analysis of variance (ANOVA) and multiple linear regression analyses demonstrated that effluent flow rate is the primary driver of clearance during CRRT and can be used to calculate optimal cefiderocol doses required to match the systemic exposure observed in patients with normal renal function. Bayesian estimation of these effluent flow rate-based optimal doses in nine patients receiving CRRT from the phase III clinical trials of cefiderocol revealed comparable mean (± standard deviation) area under the concentration-time curve values as patients with normal renal function (1709 ± 539 mg•h/L vs. 1494 ± 58.4 mg•h/L; p = 0.26). Monte Carlo simulations confirmed these doses achieved >90% PTA against minimum inhibitory concentrations ≤4 mg/L at effluent flow rates from 0.5 to 5 L/h. Conclusion The optimal dosing regimens developed from this work have been incorporated into the prescribing information for cefiderocol, making it the first and only antimicrobial with labeled dosing for CRRT. Future clinical studies are warranted to confirm the efficacy and safety of these regimens.

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“…13 , 14 There are scant data other than the above studies for mortality of carbapenem-resistant Enterobacteriaceae (CRE) in haemodialysis patients. Eilertson et al 25 reported higher mortality with CRE infections in patients on renal replacement therapy, although only one-quarter of patients had bacteraemia and the median age was 62 years. We did not see a different or higher mortality rate for CRE bacteraemia in our cohort comprising mainly haemodialysis patients, due in part to the younger median age and prompt source control.…”

Section: Discussionmentioning

confidence: 99%

Outcome, risk factors and therapeutic strategies in carbapenem-resistant Gram-negative bacteraemia from Pakistan

Fatima

Dodani

Babar

et al. 2023

JAC-Antimicrobial Resistance

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Background Carbapenem-resistant Gram-negative (CRGN) bacteraemia has high mortality and limited therapeutic options. We assessed the risk factors and outcome of CRGN bacteraemia treated with limited options. Methods A prospective cohort study done at a tertiary care hospital in Pakistan, from October 2021 to August 2022. All patients >18 years with CRGN bacteraemia were assessed for demographics, source, risk factors and treatment received. Outcome was assessed as bacterial clearance and all-cause mortality at Day 14 of bacteraemia. Results We included 175 patients. Median age was 45 years (IQR 30–58) and the majority of our patients were on haemodialysis (75%). We found 14 day mortality in 26.8% of our patients; in addition, microbiological clearance was achieved in 95%. The central line (49.7%) was the most common source and Klebsiella spp. (47%) the most common organism. On multivariate analysis, risk factors for mortality were Foley’s catheter [aOR 2.7 (95% CI 1.1–6.5)], mechanical ventilation [aOR 5.1 (95% CI 1.6–15.8)] and Pitt bacteraemia score >4 [aOR 3.48 (95% CI 1.1–10.5)]. Source control was a significant protective factor [aOR 0.251 (95% CI 0.09–0.6)]. The majority received a colistin-based regimen with no difference in mortality between monotherapy and combination therapy. Conclusions Our cohort of CRGN bacteraemia is unique, comprising younger patients mostly on haemodialysis with a central line as the source of bacteraemia and we have found 14 day mortality of 27%. Colistin with various combinations can be an effective option in patients with renal failure having prompt source control.

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Carbapenem-Resistant Enterobacteriaceae Infections in Patients on Renal Replacement Therapy

Cited by 7 publications

References 34 publications

Factors Affecting Clinical Outcomes of Carbapenem-Resistant Enterobacteriaceae and Carbapenem-Susceptible Enterobacteriaceae Infections

Factors Affecting Clinical Outcomes of Carbapenem-Resistant Enterobacteriaceae and Carbapenem-Susceptible Enterobacteriaceae Infections

Pharmacokinetics, Pharmacodynamics, and Dose Optimization of Cefiderocol during Continuous Renal Replacement Therapy

Outcome, risk factors and therapeutic strategies in carbapenem-resistant Gram-negative bacteraemia from Pakistan

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