Initial Empiric Carbapenem Use Does Not Improve Mortality in Critically Ill patients With Gram-Negative Bacteremia but Increases Multidrug-Resistant Organisms

Introduction: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. Methods: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Results: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. Conclusion: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

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Effect of pharmacokinetic/pharmacodynamic ratio on tigecycline clinical response and toxicity in critically ill patients with multidrug-resistant Gram-negative infections

SAGE Open Medicine ◽

10.1177/2050312120958897 ◽

2020 ◽

Vol 8 ◽

pp. 205031212095889

Author(s):

Jesus Ruiz ◽

Paula Ramirez ◽

Esther Villarreal ◽

Mónica Gordon ◽

María Ángeles Sánchez ◽

...

Keyword(s):

Clinical Response ◽

Critically Ill ◽

Critically Ill Patients ◽

Total Bilirubin Level ◽

Optimal Dose ◽

Multidrug Resistant ◽

Pharmacokinetic Parameters ◽

Time Curve ◽

Free Concentration ◽

Gram Negative

Introduction: The information about the pharmacokinetics and optimal dose of tigecycline in critically ill patients with severe underlying diseases is limited and controversial. In this study, we evaluate the pharmacokinetic parameters of tigecycline in critically ill patients with multidrug-resistant Gram-negative infection and explore the association between the pharmacokinetic/pharmacodynamic ratio and treatment response. Methods: A prospective study was designed including critically ill patients treated with tigecycline for multidrug-resistant Gram-negative infections. Blood samples were collected at day 3–5 of treatment, and pharmacokinetics parameters were evaluated using NONMEM® software. Relationship between area under the free concentration–time curve and minimum inhibitory concentration ratio (fAUC/MIC) and treatment failure was evaluated. Association between tigecycline fAUC and hepatobiliary toxicity was also investigated. Results: Twenty-five critically ill patients were included in the study. In the pharmacokinetic model, weight and total bilirubin level were found to be significant predictors of tigecycline clearance. Fifteen (60.0%) patients achieved an fAUC/MIC ratio >4.5, seven (28.0%) an fAUC/MIC > 6.96 and only three (12.0%) an fAUC/MIC > 17.9. No differences in fAUC/MIC ratio were obtained between those patients with and without clinical failure (5.28 (IC95%: 2.57–7.94) vs 8.71 (3.57–13.84)). fAUC values were higher in those patients who suffered hepatobiliary disorders (7.63 (3.93–11.34) vs 17.63 (7.85–26.28) mg/L/h). Conclusion: An important percentage of critically ill patients with multidrug-resistant Gram-negative infection treated with tigecycline do not achieve an appropriate pharmacokinetic/pharmacodynamic value. Tigecycline fAUC seems to be associated with hepatobiliary disorders in this study population. The effect of fAUC/MIC ratio on clinical response remains unclear.

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Prevalence of Multidrug Resistant Organisms in Inter-Hospital Transferred Critically Ill Patients

JOURNAL OF ACUTE CARE SURGERY ◽

10.17479/jacs.2017.7.1.9 ◽

2017 ◽

Vol 7 (1) ◽

pp. 9-14

Author(s):

Changho Heo ◽

Dae-Sang Lee ◽

Eunmi Gil ◽

Chi-Min Park

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Multidrug Resistant ◽

Multidrug Resistant Organisms

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Multidrug resistant and carbapenemase producing Gram-negative bacteria among critically ill patients

10.26226/morressier.56d5ba2cd462b80296c96989 ◽

2016 ◽

Cited By ~ 1

Author(s):

Zied Hajjej

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Gram Negative

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Clinical Impact of Laboratory Implementation of Verigene BC-GN Microarray-Based Assay for Detection of Gram-Negative Bacteria in Positive Blood Cultures

Journal of Clinical Microbiology ◽

10.1128/jcm.00376-16 ◽

2016 ◽

Vol 54 (7) ◽

pp. 1789-1796 ◽

Cited By ~ 64

Author(s):

Tamar Walker ◽

Sandrea Dumadag ◽

Christine Jiyoun Lee ◽

Seung Heon Lee ◽

Jeffrey M. Bender ◽

...

Keyword(s):

Early Identification ◽

Detection System ◽

Bloodstream Infections ◽

Multidrug Resistant ◽

Blood Cultures ◽

Gram Negative ◽

Extended Spectrum Beta Lactamase ◽

Molecular Tests ◽

Multidrug Resistant Organisms ◽

Gram Negative Bacteremia

Gram-negative bacteremia is highly fatal, and hospitalizations due to sepsis have been increasing worldwide. Molecular tests that supplement Gram stain results from positive blood cultures provide specific organism information to potentially guide therapy, but more clinical data on their real-world impact are still needed. We retrospectively reviewed cases of Gram-negative bacteremia in hospitalized patients over a 6-month period before (n =98) and over a 6-month period after (n =97) the implementation of a microarray-based early identification and resistance marker detection system (Verigene BC-GN; Nanosphere) while antimicrobial stewardship practices remained constant. Patient demographics, time to organism identification, time to effective antimicrobial therapy, and other key clinical parameters were compared. The two groups did not differ statistically with regard to comorbid conditions, sources of bacteremia, or numbers of intensive care unit (ICU) admissions, active use of immunosuppressive therapy, neutropenia, or bacteremia due to multidrug-resistant organisms. The BC-GN panel yielded an identification in 87% of Gram-negative cultures and was accurate in 95/97 (98%) of the cases compared to results using conventional culture. Organism identifications were achieved more quickly post-microarray implementation (mean, 10.9 h versus 37.9 h;P< 0.001). Length of ICU stay, 30-day mortality, and mortality associated with multidrug-resistant organisms were significantly lower in the postintervention group (P< 0.05). More rapid implementation of effective therapy was statistically significant for postintervention cases of extended-spectrum beta-lactamase-producing organisms (P= 0.049) but not overall (P= 0.12). The Verigene BC-GN assay is a valuable addition for the early identification of Gram-negative organisms that cause bloodstream infections and can significantly impact patient care, particularly when resistance markers are detected.

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