Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia

2016 ◽  
Vol 32 (8) ◽  
pp. 487-493 ◽  
Author(s):  
Jessica L. Elefritz ◽  
Karri A. Bauer ◽  
Christian Jones ◽  
Julie E. Mangino ◽  
Kyle Porter ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Clinical Cure ◽  
Statistical Significance ◽  
Cohort Analysis ◽  
Kidney Injury ◽  
Multidrug Resistant ◽  
High Dose ◽  
Loading Dose ◽  
Gram Negative

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.

Efficacy Assessment of High Dose Colistin against Carbapenem-Resistant Gram-Negative Bacteria (CR-GNB) in Critically Ill Patients: A Retrospective Non-Inferiority Trial

2021 ◽  
Vol 15 (10) ◽  
pp. 2848-2852
Author(s):  
Basheer Abdulrahman ◽  
Ahmed F. Mady ◽  
Noor Monther Ali ◽  
Abdulrahman Alharthy ◽  
Waleed Tharwat ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Standard Dose ◽  
High Dose ◽  
Loading Dose ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Renal Safety

Background: Colistin is an effective treatment option, recommended for carbapenem resistant gram-negative bacilli (CR-GNB) in critically ill patients. Due to high nephrotoxicity, dose management of Colistin is a tough decision to make. At standard dosage the efficacy of Colistin is not well defined. Consequently, strategies involving higher dosages were suggested. Objective: To evaluate the high dose of Colistin as non-inferior to standard dose in the treatment of CR-GNB in critically ill patients. Study Design: Retrospective comparative study Place and Duration of Study: Intensive Care Unit, King Saud Medical City Riyadh, Saudi Arabia from 1st January 2015 to 31st December 2017. Methodology: One hundred and ninety two patients that met the inclusion criteria from all participants were further divided into two groups. Group H (High dose) given the high dose of Colistin (9 million units intravenously (IV) loading dose, and then 9 million units/day in 2 or three divided doses) whereas group S was administered with standard dose (no loading dose, 6 million units/day). The primary endpoint of the study was the assessment of nephrotoxicity after the start of Colistin and secondary endpoints were the mortality within 14 days of commencing Colistin along with clinical effects and microbial clearance upon completion of treatment. Results: The results of the study established the non-inferiority of high dose of Colistin for the renal safety and also showed significant improvement in microbial clearance and length of ICU stay as compared to the standard dose. The other secondary end points such as mortality (p = 0.99), length of hospital stay (p = 0.39), and global improvement (p value of 0.06) revealed no significant difference between the two groups. Conclusion: The high dose of Colistin for the treatment of carbapenem resistance gram negative bacilli (CRGNB) was as safe as the standard dose for renal safety. But we also found that it also accelerates microbial clearance and reduces the time spent in the intensive care unit. Key words: Colistin, Colestimethate sodium, Gram negative bacteraemia, Sepsis, Multi-drug resistant organisms, Acute kidney injury

scholarly journals Tigecycline Therapy for Nosocomial Pneumonia due to Carbapenem-Resistant Gram-Negative Bacteria in Critically Ill Patients Who Received Inappropriate Initial Antibiotic Treatment: A Retrospective Case Study

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaomai Wu ◽  
Yefei Zhu ◽  
Qiuying Chen ◽  
Liuyang Gong ◽  
Jian Lin ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Critically Ill ◽  
Nosocomial Pneumonia ◽  
Critically Ill Patients ◽  
Standard Dose ◽  
High Dose ◽  
Gram Negative Bacteria ◽  
Loading Dose ◽  
Icu Mortality ◽  
Carbapenem Resistant

Background. Nosocomial pneumonia due to carbapenem-resistant Gram-negative bacteria (CRGNB) is a growing concern because treatment options are limited and the mortality rate is high. The effect of tigecycline (TGC) on nosocomial pneumonia due to CRGNB in patients who have received inappropriate initial empiric antibiotic treatment (IIAT) is unclear. Therefore, this study aimed to examine the effect of TGC on nosocomial pneumonia due to CRGNB in critically ill patients who had received IIAT. Methods. A retrospective study was conducted in an adult respiratory intensive care unit. Data were obtained and analyzed for all patients who were treated with TGC ≥ 3 days for microbiologically confirmed nosocomial pneumonia due to CRGNB and had experienced initial antibiotic failure. Clinical and microbiological outcomes were investigated. Results. Thirty-one patients with hospital-acquired pneumonia or ventilator-associated pneumonia were included in the study. The majority of the responsible organisms were carbapenem-resistant Acinetobacter baumannii (67.7%), followed by Klebsiella pneumoniae (16.1%) and Escherichia coli (9.7%). Twenty patients were treated with high-dose TGC therapy (100 mg every 12 h after a 200 mg loading dose), and the others received a standard-dose therapy (50 mg every 12 h after a 100 mg loading dose). The duration of TGC therapy was 14.3±2.8 days. The global clinical cure rate and the microbiological eradication rate were 48.4% and 61.3%, respectively. The overall ICU mortality rate was 45.2%. A higher score on the Acute Physiology and Chronic Health Evaluation II and a longer duration of IIAT were associated with clinical failure. High-dose TGC therapy had a higher clinical success rate [65.0% (13/20) versus 18.2% (2/11), P=0.023] and a lower ICU mortality rate [30.0% (6/20) versus 72.7% (8/11), P=0.031] than the standard-dose therapy. Conclusions. TGC, especially a high-dose regimen, might be a justifiable option for critically ill patients with nosocomial pneumonia due to CRGNB who have received IIAT when the options for these patients are limited.

scholarly journals High-dose versus low-dose haemofiltration for the treatment of critically ill patients with acute kidney injury: an updated systematic review and meta-analysis

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e014171 ◽  
Author(s):  
Peng Li ◽  
Li-ping Qu ◽  
Dong Qi ◽  
Bo Shen ◽  
Yi-mei Wang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Acute Kidney Injury ◽  
Hospital Mortality ◽  
Hospital Stay ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Low Dose ◽  
Meta Analysis ◽  
Kidney Injury ◽  
High Dose

ObjectiveThe purpose of this study was to perform a systematic review and meta-analysis to evaluate the effect of high-dose versus low-dose haemofiltration on the survival of critically ill patients with acute kidney injury (AKI). We hypothesised that high-dose treatments are not associated with a higher risk of mortality.DesignMeta-analysis.SettingRandomised controlled trials and two-arm prospective and retrospective studies were included.ParticipantsCritically ill patients with AKI.InterventionsContinuous renal replacement therapy.Primary and secondary outcome measuresPrimary outcomes: 90-day mortality, intensive care unit (ICU) mortality, hospital mortality; secondary outcomes: length of ICU and hospital stay.ResultEight studies including 2970 patients were included in the analysis. Pooled results showed no significant difference in the 90-mortality rate between patients treated with high-dose or low-dose haemofiltration (pooled OR=0.90, 95% CI 0.73 to 1.11, p=0.32). Findings were similar for ICU (pooled OR=1.12, 95% CI 0.94 to 1.34, p=0.21) and hospital mortality (pooled OR=1.03, 95% CI 0.81 to 1.30, p=0.84). Length of ICU and hospital stay were similar between high-dose and low-dose groups. Pooled results are not overly influenced by any one study, different cut-off points of prescribed dose or different cut-off points of delivered dose. Meta-regression analysis indicated that the results were not affected by the percentage of patients with sepsis or septic shock.ConclusionHigh-dose and low-dose haemofiltration produce similar outcomes with respect to mortality and length of ICU and hospital stay in critically ill patients with AKI.This study was not registered at the time the data were collected and analysed. It has since been registered on 17 February 2017 athttp://www.researchregistry.com/, registration number: reviewregistry211.

scholarly journals New Colistin Population Pharmacokinetic Data in Critically Ill Patients Suggesting an Alternative Loading Dose Rationale

2014 ◽  
Vol 58 (12) ◽  
pp. 7324-7330 ◽  
Author(s):  
N. Grégoire ◽  
O. Mimoz ◽  
B. Mégarbane ◽  
E. Comets ◽  
D. Chatelier ◽  
...  
Keyword(s):  
Steady State ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Loading Dose ◽  
Liquid Chromatography Tandem Mass

ABSTRACTColistin is an old antibiotic that has recently gained a considerable renewal of interest as the last-line defense therapy against multidrug-resistant Gram-negative bacteria. It is administered as colistin methanesulfonate (CMS), an inactive prodrug, and it was shown that due to slow CMS conversion, colistin plasma concentrations increase very slowly after treatment initiation, which constitutes the rationale for a loading dose in critically ill patients. However, faster CMS conversion was observed in healthy volunteers but using a different CMS brand, which may also have a major impact on colistin pharmacokinetics. Seventy-three critically ill patients not undergoing dialysis received multiple doses of CMS. The CMS concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and a pharmacokinetic analysis was conducted using a population approach. We confirmed that CMS renal clearance and colistin concentrations at steady state are mostly governed by creatinine clearance, but we predict a typical maximum concentration of drug in serum (Cmax) of colistin close to 2 mg/liter, occurring 3 h after an initial dose of 2 million international units (MIU) of CMS. Accordingly, the estimated colistin half-life (t1/2) was relatively short (3.1 h), with rapid attainment of steady state. Our results are only partially consistent with other recently published results. We confirm that the CMS maintenance dose should be adjusted according to renal function in critically ill patients. However, much higher than expected colistin concentrations were observed after the initial CMS dose, with rapid steady-state achievement. These discrepancies challenge the pharmacokinetic rationale for a loading dose, which may still be appropriate for rapid bacterial eradication and an improved clinical cure rate.

scholarly journals High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria

Critical Care ◽  
2014 ◽  
Vol 18 (3) ◽  
pp. R90 ◽  
Author(s):  
Gennaro De Pascale ◽  
Luca Montini ◽  
Mariano Pennisi ◽  
Valentina Bernini ◽  
Riccardo Maviglia ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
High Dose ◽  
Multidrug Resistant Bacteria ◽  
Severe Infections

scholarly journals Evaluation of zinc sulfate as an adjunctive therapy in COVID-19 critically ill patients: a two center propensity-score matched study

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Khalid Al Sulaiman ◽  
Ohoud Aljuhani ◽  
Abdulrahman I. Al Shaya ◽  
Abdullah Kharbosh ◽  
Raed Kensara ◽  
...  
Keyword(s):  
Propensity Score ◽  
Hospital Mortality ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Adjunctive Therapy ◽  
Zinc Sulfate ◽  
Statistical Significance ◽  
Kidney Injury ◽  
Additional Treatment ◽  
Icu Stay

Abstract Background Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The role of zinc in critically ill patients with COVID-19 remains unclear. This study aims to evaluate the efficacy and safety of zinc sulfate as adjunctive therapy in critically ill patients with COVID-19. Methods Patients aged ≥ 18 years with COVID-19 who were admitted to the intensive care unit (ICU) in two tertiary hospitals in Saudi Arabia were retrospectively assessed for zinc use from March 1, 2020 until March 31, 2021. After propensity score matching (1:1 ratio) based on the selected criteria, we assessed the association of zinc used as adjunctive therapy with the 30-day mortality. Secondary outcomes included the in-hospital mortality, ventilator free days, ICU length of stay (LOS), hospital LOS, and complication (s) during ICU stay. Results A total of 164 patients were included, 82 patients received zinc. Patients who received zinc sulfate as adjunctive therapy have a lower 30-day mortality (HR 0.52, CI 0.29, 0.92; p = 0.03). On the other hand, the in-hospital mortality was not statistically significant between the two groups (HR 0.64, CI 0.37–1.10; p = 0.11). Zinc sulfate use was associated with a lower odds of acute kidney injury development during ICU stay (OR 0.46 CI 0.19–1.06; p = 0.07); however, it did not reach statistical significance. Conclusion The use of zinc sulfate as an additional treatment in critically ill COVID-19 patients may improve survival. Furthermore, zinc supplementation may have a protective effect on the kidneys.

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