scholarly journals Clinical Efficacy and Nephrotoxicity of the Loading Dose Colistin for the Treatment of Carbapenem-Resistant Acinetobacter baumannii in Critically Ill Patients

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 31
Author(s):  
Wasan Katip ◽  
Suriyon Uitrakul ◽  
Peninnah Oberdorfer
Keyword(s):  
Acinetobacter Baumannii ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Cohort Analysis ◽  
University Hospital ◽  
Loading Dose ◽  
Carbapenem Resistant ◽  
Significant Difference ◽  
Pre Treatment ◽  
Colistin Methanesulfonate

Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most common causes of nosocomial infections in critically ill patients. Colistin methanesulfonate (CMS), an inactive prodrug, has been considered as a last-resort treatment for CRAB infection in critically ill patients. The objective of this study was to assess 30-day survival and nephrotoxicity in critically ill patients who received non-loading dose (LD) versus LD of CMS for CRAB infection treatment. Between 2012 and 2017, this retrospective cohort analysis was performed at Chiang Mai University Hospital (CMUH), focusing on critically ill patients with CRAB infection who received either non-LD or LD of CMS. A total of 383 patients met the criteria for inclusion. At the 30th day of treatment, the survival rate of patients in the LD CMS group was 1.70 times (adjusted HR) of those in the non-LD group (95% CI = 1.17–2.50, p = 0.006). Clinical response was significantly higher in the LD CMS group than non-LD CMS group (aHR, 1.35, 95% CI, 1.01–1.82, p = 0.046). In addition, a microbiological response—eradication of pre-treatment isolated pathogens in post-treatment cultures—in patients with LD CMS was 1.57 times that of patients with non-LD CMS (95% CI, 1.15–2.15, p = 0.004). Additionally, there was a significant difference in nephrotoxicity between LD CMS and non-LD CMS (aHR, 1.57, 95% CI, 1.14–2.17, p = 0.006). Based on these results, LD CMS should be used to increase the opportunity of patients to achieve favourable outcomes. However, LD CMS was found associated with an increase in nephrotoxicity, so renal function should be closely monitored when LD colistin was administered.

scholarly journals A Comparison of Colistin versus Colistin Plus Meropenem for the Treatment of Carbapenem-Resistant Acinetobacter baumannii in Critically Ill Patients: A Propensity Score-Matched Analysis

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 647
Author(s):  
Wasan Katip ◽  
Suriyon Uitrakul ◽  
Peninnah Oberdorfer
Keyword(s):  
Propensity Score ◽  
Acinetobacter Baumannii ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
University Hospital ◽  
Apache Ii Score ◽  
Nosocomial Pathogen ◽  
Chiang Mai ◽  
Carbapenem Resistant ◽  
Significant Difference

Carbapenem-resistant Acinetobacter baumannii (CRAB), an important nosocomial pathogen, occurs particularly in the intensive care unit (ICU). Thus, the aim of this study was to compare the efficacy and safety of documented treatment with colistin monotherapy versus colistin plus meropenem in critically ill patients with CRAB infections at Chiang Mai University Hospital (CMUH). We conducted a retrospective cohort study of critically ill patients with CRAB infections in an ICU from 2015 to 2017, who received colistin monotherapy versus colistin plus meropenem. After propensity score matching, an adjusted odds ratio (aOR) of a 30-day mortality rate in patients who received colistin plus meropenem was 0.43 compared to those who received colistin monotherapy (95% CI, 0.23–0.82, p = 0.01). aORs of clinical response and microbiological response were also higher in patients who received colistin plus meropenem (1.81, 95% CI 1.01–3.26, p = 0.048 and 2.08, 95% CI 1.11–3.91, p = 0.023, respectively). There was no significant difference in nephrotoxicity (aOR, 0.76, 95% CI, 0.43–1.36, p = 0.363) between colistin monotherapy and colistin plus meropenem. In conclusion, the addition of meropenem to colistin caused a reduction in 30-day mortality, higher clinical and microbiological responses, and did not increase nephrotoxicity compared to colistin monotherapy. Furthermore, 30-day mortality was significantly related with age, receiving vasopressor, having malignancy, and the APACHE II score.

scholarly journals Clinical Efficacy and Nephrotoxicity of Colistin Alone versus Colistin Plus Vancomycin in Critically Ill Patients Infected with Carbapenem-Resistant Acinetobacter baumannii: A Propensity Score-Matched Analysis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 162
Author(s):  
Wasan Katip ◽  
Peninnah Oberdorfer
Keyword(s):  
Propensity Score ◽  
Acinetobacter Baumannii ◽  
Clinical Response ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
University Hospital ◽  
Efficacy And Safety ◽  
Inclusion Criteria ◽  
Chiang Mai ◽  
Carbapenem Resistant

Acinetobacter baumannii has emerged as a significant concern worldwide. The mortality rate of carbapenem-resistant A. baumannii (CRAB) is increasing, especially in the intensive care unit (ICU). Thus, the objective of this study is to compare the efficacy and safety of colistin plus vancomycin for the treatment of critically ill patients with CRAB in Chiang Mai University Hospital. We conducted a retrospective cohort study of critically ill patients in the ICU with CRAB infection who received colistin alone or colistin-vancomycin combination therapy at Chiang Mai University Hospital. A total of 365 critically ill patients met the inclusion criteria. The results in this study showed that after propensity score matching, colistin plus vancomycin showed no significant differences in the 30-day mortality compared to colistin alone. Likewise, for colistin plus vancomycin, compared with colistin therapy alone, there were no significant differences in the clinical response, microbiological response and nephrotoxicity. In conclusion, colistin plus vancomycin was no significant differences in 30-day mortality, clinical response, microbiological response compared to colistin alone for infections due to CRAB. The nephrotoxicity rates were similar for both groups, so colistin combination with vancomycin was not necessary for the management of infection caused by CRAB.

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.

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.

scholarly journals Pharmacodynamic profiling of optimal sulbactam regimens against carbapenem-resistant Acinetobacter baumannii for critically ill patients

2018 ◽  
Vol 8 (1) ◽  
pp. 14
Author(s):  
Wichai Santimaleeworagun ◽  
Weerayuth Saelim ◽  
Sudaluck Thunyaharn ◽  
Dhitiwat Changpradub ◽  
Piraporn Juntanawiwat
Keyword(s):  
Acinetobacter Baumannii ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Carbapenem Resistant

scholarly journals Colistin Population Pharmacokinetics after Application of a Loading Dose of 9 MU Colistin Methanesulfonate in Critically Ill Patients

2015 ◽  
Vol 59 (12) ◽  
pp. 7240-7248 ◽  
Author(s):  
Ilias Karaiskos ◽  
Lena E. Friberg ◽  
Konstantinos Pontikis ◽  
Konstantinos Ioannidis ◽  
Vasiliki Tsagkari ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Loading Dose ◽  
Gram Negative ◽  
Link Type ◽  
Colistin Methanesulfonate

ABSTRACTColistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430–3436, 2009,http://dx.doi.org/10.1128/AAC.01361-08; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241– 4249, 2012,http://dx.doi.org/10.1128/AAC.06426-11; S. M. Garonzik, J. Li, V. Thamlikitkul, D. L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284–3294, 2011,http://dx.doi.org/10.1128/AAC.01733-10). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (∼270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while colistin disposition followed a 1-compartment model. The average observed maximum colistin A plus B concentration was 2.65 mg/liter after the loading dose (maximum time was 8 h). A significantly higher availability of the measured A and B forms of colistimethate and colistin explained the higher-than-expected concentrations in the present study compared to those in previous studies. Creatinine clearance was a time-varying covariate of colistimethate clearance. The incidence of acute renal injury was 20%.

scholarly journals Population Pharmacokinetics of Colistin Methanesulfonate Sodium and Colistin in Critically Ill Patients: A Systematic Review

2021 ◽  
Vol 14 (9) ◽  
pp. 903
Author(s):  
Mohd Shafie Zabidi ◽  
Ruzilawati Abu Bakar ◽  
Nurfadhlina Musa ◽  
Suzana Mustafa ◽  
Wan Nazirah Wan Yusuf
Keyword(s):  
Plasma Concentration ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Reference Lists ◽  
Parameter Estimates ◽  
Dialysis Session ◽  
Loading Dose ◽  
Additional Dose ◽  
Comprehensive Understanding ◽  
Colistin Methanesulfonate

Understanding the pharmacokinetics parameter of colistin methanesulfonate sodium (CMS) and colistin is needed to optimize the dosage regimen in critically ill patients. However, there is a scarcity of pharmacokinetics parameters in this population. This review provides a comprehensive understanding of CMS and colistin pharmacokinetics parameters in this population. The relevant studies published in English that reported on the pharmacokinetics of CMS and colistin from 2000 until 2020 were systematically searched using the PubMed and Scopus electronic databases. Reference lists of articles were reviewed to identify additional studies. A total of 252 citation titles were identified, of which 101 potentially relevant abstracts were screened, and 25 full-text articles were selected for detailed analysis. Of those, 15 studies were included for the review. This review has demonstrated vast inter-study discrepancies in colistin plasma concentration and the pharmacokinetics parameter estimates. The discrepancies might be due to complex pathophysiological changes in the population studied, differences in CMS brand used, methodology, and study protocol. Application of loading dose of CMS and an additional dose of CMS after dialysis session was recommended by some studies. In view of inter-patient and intra-patient variability in colistin plasma concentration and pharmacokinetics parameters, personalized colistin dosing for this population is recommended.

scholarly journals Inhalation with intravenous loading dose of colistin in critically ill patients with pneumonia caused by carbapenem-resistant gram-negative bacteria

2019 ◽  
Vol 13 ◽  
pp. 175346661988552 ◽  
Author(s):  
Junsu Choe ◽  
You Min Sohn ◽  
Suk Hyeon Jeong ◽  
Hyo Jung Park ◽  
Soo Jin Na ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Gram Negative Bacteria ◽  
Loading Dose ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Optimal Dosing ◽  
Microbiological Outcome ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired

Background: Despite the increasing use of colistin in clinical practice, the optimal dosing, and administration route have not been established. This study aimed to evaluate the clinical outcome and safety of intravenous (IV) colistin with a loading dose (LD) and adjunctive aerosolized (AS) colistin administration in critically ill patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) caused by carbapenem-resistant gram-negative bacteria (CRGNB). Methods: We retrospectively reviewed 191 critically ill patients who received colistin for the treatment of HAP or VAP caused by CRGNB. Patients were divided into three groups: non-LD IV (patients received only IV colistin without LD), LD IV (patients received only IV colistin with LD), and AS–LD (patients received IV colistin with LD and adjunctive AS colistin). Results: There was no difference in clinical response between the three groups. However, the rate of microbiological eradication was significantly higher in the AS–LD group (60%) than in the non-LD IV (31%), and LD IV (33%) groups ( p = 0.010). Patients treated with adjunctive AS colistin in combination with LD IV had significantly lower 30-day mortality rates than patients treated with IV colistin alone ( p = 0.027). After adjusting for potential confounding factors, adjunctive AS colistin was still significantly associated with lower mortality (adjusted OR 0.338, CI 95% 0.132–0.864, p = 0.024). However, nephrotoxicity did not change according to the use of LD regimen and AS colistin administration ( p = 0.100). Conclusions: Adjunctive AS colistin in combination with IV colistin with LD was related to an improved 30-day mortality and microbiological outcome without an increase in nephrotoxicity in critically ill patients with HAP and VAP caused by CRGNB. The reviews of this paper are available via the supplemental material section.

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