Unresolved issues in the identification and treatment of carbapenem-resistant Gram-negative organisms

Kois, Abigail K; Nicolau, David P.; Kuti, Joseph L.

doi:10.1097/qco.0000000000000682

Cited by 15 publications

(9 citation statements)

References 89 publications

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“…One of the strategies for managing CRO infections is to use the existing antibiotics wisely and rationally to improve clinical efficacy and meanwhile reduce adverse events. For example, polymyxins are often used in combination with tigecycline (TGC) or carbapenems to treat CRO infections (7)(8)(9)(10), even though randomized controlled trials (RCTs) have confirmed that colistin/meropenem or colistin/rifampicin combinations are not superior to colistin alone in the treatment of carbapenemresistant Gram-negative bacilli or drug-resistant A. baumannii (11,12). However, only a few clinical studies have been conducted on polymyxin B/TGC (PMB/TGC) combination in treating CRO infections (13,14).…”

Section: Introductionmentioning

confidence: 99%

Polymyxin B/Tigecycline Combination vs. Polymyxin B or Tigecycline Alone for the Treatment of Hospital-Acquired Pneumonia Caused by Carbapenem-Resistant Enterobacteriaceae or Carbapenem-Resistant Acinetobacter baumannii

Chang

Wang²,

Zhao³

et al. 2022

Front. Med.

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IntroductionIt is not clear whether polymyxin B/tigecycline (PMB/TGC) combination is better than PMB or TGC alone in the treatment of hospital-acquired pneumonia (HAP) caused by carbapenem-resistant organisms (CROs).MethodsWe conducted a multicenter, retrospective cohort study in patients with HAP caused by CROs. The primary outcome was 28-day mortality, and the secondary outcomes included clinical success and the incidence of acute kidney injury (AKI). Multivariate Cox regression analysis was performed to examine the relationship between antimicrobial treatments and 28-day mortality by adjusting other potential confounding factors.ResultsA total of 364 eligible patients were included in the final analysis, i.e., 99 in the PMB group, 173 in the TGC group, and 92 in the PMB/TGC combination group. The 28-day mortality rate was 28.3% (28/99) in the PMB group, 39.3% (68/173) in the TGC group, and 48.9% (45/92) in the PMB/TGC combination group (p = 0.014). The multivariate Cox regression model showed that there was a statistically significant lower risk of 28-day mortality among participants in the PMB group when compared with the PMB/TGC combination group [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31–0.81, p = 0.004] and that participants in the TGC group had a lower risk of 28-day mortality than in the PMB/TGC combination group but without statistical significance. The incidence of AKI in the PMB group (52.5%) and the PMB/TGC combination group (53.3%) was significantly higher than that in the TGC group (33.5%, p = 0.001).ConclusionThe appropriate PMB/TGC combination was not superior to appropriate PMB therapy in the treatment of HAP caused by carbapenem-resistant Enterobacteriaceae/carbapenem-resistant Acinetobacter baumannii (CRE/CRAB) in terms of 28-day mortality.

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Section: Introductionmentioning

confidence: 99%

Polymyxin B/Tigecycline Combination vs. Polymyxin B or Tigecycline Alone for the Treatment of Hospital-Acquired Pneumonia Caused by Carbapenem-Resistant Enterobacteriaceae or Carbapenem-Resistant Acinetobacter baumannii

Chang

Wang²,

Zhao³

et al. 2022

Front. Med.

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“…Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a threat worldwide. Carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRA) are considered as carbapenem-resistant organisms (CROs) [ 5 ]. Enterobacterales is an order of Gram-negative bacteria, comprising seven families and more than 80 genera.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of Carbapenem-Resistant Gram-Negative Bacilli in Patients with Ventilator-Associated Pneumonia

et al. 2021

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Carbapenem-resistant Gram-negative bacilli (CR-GNB) has become a global threat. In hospital settings, the association of CR-GNB with ventilator-associated pneumonia (VAP) is a critical public health concern owing to their high resistance rate to most antibiotics. The present study aims to identify the frequency of carbapenem-resistance and to determine the rate of multidrug resistance (MDR), extensive drug resistance (XDR) and pan-drug resistance (PDR) among CR-GNB infections in VAP. Antimicrobial susceptibility testing was carried out using the disk diffusion method and the detection of carbapenemases was screened using the imipenem-E test and the modified carbapenem-inactivation method (mCIM). The isolates were verified by polymerase chain reaction (PCR) for the presence of blaNDM, blaSPM, blaVIM, blaIMP and blaGIM genes. 89.5%, 14%, 17.5%, 10.5%, 3.5% of isolates exhibited the presence of blaNDM, blaVIM, blaSPM, blaIMP and blaGIM, respectively. 76%, 17% and 7% of isolates were PDR, XDR, and MDR, respectively. Carbapenem-resistance genes were identified in a significant percentage and blaNDM was the most predominant gene. All isolates were highly resistant to most antibiotics. This health concern has proven to be a big challenge in developing countries such as Egypt, as it is associated with high morbidity, high mortality, and raised healthcare costs.

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“…GNB isolates testing resistant to any one of the Carbapenem group of antimicrobials (Ertapenem [only for CRE], Meropenem, Imipenem, Doripenem) were labelled as CR-GNB. 9 CFDC susceptibility testing of the CR-GNB isolates was performed by both reference BMD as well as DD. The study was approved by the institutional ethics committee of All India Institute of Medical Sciences [AIIMS], Bhubaneswar, Odisha (Ref Number: IEC/AIIMS BBSR/PG-Thesis/2019-20/100 dated 14th December 2019).…”

Section: Methodsmentioning

confidence: 99%

Analysis of In Vitro Activity of Cefiderocol Against Carbapenem-Resistant Gram-Negative Bacilli by Broth Microdilution and Disk Diffusion Method: A Single-Center Study in Odisha, India

Nayak¹,

Behera²,

Mohanty³

et al. 2022

IDR

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Introduction Cefiderocol (CFDC), a novel semi-synthetic siderophore cephalosporin has been developed to combat the menace of infections caused by carbapenem-resistant Gram-negative bacilli (CR-GNB) including Carbapenem-resistant Enterobacterales (CRE) and Carbapenem-resistant Nonfermenting Gram-negative bacilli (CR-NFGNB). Methods We determined the in vitro activity of CFDC against a contemporary collection of 503 CR-GNB isolates by the reference broth microdilution method (BMD) using Iron depleted cation adjusted Mueller-Hinton broth (ID-CAMHB). Performance of CFDC disk diffusion (DD) was evaluated against the reference BMD, as an alternative convenient testing method. Molecular characterization of carbapenemase in CR-GNB was performed by PCR targeting bla NDM-1 , bla OXA-48like alleles , bla KPC , bla IMP , and, bla VIM . Minimum inhibitory concentration (MIC) distribution of CFDC in CR-GNB harbouring different carbapenemase enzymes was also analyzed. Results In our study, 81.7% (411/503) of CR-GNB isolates [81.3%, (278/342) CRE and 82.6% (133/161) CR-NFGNB] were susceptible to CFDC ( p >0.05). Categorical agreement (CA) of DD ranged from 79.8% to 87.5%, Minor error (mE) ranged from 0 to 14%, Major error (ME) ranged from 0 to 3.5%, and Very Major error (VME) ranged from 0 to 12.5% with variations by species tested. Overall CFDC MIC50 and MIC90 values of CR-GNB isolates without any carbapenemase genes were higher as compared to those with the presence of carbapenemase genes (4 µg/mL and 128 µg/mL versus 2 µg/mL and 16 µg/mL respectively). Discussion CFDC is not yet available for clinical use in India. Hence, multicentric studies are the need of the hour in India for standardization of CFDC susceptibility using disks and CAMHB from different manufacturers as well as understanding mechanisms of high MIC values.

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Unresolved issues in the identification and treatment of carbapenem-resistant Gram-negative organisms

Cited by 15 publications

References 89 publications

Polymyxin B/Tigecycline Combination vs. Polymyxin B or Tigecycline Alone for the Treatment of Hospital-Acquired Pneumonia Caused by Carbapenem-Resistant Enterobacteriaceae or Carbapenem-Resistant Acinetobacter baumannii

Polymyxin B/Tigecycline Combination vs. Polymyxin B or Tigecycline Alone for the Treatment of Hospital-Acquired Pneumonia Caused by Carbapenem-Resistant Enterobacteriaceae or Carbapenem-Resistant Acinetobacter baumannii

Characteristics of Carbapenem-Resistant Gram-Negative Bacilli in Patients with Ventilator-Associated Pneumonia

Analysis of In Vitro Activity of Cefiderocol Against Carbapenem-Resistant Gram-Negative Bacilli by Broth Microdilution and Disk Diffusion Method: A Single-Center Study in Odisha, India

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