scholarly journals Polymyxins: To Combine or Not to Combine?

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 38 ◽  
Author(s):  
Federico Perez ◽  
Nadim G. El Chakhtoura ◽  
Mohamad Yasmin ◽  
Robert A. Bonomo
Keyword(s):  
Gram Negative Bacteria ◽  
Beta Lactamases ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Randomized Controlled ◽  
The Past ◽  
Carbapenem Resistant ◽  
Clinical Observations ◽  
New Antibiotics ◽  
Carbapenem Resistant Enterobacteriaceae

Polymyxins have been a mainstay for the treatment of extensively drug resistant (XDR) Gram-negative bacteria for the past two decades. Many questions regarding the clinical use of polymyxins have been answered, but whether the administration of polymyxins in combination with other antibiotics leads to better outcomes remains unknown. This review discusses the limitations of observational studies that suggest a benefit of combinations of colistin and carbapenems to treat infections caused by carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, and summarizes the results of randomized controlled trials in which treatment with colistin in combination with meropenem or rifampin does not lead to better clinical outcomes than colisitn monotherapy in infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). Although the introduction of new antibiotics makes it possible to treat certain strains of CRE and carbapenem-resistant P. aeruginosa (CRPA) with polymyxin-sparing regimens, the use of polymyxins is, for now, still necessary in CRAB and in CRE and CRPA harboring metallo-beta-lactamases. Therefore, strategies must be developed to optimize polymyxin-based treatments, informed by in vitro hollow fiber models, careful clinical observations, and high-quality evidence from appropriately designed trials.

scholarly journals An Update on Eight “New” Antibiotics against Multidrug-Resistant Gram-Negative Bacteria

2021 ◽  
Vol 10 (5) ◽  
pp. 1068
Author(s):  
Erlangga Yusuf ◽  
Hannelore I. Bax ◽  
Nelianne J. Verkaik ◽  
Mireille van Westreenen
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Beta Lactamases ◽  
New Antibiotics ◽  
Tract Infections ◽  
The U.S

Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam).

scholarly journals 1591. Antibiotic Utilization Trends in Veterans Affairs (VA) Patients with Carbapenem Resistant Enterobacteriaceae (CRE) Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S792-S792
Author(s):  
Alfredo Traversa ◽  
Linda Poggensee ◽  
Geneva M Wilson ◽  
Katie J Suda ◽  
Charlesnika T Evans ◽  
...  
Keyword(s):  
Treatment Options ◽  
Blood Stream ◽  
Chi Square ◽  
Blood Stream Infections ◽  
Exact Test ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
New Antibiotics ◽  
Chi Square Test ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) are classified as an “urgent threat” to public health. Historically, colistin and tigecycline had been considered the drugs of choice for CRE infections, while other agents such as aminoglycosides and carbapenems had been used as adjunctive therapy. However, the FDA approval of ceftazidime-avibactam in 2015, meropenem-vaborbactam in 2017, and plazomicin in 2018 has expanded treatment options. Our purpose was to assess trends in CRE treatment for “new” antibiotics (ceftazidime-avibactam, meropenem-vaborbactam, plazomicin) as compared with other antibiotics with CRE activity. Methods This was a retrospective cohort study describing treatment of CRE blood stream infections (BSI) across 134 VA facilities from 2012-2018. Patients were censored at their first positive blood culture with CRE. Categorical data was assessed with a Fisher’s exact test or chi-square test. Trends test and logistic regression were used to describe changes in CRE treatment over time. Results 724 patients with positive blood cultures for CRE were identified during the study period. Most patients were male (94%), white (32%) or Hispanic (38%), and the mean age was 71.5+11.9. Of those patients that received antibiotics (N=697), 53.4% carbapenems, 40.3% received aminoglycosides, 39.3% received polymyxins, 32.9% penicillins, 32.6% extended spectrum cephalosporins, 26.1% fluoroquinolones, 11.6% ceftazidime/avibactam, and 0.4% ceftolazone/tazobactam. Over the study period, there was decreased utilization of aminoglycosides (P < 0.0026) and colistin (P< 0.002) and increases in extended spectrum cephalosporins (P < 0.001) and ceftazidime/avibactam (P < 0.001). Conclusion Utilization of “older” agents such as aminoglycosides and polymyxins for the treatment of CRE blood stream infections is decreasing in the VA. Treating CRE with ceftazidime/avibactam, a newly approved antibiotic, and extended spectrum cephalosporins are increasing. Disclosures All Authors: No reported disclosures

scholarly journals THE FIRST INVESTIGATION OF AAC(6’)-Ib ENZYME IN CARBAPENEM-RESISTANT ENTEROBACTERIACEAE ISOLATED FROM INDONESIAN PATIENTS

2019 ◽  
Vol 2 (1) ◽  
pp. 8-14
Author(s):  
Beauty Novianty ◽  
Ella Amalia ◽  
Ziske Maritska ◽  
Yuwono Yuwono ◽  
Lusia Hayati
Keyword(s):  
Resistance Mechanism ◽  
Test Results ◽  
Gram Negative ◽  
Therapy Options ◽  
The Past ◽  
Carbapenem Resistant ◽  
Long Time ◽  
Pcr Method ◽  
Vitek 2 ◽  
Carbapenem Resistant Enterobacteriaceae

Background: Over the past decade, numbers of Carbapenemase Producing-Carbapenem Resistant Enterobacteriaceae (CP-CRE) has been increasing worldwide and it has been becoming a threat because of its resistance against carbapenem which is considered as the “last resort” antibiotic. Therapy options for its infection are still limited. Aminoglycoside serves as one of the most commonly used antibiotics, but the resistance against it has already been presented for a long time. Aminoglycoside Modifying Enzyme (AME) is the most important resistance mechanism against aminoglycoside. AAC(6’)-Ib enzyme is one of the most common AME produced by the gram-negative bacteria.Objectives: This study wished to identify the gene of this enzyme among CRE isolated from infected Indonesian patients in Dr. Mohammad Hoesin Hospital Palembang.Methods: Twenty-eight isolates collected from CRE-infected patients identified by Vitek 2 Compact (bioMerieux, USA) in dr. Mohammad Hoesin Hospital Palembang during September—November 2017. AAC(6’)-Ib gene was identified using PCR method, then visualize by electrophoresis. The result is then analyzed by comparing it with a susceptibility test.  Results: Out of 28 samples, AAC(6’)-Ib is identified in 22 (78.57%) samples. Samples with AAC(6’)-Ib showed to be less resistant to various antibiotics, significantly to amikacin (p=0.023).Conclusion: AAC(6’)-Ib gene is found in most of samples implying its frequent occurrence in Indonesian patients.

scholarly journals Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks

2017 ◽  
Vol 114 (5) ◽  
pp. 1135-1140 ◽  
Author(s):  
Gustavo C. Cerqueira ◽  
Ashlee M. Earl ◽  
Christoph M. Ernst ◽  
Yonatan H. Grad ◽  
John P. Dekker ◽  
...  
Keyword(s):  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Phylogeographic Structure ◽  
Aggressive Approach ◽  
Beta Lactamases ◽  
Carbapenem Resistant ◽  
Local Transmission ◽  
California Hospital ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
The Continuum

Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species. We found eight species exhibiting resistance, with the majority of our sample being the sequence type 258 (ST258) lineage ofKlebsiella pneumoniae. There was very little evidence of extensive hospital outbreaks, but a great deal of variation in resistance mechanisms and the genomic backgrounds carrying these mechanisms. Local transmission was evident in clear phylogeographic structure between the samples from the two coasts. The most common resistance mechanisms were KPC (K. pneumoniaecarbapenemases) beta-lactamases encoded byblaKPC2,blaKPC3, andblaKPC4, which were transferred between strains and species by seven distinct subgroups of the Tn4401element. We also found evidence for previously unrecognized resistance mechanisms that produced resistance when transformed into a susceptible genomic background. The extensive variation, together with evidence of transmission beyond limited clonal outbreaks, points to multiple unsampled transmission chains throughout the continuum of care, including asymptomatic carriage and transmission of CRE. This finding suggests that to control this threat, we need an aggressive approach to surveillance and isolation.

scholarly journals Intravenous Colistin Monotherapy versus Combination Therapy against Carbapenem-Resistant Gram-Negative Bacteria Infections: Meta-Analysis of Randomized Controlled Trials

2018 ◽  
Vol 7 (8) ◽  
pp. 208 ◽  
Author(s):  
I-Ling Cheng ◽  
Yu-Hung Chen ◽  
Chih-Cheng Lai ◽  
Hung-Jen Tang
Keyword(s):  
Combination Therapy ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Randomized Controlled ◽  
Carbapenem Resistant ◽  
Significant Difference ◽  
All Cause Mortality

This meta-analysis aims to compare intravenous colistin monotherapy and colistin-based combination therapy against carbapenem-resistant gram-negative bacteria (GNB) infections. PubMed, Embase, and Cochrane databases were searched up to July 2018. Only randomized controlled trials (RCTs) evaluating colistin alone and colistin-based combination therapy in the treatment of carbapenem-resistant GNB infections were included. The primary outcome was all-cause mortality. Five RCTs including 791 patients were included. Overall, colistin monotherapy was associated with a risk ratio (RR) of 1.03 (95% confidence interval (CI), 0.89–1.20, I2 = 0%) for all-cause mortality compared with colistin-based combination therapy. The non-significant difference was also detected in infection-related mortality (RR, 1.23, 95% CI, 0.91–1.67, I2 = 0%) and microbiologic response (RR, 0.86, 95% CI, 0.72–1.04, I2 = 62%). In addition, no significant difference was observed in the subgroup analysis—high or low dose, with or without a loading dose, carbapenem-resistant Acinetobacter baumannii infections, and in combination with rifampicin. Finally, colistin monotherapy was not associated with lower nephrotoxicity than colistin combination therapy (RR, 0.98; 95% CI, 0.84–1.21, I2 = 0%). Based on the analysis of the five RCTs, no differences were found between colistin monotherapy and colistin-based combination therapy against carbapenem-resistant GNB infections, especially for A. baumannii infections.

scholarly journals 621. In vitro Ceftazidime: Avibactam Resistance in Carbapenem-Resistant Enterobacteriaceae Isolates

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S288-S289
Author(s):  
Maymonah Belal ◽  
Lori Villasis ◽  
Elizabeth Diago-Navarro ◽  
Michael Motley ◽  
Allen Young; Eric Spitzer ◽  
...  
Keyword(s):  
Resistant Isolate ◽  
Ventilator Associated Pneumonia ◽  
Repeated Testing ◽  
Klebsiella Species ◽  
Carbapenem Resistant ◽  
Strain Collection ◽  
Enterobacter Species ◽  
Resistant Strains ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Ceftazidime–avibactam (CAZ-AVI) is a new antibiotic with activity against many Carbapenem-resistant Enterobacteriaceae (CRE). Although CAZ-AVI resistance in CRE has been reported, it is not consistently assessed. Our study aimed to assess the prevalence of CAZ-AVI resistance in CRE isolated from patients with and without prior exposure to CAZ-AVI. Methods We tested 116 CRE isolates for CAZ-AVI resistance by Kirby–Bauer (KB) disk diffusion susceptibility. Resistant isolates were verified by repeat KB and E-test performed by the Stony Brook Hospital laboratory. The blaKPC gene of resistant strains was amplified by PCR and sequenced. Patient data were used to determine whether patients were colonized or infected, and whether they were exposed to CAZ-AVI. Results Of the 116 CRE isolates from 86 patients (96 encounters), 50% were Klebsiella species, 23.2% were Enterobacter species, 10.3% Escherichia coli and 16.5% other CRE. They were recovered from colonized (37%) and infected (63%) patients of which 18% were treated with CAZ-AVI during their hospitalizations (median duration of therapy, 6 days). Two CRE isolates (1.7%) were found to be resistant on repeated testing. One isolate was K. pneumoniae derived from the sputum of a patient diagnosed with ventilator-associated pneumonia who received 40 days of CAZ-AVI therapy prior to isolation of the resistant isolate (KB diameter 20 mm, MIC > 512 μg/mL by E-Test). Sequencing of the strain’s blaKPC3 gene revealed a previously described Ambler-position D179Y mutation that has been shown to convey resistance. The second CAZ-AVI-resistant K. pneumoniae (KB diameter 19 mm, MIC 64 μg/mL by E-test) was isolated from the urine of a colonized patient naïve to CAZ-AVI therapy. The strain’s blaKPC10 gene had no mutations. Conclusion In our strain collection, the rate of resistance to CAZ-AVI remains low <2%. Although we found one mutation (D179Y) previously linked to CAZ-AVI resistance we also discovered one K. pneumoniae isolate with in vitro resistance to CAZ-AVI that did not exhibit any blaKPC mutations conveying CAZ-AVI resistance. Interestingly, this strain was derived from a patient with no prior CAZ-AVI exposure. Whole-genome sequencing will be performed to identify other genes or mutations that may confer resistance. Disclosures All authors: No reported disclosures.

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