Multidrug-Resistant Gram-Negative Bacterial Infections in the Hospital Setting: Overview, Implications for Clinical Practice, and Emerging Treatment Options

2016 ◽  
Vol 22 (5) ◽  
pp. 412-431 ◽  
Author(s):  
Elizabeth Cerceo ◽  
Steven B. Deitelzweig ◽  
Bradley M. Sherman ◽  
Alpesh N. Amin
Keyword(s):  
Clinical Practice ◽  
Bacterial Infections ◽  
Treatment Options ◽  
Hospital Setting ◽  
Multidrug Resistant ◽  
Gram Negative

scholarly journals Case Commentary: the Need for Cefiderocol Is Clear, but Are the Supporting Clinical Data?

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ryan K. Shields
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Salvage Therapy ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Potential Utility ◽  
Gram Negative

ABSTRACT Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.

scholarly journals The Burden of the Serious and Difficult-to-Treat Infections and a New Antibiotic Available: Cefiderocol

2021 ◽  
Vol 11 ◽  
Author(s):  
Yasaman Taheri ◽  
Nataša Joković ◽  
Jelena Vitorović ◽  
Oliver Grundmann ◽  
Alfred Maroyi ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Antimicrobial Treatment ◽  
Bacterial Cells ◽  
Gram Negative ◽  
Pubmed Database ◽  
Severe Infections ◽  
Unique Cell

Background: Infection is a disease that can occur due to the entrance of a virus, bacteria, and other infectious agents. Cefiderocol is innovative cephalosporin drug that belongs to a special class of antibiotics, sideromycins, which are taken up by bacterial cells through active transport. The unique cell entry and stability to β-lactamases allow cefiderocol to overcome the most common resistance mechanisms in Gram-negative bacteria.Objective: This article aims to highlight the therapeutic efficacy, safety and tolerability of cefiderocol, with a focus on the FDA label.Methods: The pharmacological properties of cefiderocol are also summarized. In this review, we conducted literature research on the PubMed database using the following keywords: “antimicrobial treatment”, “new antibiotic”, “cefiderocol”, “siderophore cephalosporin”; “multidrug-resistant”, “Gram-negative bacilli”, “critically ill patients”; “severe bacterial infections”.Results: There were identified the most relevant data about the pathophysiology of serious bacterial infections, antibacterial mechanism of action, microbiology, mechanisms of resistance, pharmacokinetic and pharmacodynamic properties of cefiderocol.Conclusion: The results highlighted there appeared to be clinical benefit from cefiderocol in the treatment of infections caused by Gram-negative aerobic microorganisms in adult patients with severe infections and limited treatment options.

scholarly journals Multidrug-Resistant Gram-Negative Bacilli: A Retrospective Study of Trends in a Tertiary Healthcare Unit

Medicina ◽  
2018 ◽  
Vol 54 (6) ◽  
pp. 92 ◽  
Author(s):  
Delia Muntean ◽  
Florin-George Horhat ◽  
Luminița Bădițoiu ◽  
Victor Dumitrașcu ◽  
Iulia-Cristina Bagiu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Metabolic Diseases ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Trend Test ◽  
Gram Negative ◽  
Increasing Trend ◽  
Tertiary Healthcare ◽  
Resistant Strains

Background and objective: Bacterial multidrug resistance is particularly common in Gram-negative bacilli (GNB), with important clinical consequences regarding their spread and treatment options. The aim of this study was to investigate the trend of multidrug-resistant GNB (MDR-GNB) in high-risk hospital departments, between 2000–2015, in intervals of five years, with the intention of improving antibiotic therapy policies and optimising preventive and control practices. Materials and methods: This is an observational, retrospective study performed in three departments of the most important tertiary healthcare unit in the southwestern part of Romania: the Intensive Care Unit (ICU), the General Surgery Department (GSD), and the Nutrition and Metabolic Diseases Department (NMDD). MDR was defined as acquired resistance to at least one agent in three or more antimicrobial categories. Trends over time were determined by the Cochran–Armitage trend test and linear regression. Results: During the study period, a total of 2531 strains of MDR-GNB were isolated in 1999 patients: 9.20% in 2000, 18.61% in 2005, 37.02% in 2010, and 35.17% in 2015. The most significant increasing trend was recorded in the ICU (gradient = 7.63, R² = 0.842, p < 0.001). The most common MDR-GNB in the ICU was isolated from bronchoalveolar aspiration samples. Concerning the proportion of different species, most of the changes were recorded in the ICU, where a statistically significant increasing trend was observed for Proteus mirabilis (gradient = 2.62, R2 = 0.558, p < 0.001) and Acinetobacter baumannii (gradient = 2.25, R2 = 0.491, p < 0.001). Analysis of the incidence of the main resistance phenotypes proportion identified a statistically significant increase in carbapenem resistance in the ICU (Gradient = 8.27, R² = 0.866, p < 0.001), and an increased proportion of aminoglycoside-resistant strains in all three departments, but more importantly in the ICU and GSD. Conclusion: A statistically significant increasing trend was observed in all three departments; the most significant one was recorded in the ICU, where after 2010, carbapenem-resistant strains were isolated.

scholarly journals The Odilorhabdin Antibiotic Biosynthetic Cluster and Acetyltransferase Self-Resistance Locus Are Niche and Species Specific

mBio ◽  
2022 ◽  
Author(s):  
Anne Lanois-Nouri ◽  
Lucile Pantel ◽  
Jun Fu ◽  
Jessica Houard ◽  
Jean-Claude Ogier ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Small Subunit ◽  
Cationic Peptides ◽  
Resistance Locus ◽  
Gram Negative ◽  
Species Specific ◽  
Bacterial Translation

Odilorhabdins (ODLs) constitute a novel antibiotic family with promising properties for treating problematic multidrug-resistant Gram-negative bacterial infections. ODLs are 10-mer linear cationic peptides inhibiting bacterial translation by binding to the small subunit of the ribosome.

scholarly journals Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

2020 ◽  
Vol 8 (2) ◽  
pp. 191 ◽  
Author(s):  
Despoina Koulenti ◽  
Elena Xu ◽  
Andrew Song ◽  
Isaac Yin Sum Mok ◽  
Drosos E. Karageorgopoulos ◽  
...  
Keyword(s):  
Safety Profile ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Multi Drug Resistance ◽  
Gram Positive ◽  
Treatment Regimens ◽  
Gram Positive Bacteria

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

scholarly journals Cyathea gigantea (Cyatheaceae) as an antimicrobial agent against multidrug resistant organisms

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Kathakali Nath ◽  
Anupam Das Talukdar ◽  
Mrinal Kanti Bhattacharya ◽  
Deepshikha Bhowmik ◽  
Shiela Chetri ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Property ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Synergistic Activity ◽  
Gram Positive ◽  
Traditional Use ◽  
Gram Negative ◽  
Multidrug Resistant Organisms

Abstract Background Rapid emergence of multidrug resistant (MDR) organisms in hospital and community settings often result into treatment failure, thus leading the clinicians with fewer treatment options. Cyathea gigantea, an ethnomedicinally important fern used in cuts and wound infections. So, if this medicinal plant is used in treating the MDR infections then it might bring certain relief in future treatment options. Methods Antibacterial activity of C. gigantea against MDR bacteria was assed using well diffusion and broth microdilution methods to determine the diameters of growth inhibition zones, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Synergistic activity was also determined with the conventional antibiotics by disc diffusion method followed by FIC index of each of the tested antibiotic was calculated. The active extract was then subjected to fractionation by column chromatography and antibacterial activity was done with each of the collected fractions. Results Crude extract of C. gigantea was found to be active against all the tested organisms. The MIC was 200 μg/ml against Gram-positive i.e., Staphylococcus aureus ATCC 25923 and 400 μg/ml against Gram-negative i.e., Escherichia coli ATCC 25922 and Pseudomonas aeruginosa PAO1, while the MBC was 400 μg/ml in case of Gram-positive and 800 μg/ml for Gram-negative. The synergistic activity revealed that the plant extract increased the antibacterial property of the studied antibiotics and the FIC index showed that significant synergistic activity was shown by ciprofloxacin followed by tetracycline, ampicillin and oxacillin. Antibacterial activity with the fractionated extract showed that the FR II, FR III and FR IV were active against both Gram-positive and Gram-negative bacteria, whereas FR I, FR V and FR VI did not show antibacterial property against any of the tested bacteria. Conclusions Extracts of C. gigantea was found active against both selected Gram-positive and Gram-negative organisms and thus offers the scientific basis for the traditional use of the fern. The present study also provides the basis for future study to validate the possible use against multidrug resistant organisms.

scholarly journals Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections

2019 ◽  
Vol 6 (12) ◽  
Author(s):  
Sarah C J Jorgensen ◽  
Trang D Trinh ◽  
Evan J Zasowski ◽  
Abdalhamid M Lagnf ◽  
Sahil Bhatia ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Kidney Injury ◽  
The United States ◽  
Multidrug Resistant ◽  
Clinical Failure ◽  
Gram Negative ◽  
Pseudomonas Spp ◽  
Clostridioides Difficile ◽  
Gastrointestinal Intolerance ◽  
Total Data

Abstract Background We conducted this study to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam (CZA) for a range of multidrug-resistant Gram-negative (MDR-GN) infections. Methods This is a multicenter, retrospective cohort study conducted at 6 medical centers in the United States between 2015 and 2019. Adult patients who received CZA (≥72 hours) were eligible. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of infection on CZA. Results In total, data from 203 patients were evaluated. Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas spp were isolated from 117 (57.6%) and 63 (31.0%) culture specimens, respectively. The most common infection sources were respiratory (37.4%), urinary (19.7%), and intra-abdominal (18.7%). Blood cultures were positive in 22 (10.8%) patients. Clinical failure, 30-day mortality, and 30-day recurrence occurred in 59 (29.1%), 35 (17.2%), and 12 (5.9%) patients, respectively. On therapy, CZA resistance developed in 1 of 62 patients with repeat testing. Primary bacteremia or respiratory tract infection and higher SOFA score were positively associated with clinical failure (adjusted odds ratio [aOR] = 2.270, 95% confidence interval [CI] = 1.115–4.620 and aOR = 1.234, 95% CI = 1.118–1.362, respectively). Receipt of CZA within 48 hours of infection onset was protective (aOR, 0.409; 95% CI, 0.180–0.930). Seventeen (8.4%) patients experienced a potential drug-related adverse effect (10 acute kidney injury, 3 Clostridioides difficile infection, 2 rash, and 1 each gastrointestinal intolerance and neutropenia) Conclusions Ceftazidime-avibactam is being used to treat a range of MDR-GN infections including Pseudomonas spp as well as CRE.

scholarly journals Bacteria causing ventriculoperitoneal shunt infections in a Kenyan population

2015 ◽  
Vol 15 (2) ◽  
pp. 150-155 ◽  
Author(s):  
Naomi Ochieng' ◽  
Humphrey Okechi ◽  
Susan Ferson ◽  
A. Leland Albright
Keyword(s):  
Ventriculoperitoneal Shunt ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Infectious Complications ◽  
Gram Negative Bacteria ◽  
Shunt Insertion ◽  
Gram Negative ◽  
Western Literature ◽  
Sub Saharan ◽  
Few Data

OBJECT Ventriculoperitoneal shunt (VPS) infections are a major cause of morbidity and mortality in patients with hydrocephalus. Most data about these infections come from the Western literature. Few data about infecting organisms in Africa are available, yet knowledge of these organisms is important for the prevention and treatment of infectious complications. The purpose of this study was to determine the organisms cultured from infected shunts in a rural Kenyan hospital. METHODS The authors conducted a retrospective study of patients with VPS infections recorded in the neurosurgical database of BethanyKids at Kijabe Hospital between September 2010 and July 2012. RESULTS Among 53 VPS infections confirmed by culture, 68% occurred in patients who were younger than 6 months. Seventy-nine percent of the infections occurred within 2 months after shunt insertion. Only 51% of infections were caused by Staphylococcus species (Staphylococcus aureus 25%, other Staphylococcus species 26%), whereas 40% were caused by gram-negative bacteria. All S. aureus infections and 79% of other Staphylococcus infections were sensitive to cefazolin, but only 1 of 21 gram-negative bacteria was sensitive to it. The majority of gram-negative bacterial infections were multidrug resistant, but 17 of the 20 gram-negative bacteria were sensitive to meropenem. Gram-negative bacterial infections were associated with worse outcomes. CONCLUSIONS The high proportion of gram-negative infections differs from data in the Western literature, in which Staphylococcus epidermidis is by far the most common organism. Once a patient is diagnosed with a VPS infection in Kenya, immediate treatment is recommended to cover both gram-positive and gram-negative bacterial infections. Data from other Sub-Saharan countries are needed to determine if those countries have the same increased frequency of gram-negative infections.

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