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 Emerging Treatment Options for Multi-Drug-Resistant Bacterial Infections

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 519
Author(s):  
Roberto Giurazza ◽  
Maria Civita Mazza ◽  
Roberto Andini ◽  
Pasquale Sansone ◽  
Maria Caterina Pace ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Resistance Mechanisms ◽  
Antimicrobial Treatment ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Gram Positive ◽  
Strict Adherence ◽  
Gram Negative ◽  
Gram Positive Cocci

Antimicrobial resistance (AMR) remains one of the top public health issues of global concern. Among the most important strategies for AMR control there is the correct and appropriate use of antibiotics, including those available for the treatment of AMR pathogens. In this article, after briefly reviewing the most important and clinically relevant multi-drug-resistant bacteria and their main resistance mechanisms, we describe the emerging antimicrobial options for both MDR Gram-positive cocci and Gram-negative bacilli, including recently marketed agents, molecules just approved or under evaluation and rediscovered older antibiotics that have regained importance due to their antimicrobial spectrum. Specifically, emerging options for Gram-positive cocci we reviewed include ceftaroline, ceftobiprole, tedizolid, dalbavancin, and fosfomycin. Emerging treatment options for Gram-negative bacilli we considered comprise ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, aztreonam-avibactam, minocycline, fosfomycin, eravacycline, plazomicin, and cefiderocol. An exciting scenario is opening today with the long awaited growing availability of novel molecules for the treatment of AMR bacteria. Knowledge of mechanisms of action and resistance patterns allows physicians to increasingly drive antimicrobial treatment towards a precision medicine approach. Strict adherence to antimicrobial stewardship practices will allow us to preserve the emerging antimicrobials for our future.

scholarly journals Colistin Resistance in Enterobacterales Strains – A Current View

2019 ◽  
Vol 68 (4) ◽  
pp. 417-427 ◽  
Author(s):  
ELŻBIETA M. STEFANIUK ◽  
STEFAN TYSKI
Keyword(s):  
Bacterial Resistance ◽  
Treatment Options ◽  
Animal Husbandry ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Current View ◽  
Dilution Method ◽  
Bacterial Strains ◽  
Plant Cultivation ◽  
Severe Infections

Colistin is a member of cationic polypeptide antibiotics known as polymyxins. It is widely used in animal husbandry, plant cultivation, animal and human medicine and is increasingly used as one of the last available treatment options for patients with severe infections with carbapenem-resistant Gram-negative bacilli. Due to the increased use of colistin in treating infections caused by multidrug-resistant (MDR) bacteria, the resistance to this antibiotic ought to be monitored. Bacterial resistance to colistin may be encoded on transposable genetic elements (e.g. plasmids with the mcr genes). Thus far, nine variants of the mcr gene, mcr-1 – mcr-9, have been identified. Chromosomal resistance to colistin is associated with the modification of lipopolysaccharide (LPS). Various methods, from classical microbiology to molecular biology methods, are used to detect the colistin-resistant bacterial strains and to identify resistance mechanisms. The broth dilution method is recommended for susceptibility testing of bacteria to colistin.

scholarly journals Cefiderocol, a new antibiotic against multidrug-resistant Gram-negative bacteria

2021 ◽  
Vol 34 (Suppl 1) ◽  
pp. 41-43
Author(s):  
José Tiago Silva ◽  
Francisco López-Medrano
Keyword(s):  
Bacterial Pneumonia ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Phase Iii ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Tract Infections ◽  
Transport Channels ◽  
Hospital Acquired

Cefiderocol is a novel catechol-substituted siderophore cephalosporin that binds to the extracellular free iron, and uses the bacterial active iron transport channels to penetrate in the periplasmic space of Gram-negative bacteria (GNB). Cefiderocol overcomes many resistance mechanisms of these bacteria. Cefiderocol is approved for the treatment of complicated urinary tract infections, hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia in the case of adults with limited treatment options, based on the clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In the CREDIBLE-CR trial, a higher all-cause mortality was observed in the group of patients who received cefiderocol, especially those with severe infections due to Acinetobacter spp. Further phase III clinical studies are necessary in order to evaluate cefiderocol´s efficacy in the treatment of serious infections.

scholarly journals Intra-pleural colistin methanesulfonate therapy for pleural infection caused by carbapenem-resistant Acinetobacter baumannii: a successful case report

2014 ◽  
Vol 6 (3) ◽  
Author(s):  
Muhammad Asim Rana ◽  
Basheer Abd El Rahaman ◽  
Ahmed Fouad Mady ◽  
Mohammed Al Odat ◽  
Abdurehman Al Harthy ◽  
...  
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Unsuccessful Treatment ◽  
Successful Case ◽  
Pleural Infection ◽  
Colistin Methanesulfonate

Infections caused by carbapenem-resistant, Gram-negative bacteria are an increasing clinical challenge, since the antimicrobial treatment options are often limited to colistin methanesulfonate. No data are available regarding the pharmacokinetics of colistin in pleural fluid. We report the case of a 92-year old man with ventilator-associated pneumonia and pleurisy caused by <em>Acinetobacter</em> <em>baumannii</em> and <em>Escherichia coli</em>, which were both multidrug-resistant. After an unsuccessful treatment with intravenous colistin methanesulfonate and imipenem-cilastatin, the addition of intra-pleural colistin methanesulfonate to the intravenous treatment led to a prompt clinical, radiological and microbiological resolution. This is the first report of a successful use of intra-pleural colistin in the literature. The intra-pleural colistin therapy should be considered in selected cases of pleurisy caused by multi-resistant Gram-negative bacteria.

Colicin-like bacteriocins as novel therapeutic agents for the treatment of chronic biofilm-mediated infection

2012 ◽  
Vol 40 (6) ◽  
pp. 1549-1552 ◽  
Author(s):  
Carla L. Brown ◽  
Karen Smith ◽  
Laura McCaughey ◽  
Daniel Walker
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Wide Range ◽  
Species Specific

The emergence of pan-resistant strains of Gram-negative pathogens and the ability of many bacteria to form multidrug-resistant biofilms during chronic infection poses the grave threat of bacterial infections that are truly untreatable with our current armoury of antibiotics. Despite obvious clinical need, few new antibiotics have entered clinical practice in recent years. For ‘difficult to treat’ Gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli, where the presence of outer membrane and multidrug-efflux pumps severely limit the effectiveness of whole classes of antibiotics, the need is particularly pressing. An alternative approach to antimicrobial treatment is to use the well-characterized species-specific colicin-like bacteriocins which are produced by a wide range of Gram-negative bacteria, including Pseudomonas aeruginosa and Escherichia coli. Our current work on colicin-like bacteriocins aims to determine whether these potent antimicrobial agents are effective at killing bacteria growing in the biofilm state and during infection.

scholarly journals Efficacy of Lysophosphatidylcholine as Direct Treatment in Combination with Colistin against Acinetobacter baumannii in Murine Severe Infections Models

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 194
Author(s):  
Andrea Miró-Canturri ◽  
Rafael Ayerbe-Algaba ◽  
Manuel Enrique Jiménez-Mejías ◽  
Jerónimo Pachón ◽  
Younes Smani
Keyword(s):  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Experimental Models ◽  
Antimicrobial Treatment ◽  
Clinical Settings ◽  
Monotherapy Group ◽  
Bacterial Concentration ◽  
Sepsis Model ◽  
Severe Infections ◽  
Stimulation Of

The stimulation of the immune response to prevent the progression of an infection may be an adjuvant to antimicrobial treatment. Here, we aimed to evaluate the efficacy of lysophosphatidylcholine (LPC) treatment in combination with colistin in murine experimental models of severe infections by Acinetobacter baumannii. We used the A. baumannii Ab9 strain, susceptible to colistin and most of the antibiotics used in clinical settings, and the A. baumannii Ab186 strain, susceptible to colistin but presenting a multidrug-resistant (MDR) pattern. The therapeutic efficacies of one and two LPC doses (25 mg/kg/d) and colistin (20 mg/kg/8 h), alone or in combination, were assessed against Ab9 and Ab186 in murine peritoneal sepsis and pneumonia models. One and two LPC doses combined with colistin and colistin monotherapy enhanced Ab9 and Ab186 clearance from spleen, lungs and blood and reduced mice mortality compared with those of the non-treated mice group in both experimental models. Moreover, one and two LPC doses reduced the bacterial concentration in tissues and blood in both models and increased mice survival in the peritoneal sepsis model for both strains compared with those of the colistin monotherapy group. LPC used as an adjuvant of colistin treatment may be helpful to reduce the severity and the resolution of the MDR A. baumannii infection.

scholarly journals Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2047
Author(s):  
Magda Ferreira ◽  
Maria Ogren ◽  
Joana N. R. Dias ◽  
Marta Silva ◽  
Solange Gil ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Private Investment ◽  
Therapeutic Index ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Delivery Systems ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Antimicrobial Drugs

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

scholarly journals Radiation-Inactivated Acinetobacter baumannii Vaccine Candidates

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 96
Author(s):  
Stephen J. Dollery ◽  
Daniel V. Zurawski ◽  
Elena K. Gaidamakova ◽  
Vera Y. Matrosova ◽  
John K. Tobin ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Bacterial Cells ◽  
Wound Infections ◽  
Protein Profiles ◽  
Vaccine Candidates ◽  
Rich Media ◽  
Life Threatening

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

Sign in / Sign up

Export Citation Format

Share Document