eravacycline and Gram-Negative-Bacterial-Infections

Antimicrobial resistance is a growing threat to public health and an increasingly common problem for acute care physicians to confront. Several novel antibiotics have been approved in the past decade to combat these infections; however, physicians may be unfamiliar with how to appropriately utilize them. The purpose of this review is to evaluate novel antibiotics active against resistant gram-negative bacteria and highlight clinical information regarding their use in the acute care setting. This review focuses on novel antibiotics useful in the treatment of infections caused by resistant gram-negative organisms that may be seen in the acute care setting. These novel antibiotics include ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilistatin/relebactam, cefiderocol, plazomicin, eravacycline, and omadacycline. Acute care physicians should be familiar with these novel antibiotics so they can utilize them appropriately.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Boronic Acids; Cefiderocol; Ceftazidime; Cephalosporins; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Design; Drug Resistance, Multiple; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Heterocyclic Compounds, 1-Ring; Humans; Meropenem; Sisomicin; Tazobactam; Tetracyclines

To discuss a possible clinical reasoning for treating resistant Gram-negative bacteria (GNB) infections in daily clinical practice, as well as developing a research agenda for the field.. Novel agents, both belonging to β-lactams and to other classes of antimicrobials, have recently become available, likely replacing polymyxins or polymyxin-based combination regimens as the preferred choices for the first-line treatment of severe resistant GNB infections in the near future.. The peculiar characteristics of novel agents for severe resistant GNB infections have abruptly made the structure of previous therapeutic algorithms somewhat obsolete, in view of the differential activity of most of them against different classes of carbapenemases. Furthermore, other agents showing activity against resistant GNB are in late phase of clinical development. Optimizing the use of novel agents in order both to guarantee the best available treatment to patients and to delay the emergence and spread of resistance is an important task that cannot be postponed, especially considering the unavailability of well tolerated and fully efficacious options for treating resistant GNB infections that we faced in the last 15 years.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azabicyclo Compounds; beta-Lactams; Carbapenems; Cefiderocol; Ceftazidime; Cephalosporins; Drug Combinations; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Humans; Imipenem; Microbial Sensitivity Tests; Polymyxins; Sisomicin; Tazobactam; Tetracyclines

Complicated intra-abdominal infections (cIAIs) are commonly associated with multimicroorganisms and treatment choices are becoming narrower due to developing resistance, especially in the gram-negative Enterobacteriaceae species. Eravacycline is a newly developed, fully synthetic tetracycline derivative that has shown potent broad-spectrum activity against a wide variety of microorganisms, including those such as extended spectrum β-lactamase producing Enterobacteriaceae and Acinetobacter. Eravacycline has shown activity against many gram-positive organisms such as methicillin-resistant S. aureus and vancomycin resistant Enterococcus faecalis and Enterococcus faecium (VRE), gram-negative organisms such as Escherichia coli, and anaerobic species of microorganisms such as Bacteroides. This fluorocycline has been compared to ertapenem and meropenem for the treatment of complicated intra-abdominal infections and levofloxacin for the treatment of complicated urinary tract infections. Eravacycline was shown to be noninferior to ertapenem but did not meet noninferiority criteria in comparison to levofloxacin. Oral and IV formulations on eravacycline were tested in clinical trials, but at this time, only the IV formulation is FDA approved. Eravacycline has been noted to have a half-life of 20 h with protein binding around 80%; AUC over minimum inhibitory concentration (MIC) has also been shown to be eravacycline's best predictor of efficacy. Of note, eravacycline does not require any renal dose adjustments, as the majority of its clearance is by nonrenal pathways.

Topics: Administration, Intravenous; Administration, Oral; Anti-Bacterial Agents; Bacteria, Anaerobic; Clinical Trials as Topic; Coinfection; Drug Approval; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Tetracyclines; Treatment Outcome

There has been a dramatic increase in the incidence of multidrug-resistant pathogens over the past few years, which highlights the need for new anti-infective therapeutics. Eravacycline is a novel, broad-spectrum synthetic tetracycline indicated for the treatment of severe infections caused by Gram-positive and Gram-negative bacteria.. In this review, the authors report eravacycline's pharmacokinetic characteristics and its microbiological spectrum of activity. Furthermore, the authors also highlight the safety and efficacy data from the recent studies on urinary and intra-abdominal infections.. The profile of eravacycline offers several advantages. Indeed, eravacycline has a broad-spectrum activity toward pathogens involved in complicated urinary tract (cUTIs) and intra-abdominal infections (cIAIs), including extended-spectrum beta-lactamase and carbapenem-resistant Enterobacteriaceae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. The availability of an oral formulation supports eravacycline's possible use in sequential therapy. High urinary concentrations favor its use in cUTIs and may reduce the overuse of other antimicrobials that may select resistance, such as carbapenems. Eravacycline efficacy and tolerability have been investigated in a Phase II clinical trial in cIAIs comparing two dosages of eravacycline with ertapenem, showing comparable efficacy among the three arms and a low rate of adverse effects. The results of new Phase III studies are awaited to confirm eravacycline's future applications in severe nosocomial infections.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; beta-Lactams; Drug Resistance, Multiple, Bacterial; Ertapenem; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Tetracyclines

Eravacycline (TP-434 or 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline) is a novel fluorocycline that was evaluated for antimicrobial activity against panels of recently isolated aerobic and anaerobic Gram-negative and Gram-positive bacteria. Eravacycline showed potent broad-spectrum activity against 90% of the isolates (MIC90) in each panel at concentrations ranging from ≤0.008 to 2 μg/ml for all species panels except those of Pseudomonas aeruginosa and Burkholderia cenocepacia (MIC90 values of 32 μg/ml for both organisms). The antibacterial activity of eravacycline was minimally affected by expression of tetracycline-specific efflux and ribosomal protection mechanisms in clinical isolates. Furthermore, eravacycline was active against multidrug-resistant bacteria, including those expressing extended-spectrum β-lactamases and mechanisms conferring resistance to other classes of antibiotics, including carbapenem resistance. Eravacycline has the potential to be a promising new intravenous (i.v.)/oral antibiotic for the empirical treatment of complicated hospital/health care infections and moderate-to-severe community-acquired infections.

Topics: Anti-Bacterial Agents; ATP-Binding Cassette Transporters; beta-Lactamases; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Gene Expression; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Tetracyclines