Correction to: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-β-Lactamase Inhibitor Combinations.

Section heading 5.2, which currently reads 5.2 Meropenem-Relebactam.

Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-β-Lactamase Inhibitor Combinations.

Relebactam (formerly known as MK-7655) is a non-β-lactam, bicyclic diazabicyclooctane, β-lactamase inhibitor that is structurally related to avibactam, differing by the addition of a piperidine ring to the 2-position carbonyl group. Vaborbactam (formerly known as RPX7009) is a non-β-lactam, cyclic, boronic acid-based, β-lactamase inhibitor. The structure of vaborbactam is unlike any other currently marketed β-lactamase inhibitor.

Solithromycin: A Novel Fluoroketolide for the Treatment of Community-Acquired Bacterial Pneumonia.

Solithromycin is a novel fluoroketolide developed in both oral and intravenous formulations to address increasing macrolide resistance in pathogens causing community-acquired bacterial pneumonia (CABP). When compared with its macrolide and ketolide predecessors, solithromycin has several structural modifications which increase its ribosomal binding and reduce its propensity to known macrolide resistance mechanisms. Solithromycin, like telithromycin, affects 50S ribosomal subunit formation and function, as well as causing frame-shift errors during translation.

Review of Eravacycline, a Novel Fluorocycline Antibacterial Agent.

Eravacycline is an investigational, synthetic fluorocycline antibacterial agent that is structurally similar to tigecycline with two modifications to the D-ring of its tetracycline core: a fluorine atom replaces the dimethylamine moiety at C-7 and a pyrrolidinoacetamido group replaces the 2-tertiary-butyl glycylamido at C-9. Like other tetracyclines, eravacycline inhibits bacterial protein synthesis through binding to the 30S ribosomal subunit. Eravacycline demonstrates broad-spectrum antimicrobial activity against Gram-positive, Gram-negative, and anaerobic bacteria with the exception of Pseudomonas aeruginosa.

Tedizolid: a novel oxazolidinone with potent activity against multidrug-resistant gram-positive pathogens.

Tedizolid phosphate is a novel oxazolidinone prodrug (converted to the active form tedizolid by phosphatases in vivo) that has been developed and recently approved (June 2014) by the United States FDA for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Tedizolid is an oxazolidinone, but differs from other oxazolidinones by possessing a modified side chain at the C-5 position of the oxazolidinone nucleus which confers activity against certain linezolid-resistant pathogens and has an optimized C- and D-ring system that improves potency through additional binding site interactions. The mechanism of action of tedizolid is similar to other oxazolidinones and occurs through inhibition of bacterial protein synthesis by binding to 23S ribosomal RNA (rRNA) of the 50S subunit of the ribosome.

Ceftolozane/tazobactam: a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli.

Ceftolozane is a novel cephalosporin currently being developed with the β-lactamase inhibitor tazobactam for the treatment of complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), and ventilator-associated bacterial pneumonia (VABP). The chemical structure of ceftolozane is similar to that of ceftazidime, with the exception of a modified side-chain at the 3-position of the cephem nucleus, which confers potent antipseudomonal activity. As a β-lactam, its mechanism of action is the inhibition of penicillin-binding proteins (PBPs).

Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination.

Avibactam (formerly NXL104, AVE1330A) is a synthetic non-β-lactam, β-lactamase inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some Ambler class D enzymes. This review summarizes the existing data published for ceftazidime-avibactam, including relevant chemistry, mechanisms of action and resistance, microbiology, pharmacokinetics, pharmacodynamics, and efficacy and safety data from animal and human trials. Although not a β-lactam, the chemical structure of avibactam closely resembles portions of the cephem bicyclic ring system, and avibactam has been shown to bond covalently to β-lactamases.

Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin.

Plazomicin (formerly ACHN-490) is a next-generation aminoglycoside that was synthetically derived from sisomicin by appending a hydroxy-aminobutyric acid substituent at position 1 and a hydroxyethyl substituent at position 6'. Plazomicin inhibits bacterial protein synthesis and exhibits dose-dependent bactericidal activity. Plazomicin demonstrates activity against both Gram-negative and Gram-positive bacterial pathogens, including isolates harboring any of the clinically relevant aminoglycoside-modifying enzymes.

New lipoglycopeptides: a comparative review of dalbavancin, oritavancin and telavancin.

Dalbavancin, oritavancin and telavancin are semisynthetic lipoglycopeptides that demonstrate promise for the treatment of patients with infections caused by multi-drug-resistant Gram-positive pathogens. Each of these agents contains a heptapeptide core, common to all glycopeptides, which enables them to inhibit transglycosylation and transpeptidation (cell wall synthesis). Modifications to the heptapeptide core result in different in vitro activities for the three semisynthetic lipoglycopeptides.

Ceftaroline: a novel broad-spectrum cephalosporin with activity against meticillin-resistant Staphylococcus aureus.

Ceftaroline is a broad-spectrum cephalosporin currently under clinical investigation for the treatment of complicated skin and skin-structure infections (cSSSI), including those caused by meticillin-resistant Staphylococcus aureus (MRSA), and community-acquired pneumonia (CAP). Ceftaroline has the ability to bind to penicillin-binding protein (PBP)2a, an MRSA-specific PBP that has low affinity for most other beta-lactam antibacterials. The high binding affinity of ceftaroline to PBP2a (median inhibitory concentration 0.

Association between fluoroquinolone usage and a dramatic rise in ciprofloxacin-resistant Streptococcus pneumoniae in Canada, 1997-2006.

This study evaluated the prevalence of fluoroquinolone usage and investigated the association between usage and resistance in respiratory isolates of Streptococcus pneumoniae in Canada. Fluoroquinolone susceptibility testing was conducted on S. pneumoniae collected from 25 medical centres across Canada over nine study years.

Dalbavancin and telavancin: novel lipoglycopeptides for the treatment of Gram-positive infections.

Two glycopeptide analogues of vancomycin and teicoplanin have been developed with improved pharmacokinetic/pharmacodynamic parameters. Dalbavancin was derived from teicoplanin, and telavancin is a derivative of vancomycin. The half-life of dalbavancin in humans is 147-258 h (6-11 days) allowing for weekly administration.

A Review of New Fluoroquinolones : Focus on their Use in Respiratory Tract Infections.

The new respiratory fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, and on the horizon, garenoxacin) offer many improved qualities over older agents such as ciprofloxacin. These include retaining excellent activity against Gram-negative bacilli, with improved Gram-positive activity (including Streptococcus pneumoniae and Staphylococcus aureus). In addition, gatifloxacin, moxifloxacin and garenoxacin all demonstrate increased anaerobic activity (including activity against Bacteroides fragilis).

The ketolides: a critical review.

Ketolides are a new class of macrolides designed particularly to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides are semi-synthetic derivatives of the 14-membered macrolide erythromycin A, and retain the erythromycin macrolactone ring structure as well as the D-desosamine sugar attached at position 5. The defining characteristic of the ketolides is the removal of the neutral sugar, L-cladinose from the 3 position of the ring and the subsequent oxidation of the 3-hydroxyl to a 3-keto functional group.

A critical review of the fluoroquinolones: focus on respiratory infections.

The new fluoroquinolones (clinafloxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin) offer excellent activity against Gram-negative bacilli and improved Gram-positive activity (e.g. against Streptococcus pneumoniae and Staphylococcus aureus) over ciprofloxacin.