*4.1.2.4. Target bypass*

This kind of resistance mechanisms is somewhat specific. Bacteria produce two kinds of targets: one is sensitive to antibiotics and the alternative one (usually an enzyme) that is resistant to inhibition of antibiotic. In ampicillin-resistant mutant Enterococcus faecium selected in vitro, bypass of the DD-transpeptidases by a novel class of peptidoglycan polymerases, the LD-transpeptidases, conveyed resistance to all β-lactams, except the carbapenems [55; 56].

**Figure 2.** Innovation gap between 1962 and 2000 [59].

PHASE OF DEVELO-PMENT

Oxazolidinones FDA Approved 2000

Glycylcyclines FDA Approved 2005

Carbapenems FDA Approved 2007

Fluoroquinolones Preclinical JNJ-Q2,

**Table 1.** New antibiotics of existing scaffolds

Glycopeptides Phase III

CLASS OF COMPOUND

des, ketolides, lycylcyclines, carbapenems and fluoroquinolones.

**ANALOGS**

Linezolid, Radezolid, Torezolid, RWJ-416457

Oritavancin, Dalbavancin, Telavancin

Tigecycline, PTK0796

Doripenem, Razupenem

finafloxacin

Ketolides Phase III Cethromycin Inhibits protein

Streptogramins Phase II NXL103/XRP2868 Inhibits protein

Despite the current grim situation in management of resistant bacteria, some new drugs have recently been approved by the FDA or are in late stages of the pipeline (Table 1, 2) [60]. The new drugs belong to the following classes of compounds: oxazolidinones, glycopepti‐

> MECHANISM OF ACTION

Inhibits protein translation (initiation/ elongation)

Inhibit peptidoglycan biosysnthesis/ transglycosylation

synthesis

Inhibits peptidoglycan biosynthesis

Inhibits protein

Inhibit type II topoisomerase RESISTANCE MECHANISM

rRNA mutations

unidentified

synthesis Efflux pumps Wyeth, Paratek

translation unidentified Novexel

gyrA, parC mutations

Carbapenemases, Efflux pumps, Porin mutations

rRNA dimethylation, ribosomal protein mutations

DRUG COMPANY

The Antibacterial Drug Discovery http://dx.doi.org/10.5772/52510 297

Pfizer, Rib-X, Trius Therapeutics, Johnson & Johnson

Targanta/The Medicines Co., Pfizer, Theravance

Advanced Life Sciences

Pharmaceuticals

Johnson & Johnson, Protez Pharmaceuticals

Johnson & Johnson, MerLion Pharmaceuticals
