Newer antibiotics approved and in pipeline since 2000-2015

1. NEWER ANTIBIOTICS
Dr. Arun Sharma

4. 5TH GENERATION
CEPHALOSPORINS
 Ceftaroline
◦ Injectable cephalosporin active against MRSA &
MSSA [ & RTI pathogens].
◦ It is approved for use in cSSSI & CABP
◦ Dose: 600 mg bd slow iv infusion.
 Ceftobiprole
◦ Approved in Canada and EU.
◦ Recently FDA issued warning letter over skin
reactions in CT (2009).

5. FIDAXOMICIN
 Novel macrolide antibiotic.
 Approved for C.difficile infections (CDI) by FDA
(2011).
 CT demonstrated that fidaxomicin was deemed to be
no inferior in the treatment of mild to moderate CDI
compared with oral vancomycin.
 Recurrence rates for all strains of CDI were lower
with fidaxomicin than vancomycin.
 Nausea and vomiting most common side effects.
 Price exceeds $2500 (US) per treatment course
(pharmacoeconomic diasdvantage)

6. BEDAQUILINE (TMC 207)
 Approved for MDR-TB in 2012 by FDA.
 Inhibits the proton pump of mycobacterial ATP synthase.
 Only drug which targets the energy metabolism of mycobacteria .
 Bedaquiline follows triphasic elimination and characterized by an
outstandingly long terminal half-life, around 173 h in humans.
 This is very important because it may allow intermittent drug
administration when it is combined with others drugs in the regimen
for MDR-TB and XDR-TB.
 Effective synergism is ensued when Bedaquiline and Pyrazinamide (Z)
are combined.
 Amongst all anti MDR-TB drugs, Bedaquiline (25 mg/kg) has displayed
highest bactericidal potency and second best sterilizing activity.
 Bedaquiline at a dose of 400 mg once daily displayed significant
bactericidal activity with similar magnitude of H and R.
 AE: Nausea, vomiting, arthralgia, headache, hyperuricemia,
hepatotoxicity and neuropathy.
 However, the drug's potential risks, including increased risk of death,
have raised concerns.

7. TEIXOBACTIN
 New class of bacteria isolated from soil bacterium E.terrae using
iCHIP (isolation chip)method.
 Active against Gram positive bacteria.
 Teixobactin inhibits cell wall synthesis by binding to a highly
conserved motif of lipid II (precursor of peptidoglycan) and lipid
III (precursor of cell wall teichoic acid).
 In a study published in Nature in 2015, teixobactin was shown
to kill S.aureus or M.tuberculosis without the bacteria
developing resistance.
 Has given new hope against some notorious G +ve infections:
MRSA, CDI (C.difficile infections), M.tuberculosis etc.
 Unfortunately, Teixobactin does not have activity against Gram
negative pathogens—such as Carbapenem-resistant
Enterobacteraceae (CRE) or NDM bugs—which are a growing
threat to patients.