This document discusses various classes of newer antimicrobials that are used to treat resistant bacterial infections. It provides details on the mechanisms of action and modes of resistance for classes such as oxazolidinones, glycopeptides, lipopeptides, ketolides, glycylcyclines, carbapenems, cephalosporins, pleuromutilins, macrocyclic antibiotics, rifamycins, streptogramins, and quinolones. Newer drugs within these classes have improved properties compared to older drugs like having additional mechanisms of action, fewer drug interactions and side effects, and activity against drug-resistant bacteria.

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2. Antimicrobials
Substance that kills or inhibits the growth of
microorganisms such as bacteria, fungi, or protozoans.
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3. Antimicrobials Targets
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COMMON MODES OF ANTIMICROBIAL RESISTANCE
e.g.
Penicillins
e.g. aminoglycosides ,
chloramphenicol &
penicillins
e.g.tetracyclines
e.g. aminoglycosides &
tetracyclines

5. Why do we need newer
antimicrobials
 Bacterial resistance to antimicrobials-health and
economic problem
 Chronic resistant infections contribute to increasing
health care cost
 Increase morbidity & mortality
with resistant microorganisms
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6. NEWER ANTIBACTERIALS
1. Oxazolidinones
2. Glycopeptides
3. Lipopeptides
4. Ketolides
5. Glycylcyclines
6. Carbapenems
7. Cephalosporins
8. Pleuromutilins
9. Macrocyclic antibiotic
10. Rifamycins
11. Streptogramins
12. Quinolones
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7. Oxazolidinones
MOA: Protein synthesis inhibitor at 50s subunit of ribosome
Linezolid
Acts on Gram-positive bacteria including streptococci
, vancomycin-resistant enterococci (VRE), and methicillin-
resistant Staphylococcus aureus (MRSA)
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8. Newer Oxazolidinones
 MOA:
Bind to the 23S portion of the 50S subunit preventing
translation initiation
 ADVANTAGE OVER LINEZOLID:
Improved potency
Aqueous solubility
Reduced toxicity
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Radezolid Torezolid
Uncomplicated skin and
skin structure infections
Complicated skin and skin
structure infections

9. Oxazolidinones
Mechanism of Resistance in older oxazolidinones
occurs due to mutations in ribosomal RNA (rRNA)
Resistance overcome by: Newer oxazolidinones by
additional hydrogen bond interactions with 23S rRNA
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10. GlycopeptidesMOA:
Inhibits peptidoglycan chain formation through
blockage of both, transpeptidation and transglycosylation
during cell wall formation. Dissipates membrane potential
of the bacterial cell membrane causing an increase in
permeability.
1)Vancomycin & Teicoplanin
Active against staphylococci (including methicillin
resistant strains), streptococci, enterococci
and Clostridium.
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11. Glycopeptides
2)Telavancin :
Newer glycopeptides
Approved for complicated skin and skin structure
infections(MRSA)
Additional mode of action
1) Causes disruption of membrane potential
2) Increases cell permeability causing rapid bactericidal
activity
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12. Glycopeptides Advantage over Vancomycin
Additional mechanisms of action
Renal and hepatic excretion
No known nephrotoxicity or dose adjustments
Less frequent dosing
Longer t 1/2 life
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13. LipopeptidesMOA:
Binds to bacterial membranes and causes a rapid
depolarization leads to Inhibition of protein, DNA, and
RNA synthesis
Developed for the treatment of vancomycin-resistant
enterococcal infections
Indication:
Treatment of complicated skin and skin structure
infections
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14. Lipopeptides Equal in efficacy to vancomycin, oxacillin, or nafcillin, in
the treatment of complicated skin and skin structure
infections
 Daptomycin-
 Rapidly bactericidal
 No cross resistance
 Can cause life-threatening eosinophilic pneumonia.
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15. Ketolides
MOA- Inhibits bacterial RNA polymerase.
Indication : Clostridium difficile-associated diarrhoea,
community acquired pneumonia , prevention of post-
exposure inhalational anthrax
It is minimally or not absorbed following oral
administration, thus systemic side effects are reduced.
It does not affect the normal flora of the lower
gastrointestinal tract since it does not show any activity
against gram-negative organisms.
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16. Glycylcyclines
Derived from tetracycline
 MOA:
 Bind to 30 S subunit of bacterial ribosome
Does not undergo active efflux easily in gram-positive
organisms
Designed to overcome two common mechanisms of
tetracycline resistance
1) Resistance mediated by acquired efflux pumps
2) Ribosomal protection
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17. Glycylcyclines
Tigecycline:
Indication
Complicated skin and skin structure infections &
Intra-abdominal infections
Active against MRSA
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18. Carbapenems
MOA: Bind to the PBPs inhibiting the bacterial cell
wall synthesis
Beta-lactam antibiotics with a broad spectrum of
antibacterial activity over Gram - and Gram + aerobic
and anaerobic bacteria.
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19. Carbapenems
1)Imipenem-cilastatin
Activity against gram-positive cocci and gram-negative
bacilli, including P. aeruginosa and anaerobes.
Cautions: β-Lactam safety profile (rash, eosinophilia),
nausea, seizures.
Cilastatin possesses no antibacterial activity; reduces
renal imipenem metabolism. Primarily renally
eliminated.
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20. Carbapenems
2)Meropenem •
 Activity against gram-positive cocci and gram-negative
bacilli, including P. aeruginosa and anaerobes.
 Preferred for treatment of CNS infections .
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21. Carbapenems
3)Ertapenem :
Spectrum: Gram-positive and negative aerobic as well
as anaerobic bacteria excluding the nonfermenters,
MRSA and drug-resistant enterococci.
 Effective against most resistant enterobacteriaceae
producing ESBLs and/or AmpC-type β-lactamases.
 Recommended for prophylaxis of surgical-site
infection following elective colorectal surgery.
 Unlike imipenem, ertapenem does not require co-
administration with cilastin
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22. Carbapenems
4) Doripenem
 Effective against gram-positive and negative aerobes and
anaerobes including Pseudomonas aeruginosa,
Acinetobacter species.
It is effective against β-lactamase producing strains of
enterobacteriaceae.
Approved for the treatment of intra-abdominal infections
and complicated urinary tract infections including
pyelonephritis.
Dosage adjustment is required in renal failure patients.
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23. Cephalosporins
MOA:
Bind strongly to PBP2a of methicillin resistant
Staphylococci
Novel cephalosporin have
Broad spectrum activity against MRSA and multi-drug
resistant S. pneumonia.
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24. Cephalosporins1)Cefuroxime
 second-generation cephalosporins
 Active against Haemophilus influenzae, Neisseria
gonorrhoeae, and Lyme disease
2)Ceftaroline:
Approved for the treatment of
o community - acquired pneumonia &
o complicated skin and soft - tissue infections
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25. Pleuromutilins
MOA: Bind to 50S subunit of ribosomes inhibiting
protein synthesis.
Retapamulin:
Topical antibiotic
Treatment of skin infections such as impetigo S. aureus
(methicillin-susceptible only) or S. pyogenes
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26. Macrocyclic antibioticFidaxomicin
MOA:
Inhibit bacterial enzyme RNA polymeras
Narrow spectrum bactericidal agent.
Demonstrated selective eradication of pathogenic
Clostridium difficile.
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27. Rifamycins
 Rifampin, Rifabutin & Rifapentine are already
approved dugs
 Rifaximin : Newer non systemic rifamycin
- Approved for traveler's diarrhea, hepatic
encephalopathy
- Irritable bowel syndrome, small intestinal bacterial
overgrowth & Clostridium difficile infection
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28. Streptogramins MOA:
Inhibits DNA gyrase and topoisomerase IV.
 Available in a parenteral formulation.
 Dalfopristin-Quinupristin
 Spectrum - MRSA, CONS, penicillin-susceptible and
penicillin-resistant S. pneumoniae, and vancomycin-
resistant E. faecium but not E. faecalis,VISA
 Indication- – serious infection with VISA and VRE –
Serious infection with MRSA when Vancomycin is not
tolerated .
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29. Quinolones
 Drug interactions: potent inhibitor of CYP 3A4
 The newer quinolones include: Gemifloxacin,
esifloxacin , Gemifloxacin •
 Oral fluoroquinolone approved for chronic bronchitis
and community-acquired pneumonia.•
 High concentrations are achieved in the respiratory
tract after oral administration, making it an ideal drug
for the treatment of respiratory tract infections.
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30. THANK YOU
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