Antibacterial

s
Pacitti, Smith, Pharmacology for Nurses
(2020)
Lecture Outline
• Cell Wall Synthesis Inhibitors
• Beta lactam antibiotics
• Beta lactamase inhibitors
• Carbapenems
• Vancomycin
• Protein Synthesis Inhibitors
• Tetracyclines
• Aminoglycosides
• Macrolides
• Lincosamide
• Linezolid
• Anti-Metabolites
• Sulfonamides
• DNA Synthesis Inhibitor
• Quinolones/Fluoroquinolones
• Anti-TB drugs
Cell Wall Synthesis
Inhibitors
Beta lactam antibiotics
Beta lactamase
inhibitors Carbapenems
Vancomycin
Beta-Lactam Antibiotics
•Derives its name from the beta-lactam ring that is the source of
their bactericidal activity
•Coverage: Gram-positive and some Gram-negative
•Includes penicillins, cephalosporins, carbacephems,
clavams, monobactams, carbapenems.
•SE: Allergy
• EBV infection + amoxicillin  pruritic rashes, mistake as allergic reaction
•MOA: inhibits cell wall synthesis
• Binds to penicillin-binding protein, a protein within the peptidoglycan layer of
the bacterial cell wall  interrupt synthesis
Beta-Lactam Antibiotics
PENICILLINS
•Most commonly used to kill gram-positive bacteria
•The basic B-lactam structure is susceptible to the enzymes
B- lactamase (aka penicillinase), which are produced by
bacteria
•  compromised effectiveness
• This is why some penicillins are combined with a beta-lactamase inhibitor
• E.g. Amoxicillin + Clavulanic Acid (Co-Amoxiclav)
• BLI alone are not useful; only considered adjuncts to specified beta-lactams
•SE: Few, usually well tolerated
Beta-Lactam Antibiotics
CEPHALOSPORINS
•Slight difference in chemical structure with penicillins
•First to Fourth Generation coverage: From Gram-positive to
more Gram-negative organisms
•Fourth generation: Used in hospitalized patients who have
infections with G(+), Enterobacteriaceae, or Pseudomonas
•SE: Lower incidence of anaphylaxis than that of penicillins
• Cross-sensitivity between PCN and cephalosporins is quite low
• But, cephalosporins are still contraindicated in patients with a history of
severe allergic reaction to them and/or to penicillins
Beta-Lactam Antibiotics
Monobactams
•Contain a monocylic beta-lactam ring
•Aztreonam: relatively resistant to beta-lactamases
• Spectrum: G(-) rods; no activity against G(+) or anaerobic organisms
•SE: generally well-tolerated
CARBAPENEMS
•Have broader spectrum of activity vs penicillins and cephalosporins
•More potent against severe infection
•Are called extended-spectrum beta-lactamases (ESBLs)
• Only agents that have activity against organism capable of resisting
beta- lactam antibiotics and combination against that utilize beta-
lactamase inhibitor
•Agents of choice for mixed aerobic and anaerobic infections
resistant to treatment with other antibiotics
•SE: Allergies, nephrotoxicity, neurotoxicity, seizures in patients
with renal impairments, hepatic impairment
• Monitor renal and liver function
CARBAPENEMS
•Imipinem, panipenem, doripenem – most effect for G(+)
•Meropenem, biapenem, ertapenem – sl. Greater efficacy against G(-)
•Meropenem and doripenem: same coverage with imipenem,
with greater activity against G(-) aerobes but less against G(+)
aerobes
• Effective against Pseudomonas
Vancomycin
•Attaches to pentapeptides of peptidoglycan  decreased cell
wall synthesis
•Not much used nowadays to limit the spread of vancomycin-
resistant organisms
•Usually given IV for serious infections not responsive to other
anti- infective medications
•Parenterally, DOC for MRSA
•Orally, DOC for pseudomembranous colitis caused by C. difficile
Protein Synthesis
Inhibitors
Aminoglycosides
Tetracyclines
Macrolides
Lincosamide
Linezolid
Aminoglycosides
•Prototype: streptomycin
•Primarily used against G(-), aerobic bacteria
•SE: Narrow therapeutic indices
• Most notable: nephrotoxicity, otoxocitiy
•Amikacin, gentamicin, kanamycin, neomycin,
paromomycin, streptomycin, tobramycin.
•Most are administered via IM
•Neomycin and paromomycin: Oral
Tetracyclines
•Natural: Tetracycline, demeclocycline, oxytetracycline
•Synthetic: Doxycycline, minocycline
•Coverage: G(+), G(-), Rickettsia, Coxiella, Mycoplasma,
Chlamydia, Legionella, Ureaplasma
• Also effective for some atypical mycobacteria and plasmodium species
•Cautions: avoid concomitant ingestion of dairy products,
vitamins, and antacids, with oral tetracyclines
• They chelate metal ions
• Allergies
• NOT FOR PREGNANT AND LACTATING PATIENTS
• NOT FOR CHILDREN YOUNGER THAN AGE OF EIGHT
• Forming teeth, drugs bind to calcium  permanent staining of teeth
Chloramphenicol
•Uses: superficial eye infections, otitis externa, severe infections
of rickettsial diseases, meningitis, typhoid, cholera
•Rarely used drug in the US because of its known severe
adverse effects, like bone marrow toxicity and grey baby
syndrome
Macrolides
•Erythromycin, clarithromycin, azithromycin
•Most useful for aerobic G(+) cocci and bacilli
•Most important adverse effects:
• Gastric distress (when taken orally), thus take with food
•E & A: less evidence of fetal or infant harm vs C
• Spontaneous abortion is higher for pregnant patients taking clarithromycin
Lincosamides
•Lincomycin, replaced by clindamycin
•Coverage: Both bacterial and protozoan pathogens
• Good for G(+) and anaerobic coverage
•Has similarities in structure with macrolides
• If organism is resistant to macrolide, likely also resistant to clindamycin
•Cautions:
• Should NOT be used for lactating women
• Transfers into breast milk  gastric disturbance in infant
• Associated with pseudomembranous colitis
Linezolid
•For methicillin-resistant and vancomycin-resistant bacteria
•Coverage: Anerobic, G(+), G(-)
•Must be used cautiously
•Precautions:
• Patients with phenylketonuria as it contains aspartame
• Have many interactions with over-the-counter medications and other drugs
like
• SSRI
• Monoamine oxidase inhibitors
• sympathomimetics
Anti-Metabolites
Sulfonamides
Sulfonamides
•First therapeutic antibacterial agents
•Coverage: G(+) and G(-)
•Bacteriostatic, but becomes
bactericidal if paired with other
drugs
• E.g. Sulfamethoxazole with
Trimethoprim (Co-trimoxazole)
(TMP- SMX)
•Sulfonamide inhibits
dihydropterate synthetase
•Trimethoprim (not a
sulfonamdie) inhibit
dihydrofolate reductase
Sulfonamides
•AE:
• Hypersensitivity reactions (Toxic
Epidermal Necrolysis, Stevens-
Johnson syndrome)
• Crystalluria
• Some anemia
• Avoid in pregnant or lactating women
DNA Synthesis Inhibitor
Quinolones/Floroquinolones
Fluoroquinolones and Quinolones
•Quinolones: nalidixic acid, cinoxacin
•Fluoroquinolones (improved coverage, more used):
ciprofloxacin, ofloxacin, moxifloxacin, levofloxacin
•Inhibits DNA gyrase (enzyme needed to synthesize bacterial
DNA) and/or topoisomerase IV
•Broad spectrum:
• Inhibits DNA gyrase in G(+)
• Inhibits Topoisomerase IV in G(-)
•Usually used for UTI, STD, GI, Respi, Bone, Joint, Soft-tissue infections
•CI: generally safe, but CI on those with allergies, pregnant
and lactating women, children younger than age of 18
Anti-Tuberculosis Drugs