Antibiotics that Inhibit Nucleic Acid Synthesis.

Prevents RNA & DNA Production

(Sulphonamides, Trimethoprim, Quinolones & Nitroimidazoles S-T-Q-N)

Drug Fact/Action Bacteriostatic/ Uses Side Effects

Bactericidal

1. Sulphonamides - rarely used Bacteriostatic - UTIs caused by sensitive 1. Allergic reactions:

(Sulfadiazine, - Structure SIMILAR to (inhibit bacterial organisms. o Commonly skin
Sulfamethoxazole, p-aminobenzoic acid growth rather than rashes, (measles-like)
Sulfadoxine) (PABA). directly killing - A notable use: Sulfadiazine or urticarial (hives),
o PABA is essential for bacteria). + Pyrimethamine for often with fever.
(Bactrim/Septra) folic acid synthesis Toxoplasma gondii o Rare, but severe
in bacteria. infections (toxoplasmosis). reactions include
(Combination prevents o competitively Stevens–Johnson
resistance- rarely used inhibits the enzyme Co-trimoxazole (used syndrome (a severe
alone) dihydropteroate with trimethoprim) to treat skin reaction).
synthetase. infections better
*Assess CYP interaction o This prevents folate PNEUMOCYSTIS J. 2. Blood dyscrasias (rare):
prior to prescribing* production required (PJP) + MRSA (STAPH o Agranulocytosis (low
for DNA synthesis. AUERUS) white blood cell count)
BROAD SPECTRUM o Aplastic anemia
- Selective toxicity: *AVOID in pts with (failure of bone
o Human cells do not marrow)
SULFA ALLERGY*
synthesize folate; o Hemolytic anemia
they obtain it from (especially if G6PD-
the diet. deficient)- cannot give
o Bacteria must to patients with G6PD
synthesize their own deficiencies
folate.
**Avoid in Pregnancy**

Drug Fact/Action Bacteriostatic/ Uses Side Effects

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 Bactericidal

- Inhibits dihydrofolate - uncomplicated UTIs.

reductase (DHFR) in - Generally well tolerated;
bacteria. - Sometimes used for the main issues often arise
o Blocks folate respiratory tract when combined with
2. Trimethoprim
production (and thus Bactericidal infections, although it has sulphonamides.
DNA formation) at a poor activity against
later step than certain Streptococci (S.
WIDE- SPECTRUM pneumoniae and S.
sulphonamides.
pyogenes).
- Selective toxicity:
o Its affinity for
bacterial DHFR is
50,000 times greater
than for the human
enzyme.

Co-Trimoxazole (Trimethoprim + Sulfamethoxazole)  BROAD SPECTRUM: MRSA

Check CYP: Lots of drug interactions!
 Combining trimethoprim and sulphonamide can lead to a synergistic effect: they block two steps in folate metabolism.
 Side Effects: SJS, TEN (Toxic Epidermal Necrolysis) & Blood Dyscrasias mostly mirror those of the sulphonamides.

Uses
 GRAM + & - bacteria Staphylococci * CA-MRSA
 Largely replaced by safer single-agent therapies for routine bacterial infections.
 Important uses:
o Pneumocystis Jiroveci (PJP) (previously called Pneumocystis carinii pneumonia)
o Toxoplasmosis

Drug Fact/Action Bacteriostatic/ Uses Side Effects

Bactericidal
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 3. Quinolones - Inhibits DNA Gyrase Gram (-) * - Broad-spectrum: good - Generally, well tolerated
(Ciprofloxacin, by binding to it (an treatment for o N/V/rashes
fluroquinolones) enzyme that supercoils PSEUDOMONAS. o Articular Tendonitis
bacterial DNA for Pseudomonades are hard Damage/rupture
replication) and leads Bactericidal to treat! o Hepato/Nephrotoxicity
BROAD-SPECTRUM (leads to bacterial
to bacterial cell death. o Convulsions (GABA
cell death; kills - Complicated UTIs & antagonists)
- Selective toxicity: bacteria). intra-abdominal infx o Rare but serious: QT
*Treat ATYPICAL o Procaryotic cells PROLONGATION
bacteria* (bacteria- lack - Avoid taking with iron,
nucleus) have dairy products, antacids
Check for drug interactions
**RESERVE WHEN DNA Gyrase, and (CYP inhibition)
POSSIBLE** - Good oral absorption &
eukaryotic cell/
tissue penetration
human cells do
*Watch for resistance* not

4. Nitroimidazoles - Disrupts DNA Bactericidal - Covers Gram (-); - Disulfiram-Like Reaction;

(Metronidazole) formation of (generates toxic ANAEROBES cannot drink ETOH with this
bacterial cells for intermediates that (no aerobic coverage) medication!
*Amazing medication anaerobic bacteria damage DNA) (DRUNK EFFECT- No
for anaerobic C-DIFF* - Intra-abdominal ETOH 3 days before or after
and protozoa
(C-DIFF, use: DISULFIRAM-LIKE
NARROW TRICHAMONAS, REACTION)
**check drug Giardiasis), diabetic
SPECTRUM, BUT
interactions foot infx, Crohn’s - GI upset, metallic taste
HIGHLY TARGETED
disease

Rifampicin (needs to be used in combination with TB treatment)

- Bactericidal **RAPID DEVELOPMENT OF RESISTANCE** if used ALONE/ Blocks bacterial RNA transcription

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Selective Toxicity
- Chemotherapy aims to target cells of a parasite, bacterium, virus, or cancer while sparing human cells.
- Bacteria have several major biochemical differences from human cells, so some antibacterials have low toxicity for humans.
- Cancer cells are very similar to normal human cells → most anticancer drugs have less selective toxicity and more severe side
effects. **Selective toxicity is crucial for chemotherapy—but resistance develops (USE ABX JUDICIOUSLY)

Bacteriostatic vs. Bactericidal

- Bacteriostatic: Inhibit growth; rely on the host immune system to clear the infection.
- Bactericidal: Directly kill bacteria.
- Clinically, the distinction often does not matter in patients with normal immune function.
- In immunocompromised patients (e.g., AIDS, or those on immunosuppressants), using a bactericidal agent is crucial.

Resistance to Antimicrobial Drugs

Types of Resistance
1. Innate (Intrinsic) Resistance:
o An entire bacterial species is naturally resistant (e.g., Pseudomonas aeruginosa to flucloxacillin).
2. Acquired Resistance:
o Bacteria that were once sensitive become resistant via genetic changes.

Mechanisms (How bacteria become resistance to antibiotics):

1. Producing enzymes:
o Bacteria are smart and produce enzymes β-lactamases (many Staphylococci) that destroy penicillin/cephalosporins.
2. Decreased drug accumulation (not taking the medication for the intended duration):
o Tetracycline resistance via changes in permeability or increased efflux pumps.
3. Altered binding sites:
o Aminoglycoside or erythromycin resistance due to modified ribosomal binding sites.
4. Alternative metabolic pathways:
o Bacteria produce modified dihydropteroate synthetase or dihydrofolate reductase to trick
sulphonamides/trimethoprim.
Spread of Resistance

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 1. Selection:
- When using an antibiotic, it kills off bacteria that are sensitive to it
- However, some bacteria that are naturally resistant (or that have picked up a resistance gene) survive
- These resistant bacteria survive and proliferate (grow and multiply), so they end up dominating the population.

2. Transferred resistance:
- Sometimes, resistance isn’t just passed down to offspring; it can move directly between bacteria. This transfer can
happen in a few ways:
a) Plasmids: Plasmids are small circles of DNA that carry genes for antibiotic resistance. Bacteria can share these plasmids
with each other, passing the resistance genes.
b) Conjugation: A tube forms between bacteria to exchange plasmids to the other.
c) Transduction: In transduction, viruses that infect bacteria (Bacteriophages) pick up resistance genes when infecting the
bacteria.

Antibiotics that Inhibit Cell Wall Synthesis – Prevents Cell Wall Formation
(Beta-Lactam Abx: Penicillin, Cephalosporins, Vancomycin, & Other B-Lactams P-C-O-V)

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 **Beta-lactam antibiotics have a B-lactam ring similar to bacteria. However, resistance can occur because bacteria end up
producing B-lactamases (enzymes that can open the B-lactam ring)**

Drug Fact/Action Bacteriostatic/ Uses Side Effects

Bactericidal

1. Penicillin - Prevents the “cross- - Generally low toxicity,

linkage” between but hypersensitivity
Subclasses: horizontal Bactericidal reactions my occur
peptidoglycan (rash, anaphylaxis)
Narrow-Spectrum
polymer chains that
Penicillinase-Resistant make up the cell wall
Broad-Spectrum (contain their own *Safe in Pregnancy*
Antipseudomonal BETA-LACTAM
RINGS- similar to
NARROW-SPECTRUM: bacteria) Pen V (oral): Gram (+)
(S. Pneumoniae, Group
PENICILLIN V & - Inhibits formation of Strep A)
PENICILLIN G cell wall
First Line for Strep
*Resistance occurs with - Breaks cell wall with Pharyngitis
B-LACTAMASES* unique BETA-
LACTAM RINGS Pen G (IV/IM):
Acid Labile
Only really treats Strep A GRAM (+ mostly/-)
Mostly Gram + Infections (Syphilis: Treponema P.)

*Poor for CSF diffusion*

(not for meningitis)
NARROW SPECTRUM
*Created for beta- Oral *Less ADRs
PENICILLINASE
lactamase resistant Safe for pregnancy

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 RESISTANT: organisms, for Acid Labile
Methicillin-Sensitive (take on empty Stomach)
CLOXACILLIN Staph Aureus* *Safe in Pregnancy
(Flucloxacillin/Methicillin)
Has isoxazolyl group NOT EFFECTIVE
(Choice of Drug for MSSA that PROTECTS B- AGAINST MRSA
only: STAPH) lactam rings

ONLY FOR GRAM +

BROAD SPECTRUM: Effective against

non-B-lactamase
AMOXICILLIN/ producing bacteria Gram + (STREP) / Gram -
AMPICILLIN Better Taste (used in kids)
*Inactivated by
Penicillinases* First Line- Treats a lot!
= can ADD CLAVULIN to
protect against penicillinases, (GRAM +/-) *NOT USED FOR
add MORE coverage STAPH*

BROAD-SPECTRUM: Amox-Clav gives For: Resistant Respiratory

coverage and protects Infx & UTIs
against B-lactamase
Amoxicillin-Clavuli
producing organisms *Can add Clavulinic Acid*
(Co-Amoxclav)
For Beta-lactamase
Cat Bites, dental/oral organisms or if need to
cover anaerobes

BROAD-SPECTRUM
GRAM - - Given via IV for

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 ANTIPSEUDOMONAL SERIOUS
PENICILLINS: INFECTIONS

PIPERACILLIN & - Combined with

TICARCILLIN aminoglycosides to
treat:
FOR: PSEUDOMONAS A. Sepsis/Endocarditis
Bacteria (Gram -)

Drug Fact/Action Bacteriostatic/ Uses Side Effects

Bactericidal

2. Cephalosporins
(Similar to PCNs) Risk of allergic cross- *Safe in pregnancy
5 Generations: reactivity with penicillin
1st: Cefadroxil/Cephalexin/ *More effective to beta-
Ancef (Narrow) lactamase compared to * ON TEST: Avoid
nd
2 : Cefuroxime (Wide) Penicillin* Cephalosporins with Risk of allergic cross-
3rd: Cefixime/ Ceftriaxone/ patients who have reactivity with penicillin
Ceftazidime (Broad) Penicillin Allergies! *

*5TH Generation can treat

MRSA*

NARROW SPECTRUM:
**Similar to Soft tissue Infx, UTIs, Sx Take with food, GI upset
1st Generation: Amox- Clav** Prophylaxis
Renal Excretion (prolonged
Cefadroxil/ Cephalexin/ (Gram + mostly, Gram + (Staph & Strep) with PROBENECID)
minimal Gam -) NOT MRSA
Ancef
MSSA ONLY

Soft tissue & Surgical

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 WIDE SPECTRUM: Prophylaxis, Resp Infx
(otitis media, sinusitis,
2nd Generation: (Gram + and with some CAP)
Gram-)
Cefuroxime Gram + (Staph & Strep)
NOT MRSA/ MSSA
ONLY

Gram (-) H-Influenzae,

Klebsiella & Proteus

BROAD-SPECTRUM: Severe Systemic Infx

For:
3rd Generation: Meningitis, PNA,
Septicaemia, Gonorrhea
(Gram – with some +) Pseudomonas A.
Complicated UTIs,
Ceftriaxone/ Ceftazidime/
Meningitis, PNA, Sepsis
Cefixime * Can penetrate CSF! *

Drug Fact/Action Bacteriostatic/ Uses Side Effects

Bactericidal

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 3. Other B-Lactam
Antibiotics Binds to bacterial Gram - & +
Carbapenems- Meropenem & enzymes (PBPs), For serious infections
Monobactams inhibiting bacterial cell (Sepsis)
wall synthesis

BROAD-SPECTRUM:

CARBAPENEMS
(Meropenem)

4. Vancomycin NOT a B-Lactam PO Drug is PO: For C-Diff Only HD patients may require
EXPENSIVE! **Only works in random “trough level” if
GRAM + (MRSA) Inhibits peptidoglycan Special Authority intestine** toxicity suspected
synthesis needed— don’t
(Inhibits cell wall prescribe IV Route: Rare side effects:
formation) Clindamycin For MRSA Sepsis, Renal Failure
because = causes Endocarditis Hearing loss (Ototoxic)
C-DIFF

**BETA-LACTAM DRUGS CANNOT TREAT ATYPICAL BACTERIA  They do not have Cell Walls!!**

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Beta-lactamase (ESBLs)
- Bacteria become resistant and produce Beta-lactamase (that can inactivate Beta-Lactam Drugs)
- Common Bacteria that produce this are H. influenzae, N. gonorrhea, E. coli (MOSTLY GRAM (-))
- Resistance to most penicillin, cephalosporin and beta-lactamase inhibitors!
- Staph Aureus (GRAM +) was treatable with ALL penicillin but now is RESISTANT to all (Penicillin, Ampicillin,
Amoxicillin)
o Methicillin, Cloxacillin and Clavulanic Acid were created for MSSA (Methicillin-Sensitive Staph Aureus)
o But MRSA soon emerged. Resistant to ALL Beta-Lactams  must use different class
 Community-Acquired: Less likely to be multi-drug resistant
 Hospital Acquired

Key Resistance Mechanisms

1. β-Lactamases:
o Enzymes that degrade β-lactam antibiotics.
o Overcome by β-lactamase inhibitors (e.g., clavulanic acid in co-amoxiclav).
2. Outer Membrane in Gram-Negative Bacteria:
o Prevents drug penetration.
o Broad-spectrum penicillins can pass through porins.
3. MRSA:
o Resistant to penicillinase-resistant penicillins (e.g., flucloxacillin).
o Treated with vancomycin or teicoplanin

Allergic Reactions Can Occur with Any Antibiotic: (Penicillin most common)
Types of Allergic Reactions:
 Immediate Reactions:
o Mediated by IgE antibodies.
o Occur within minutes to hours of drug exposure.
o Can lead to anaphylaxis, a life-threatening allergic reaction.
 Delayed Reactions:
o Usually mediated by IgG antibodies or T cells.
o Occur days to weeks after starting the antibiotic.
o Typically present as rashes and are less severe compared to IgE-mediated reactions
Antibiotics that Inhibit Protein Synthesis. Prevents Proteins from Being Made
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 (Tetracyclines, Aminoglycosides, Macrolides, Chloramphenicol, Streptogramins, Oxalizidonone- T-A-M-C-S-O)

Drug Fact/Action Bacteriostatic/ Uses Side Effects

Bactericidal
- Act on bacterial
ribosomes (30S &
50S)

- Ribosome
structures are
different in human
vs. bacteria, so
don’t harm humans
 SELECTIVELY
TOXIC

Bacteriostatic Bone & teeth discoloration

1. Tetracyclines - Bind to 30S Staph A and Strep Photosensitivity (avoid sun)
(Tetracycline, Doxycycline, ribosomal subunit MRSA/VRE (Gram +) Hepatotoxicity
Minocycline) Doxycycline Uses: Chlamydia, Esophagitis/Ulcers
- Blocks protein (most commonly used) Rickettsial Infx (Q-fever), GI upset (N/V)
BROAD-SPECTRUM elongation by Staph & Strep Acne Candida (oral/vaginal)
attaching to (MRSA)
(Gram - & +) aminoacyl- tRNA Lyme disease RARE: LUPUS-LIKE RX
ATYPICAL BACTERIA (Borrelia B.)
*Not for: CHILDREN (<8)
Esophagitis/ Esophageal *Sit Up After Taking Take on Empty Stomach OR PREGNANT/
Ulcers Medication* Avoid dairy, iron, LACTATING WOMEN*
antacids

ADR:
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 - Binds to 30S, For Serious Infections! Ototoxicity
2. Aminoglycosides “tricks” or causes Sepsis, Endocarditis Nephrotoxicity
(Gentamycin, Tobramycin) misreading of Neuromuscular Blockade
mRNA, leading to TB (STREPTOMYCIN) (cannot give to Myasthenia
NARROW-SPECTRUM nonfunctioning Gravis patients)
proteins PSEUDOMONAS A.
(Gram – MOSTLY)
(Some Gram +) Combine with B-Lactams
for Streptococci
(synergistic effect)

GI upset: N/V
3. Macrolides -Bind to 50S Bactericidal at High - Used in people with Hepatotoxicity
(Azithromycin, Erythromycin, ribosomal subunit concentrations TRUE Penicillin QT-Prolongation
Clarithromycin) (inhibits Allergies Ototoxicity
translocation/ protein **Reserve - Mycoplasma
NARROW- SPECTRUM Pneumoniae- Drug Interactions
synthesis) Medication, so it (Inhibits CYP450- Affects
doesn’t become ATYPICAL PNA
(Gram +/-) Warfarin Metabolism)
Resistant** Azithromycin (the least drug
& - Chlamydia
(ATYPICAL Bacteria) interactions- covers a lot of
(Azithromycin- Long
things)!
half-life good for
chlamydial urethritis)
4. Chloramphenicol ADR:
-Inhibits Peptidyl Aplastic Anemia
Transferase on the Use: Typhoid Fever,
BROAD- SPECTRUM Bone Marrow
Meningitis, Bacterial
50S ribosome (Blocks Suppression
conjunctivitis
(Gram - & +) peptide bond
(Anaerobes & Rickettsia) Limited Use: Severe
formation)
ADR
ADR:
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 5. Streptogramins -Binds to the 50S *Reserved for Serious GI Upset (N/V/D)
(Quinupristin, Dalfoprostin) ribosomal subunit, Infections* Muscle & Joint Pain
inhibits elongation MRSA/VRE (myalgia, arthralgia)
NARROW- SPECTRUM and translocation of
the peptide chain
(Gram +)
(MRSA/VRE)

ADR: Bone marrow

-Inhibits 50S *Reserved for Serious suppression (Anemia &
6. Oxalizidonone
(Linezolid) ribosomal unit Infections* Thrombocytopenia)
(prevents the start of MRSA/VRE
NARROW- SPECTRUM protein synthesis) *Peripheral Neuropathy
with long time use!*
(Gram +)
(MRSA/VRE)

Other Antibiotics that Important

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 (Nitrofurantoin, Clindamycin- N-C)

Drug Fact/Action Bacteriostatic/ Uses Side Effects

Bactericidal

1. Nitrofurantoin - Damages bacterial Bactericidal KIDNEY needs to metabolize Avoid if suspected

(Macrobid) DNA, Proteins & in order for the drug to be Pyelonephritis
Class: Nitrofurans Cell Wall Synthesis used in BLADDER
ADRs: Dark Urine, Nausea,
(PRODRUG) First-Line: Uncomplicated Headaches
UTIs
(Doesn’t work for Kidney RARE: SJS, TEN
Infx/ Pyelonephritis)

- Inhibits protein Bacteriostatic GOOD FOR ADRs:

2. Clindamycin
synthesis (Gram + ANAEROBES) SJS, Leukopenia,
Class: LINCOSAMIDE
Thrombocytopenia
(Gram +) Soft tissue and Dental **High RISK OF C-DIFF

*NO COVERAGE FOR

GRAM (–) AEROBES* *Avoid this: High Risk of C-
Diff and Serious ADRs*

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