MT6314 - PHARMACOLOGY & TOXICOLOGY IMT 2025

11.2 | OTHER CELL WALL SYNTHESIS INHIBITORS

ALFEROS | A.Y. 2022-2023 | 3RD SHIFTING

CLINICAL USES
OUTLINE
I. Cephalosporins ● Clinical Uses (Cefazolin & Cephalexin):
A. First Generation ○ Gram (+) cocci
B. Second Generation ■ Staphylococci
C. Third Generation
■ Streptococci
D. Fourth Generation
E. Advanced Generation ○ E. coli
II. Adverse Reactions of Cephalosporins ○ K. pneumoniae
III. Aztreonam ○ Surgical prophylaxis in selected
IV. Carbapenems conditions
A. Imipenem ○ Minimal activity
B. Meropenem
■ Gram (-) cocci
C. Ertapenem
V. Vancomycin ■ Enterococci
VI. Fosfomycin ■ MRSA
VII. Bacitracin ■ Most gram (-) rods
VIII. Cycloserine
IX. Daptomycin
SECOND GENERATION

CEPHALOSPORINS CEFUROXIME SODIUM

FIRST GENERATION
● Cefazolin
● Cefadroxil
● Cephalexin
CEFAZOLIN
● This first-generation parenteral cephalosporin has
a longer duration of action and a similar spectrum
CEFUROXIME AXETIL
of action, compared to other first-generation
drugs. It penetrates well into bone.
● Administered intravenously
● Coverage: Gram (+), very limited Gram (-)
● This prototype second-generation, parenteral
cephalosporin has a longer half-life than similar
agents. It crosses the blood-brain barrier (first
generation drugs cannot), and it can be used for
community-acquired bronchitis or pneumonia in
the elderly and for patients who are
immunocompromised.
● Administered twice daily, this drug is well
absorbed and is active against
β-lactamase-producing organisms.

CEPHALEXIN CLINICAL USES

● This is the prototype of first-generation, oral ● Less activity against gram (+)
cephalosporins. Oral administration twice daily is ● Extended coverage for gram (-)
effective against pharyngitis. ● Marked differences in activity occur among the
● Prototype: meaning pharmacokinetics were all drugs
based on Cephalexin (if they follow the ○ Cefotetan, Cefoxitin
pharmacokinetics of cephalexin, they will be ■ B. fragilis
grouped here even if they are newly discovered) ○ Cefamandole, Cefuroxime, Cefaclor
● Originally developed for pharyngitis ■ H. influenzae or M. catarrhalis
● Mostly gram (+)
○ Cell wall are thicker THIRD GENERATION
○ Most gram (-) are resistant to ● Greater coverage for gram (-)
beta-lactams ● Cefdinir & Cefixime
● Administered orally ● Cefotaxime
● Ceftazidime
● Ceftriaxone

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MT6314 - PHARMACOLOGY & TOXICOLOGY IMT 2025

CEFDINIR AND CEFIXIME Ceftizoxime for serious

● These are administered orally once daily (long infection
half-life) ■ Ceftriaxone (IV) and Cefixime
● Drug of choice for
CEFOTAXIME gonorrhea
■ Ceftriaxone
● This penetrates well into the CSF.
● Single injection for acute
● Good for bacterial encephalitis and bacterial
otitis media
meningitis because it penetrates the BBB into the
● As effective as 10 days of
CSF
amoxicillin

CEFTAZIDIME
FOURTH GENERATION
● This is active against Pseudomonas aeruginosa
(hospital acquired, meaning it has a lot of
CEFEPIME
resistance since it has met almost all antibiotics)
● This is active against Pseudomonas aeruginosa
CEFTRIAXONE ● Clinical Uses:
● This drug has the longest half-life of any ○ More resistant to beta-lactamases
cephalosporin (6 to 8 hours), which permits produced by gram (-) organisms
once-a-day dosing. High levels of the drug can be ■ Enterobacter
achieved in blood and CSF. It is effective against ■ Haemophilus
genital, anal, and pharyngeal penicillin-resistant ■ Neisseria
Neisseria gonorrhoeae. The drug is excreted in bile ■ Some penicillin-resistant
and may be used in patients with renal pneumococci
insufficiency. It has good penetration into bone. ○ Combines the gram (+) activity of 1st gen
● Prototype and wider gram (-) spectrum of 3rd gen
● We must know how the drug is going to be ○ Habang tumataas yung generation,
excreted so the dose may be adjusted accordingly nababawasan ang coverage sa gram (+),
(ex: if the patient has a renal insufficiency or a pero nagwwiden and spectrum sa gram (-)
liver disease) ○ Nasakanya na lahat

CLINICAL USES ADVANCED GENERATION

● Ceftazidime, Cefoperazone, Cefotaxime
○ Increased activity against gram (-) CEFTAROLINE
organisms resistant to other beta-lactam ● This is active against MRSA (also
drugs hospital-acquired).
○ Ability to penetrate the blood-brain barrier
ADVERSE REACTIONS OF CEPHALOSPORINS
■ Except cefoperazone, cefixime
● RENAL: interstitial nephritis (especially if
○ Providencia
combined with aminoglycosides - penicillins go
○ S. marcescens
well with aminoglycosides) and tubular necrosis
○ Beta-lactamase producing strains
● HEMATOLOGIC: Hypoprothrombinemia and
■ H. influenzae
bleeding disorders (Cefotetan, cefamandole,
■ Neisseria
cefmetazole, and cefoperazone)
○ Less active against enterobacter strains
● OTHERS: Local irritation and pain (IM),
that produce extended-spectrum
thrombophlebitis (IV), Increase nephrotoxicity of
beta-lactamases
aminoglycosides, Disulfiram-like reactions with
○ Individual activity of drugs
ethanol
■ Cefoperazone, Ceftazidime
● ALLERGY:
● Pseudomonas
○ Skin rashes to anaphylactic shock
■ Ceftizoxime
○ Occurs less frequently than penicillins
● B. fragilis
○ Complete cross-hypersensitivity exists
● Cefoperazone,
○ Cross-reactivity with penicillins
Ceftazidime, and
■ Incomplete (5-10%)
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MT6314 - PHARMACOLOGY & TOXICOLOGY IMT 2025

■ Penicillin allergic patients are ○ Imipenem is combined with cilastatin,

sometimes treated successfully inhibiting dehydropeptidases-enzymes in
with cephalosporin renal tubules that inhibit imipenem
■ Those with history of anaphylaxis ● Useful for infections caused by organisms
to penicillin should not be treated resistant to other antibiotics
with drug ● Drug of choice for Enterobacter
● Other adverse effects ● Penetrate CSF well (can opt for when patient has
meningitis or encephalitis) except ertapenem
MONOBACTAM - AZTREONAM ● Excretion: renal, adjust dose in renal insufficiency
● Resistant to beta-lactamases by some organisms
IMIPENEM
● Coverage is limited to aerobic Gr(-) organisms
● For serious infections ● Rapidly inactivated by renal dehydropeptidases I
● Aztreonam - only monobactam available ● Cilastatin
● Penicillin-allergic patients tolerate aztreonam ○ Inhibitor of the enzyme
without reaction ○ Increases the half-life
● Major toxicity is uncommon ○ Inhibits formation of nephrotoxic
● Parenteral administration metabolites
● Resistant to beta-lactamases produced by certain ○ Adverse effects:
gram (-) rods ■ GI distress
○ Klebsiella ■ Skin rash
○ Pseudomonas ■ At very high plasma levels, CNS
○ Serratia toxicity
● No activity against gram (+) and anaerobes ● Confusion
● An inhibitor of cell wall synthesis binding to PBP3 ● Encephalopathy
● Synergistic with aminoglycosides ● Seizures
● Given IV ○ Partial cross-allergenicity with penicillins
● Eliminated via renal tubular secretion
● Half-life is prolonged in renal failure MEROPENEM
● No cross-allergenicity with penicillin ● Similar to imipenem
● Adverse Effects: ● Not metabolized by renal dehydropeptidases
○ GI upset with possible superinfection ● Less likely to cause seizure
○ Vertigo
○ Headache ERTAPENEM
○ Rare hepatotoxicity ● Long half-life
○ Skin rash ● Less active against Pseudomonas
● IM injection causes pain and irritation
CARBAPENEMS
● Coverage: Gram-negative rods including P. VANCOMYCIN
aeruginosa, Gram-positive organisms, and ● Isolated from the bacterium Amycolatopsis
anaerobes orientalis
● Wide activity against: ● Bactericidal glycoprotein
○ Gram (+) cocci ● Coverage: bactericidal against Gram-positive
○ Gram (-) rods cocci and anaerobes (i.e. Enterococcus faecium);
○ Anaerobes Active against MRSA (drug of choice)
● For pseudomonal infections ● Drug-resistant gram (+) organisms
○ Combine with aminoglycosides ○ MRSA
● Chemically different from penicillins ○ Penicillin-resistant pneumococci
● Retain the beta-lactam ring ○ C. difficile
● Low susceptibility to beta-lactamases ● Not absorbed orally
● Resistant to most beta-lactamases, ESBL ● Maybe given for bacterial enterocolitis
● Doripenem, ertapenem, imipenem, and ● When given IV, penetrates most tissues
meropenem - IV ● Eliminated unchanged in urine

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MT6314 - PHARMACOLOGY & TOXICOLOGY IMT 2025

● Similar Drug: Teicoplanin ○ Interferes with a late stage in cell wall

● MOA: Binds to D-Ala-D-Ala terminal of nascent synthesis in gram (+) organisms
peptidoglycan pentapeptide side chain ● Marked toxicity
○ inhibits transglycosylation ● Adverse Reaction: Highly nephrotoxic when
○ Prevents elongation of peptidoglycan administered systemically
chain ● Clinical Use: topical antibiotic
○ Interferes with cross-linking
○ Narrow spectrum of activity CYCLOSERINE
● Vancomycin-resistant enterococci (VRE) and
● Produced by Streptomyces orchidaceous
vancomycin-resistant S. aureus (VRSA)
● Antimetabolite
○ Due to decreased affinity of the drug to
● MOA: inhibits incorporation of d-alanine into
the binding site
peptidoglycan pentapeptide side chain
○ Replacement of D-Ala by D-lactate
○ by inhibiting alanine racemase, which
● Dosage modification in patients with renal
converts l-alanine to d-alanine, and
impairment
d-alanyl-d-alanine ligase.
● Reserved for toxic and septic patients
● Pharmacokinetics: widely distributed in tissues,
● Adverse Reaction: Red Man Syndrome / Red Neck
excreted in urine
Syndrome (Rapid IV infusion causing diffuse
● Clinical Use: second-line treatment of
blushing or rash)
tuberculosis caused by strains of Mycobacterium
● Toxic Effects: chills, fever, phlebitis, ototoxicity,
tuberculosis resistant to first-line agents
nephrotoxicity
● Adverse Reactions: headaches, tremors, acute
psychosis, and convulsions
FOSFOMYCIN ● Potentially neurotoxic (because it can also
● Antimetabolite inhibitor of cytosolic enolpyruvate penetrate CSF)
transferase ○ Tremors
○ Inhibits addition of phosphoenolpyruvate ○ Seizures
to UDP-N-acetylglucosamine ○ Psychosis
● Prevents the formation of N-acetylmuramic acid
which is essential in peptidoglycan chain DAPTOMYCIN
formation
● Fermentation product of Streptomyces roseosporus
● Resistance occurs via decreased intracellular
● Coverage: vancomycin-resistant strains of
accumulation of the drug
enterococci and S. aureus (VRE, VRSA)
● Usually used in renal tract infection
● MOA: depolarization of the cell membrane with
● In a single dose, drug is less effective than the
potassium efflux and rapid cell death
7-day course of treatment with fluoroquinolones
● Excretion: Renal
● Multiple dosing can result to resistance rapidly
● Adverse Reactions: myopathy - monitor creatine
● Coverage: gram-positive and gram-negative
phosphokinase levels, allergic pneumonitis in
● Synergistic with beta-lactam and quinolones in
patients receiving prolonged therapy (>2 weeks)
specific infections
● Pulmonary surfactant antagonizes daptomycin,
● Excretion: renal, with urinary concentrations
and it should not be used to treat pneumonia
exceeding MICs for most urinary tract pathogens
● Diarrhea is common
● Clinical Use: Uncomplicated cystitis (UTI)

BACITRACIN
● Obtained from the Tracy strain of Bacillus subtilis
in 1943
● Peptide antibiotic
● Coverage: gram-positive microorganisms
● MOA: Inhibits cell wall formation by interfering
with the lipid carrier that transfers peptidoglycan
subunits to the growing cell wall