MT6314 - PHARMACOLOGY & TOXICOLOGY IMT 2025

11.1 | INTRODUCTION TO ANTIMICROBIALS,

BETA-LACTAM & OTHER CELL INHIBITORS
ALFEROS | A.Y. 2022-2023 | 3RD SHIFTING

Selective toxicity More toxic to the invader than to

OUTLINE the host; a property of useful
I. Introduction to Antimicrobials antimicrobial drugs
II. Beta-Lactam compounds
A. Cephalosporins and cephamycins Transpeptidases Bacterial enzymes involved in the
B. Other beta-lactam drugs cross-linking of linear
III. Glycopeptide antibiotics peptidoglycan chains, the final
IV. Other cell wall or membrane-active agents step in cell wall synthesis

CHEMOTHERAPEUTIC AGENTS
DEFINITION OF TERMS

MICROBIAL RESISTANCE
Bactericidal An antimicrobial drug that can ● Production of antibiotic-inactivating enzymes
eradicate an infection in the
absence of host defense ● Changes in the structure of target receptors
mechanisms; kills bacteria ● Increased efflux via drug transporters
● Decreases in the permeability of microbes’
Bacteriostatic An antimicrobial drug that inhibits cellular membrane to antibiotics
antimicrobial growth but requires
host defense mechanisms to STRATEGIES
eradicate the infection; does not
kill bacteria ● Use of adjunctive agents that can protect against
antibiotic inactivation
Beta-lactam Drugs with structures containing a ● Use of antibiotic combinations
antibiotics beta-lactam ring: includes the
● Introduction of new (and often expensive)
penicillins, cephalosporins and
carbapenems. This ring must be chemical derivatives of established antibiotics
intact for antimicrobial action ● Efforts to avoid indiscriminate use or misuse of
antibiotics
Beta-lactamases Bacterial enzymes (penicillinases,
cephalosporinases) that hydrolyze MICROORGANISMS & ANTIMICROBIALS
the beta-lactam ring of certain
penicillins and cephalosporins ● ​Bacteria - Antibacterial
● Viruses - Antiviral
Beta-lactam Potent inhibitors of some bacterial ● Fungi - Antifungal
inhibitors beta-lactamases used in ● Parasites - Antiparasitic
combinations to protect
hydrolyzable penicillins from
inactivation ANTIMICROBIALS
● Drugs that inhibit the growth/replication, or kill
Minimal Lowest concentration of
microorganisms
inhibitory antimicrobial drug capable of
concentration inhibiting growth of an organism ○ Antibacterial
(MIC) in a defined growth medium ○ Antifungal
○ Antiviral
Penicillinbinding Bacterial cytoplasmic membrane ○ Anti-protozoal
proteins (PBPs) proteins that act as the initial ○ Anti parasitic
receptors for penicillins and other
● Under chemotherapeutic drugs
beta-lactam antibiotics

Peptidoglycan Chains of polysaccharides and GENERAL TERMINOLOGIES

polypeptides that are cross-linked ● Bactericidal = suicide/homicide; kills intended
to form the bacterial cell wall
bacteria

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● Bacteriostatic = does not kill bacteria, rather ● Not as important as beta-lactam drugs
prevents its reproduction; allow immune system ○ Vancomycin
to take over; effective if you have a competent ○ Fosfomycin
immune system ○ Bacitracin
● Minimum inhibitory concentration = in vitro ● More than 50 drugs that act as cell wall inhibitors
quantitative measure; how much concentration of are currently available
antibiotic will inhibit growth of bacteria when
growing it in the laboratory
● Selective toxicity = toxic to pathogen but not to
our own cells; involves different mechanisms
● Antibacterials
○ Shorten infective stage
○ Help body heal itself

GENERALITIES
● Major antibiotics that inhibit cell wall synthesis
○ Penicillins
○ Cephalosporins
● Beta-lactams because of the unusual 4-member
ring that is common to all members

BACTERIAL STRUCTURE

● No nuclear membrane and nucleus

● Has a nucleoid structure containing
chromosomes
● Bacterial cell wall = very important protection;
different chemical composition
● Cell membrane composition = lipid; phospholipid
bilayer; easily disrupted
● Cell wall composition = present in plants and
bacteria but not in humans; composition in
plants is carbohydrates; composition in bacteria
is peptidoglycan
● Capsule = calcium-containing
● Most effective ● Capsule and cell wall are one of the mechanisms
● Widely used of how they evade; phagocytosis and chemical
● Well-tolerated attacks
● Antibiotics that inhibit cell wall synthesis
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● Bacteria is classified as either gram-positive or ● Tetrapeptide Cross-linking

gram-negative depending on the structure of the ○ Makes it tough
cell wall ○ Not easily ripped and penetrated

● Gram-positive and Gram-negative

○ Anything above umbilicus is considered
gram-positive (ex. Sore throat, lung
infection)
○ Anything below umbilicus is
gram-negative (ex. UTI, foot wounds,
diarrhea)
○ However, due to mutation, the
classification above is not applicable as
much ● Beta-lactams = most popular
● Gram-positive ● If bacteria is not able to produce a cell wall, they
○ Thick layer of peptidoglycan for become susceptible to immune defenses; making
gram-positive them easier to kill
● Gram-negative ● Penicillins
○ Harder to combat ○ Narrow spectrum
○ Outer membrane ■ Culture and sensitivity
■ Lipid bilayer; similar to plasma ■ Targetted treatments
membrane ■ Advantages = you may target
■ Hydrophobic specific organisms
■ Not easily penetrated and ■ Penicillinase susceptible and
destroyed penicillinase resistant
○ Peptidoglycan ○ Wider spectrum
■ Thin layer ■ Affect other commensal and
■ Slightly hydrophilic as compared non-pathogenic bacteria
to outer membrane ● Miscellaneous
○ Carbapenems, aztreonam, and
vancomycin do not contain a beta-lactam
ring

HISTORY OF PENICILLIN

ALEXANDER FLEMING
● Serendipitous discovery
● First to suggest that a Penicillium mold (now
known as Penicillium chrysogenum) must secrete
an antibacterial substance
● N-acetylglucosamine (NAG) and N-acetylmuramic
● First to concentrate the active substance involved,
acid (NAM)
which he named penicillin, in 1928.
○ Repeating units

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● Clear area in the middle of Picture A shows the

growth inhibition of bacteria

PENICILLINS

CLASSIFICATION
● Derivatives of 6-aminopenicillamic acid
PHARMACOKINETICS
● Contain a beta lactam ring structure
○ Essential for antibacterial activity ● Vary in resistance to gastric acid
● Vary in their oral bioavailability
● Polar compounds
○ Not metabolized extensively
● Excreted unchanged in urine via
○ Glomerular filtration
○ Tubular excretion
■ Inhibited by probenecid
● Ampicillin and Nafcillin
○ Partly excreted in bile
● Square = Peculiar beta-lactam ring
● Plasma half-life vary from 30 min to 1 h
○ Peculiar because it only contains 4
● Procaine and Benzathine Penicillin G
members
○ Given intramuscularly
○ In sterric effect, it already looks like it can
○ Long half-lives
be easily disrupted BUT it is stable
○ Drug is released slowly
○ Beta-lactam ring is hydrolyzed by
○ Cross blood-brain barrier when meninges
penicillinase enzyme by resistant bacteria
are inflamed

MECHANISM OF ACTION
● Bactericidal
● Cross-linked peptidoglycans
● If damaged will result to cell lysis (bactericidal)

6-Aminopenicillanic acid
● Subclasses
○ Additional chemical substituents that
confer differences in
■ Antimicrobial activity
■ Susceptibility to acid and
enzymatic hydrolysis
■ Biodisposition

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○ Major mechanism for bacterial resistance

○ Inhibitors of this enzymes are used in
combination with penicillin to prevent
their inactivation
■ Clavulanic acid
■ Sulbactam
■ Tazobactam
● Structural changes in target PBPs
○ Another mechanism of bacterial
resistance
■ Methicillin resistance in
staphylococci
■ Penicillin G resistance in
pneumococci
● Changes in the porin structure in the outer
membrane
○ Contribute to resistance by impeding
access of penicillin to PBPs
○ Resistance in some gram (-) rods like P.
aeruginosa

CLINICAL USES
1. Narrow-spectrum penicillinase-susceptible
agents
● PENICILLIN G
○ Prototype
○ Parenteral
○ Limited spectrum of activity
○ Susceptible to beta-lactamases
○ Infections caused by
○ Streptococci
○ Meningococci
○ Gram (+) bacilli
○ Spirochetes
○ Penicillin-resistant S. pneumoniae (PRSP)
● Inhibit cell wall synthesis by the following steps: ○ strains
1. Binding of the drug to specific receptors ○ Some strains resistant via production of
(penicillin-binding proteins [PBPs]) beta-lactamases
located in the bacterial cytoplasmic ■ S. aureus
membrane ■ N. gonorrhea
2. Inhibition of Transpeptidase enzymes that ○ Drug of choice for syphilis
act to cross-link linear peptidoglycan ○ Activity against enterococci is enhanced
chains by aminoglycoside
3. Activation of autolytic enzymes that cause ● PENICILLIN V
lesions in the bacterial cell wall ○ Oral
● Enzymatic hydrolysis of the beta-lactam ring ○ Oropharyngeal infections
results in the lost of antibacterial activity 2. Very-narrow-spectrum penicillinase-resistant
agents
RESISTANCE ● METHICILLIN (prototype), NAFCILLIN, OXACILLIN
● Beta-lactamases ○ Treatment of known or suspected
○ Penicillinases staphylococcal infections
○ Formed by most staphylococci and gram ○ Methicillin-resistant S. aureus (MRSA)
(-) organisms

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○ S. epidermidis (MRSE) are resistant to other
members of this subgroup and often to
multiple antimicrobial drugs
3. Wider spectrum penicillinase-susceptible agents
● AMPICILLIN and AMOXICILLIN
○ Wider spectrum than pen G
○ Susceptible to penicillinases
○ Uses similar to pen G
■ Enterococci (L. monocytogenes)
■ E. coli (P. mirabilis)
■ H. influenzae (M. catarrhalis)
○ Enhanced activity in combination with
inhibitors of penicillinases
○ Synergistic (1+1=3) with aminoglycosides
in enterococcal and listerial infections
● PIPERACILLIN and TICARCILLIN
○ Activity against gram (-) rods
■ Pseudomonas
■ Enterobacter
■ Some cases of klebsiella species
○ Synergistic action with aminoglyclosides
○ Susceptible to penicillinases
○ Enhanced activity in combination with
inhibitors of penicillinases
Penicillin basic structure:
R GROUPS
TOXIXITY
1. Allergy
● Urticaria Severe pruritus
● Fever Joint swelling
IMT 2025
● Hemolytic anemia Nephritis
● Anemia
● Nafcillin can cause neutropenia
● Ampicillin causes maculopapular rashes
● Methicillin causes interstitial nephritis more
than other penicillins
● 5-10% of patients with history of allergy will have
the same reaction when given again
● Antigenic determinants include degradation
products like penicilloic acid
● Complete cross-allergenicity exists
2. GI disturbances
● Oral penicillins especially ampicillin
○ Nausea and diarrhea
○ Pseudomembranous colitis
■ Maybe caused by direct irritation
or by overgrowth of gram (+)
organisms or yeasts
BETA-LACTAM COMPOUNDS
1. Thiazolidine ring (A) = containing sulfur
2. β-lactam ring (B) that carries a secondary amino
group (RNH–)
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● Methicillin = not used as much anymore due to ● Inhibit transpeptidation reaction of bacterial cell
resistance wall synthesis

RESISTANCE
PHARMACOKINETICS
● Hydrolysis of the β -lactam ring by bacterial β
● Vary in their oral F (absorption)
-lactamases (cuts the beta-lactam ring)
● Penicillins – polar and not metabolized
● Modification of PBP
extensively
● Changes in membrane permeability =
○ Excreted unchanged in urine = early
gram-negative have resistance because of their
generation penicillins would have more
outer membrane permeability; Di makapasok si
gram-positive
penicillin
○ Inhibited by Probenecid
● Cross the BBB when meninges are inflamed =
some penicillins are used to treat meningitis
● Must be given on an empty stomach (to improve
absorption); except Amoxicillin (taken together
with meals)

MECHANISM OF ACTION
● Bactericidal drugs
● Inhibit cell wall synthesis
1. Binds to PBP (Penicillin-binding protein
regions - found in cytoplasmic
membrane)
2. Inhibits transpeptidation (weaving layers
of peptidoglycans)
a. By doing so, it can easily be
dislodged (?) off; madaling
balatan
3. Activation of autolytic enzymes = causing
peptidoglycan layer to be disintegrated
● Gram-positive with thick peptidoglycan layer =
more effective with this
● Gram-negative with outer membrane = resistance
is the inhibition of penicillins to enter through
outer membrane
CLINICAL USES
● Narrow spectrum penicillinase susceptible
agents
1. Penicillin G (“Pen G”) - limited spectrum;
susceptible to β-lactamases (if present,
Pen G is not effective)
● For streptotocci (causing sore
throat), meningococci (causing
meningitis), gram-positive bacilli,
spirochetes (ex. Sexually
transmitted syphilis)
● Benzathine Penicillin G – first line
drug for syphilis; IM
2. Penicillin V – P.O. (per orem/given orally)
● narrow spectrum
● Very Narrow spectrum penicillinase resistant
agents – against Staphylococcus aureus
- Antistaphylococcal penicillin
- carbuncles, skin infections, “pigsa”, leg
lesions

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○ Methicillin
■ prototype drug
■ due to shorter half life, given
4x/day; every 6 hrs
■ if given only 3x/day; there would
be a period where they would not
be in the minimum inhibitory
concentration = Staph. is able to
reproduce
○ Oxacillin
○ Cloxacillin (Dicloxacillin)
■ more available in the market now
● Wider spectrum penicillinase susceptible
drugs
○ Ampicillin and Amoxicillin - wider
spectrum than Pen G
■ Enhanced when used with
penicillinases (BLIC)
● penicillinases = anti beta
lactams
● Eg. Co-amoxiclav which is
Amoxicillin + Clavulanic
acid (the penicillinase)
■ Ampicillin is given IV since
hydrochloric acid in the stomach
degrades it
■ Amoxicillin is given orally
● Piperacillin and Ticarcillin
■ Enhanced activity against gram
negative (Pseudomonas,
Enterobacter, Klebsiella)
● Pseudomonas
nosocomial
■ Usually also combined with
penicillinase inhibitors
■ Has wider coverage, even with
gram negative
■ PIP TAZO - Piperacillin
penicillinase Tazobactam/
Ticarcillin sulbactam
● IV preparations & reserved
for more serious
infections
● Ampicillin also used for
veterinary uses; oral
preparation is used for vet
● Oral prep. of Ampicillin
used if in the luminal
mucosal membrane
TOXICITY
● Allergy – urticaria, pruritus, fever, joint swelling,
anemia, anaphylaxis
IMT 2025
○ CROSS REACTIVITY OF PENICILLINS
■ If a person is allergic to one
penicillin, it is likely that he/she is
allergic to other penicillins
○ KISSING DISEASE
■ viral infection (sore throat) which
induces penicillin allergy
■ if patient is given penicillin,
ampicillin, amoxicillin; they
manifest with a rash due to
reactivity
● Methicillin – interstitial nephritis (kidney
inflammation)
● Nafcillin – neutropenia (affects bone marrow)
● Ampicillin - rash (not allergic)
● GI disturbances :
○ nausea, diarrhea
● Ampicillin – pseudomembranous colitis
○ Ampicillin is broad spectrum and kills
some of the normal flora
○ may develop pseudomembranous colitis
○ either due to a fungal overgrowth or
resistant bacteria in the colon due to lack
of competition
BETA-LACTAMASE INHIBITORS
● Resemble β -lactam molecules, but have very
weak antibacterial action
● Combined with beta-lactam antibiotics to protect
them from β-lactamases, protecting them from
inactivation
is
● Beta-lactamase inhibitors are available only in
fixed combinations with specific penicillins and
cephalosporins
● Cannot work on the bacteria alone; function is to
protect the antibacterial penicillin from hydrolysis
so that it can target the cell wall of the bacteria
+
CEPHALOSPORINS
● Derivatives of 7-aminocephalosporanic acid, and
contain B-lactam ring structure
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HISTORY OF CEPHALOSPORINS
Giuseppe Brotzu
● Isolated Cephalosporin C compound in from the
fungus Acremonium, previously known as
"Cephalosporium” in 1945.
● Found in the sea near a sewage outfall in Su Siccu,
by Cagliari harbour in Sardinia, Italy

● Cephalosporins now have 5 generations based on

properties/antibacterial coverage

PHARMACOKINETICS
CEPHALOSPORINS and CEPHAMYCINS ● Oral
● More stable to many bacterial β–lactamases, has ● Most are parenteral (Some given parenterally )
broader spectrum of activity ○ Although per orem preparations still exist
● With 2 sites of attachment for various R1 and R2 ● Cephalosporins with side chains undergo hepatic
groups metabolism
● Major elimination is by renal tubular excretion
(meaning water soluble); some with side chains –
hepatic metabolism
● Cefoperazone and ceftriaxone (3rd generation) –
excreted in the bile
● 1st and 2nd generation: do not cross CSF/BBB
even in inflamed meninges (cannot be used for
meningitis)
7-aminocephalosporonic acid
MECHANISM OF ACTION AND RESISTANCE
● Bind to PBP – inhibit cell wall synthesis, similar to
penicillins
● Cephalosporins are bactericidal
● Structural differences render them less
susceptible to penicillinases produced by
staphylococci
○ Some organisms are resistant through
production of other beta-lactamases vs
cephalosporins
● MRSA/Methicillin resistant Staphylococcus
aureus – resistant to cephalosporins

R2 group at 7-position: alters antibacterial activity RESISTANCE

R1 group at 3-position: modifies pharmacokinetic profile
● Structural differences from penicillin
● Less susceptible to penicillinases produced by
staphylococci
R1 AND R2 GROUPS
● Resistance develops through the production of
other beta-lactamases
● Decrease membrane permeability to the drug
● Changes in PBPs

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● MRSA are also resistant to this drug
CLINICAL USES
● 1st Generation drugs:
○ Cefazolin and cephalexin
■ against G+ cocci, E coli, K
pneumoniae
■ better coverage against gram
positive bacteria
● 2nd Generation drugs:
○ Less activity against G+, extended G-
overage
○ Cefotetan, Cefoxitin: Anaerobic coverage
○ Cefamandole, cefuroxime, cefaclor: H
influenzae, M catarrhalis
● 3rd Generation drugs:
○ Increased activity for G-; penetrates BBB
(except Cefoperazone and Cefixime)
○ Ceftriaxone: gonococcal urethritis
● 4th Generation drugs:
○ Cefepime
■ more resistant to beta lactamases
■ combines gram positive activity of
1st gen. with wider gram neg.
spectrum of 3rd gen.
○ Ceftaroline: active against MRSA
CLINICAL USES
1. FIRST-GENERATION DRUGS
● Cefazolin (IV), cephalexin (oral)
○ Gram (+) cocci
■ Staphylococci
■ Streptococci
○ E. coli
○ K. pneumoniae
● Surgical prophylaxis in selected conditions
○ Minimal activity
■ Gram (-) cocci
■ Enteroccoci
■ MRSA
■ Most gram (-) rods
2. SECOND-GENERATION DRUGS
● Less activity against gram (+)
● Extended coverage for gram (-)
● Marked differences in activity occur among the
drugs
● Cefofetan, cefoxitin
○ B. fragilis
● Cefamandole, cefuroxime, cefaclor
○ H. influenzae or M. catarrhalis
3. THIRD-GENERATION DRUGS
● Ceftazidime, cefoperazone, cefotaxime
IMT 2025
○ Increased activity against gram (-)
organisms resistant to other beta-lactam
drugs
○ Ability to penetrate the blood-brain barrier
■ Except cefoperazone, cefixime
● Providencia
● S. marcescens
● Beta-lactamase producing strains
○ H. influenzae
○ Neisseria
● Less active against enterobacter strains that
produce extended-spectrum beta-lactamases
● Individual activity of drugs
a) Cefoperazone, ceftazidime
■ Pseudomonas
b) Ceftizoxime
■ B. fragilis
■ a & b for serious infection
c) Ceftriaxone (IV) and cefixime
■ Drug of choice for gonorrhea
d) Ceftriaxone
■ Single injection for acute otitis
media
■ As effective as 10 days of
amoxicillin
4. FOURTH-GENERATION DRUGS
● Cefepime
○ More resistant to beta-lactamases
produced by gram (-) organisms
■ Enterobacter
■ Haemophilus
■ Neisseria
■ Some penicillinase-resistant
pneumococci
○ Combines the gram (+) activity of 1st gen
and wider gram (-) spectrum of 3rd gen
TOXICITY
● Allergy – from rashes to anaphylactic shock
○ Complete cross reactivity should be
assumed
○ Partial Cross reactivity between penicillin
and cephalosporin : 5-10%
TOXICITY
1. Allergy
● Skin rashes to anaphylactic shock
● Occurs less frequently than penicillins
● Complete cross-hypersensitivity exists
● Cross-reactivity with penicillins
○ Incomplete (5-10%)
○ Penicillin allergic patients are sometimes
treated successfully with cephalosporin
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○ Those with history of anaphylaxis to succeeding generations progressively more active

penicillin should not be treated with drug against Gr(-) strains (often with reduced Gr(+)
2. Other adverse effects activity except 4th generation, which are extended
● Pain at IM injection site spectrum agents)
● Phlebitis after IV injection ● Cephalosporins are “LAME” because they are
● Increase nephrotoxicity of aminoglycosides inactive against:
● Drugs containing a methlythiotetrazole group ● Listeria
○ Cefamandole, cefoperazone, cefofetan ● Atypicals
○ May cause hypoprothrombinemia ● Methicillin-resistant staphylococcus aureus
○ Disulfiram-like reactions with ethanol (MRSA) - except Ceftaroline
● Enterococcus
CLASSIFICATION OF CEPHALOSPORINS ● Not all 2nd gen. would have anaerobic activity,
only the specified ones.
Classification of Cephalosporins
OTHER BETA-LACTAM DRUGS
1st 2nd 3rd generation 4th generation
generation generation AZTREONAM

Cefazolin, Cefaclor, Cefotaxime, Cefepime ● Monobactam

cefadroxil, cefamandole ceftazidime, ● Resistant to beta-lactamases produced by certain
cephalexin, , cefonicid, ceftizoxime*, gram (-) rods
cephalothi cefuroxime, ceftriaxone, ○ Klebsiella
n, cefprozil, cefixime, ○ Pseudomonas
cephapirin, loracarbef, cefpodoxime
○ Serratia
cephradine and proxetil,
ceforanide cefdinir, ● No activity against gram (+) and anaerobes
cefditoren ● An inhibitor of cell wall synthesis binding to
pivoxil, PBP3
ceftibuten, ● Synergistic with aminoglycosides
moxalactam*, ● Given IV
cefoperazone*
● Eliminated via renal tubular secretion
Coverage: Coverage: Expanded Coverage: ● Half-life is prolonged in renal failure
Gr(+) cocci, same as 1st Gram-negativ Pseudomonas ● No cross-allergenicity with penicillin
E.coli, K gen but with e coverage: , ● Adverse effects
pneumonia extended Citrobacter, Enterobacteri ○ GI upset with possible superinfection
e, and Gr(-) activity- serratia, aceae , ○ Vertigo
Proteus Klebsiella, H. providencia, methicillin-su
○ Headache
mirabilis influenzae, Pseudomonas sceptible S.
Bacteroides (Ceftazidime) aureus, S. ○ Rare hepatotoxicity
fragilis, pneumoniae., ○ Skin rash
Serratia Some able to Haemophilus
cross the and Neisseria
IMIPENEM, MEROPENEM, AND ERTAPENEM
Not useful blood-brain-b sp.
against arrier ● Carbepenems
Enterobacter Not useful Penetrates ○ Chemically different from penicillins
against well into ○ Retain the beta-lactam ring
Enterobacter cerebrospinal ○ Low susceptibility to beta-lactamases
fluid.
○ Wide activity against
No longer Useful in
commercially treatment of ■ Gram(+) cocci
available Enterobacter ■ Gram (-) rods
infections. ■ Anaerobes
○ For pseudomonal infections
■ Combine with aminoglycosides
○ Given IV
SOME CEPHALOSPORINS GENERALITIES ○ Useful for infections caused by
organisms resistant to other antibiotics
● First generation cephalosporins are
predominantly active against Gr(+)’s, with ○ Drug of choice for Enterobacter

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● IMIPENEM
○ Rapidly inactivated by renal
dehydropeptidases I
○ Cilastatin
■ Administered in combination
■ Inhibitor of the enzyme
■ Increases the half-life
■ Inhibits formation of nephrotoxic
metabolites
○ Adverse effects of imipenem-cilastatin
■ GI distress
■ Skin rash
■ At very high plasma levels, CNS
toxicity
● Confusion,
encephalopathy, seizures
■ Partial cross-allergenicity with
penicillins
● MEROPENEM
○ Similar to imipenem
○ Not metabolized by renal
dehydropeptidases
○ Less likely to cause seizure
● ERTAPENEM
○ Long half-life
○ Less active against pseudomonas
○ IM injection causes pain and irritation

BETA-LACTAMASE INHIBITORS
● CLAVULANIC ACID, SULBACTAM, and
TAZOBACTAM
○ Used in fixed combination with certain
hydrolyzable penicillins
○ Plasmid-encoded beta-lactamases
■ Gonococci
■ Streptococci
■ E. coli
● H. influenzae

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