UNIT XII: INTRODUCTION TO ANTIMICROBIALS, BETA-LACTAM AND OTHER CELL WALL INHIBITORS

BACTERIAL STRUCTURE
OUTLINE
I Introduction to Antimicrobials
A Subtopic A
II Beta-Lactam Compounds
A Cephalosporins and Cephamycins
B Other Beta-lactam Drugs
III Glycopeptide Antibiotics
IV Other Cell Wall- or Membrane-Active Agents

INTRODUCTION TO ANTIMICROBIALS ➔ all cells have cell membranes, may it be

eukaryotic or prokaryotic
ANTIMICROBIALS ➔ has a nucleus but does not have nuclear
➔ Drugs that inhibit the growth/replication, or membrane
kill microorganisms ◆ has nucleoid structure containing the
◆ Antibacterial chromosome
◆ Antifungal ➔ capsule is a different protection of the
◆ Antiviral bacteria
◆ Anti-protozoal ◆ usually calcium-containing
◆ Anti parasitic ➔ the very important protection of the bacteria
➔ Under chemotherapeutic drugs would be the bacterial cell wall
◆ has different chemical composition
GERMINAL TERMINOLOGIES ● cell membrane has a chemical
composition of phospholipid
BACTERICIDAL bilayer that’s why this can be
➔ kills the intended bacteria easily disrupted by anything
that can disrupt this
BACTERIOSTATIC hydrophobic structure such as
➔ does not kill the bacteria alcohol
➔ prevents reproduction thereby allowing the ➔ as an added protection, these bacteria also
immune system to take over produces the cell wall which has a chemical
➔ the immune system can actually cure the body composition of a carbohydrate, a
from infections but because of mutations to peptidoglycan
these bacteria, it became pathogenic and ◆ has peptides and proteins but has
evades the immune system or overwhelms it more repeating units of carbohydrate
which in turn cannot be resolved by the component
immune system ➔ cell wall and capsule are examples of
➔ antibacterials shortens the infective stage mechanisms on how the bacteria evade
➔ only when the wound has an infection it lasts phagocytosis or even the chemical attacks by
long the immune system

MINIMUM INHIBITORY CONCENTRATION

➔ an in-vitro quantitative measure on how much
concentration of the antibiotic will be able to
inhibit the growth of bacteria when cultured
in the laboratory

SELECTIVE TOXICITY
➔ antibacterials will be toxic to the pathogen but
not in the human cells

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 1

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

➔ a bacteria can be a gram negative or a gram ➔ Beta lactams are the most popular which are
positive bacteria depending on its cell wall penicillins and cephalosporins
➔ in the past, anything above the umbilicus ➔ does not contain beta lactam ring are:
(pusod) would mostly be a gram-positive ◆ carbapenems, aztreonam, and
bacteria i.e. sore throat, lung infection while vancomycin
anything below the umbilicus i.e. UTI, wound ➔ when a bacteria did not produce a cell wall, it
on the feet, diarrhea would be a will be susceptible to the immune defences
gram-negative bacteria making it easier to be killed
◆ but because of the mutation of ➔ usually beta lactams are divided into two
bacterial pathogenicity, it has already which are:
changed ◆ narrow spectrum
➔ a gram-positive cell wall would have thick ● can also be classified whether
layer of peptidoglycan layer it is
➔ a gram-negative cell wall would have a thin ○ penicillinase
peptidoglycan layer, however the cell wall susceptible - an
would have another layer known as the outer enzyme the can break
membrane which is also a lipid bilayer similar the beta lactam
to the plasma membrane ○ penicillinase resistant
➔ peptidoglycan are likely to be hydrophilic ● advantage is that it can target
compared to the outer membrane because of specific organisms
its lipid major, it is hydrophobic ● in the case of the Philippines
◆ this peptidoglycan cannot just be where culture and sensitivity
disrupted, the reason why this is of antibiotics are not routinely
harder to kill gram-negative bacteria done, it is not applicable since
it would be costly
◆ wider spectrum
● disadvantage of this is that it
will also affect other
commensal/non-pathogenic
bacteria

HISTORY OF PENICILLIN
➔ Penicillin is a serendipitous discovery when
Alexander Flemming was growing an organism
➔ peptidoglycan is a repeating units of NAG and which happens to be contaminated by a
NAM bacteria and saw that where the Penicillin
◆ carbohydrates grows, it inhibits the contaminating mold
➔ these are interconnected by the Tetrapeptide
Cross-Linking which makes it tough and harder SIR ALEXANDER FLEMMING
to be penetrated
◆ the four amino acids in the
Tetrapeptide Cross-Linking are:
● L - alanine
● D - glutamine
● L - lysine
● D - alanine

➔ First to suggest that a Penicillium mold (now

known as Penicillium chrysogenum) must
secrete an antibacterial substance
➔ First to concentrate the active substance
involved, which he named penicillin, in 1928.

PENICILLINS
➔ Derivatives of 6-aminopenicillamic acid and
contain a peculiar beta lactam ring structure

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 2

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

◆ peculiar because the ring formation 2. β-lactam ring (B) that carries a
usually would require at least five secondary amino group (RNH–)
members, however these
four-member ring, the steering effect R GROUPS
would likely to be seen as can easily
disrupted
● however this is a stable beta
lactam ring from which
penicillins and cephalosporins
are built on

6-AMINOPENICILLANIC ACID

➔ methicillin is not commonly used today

because of the methicillin resistance
➔ ticarcillin and piperacillin are some of the
broad spectrum which are usually reserved for
more serious infections

PHARMACOKINETICS
➔ Vary in their oral F (absorption)
➔ Penicillins – polar and not metabolized
➔ the beta lactam ring is the one that is extensively
hydrolyzed by penicillinase, an enzyme ◆ Excreted unchanged in urine
produced by resistant bacteria ● most of the earlier generation
➔ the nature of the R group would usually penicillins would have more
determine the specific beta lactam stability to gram-positive which are
acid which explains why some drugs cannot below the umbilicus
be taken orally because of the acid in the ● most of the UTI would be
stomach gram-negative
◆ Inhibited by Probenecid
BETA-LACTAM COMPOUNDS ➔ Cross the BBB when meninges are inflamed
◆ the reason why some penicillins are
used in treating meningitis
➔ Must be given on an empty stomach (to
improve absorption); except Amoxicillin

MECHANISM OF ACTION

➔ Penicillin basic structure:

1. Thiazolidine ring (A) - contains sulfur

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 3

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

◆ Modification of PBP
◆ Changes in membrane permeability
● causes resistance

CLINICAL USES
➔ Narrow spectrum penicillinase susceptible
agents

➔ Bactericidal drugs
➔ Inhibit cell wall synthesis
1. Binds to PBP (Penicillin Binding
Protein) regions of the bacteria
● in the cytoplasmic membrane
● it needs to enter in the porins
to bind in the PBP and by
doing so it inhibits
transpeptidation 1. Penicillin G
2. Inhibits transpeptidation ● limited spectrum; susceptible
● transpeptidation is like to β-lactamases
weaving the layers of ● For streptococci (causes sore
peptidoglycan throat), meningococci (causes
● when peptidoglycans are not meningitis), gram-positive
able to bind on one another, it bacilli, spirochetes i.e.
can easily sluff off sexually-transmitted syphilis
3. Activation of autolytic enzymes ● Benzathine Penicillin G – first
● causing the peptidoglycan line drug for syphilis; IM
layer to be disintegrated ○ single intramuscular
injection
➔ on gram-positive bacteria which has a thick 2. Penicillin V – P.O.
peptidoglycan, the target of the penicillin, it
will be more effective but for the ➔ Very Narrow spectrum penicillinase resistant
gram-negative bacteria that has an outer agents – against Staphylococcus aureus
membrane, it will manifest some of the (antistaphylococcal penicillins) for skin
resistance is the inhibition of the penicillins to infections
enter the outer membrane

◆ Methicillin
● a prototype drug
◆ Oxacillin
● available in the market
◆ Cloxacillin (Dicloxacillin)
➔ Inhibit transpeptidation reaction of bacterial ● available in the market
cell wall synthesis ◆ methicillin group, because of its
shorter half-life, it is taken 4x a day
➔ Resistance: (every 6 hours)

➔ Wider spectrum penicillinase susceptible

drugs
◆ Ampicillin (given IV since it can be
◆ Hydrolysis of the β-lactam ring by degraded by the stomach) and
bacterial β-lactamases

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 4

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

Amoxicillin (P.O.) - wider spectrum ➔ Methicillin – interstitial nephritis (kidney

than Pen G
● Enhanced when used with
penicillinases (BLIC)
○ i.e. Co-amoxiclav
(Amoxicillin
Clavulanic acid)
◆ Piperacillin and Ticarcillin
● have a wider coverage even
with gram-negative
○ since penicillins are
much more effective
in gram-positive
bacteria
● much more costly
● oral preparations of ampicillin
are for veterinary use/for
luminal targets in the human
body
● Enhanced activity against
gram negative (Pseudomonas,
Enterobacter, Klebsiella)
○ pseudomonas are
nosocomial bacteria
(can be acquired in
the hospital)
● Usually also combined with
penicillinase inhibitors
○ i.e. piperacillin +
tazobactam; ticarcillin
+ sulbactam
● most preparation of these
drugs are IV preparations and
are reserved for more serious
infections
◆ clavulanic acid, tazobactam, and
sulbactam are examples
penicillinase inhibitors
TOXICITY
inflammation)
◆ not commonly used nowadays as it
induces this disease
➔ Nafcillin – neutropenia
+ ◆ affects bone marrow
➔ Ampicillin - rash (not allergic)
➔ GI disturbances:
◆ nausea, diarrhea
➔ *Ampicillin – pseudomembranous colitis
◆ ampicillin are broad spectrum which
kills some of the normal flora
◆ this disease occurs due to a fungal
overgrowth where resistant bacteria
will not have a competition in the
colon which will cause diarrhea as it
will not absorb the excess water
BETA-LACTAMASE INHIBITORS
➔ since the rise of the resistance to beta
lactams, it is now combined with any of these
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
◆ amoxicillins are still effective for most
upper respiratory tract infections but
when it is ineffective, it may need
of some additional clavulanic acid
(Co-amoxcilav)
➔ Beta-lactamase inhibitors are available only in
fixed combinations with specific penicillins
and cephalosporins

➔ alone, these will not work against the bacteria

➔ Allergy – urticaria (itchy, develops skin
manifestation i.e. hives), pruritus, fever, joint
swelling, anemia, anaphylaxis
◆ kissing disease is a viral infection (sore
throat) that induces penicillin allergy
◆ CROSS REACTIVITY OF PENICILLINS
● means that when one is
allergic in some penicillin,
he/she is already allergic to all
penicillins
➔ the function of these beta lactamase
inhibitors 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

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 5

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

◆ whether they can traverse the BBB or

not; whether it will hydrophobic or
hydrophilic, it id is biliary or urinary
excreted

R1 AND R2 GROUPS
➔ 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

➔ groups are based on properties

PHARMACOKINETICS
➔ Most are parenteral
CEPHALOSPORINS AND CEPHAMYCINS ◆ there are oral preparations i.e.
➔ “mycins” pertains that they are of fungal cephalexin, especially the older
origin generations
➔ More stable to many bacterial β–lactamases, ➔ Major elimination is by renal excretion
has broader spectrum of activity (water-soluble); some with side chains –
➔ With 2 sites of attachment for various R1 and hepatic metabolism
R2 groups ➔ Cefoperazone and ceftriaxone – excreted in
◆ whether it is hydrophobic or the bile
hydrophilic; whether it can traverse ➔ 1st and 2nd generation: do not cross BBB even
the BBB or not in inflamed meninges
7-AMINOCEPHALOSPORANIC 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

CLINICAL USES
➔ 1st Generation Drugs:
◆ has better coverage to gram-positive
bacteria
◆ Cefazolin and cephalexin – against G+
➔ R group at 7-position: alters antibacterial cocci, E coli, K (Klebsiella) pneumoniae
activity
➔ R group at 3-position: modifies
pharmacokinetic profile

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 6

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

where a diluted sample is

injected into the skin to check
reactivity after 15 minutes

CLASSIFICATION OF CEPHALOSPORINS
1ST 2ND 3RD 4TH
GENERATION GENERATION GENERATION GENERATION
➔ 2nd Generation Drugs:
Cefazolin, Cefaclor, Cefotaxime Cefepime
◆ as the generation gets further in the cefadroxil, cefamandole (prototype
generation of cyclosporine, it loses its cephalexin , cefonicid, drug),
activity coverage on gram-positive but (prototype cefuroxime, ceftazidime,
develops extension to gram-negative drug), cefprozil, ceftizoxime*
cephalothin, loracarbef, , ceftriaxone,
◆ Less activity against G+, extended G-
cephapirin, and cefixime,
overage cephradine ceforanide cefpodoxime
◆ Anaerobic coverage: Cefotetan, proxetil,
Cefoxitin cefdinir,
◆ H influenzae (can cause meningitis), M cefditoren
pivoxil,
catarrhalis: Cefamandole, cefuroxime, ceftibuten,
cefaclor moxalactam*
● most of the ,
meningitis-causing bacteria cefoperazone
Coverage: * Coverage:
starts if with a respiratory
same as 1st Pseudomona
tract infection which can be Coverage: gen but with Expanded s,
covered by these drugs Gr(+) cocci, extended Gram-negati Enterobacter
E.coli, K Gr(-) ve coverage: iaceae ,
➔ 3rd Generation Drugs – Ceftazidime, pneumoniae, activityKlebsi Citrobacter, methicillin-su
and Proteus ella, H. serratia, sceptible S.
cefoperazone, cefotaxime mirabilis influenzae, providencia, aureus, S.
◆ Increased activity for G-; penetrates Bacteroides Pseudomona pneumoniae.
BBB (except Cefoperazone and fragilis, s ,
Cefixime) Serratia (Ceftazidime) Haemophilus
and Neisseria
◆ Ceftriaxone = gonococcal urethritis
sp.
● prototype for third generation
cephalosporins; IV Penetrates
well into
Some able to cerebrospina
cross the l fluid
blood-brain-
Not useful barrier Useful in
against treatment of
Enterobacter Not useful Enterobacter
against infections
Enterobacter
➔ 4th Generation Drugs:
*No longer commercially available
◆ Cefepime – more resistant to beta
lactamases; combines gram positive
SOME CEPHALOSPORIN GENERATILITES
activity of 1st gen. with wider gram
➔ First generation cephalosporins are
neg. spectrum of 3rd gen.
predominantly active against Gr(+)’s, with
◆ Ceftaroline – active against MRSA
succeeding generations progressively more
TOXICITY
active against Gr(-) strains (often with reduced
Gr(+) activity except 4th generation, which are
➔ Allergy – from rashes to anaphylactic shock
extended spectrum agents)
◆ Complete cross reactivity should be
➔ Cephalosporins are “LAME” because they are
assumed
inactive against atypical causes of pneumonia:
◆ (Partial) Cross reactivity between
◆ Listeria
penicillin and cephalosporin : 5-10%
◆ Atypicals
● before giving IV antibiotics, a
◆ Methicillin-resistant staphylococcus
skin test is first performed
aureus (MRSA) - except Ceftaroline

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 7

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

◆ Enterococcus and second generation

➔ anaerobic side of infection is far from cephalosporin does not cross
atmospheric air; some would require for nana the BBB, but this specific drug
to be drained because it the middle of it, it can traverse the BBB and has
can have anaerobic that would be pathogenic been used for
➔ not all second generation would have community–acquired
anaerobic activity, only those which are bronchitis and pneumonia
specified ● sometimes, it is an extension
of an upper respiratory tract
i.e. bronchitis and pneumonia
are already a lower
respiratory tract infections
which are very common
especially for senior citizens
and are required to have
vaccines against this; having
comorbidity increases risk of
acquiring infections
◆ Cefuroxime axetil is taken twice a day
● quite resistant even against
➔ First generation cephalosporin beta lactamase producing
◆ cephalexin is the prototype drug - organism
meaning, the pharmacokinetics were ➔ Third generation cephalosporin
all based from cephalexin ◆ ceftriaxone is the prototype drug
● if they follow the ● has greater coverage for
pharmacokinetics of gram-negative that includes
cephalexin, they will be Nisseria gonorrhoeae which is
grouped even if they are just a sexually-transmitted
newly discovered infection
● originally, this was developed ● excreted through the bile
for the pharyngitis - above the ● knowing where drugs are
umbilicus infection which excreted (bile or kidney) will
back then, were mostly help in determining
gram-positive adjustment to the dose
● cell wall will be triggered for accordingly if a patient has
gram-positives renal deficiency or a liver
● most of the gram negatives disease; there should be a
are resistant already with beta corresponding dose
lactams adjustment
◆ other well-known first generation is ◆ ceftazidime is the one that has
the cefazolin anti-pseudomonal coverage - a
● parenteral route which means nosocomial infection
it can be given IV (hospital-acquired) - these organisms
● has longer duration of action already possesses a lot of resistance
but similar spectrum to which since it already met a lot of antibiotics
gram-positive bacteria are hence it is very important to take note
expected to be resolve by first of the antibiotics that can cover
generation; very limited pseudomonas infection
coverage on gram-negative ◆ cefotaxime is also a good choice for
bacteria infection like bacterial encephalitis as
➔ Second generation cephalosporin well as bacterial meningitis as it can
◆ the prototype drug is the cefuroxime penetrate the BBB into the cerebrum
● can be given parenterally(IV); spinal fluid
has longer half life; although
generally have said that first

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 8

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

◆ drugs that have longer half-lives such

as cefdinir and cefixime are given MONOBACTAM - AZTREONAM
once a day
➔ Fourth generation cephalosporin
◆ it combines first generation coverage
on gram-positive even
antipseudomonal property , the
reason why cefepime is very ➔ also targets the cell wall
expensive ➔ most of these are reserved because it has high
➔ Advanced generation toxicity when given systemically, some are just
◆ do not fit well on the categories of for topical and for serious type of infection
first to third generation which ➔ Resistant to beta-lactamases by some
includes ceftaroline organisms
● this drugs already contains ◆ given for infections for which
the methicillin-resistant infectious agent would produce beta
staphylococcus aureus lactamases
(MRSA) coverage - one of the ➔ Coverage is limited to aerobic Gr(-) organisms
dreaded; also a ◆ penicillins are usually for
hospital-acquired infection, gram-positive bacteria as well as the
although in the US and lower generation cephalosporins
Europe, they do not usually ➔ Aztreonam- only monobactam available
use amoxicillin cause MRSA is ➔ Penicillin-allergic patients tolerate aztreonam
the one already been utilized without reaction
● here, we already have our ◆ given to patients that has penicillin
own antibiotic resistance allergy
milieu ◆ penicillins are the most popular
choice for antibiotics
ADVERSE REACTIONS OF CEPHALOSPORINS ➔ Major toxicity is uncommon
➔ Parenteral administration
◆ usually for serious type of infections

CARBAPENEMS

➔ Renal: interstitial nephritis (especially when

combined with aminoglycosides, protein
synthesis inhibitors) and tubular necrosis
◆ usually, penicillin go along well with
aminoglycosides i.e. ampicillin,
gentamicin for sepsis cases
◆ cephalosporins does not go along well
with aminoglycosides but it can
actually increases risk for developing
interstitial nephritis and also the
nephrotoxicity of aminoglycosides on
the tubular necrosis (kidney damage)
➔ Hematologic: Hypoprothrombinemia and
bleeding disorders (Cefotetan, cefamandole,
cefmetazole, and cefoperazone)
➔ Others: Local irritation and pain (IM),
thrombophlebitis (IV)
◆ Pen G is the drug of choice for syphilis
infection
➔ Coverage: Gram-negative rods including P.
aeruginosa, Gram-positive organisms, and
anaerobes
➔ Resistant to most β–lactamases, ESBL
(Extended-Spectrum Beta-Lactamases)
➔ Doripenem, ertapenem, imipenem, and
meropenem - IV
◆ Imipenem is combined with cilastatin
which inhibits dehydropeptidase
enzymes in renal tubules that inhibit
imipenem
● always given in combination
➔ Penetrate CSF well except ertapenem
➔ Excretion: renal, adjust dose in renal
insufficiency
VANCOMYCIN

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 9

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

➔ Excretion: renal, with urinary concentrations

exceeding MICs for most urinary tract
pathogens
◆ most physicians would choice
quinolones
➔ Clinical use: uncomplicated cystitis (UTI)

➔ Isolated from the bacterium Amycolatopsis
orientalis
➔ Coverage: bactericidal against Gram-positive
cocci and anaerobes (i.e. Enterococcus
faecium); Active against MRSA
➔ the drug of choice for MRSA
◆ there is already the presence of
vancomycin-resistant MRSA
➔ Similar drug: Teicoplanin
➔ MOA – binds to D-Ala-D-Ala terminal of
peptidoglycan; inhibits transglycosylation
◆ the terapeptide that cross-links the
peptidoglycan layer (D-Ala terminal)
does inhibits the transglycosylation
➔ Adverse reaction – red man syndrome (also
known as the red neck syndrome
◆ develop rash on the face and neck
◆ very prominent to caucasians; not
readily seen in the Philippines
➔ this drugs is reserved for septic toxic patients
confined in the ICU setting
FOSFOMYCIN
➔ another cell wall active antibiotic
➔ Antimetabolite inhibitor of enolpyruvate
transferase -nan important enzyme in the
addition of phosphoenolpyruvate
◆ Inhibits addition
phosphoenolpyruvate
UDP-N-acetylglucosamine
➔ Monurol (brand name) is a single dose drug
➔ Coverage: gram-positive and gram negative
BACITRACIN
➔ Obtained from the Tracy strain of Bacillus
subtilis in 1943
➔ Coverage: gram-positive microorganisms
➔ usually for topical use; highly nephrotoxic
when given systemically
➔ Mechanism of action: Inhibits cell wall
formation by interfering with the lipid carrier
that transfers peptidoglycan subunits to the
growing cell wall
➔ Adverse reaction: highly nephrotoxic when
administered systemically
➔ Clinical use: topical antibiotic
CYCLOSERINE
➔ Produced by Streptomyces orchidaceous
➔ Mechanism of action: inhibits incorporation of
d-alanine into peptidoglycan pentapeptide by
inhibiting alanine racemase, which converts
l-alanine to d-alanine, and d-alanyl-d-alanine
ligase
➔ Pharmacokinetics: widely distributed in
tissues, excreted in urine
◆ applicable for soft tissue infection,
respiratory, and UTI
➔ Clinical use: treatment of tuberculosis caused
by strains of Mycobacterium tuberculosis
resistant to first-line agents
◆ second-line drug for TB especially for
patients that are MDR
➔ Adverse reactions: headaches, tremors, acute
of psychosis, and convulsions
to ◆ since it can penetrate the CNS
DAPTOMYCIN
➔ Fermentation product of Streptomyces
roseosporus

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 10

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

➔ Coverage: vancomycin-resistant strains of

enterococci and S aureus (VRE, VRSA)
➔ Mechanism of action: depolarization of the
cell membrane with potassium efflux and
rapid cell death
➔ Excretion: renal
➔ Adverse reactions: myopathy - monitor
creatine phosphokinase levels, allergic
pneumonitis in patients receiving prolonged
therapy (>2 weeks)
➔ Pulmonary surfactant antagonizes
daptomycin, and it should not be used to treat
pneumonia

REFERENCES

Notes from the discussion of:

University of Santo Tomas PowerPoint Presentation

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 11

 Introduction to Antimicrobials, Beta-Lactam and Other Cell Wall Inhibitors

➔ Coverage: vancomycin-resistant strains of

enterococci and S aureus (VRE, VRSA)
➔ Mechanism of action: depolarization of the
cell membrane with potassium efflux and
rapid cell death
➔ Excretion: renal
➔ Adverse reactions: myopathy - monitor
creatine phosphokinase levels, allergic
pneumonitis in patients receiving prolonged
therapy (>2 weeks)
➔ Pulmonary surfactant antagonizes
daptomycin, and it should not be used to treat
pneumonia

REFERENCES

Notes from the discussion of:

University of Santo Tomas PowerPoint Presentation

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY JIAN CARLO ORTEGA | 2I-MT 11