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PHARMACOLOGY OF

ANTIBIOTIC AGENTS
Antimicrobial agents
1. Antibiotics
2. Antivirals
3. Antifungals
4. Antiparasitics
PRINCIPLE USE OF ANTIBIOTICS
Antimicrobial agents are among the most
commonly used and misused of all drugs.
The antibiotic-resistant pathogens
increasing need for new drugs
Reducing inappropriate antibiotic use is
thought to be the best way to control
resistance.
Actions of antibacterial drugs on
bacterial cells
Mechanisms of Action
(1) Agents that inhibit synthesis of bacterial cell walls
eg. b-lactam class and other agents such as vancomycin, penicillin,
amoxicillin, cephalosporin

(2) Agents that act directly on the cell membrane to increase permeability
and cause leakage of intracellular compounds
e.g., aminoglycosides, tetracyclines, erythromycin, and clindamycin

(3) Agents that disrupt function of ribosomal subunits to reversibly inhibit


protein synthesis
e.g., chloramphenicol, tetracyclines, erythromycin, and clindamycin

(4) Agents that bind to the 30S ribosomal subunit and alter protein
synthesis
e.g., the aminoglycosides

(5) Agents that affect bacterial nucleic acid metabolism by inhibiting RNA
polymerase (e.g., rifampin) or topoisomerase (e.g., the quinolones)

(6) The antimetabolites, including trimethoprim and the sulfonamides,


which block essential enzymes of folate metabolism.
Daya bunuh kuman
Host defenses are intact and Host defenses are impaired,
active, a minimum inhibitory antibiotic-mediated killing
effect (bacteriostatic agents) (bactericidal effect)
may be sufficient may be required to
eradicate the infection.
Successful antimicrobial therapy of an infection ultimately
depends on the concentration of antibiotic at the site of infection

The inhibitory concentration of drug at the site of infection also


must remain below the level that is toxic to human cells

If this can be achieved, the microorganism is considered sensitive;


if not, the microorganism is considered resistant to the drug.
Mechanism bacterial resistance
Bacterial resistance to an antimicrobial agent is attributable to three
general mechanisms:

(1) the drug does not reach its target


Small polar molecules, including antibiotics, enter the cell through
protein channels called porins.
Absence of, mutation in, or loss of a favored porin can slow drug entry
into a cell or prevent entry altogether, effectively reducing drug
concentration at its active site resistance
eg. Gentamycin

(2) the drug is not active


Production of enzymes that modify or destroy the antibiotic
eg. Isoniazid

(3) the target is altered


- mutation of the natural target (e.g., fluoroquinolone resistance),
- target modification (e.g., ribosomal protection from macrolides and
tetracyclines)
- acquisition of a resistant form of the susceptible target (e.g.,
staphylococcal resistance to methicillin caused by production of a low-
affinity variant of penicillin-binding protein).
Antibiotics have three general uses:
1. Empirical therapy
2. Definitive therapy
3. Prophylactic or preventive therapy

Empirical, or initial therapy:


AM should cover all the likely pathogens because the infecting
organism(s) has not yet been defined.
Preferably, treatment with a single broad-spectrum agent
Definitive therapy:
when the infecting microorganism is identified
a narrow-spectrum, low-toxicity agent
Pharmacological aspect
Prophylaxis therapy
Antibiotic prophylaxis is highly effective in some clinical settings
In others, it accounts for some of the most misuses of antimicrobials,
is totally without value, and may be deleterious
Use of antimicrobial compounds to prevent infections remains
controversial in numerous situations

may be used to protect healthy persons from acquisition of or


invasion by specific microorganisms to which they are exposed
e.g. rifampin administration to prevent meningococcal meningitis in
people who are in close contact with a case
Chemoprophylaxis
Consideration:
The diagnosis may be masked if therapy is started and
appropriate cultures are not obtained.
Antibiotics are potentially toxic, and antimicrobial agents
promote selection of resistant microorganisms.
In the absence of a clear indication, antibiotics often may be
used if disease is severe and if it seems likely that withholding
therapy will result in life-threatening infection

Pharmacological aspect
When a drug enters the body, the body begins immediately to work
on the drug: absorption, distribution, metabolism (biotransformation),
and elimination.
Pharmacokinetics

The drug also acts on the body, an interaction to which the concept
of a drug receptor is key, since the receptor is responsible for
the selectivity of drug action and for the quantitative relationship
between drug and effect
Pharmacodynamics

PK-PD
The location of the infection may dictate the choice of drug
and the route of administration
There is an evidence to suggest that even subinhibitory
concentrations of antibiotics may enhance phagocytosis

Pharmakokinetic aspect
Pharmacodynamic properties can be used to divide antibiotics into
two major classes based on their mechanism of bactericidal action:
(1) concentration-dependent drugs,
such as aminoglycosides and fluoroquinolones
- the higher the drug concentration, the faster the eradication of
pathogens.
(2) concentration-independent drugs, e.g. the -lactams
- peak concentrations are relatively unimportant
- time-dependent drugs
.

Pharmacodynamic aspect
The postantibiotic effect (PAE):
is the phenomenon of continued suppression of bacterial
growth after a short exposure of bacteria to antimicrobial
agents
This effect is probably the result of:
nonlethal damage caused by the antibiotic and
continued persistence of the drug at the bacterias drug-
binding site for a time after drug is removed

For -lactam agents,


- the PAE against Gram-positive pathogens lasts approximately
1 to 2 hours
Aminoglycosides and fluoroquinolones
a Gram-negative PAE of about 2 h
Pharmacodynamic aspect
Factors to accomplish therapeutic goal
1. Sites of infection
2. Route of administration
3. Host Factors
4. Host Defense Mechanisms
5. Local Factors
6. Age
7. Genetic Factors
8. Pregnancy
9. Drug Allergy
10. Comorbid Conditions
therapeutic goal factor
Sites of infection
cerebrospinal fluid (CSF), the drug must pass the
blood-brain barrier

Antimicrobial agents that are polar at physiological pH generally


penetrate poorly; some, such as penicillin G, are actively
transported out of the CSF by an anion transport mechanism in
the choroid plexus
The integrity of the blood-brain barrier is diminished
during active bacterial infection; tight junctions in cerebral
capillaries open, leading to a marked increase in the
penetration of even polar drugs
therapeutic goal factor
Penetration of drugs into sites of infection almost always
depends on passive diffusion
The rate of penetration is thus proportional to the concentration
of free drug in the plasma or extracellular fluid.
Drugs that are extensively bound to protein thus may not
penetrate to the same extent as those bound to a lesser extent.
Drugs that are highly protein bound also may have reduced
activity because only the unbound fraction of drug is free to
interact with its target.

therapeutic goal factor


Route of Administration
- oral administration is preferred whenever possible
- parenteral administration of antibiotics usually is
recommended in seriously ill patients in whom predictable
concentrations of drug must be achieved.

therapeutic goal factor


Host Factors
Innate host factors can be the prime determinants not only of
the type of drug selected but also of its dosage, route of
administration, risk and nature of untoward effects, and
therapeutic effectiveness
- Knowledge of the status of the individual patient's renal and
hepatic function also is essential, especially when excessive plasma
or tissue concentrations of the drugs may cause serious toxicity

therapeutic goal factor


Host Defense Mechanisms
A critical determinant of the therapeutic effectiveness of
antimicrobial agents is the functional state of host defense
mechanisms
Both humoral and cellular immunity are important.

- Inadequacy of type, quality, and quantity of the Ig


- Alteration of the cellular immune system
- A qualitative or quantitative defect in phagocytic cells

may result in therapeutic failure despite the use of otherwise appropriate


and effective drugs (meningitis, endocarditis, AIDS)

therapeutic goal factor


Local Factors
- Antimicrobial activity may be reduced significantly in pus,
which contains phagocytes, cellular debris, and proteins that
can bind drugs or create conditions unfavorable to drug action
- Anaerobic conditions can reduce the antimicrobial activity of
some agents markedly, particularly the aminoglycosides
- Foreign body as prosthetic material (e.g., prosthetic cardiac
valves, prosthetic joints, pacemakers, vascular grafts, and
various vascular and CNS shunts) promotes formation of a
bacterial biofilm that impairs phagocytosis

therapeutic goal factor


Age
- Mechanisms of elimination, especially renal excretion and
hepatic biotransformation, are poorly developed in the newborn,
especially the premature infant
- Elderly patients clear drugs eliminated by the kidneys less well
because of reduced creatinine clearance
Elderly patients therefore are more likely to suffer toxicity at
otherwise safe concentrations of drugs, as is the case for
aminoglycoside ototoxicity

therapeutic goal factor


Genetic Factors

Certain genetic or metabolic abnormalities must be considered


when prescribing antibiotics

A number of drugs (e.g., sulfonamides, nitrofurantoin,


chloramphenicol, and nalidixic acid) may produce acute
hemolysis in patients with glucose-6-phosphate
dehydrogenase deficiency (G6PD)

therapeutic goal factor


Pregnancy

- Pregnancy may impose an increased risk of reaction to


antimicrobial agents for both mother and fetus
hearing loss in the child has been associated with
administration of streptomycin to the mother during pregnancy

- The lactating female can pass antimicrobial agents to her


nursing child

therapeutic goal factor


Drug Allergy

Antibiotics, especially -lactams, are notorious for provoking


allergic reactions. Patients with a history of atopy seem
particularly susceptible to the development
of these reactions

therapeutic goal factor


Comorbid conditions

Patients predisposed to seizures are at risk for localized or


major motor seizures while taking high doses of penicillin G.
This neurotoxicity of penicillin and other -lactam antibiotics
correlates with high concentrations of drug in the CSF and
typically occurs in patients with impaired renal function who are
given large doses of the drugs

therapeutic goal factor


Combined Antimicrobial Agents

Advantage
- The simultaneous use of two or more antimicrobial agents is recommended in specifically
defined situations based on pharmacological rationale
- However, selection of an appropriate combination requires an understanding of the potential
for interaction between the antimicrobial agents. Interactions may affect either the
microorganism or the patient

Disadvantages
- increased risk of toxicity from two or more agents,
- selection of multiple-drug-resistant microorganisms,
- eradication of normal host flora with subsequent superinfection,
- increased cost to the patient
The addition of a bacteriostatic drug to a bactericidal drug frequently results in a
bacteriostatic effect, antagonism between antibiotics probably is relatively
unimportant when host defenses are adequate e.g. Penicillin - Chlortetracycline

Therapy with Combined Antimicrobial Agents


Superinfections
All individual who receive therapeutic doses of
antibiotics undergo alterations in the normal microbial
population of the GI, upper respiratory, and
genitourinary tracts superinfection

Such superinfection is due to the removal of the


normal flora, which produces antibacterial substances
and competes for essential nutrients.

The broader the spectrum and the longer the period of


antibiotic treatment, the greater the risk of
superinfection.

The most specific and narrowest spectrum antibiotics


should be chosen to treat infections whenever feasible.
Misuses of Antibiotics
TREATMENT OF NONRESPONSIVE INFECTIONS
Most viral diseases are self-limited and do not respond to any of
the currently available anti-infective compounds.
Antibiotic therapy of at least 90% of infections of the upper
respiratory tract and many GI infections is ineffective.

THERAPY OF FEVER OF UNKNOWN ORIGIN


Fever of short duration in the absence of localizing signs usually is
associated with undefined viral infections.
Antimicrobial therapy is unnecessary, and resolution of fever
usually occurs spontaneously within a week.
Inappropriately administered antibiotics may mask an underlying
infection, delay the diagnosis, and prevent the identification of the
infectious pathogen by culture.

IMPROPER DOSAGE
Excessive dosing can result in significant toxicities, while too low a
dose may result in treatment failure and is most likely to select for
antibiotic resistance.
INAPPROPRIATE RELIANCE ON ANTIBIOTICS ALONE
Infections complicated by abscess formation or the
presence of necrotic tissue or a foreign body often cannot
be cured by antibiotic therapy alone.
Drainage, debridement, and removal of the foreign body
are at least as important as the choice of antibiotic agent.

LACK OF ADEQUATE BACTERIOLOGICAL INFORMATION


Antibiotic therapy too often is given in the absence of
supporting microbiological data.
Bacterial cultures and Gram stains of infected material are
obtained too infrequently, and, when available, the results
often are disregarded in the selection and application of
drug therapy.
Implikasi Keperawatan
Menggunakan pengobatan antibiotik atas resep dokter dan juga
atas petunjuk dokter atau medis.
Dosis yang tertera dan juga aturan pakainya harus diikuti
dengan taat sesuai dengan petunjuk dokter ataupun penjelasan
apoteker di apotek tempat kita membeli obat antibiotik itu.
Pemberian antibiotika dan jenis macam obat antibiotika sendiri
harus diminum terus sampai habis meskipun gejala atau sakit
yang diobati sudah sembuh.
Bentuk-bentuk sedian antibiotik seperti sediaan antibiotik yang
berbentuk sirup ( biasanya untuk anak ) ada yang harus
disimpan dalam suhu dingin ( di almari es, jangan di dalam
frezernya ).
Jangan pernah gunakan antibiotika yang telah mengelami
kadaluarsa atau yang sudah lama disimpan di rumah.
Pengobatan menggunakan antibiotik hanya
digunakan pada seseorang pasien setelah dokter
mendiagnosa adanya penyakit infeksi yang berat
ataupun pada kasus-kasus cidera berat dan kasus
bedah / operasi.

Pengobatan antibiotik baru diperlukan bila infeksi


tesebut berlangsung lebih dari beberapa hari dan hal
tersebut dapat menimbulkan akibat merugikan pada
pasien.

Pada beberapa jenis penyakit infeksi dengan gejala


ringan tidak memerlukan pengobatan antibiotik justru
hal tersebut akan memberikan kesempatan
terangsangnya mekanisme kekebalan tubuh.
Reaksi alergi antibiotik. dari hal yang paling yang ringan yang bisa berupa
gatal-gatal, yang lebih berat berupa syok anafilaksis / pingsan, bahkan
sampai menimbulkan kematian.
Yang perlu diwaspadai adalah seseorang dengan riwayat alergi dapat
muncul reaksi alergi pada penggunaan ulang suatu antibiotika tertentu.

Reaksi toksik antibiotik ini juga tergantung pada jenis obat dan faktor pada
tubuh pasien.
Contoh tetrasiklin bisa mengganggu pertumbuhan jaringan tulang
termasuk gigi bila diberikan pada anak-anak.

Super Infeksi, yakni timbulnya infeksi baru karena penggunaan pengobatan


antibiotik tertentu.

Resistensi Bakteri, yakni kemampuan antibiotik untuk membasmi bakteri


tertentu berkurang, bahkan efek yang ditimbulkannya hilang sama sekali.
TERIMA KASIH
SELAMAT BELAJAR
Antibiotic agents
General Outline for
Antibiotics
Chemistry
Effect on microbes
Spectrum of coverage
Mechanism(s) of action
Mechanism(s) of resistance
Pharmacology of antibiotic class
Absorbance
Fate after absorption
Excretion
Pharmacology of select agents
Therapeutic uses
Toxicity/contraindications
Common (> 10%)
Uncommon (1-9%)
Rare (< 1%)
Sulfonamides
Analogues of para-aminobenzoic acid

Broad spectrum

Competitive inhibitors of dihydropteroate synthase


needed for folic acid synthesis
Sulfonamides
Sulfonamides
Cidal in urine
Mechanisms of resistance
Altered affinity of enzyme for
drug
Decreased permeability or active
efflux
New pathway of folic acid
synthesis
Sulfonamides
Mostly absorbed from GI tract
Binds variably to serum albumin
Wide tissue distribution,
including transplacentally
Variably inactivated in liver by
acetylation and then excreted in
urine
Some agents can precipitate in
acid urine
Rapidly Absorbed and Eliminated
Sulfonamides
Sulfisoxazole, sulfamethoxazole, sulfadiazine

Bind extensively to plasma


proteins

Highly concentrated in urine


(cidal)

Sulfamethoxazole combined with


trimethoprim (Bactrim) is widely used to
treat a variety of infections (esp. UTI)
Poorly Absorbed in GI tract
Sulfonamides
Sulfasalazine

Used to treat ulcerative


colitis and irritable
bowel syndrome

Gut flora metabolize


drug into 2 compounds,
1 toxic, 1 therapeutic
(5-aminosalicylate)

Ulcerative Colitis
Sulfonamides for Topical Use
Sulfacetamide
Good penetration in eye
Non-irritating

Silver sulfadiazine
Prevention and
treatment of burn wound
infections
Bacterial corneal
infection
Long Acting
Sulfonamide
Sulfadoxine

Serum half-life is
measured in days rather
than minutes or hours
Combined with
Pyrimethamine to treat
malaria
Plasmodium
vivax
Therapeutic Uses
of Sulfonamides
Urinary tract infections

Nocardiosis:
Nocardia asteroides
Nocardia brasiliensis

Toxoplasmosis (avoid
using in pregnant women)
Nocardia asteroides
Toxicity/Contraindications
of Sulfonamides - UT
Crystallization in acid urine
Common to uncommon depending on drug
Alkalize urine or increase hydration
Toxicity/Contraindications
of Sulfonamides - blood
Acute hemolytic anemia
Rare to extremely rare
Associated with glucose-6-phosphate
dehydrogenase activity in RBC

Agranulocytosis (extremely rare)

Aplastic anemia (extremely rare)


Toxicity/Contraindications
of Sulfonamides - immune
Hypersensitivity reactions (common to
uncommon)
Skin and mucous membrane manifestations
(rashes)
Serum sickness
Focal or diffuse necrosis of the liver (rare)
Toxic Epidermal Necrolysis
(TEN)
Toxicity/Contraindications
of Sulfonamides -
miscellaneous
Nausea, anorexia, vomiting
(common)
Kernicterus
Displacement of bilirubin
from plasma albumin to brain
resulting in encephalopathy
Never give sulfa drugs to a
pregnant or lactating woman
Potentiation of oral
anticoagulants, sulfonylurea
hypoglycemic drugs, and
Bilirubin hydantoin anticonvulsants
deposits in
neonatal
brain
The Quinolones
Naladixic acid was a byproduct of chloroquine synthesis
Current drugs are fluorinated 4-quinolones
Broad coverage (some broader than others)
Targets DNA topoisomerase II (DNA gyrase) (G-) and
topoisomerase IV (G+)
Resistance due to efflux and mutations in targets
Quinolones
Favorable pharmacological attributes
Orally administered, quickly absorbed,
even with a full stomach
Excellent bioavailability in a wide range
of tissues and body fluids (including
inside cells)

Mostly cleared by the kidneys


Exceptions are pefloxacin and
moxifloxacin which are metabolized by
liver

Ciprofloxacin, ofloxacin, and pefloxacin are


excreted in breast milk
Therapeutic Uses of
Quinolones
Urinary tract infections
Prostatitis
STDs
Chlamydia
Chancroid
Not syphilis or gonorrhea
(due to increased
resistance)
Therapeutic Uses of
Quinolones
GI and abdominal
Travelers diarrhea
Shigellosis
Typhoid fever

Therapeutic Uses of
Quinolones
Respiratory tract
All work well against atypical pneumonia
agents (eg, chlamydia, mycoplasma, and
legionella),
New agents for strep. Pneumonia
Respiratory fluoroquinolones: Levofloxacin,
gatifloxacin, gemifloxacin, and moxifloxacin.
are effective and used increasingly for
treatment of upper and lower respiratory
tract infections.
Therapeutic Uses of
Quinolones
Bone, joint, soft tissue
Ideal for chronic
osteomylitis
Resistance
developing in
S. aureus, P.
aeruginosa, and S.
marcesens
Good against polymicrobial
infections like diabetic foot
ulcers
Therapeutic Uses of
Quinolones
Ciprofloxacin for
anthrax and tularemia
(Francisella tularensis)

Combined with other


drugs, useful for
atypical Mycobacterium
sp. or for prophylaxis in
neutropenic patients

Pulmonary
Anthrax
Toxicity/Contraindications of
Quinolone
Nausea, vomiting, abdominal discomfort (common)
Diarrhea and antibiotic-associated colitis
(uncommon to rare)
CNS side effects
Mild headache and dizziness (common to rare)
Hallucinations, delirium, and seizures (rare)
May damage growing cartilage and cause an
arthropathy. Thus, these drugs are not routinely
recommended for patients under 18 years of age
(common)
Quinolones not given to children unless benefits
outweigh the risks
Leukopenia, eosinophila, heart arrhythmias (rare)
The Beta-Lactams
Penicillins
Penicillium notatum
produces the only
naturally occuring
agent penicillin G or
benzylpenicillin

P. chrysogenum
produces 6-
aminopenicillanic acid,
raw material for
semi-synthetics
Penicillins
Spectrum of activity based on R groups
added to 6-aminopenicillanic acid core

All are bactericidal and inhibit


transpeptidases

Mechanisms of resistance
Alter affinity of transpeptidase
Enzymatically cleave the beta-lactam ring
Efflux pumps
Poor penetration into cell
Penicillins
Administered orally, intramuscularly, or
intravenously depending on agent

After oral dose, widely distributed in tissues and


secretions (except CNS, prostatic fluid, and the
eye)

Do not kill intracellular pathogens

Food interferes with adsorption

Rapid elimination through kidney, secreted in


breast milk
1. Penicillins G and V
Effective against aerobic G+ organisms
except Staphylococcus, Pen G active
against Neisseria and anaerobes

2/3 of oral Pen G destroyed by stomach


acid, Pen V is more resistant so more is
delivered to serum

Rapid elimination through kidney so


probenecid is added to slow excretion.

Procaine, or benzathine forms of Pen G


(im)
Most drug is bound to serum albumin but
significant amounts show up in liver, bile,
kidney, semen, joint fluid, lymph, etc.

Cautious use in neonates and infants


because renal function is not fully
established

Patients with renal failure clear the drugs


through liver although at a slow pace
Penicillins G and V Therapeutic
Uses
Streptococcus pneumoniae
infections
S. pyogenes infections
Viridans strep endocarditis (also
given prophylactically)
Anaerobes except Bacteroides
fragilis group
Meningococcal infections
Syphilis and other diseases
caused by spirochetes
2. Isoxazolyl Penicillins
Oxacillin, cloxacillin, dicloxacillin, nafcillin
Designed to resist staphylococcal beta-
lactamases
Like Pen V, stable in stomach acid but
usually given parentally for serious staph
infections
MRSA not covered
Absorption and fate of drugs after
absorption, excretion similar to Pen G and
Pen V
3. Aminopenicillins
Ampicillin and amoxicillin
Broad spectrum
Not effective against beta-lactamase
producers
Beta-lactamase inhibitors extend spectrum
(clavulanic acid, sulbactam, tazobactam)
Both are acid resistant but amoxicillin is
better absorbed, even with food
Dont bind plasma proteins as much as
predecessors
Secreted through the kidney
Aminopenicillins
Therapeutic Uses

Upper respiratory tract infections


Otitis media
Uncomplicated UTI
Acute bacterial meningitis in kids
Typhoid fever
4. A Carboxypenicillin and
a Ureidopenicillin
Ticarcillin and piperacillin
Ticarcillin is anti-Pseudomonas
drug
Piperacillin + tazobactam has
the broadest spectrum
Given parentally
Used for serious infections
Toxicity/Contraindications
of Penicillins
1. Hypersensitivity reactions
(uncommon)
Rash, fever, bronchospasm, vasculitis,
serum sickness, exfoliative dermatitis, SJS,
anaphylaxis
Drugs act as haptens when bound to
serum proteins
Rashes will disappear when drug is
withdrawn or can treat with antihistamines
For patients with allergies, switch to a
different class of antibiotics
Toxicity/Contraindications
of Penicillins
GI disturbances with oral
penicillins.
Large doses given to
patients with renal failure
can cause lethargy,
confusion twitching and
seizures
Sudden release of
procaine can cause
dizziness, tinnitus,
headache and Pseudomembranous colitis
hallucinations (Ampicillin).
Cephalosporins
Base molecule is 7-
aminocephalosporanic acid
produced by a Sardinian
sewer mold

R groups determine
spectrum of activity and
pharmacological properties

Mechanism of
action/resistance and class
pharmacology essentially
the same as penicillins
First Generation
Cephalosporins
Cefazolin, cephalexin, cephadroxil
Excellent against susceptible staph and strep
Modest activity against G-
Cefazolin given parentally, others orally
More than half of the drug is bound to plasma
proteins
Excreted by kidneys unmetabolized
Good for staph and strep skin and soft tissue
infections
Second Generation
Cephalosporins
Cefaclor, cefuroxime, cefprozil, cefotetan,
cefoxitine, cefamandole
Modest activity against G+, increased
activity against G-, works against anaerobes
Cefaclor and cefprozil given orally
Absorption and excretion same as first gen.
Good for treating
respiratory tract infections
intra-abdominal infections
pelvic inflammatory disease
diabetic foot ulcers
Third Generation
Cephalosporins
Cefotaxime, ceftriaxone, cefoperazone, cefpodoxime, cefixime
Broad spectrum killers
Drugs of choice for serious infections
No effect against Listeria and beta-lactamase producing
pneumococci
Cefpodoxime and cefixime are given orally, others parentally
Most excreted by kidney

Therapeutic uses
Bacterial meningitis
(2 exceptions cefoperazone, cefixime)
Lyme disease
Life-threatening G- sepsis
Fourth Generation
Cephalosporin
Cefepime
Same antimicrobial spectrum as third
generation but resists more beta-lactamases

Given parentally, excellent penetration into


CSF

Good for nosocomial infections


Toxicity/Contraindications
of Cephalosporins
Hypersensitivity reactions (uncommon)
essentially same as for penicillins
Cross-reaction between 2 classes
Other adverse effects:
Pain at injection site
Phlebitis after iv
When given with aminoglycosides, may
increase nephrotoxicity
Drugs containing methylthiotetrazole (eg
cefamandole, cefaperazone, cefotetan) may
cause hypoprothrombinemia and disulfiram-
like reaction.
Carbapenems
Imipenem, Meropenem, Ertapenem
Beta-lactam ring is fused to a 5 member ring system
Carbapenems
Effect on microbes and pharmacology of
carbapenems similar to penicillins
Wider G+ activity, G- and anaerobes

For pseudomonal infections: given with aminoglycosides

Parenteral administration

Drugs of choice for infections caused by


Enterobacter.
Imipenem
-Rapidly inactivated by renal dehydropeptidase I.

Should be given in combination with an inhibitor


(Cilastatin)

Adverse effects of imipenem-cilastatin: GI


distress, CNS toxicity, partial cross-
allerginicity with penicillins.
Meropenem:
- not metabolized by dehydropeptidases
- less likely to cause seizures.

Ertapenem:
has longer half-life
Less effective against pseudomonas
Causes pain at site of injection
Aztreonam a monobactam
Works only on G-, including
Pseudomonas aeruginosa

Useful for treating G- infections that


require a beta-lactam because it does
not elicit hypersensitivity reactions
Toxicity/Contraindications
of Carbapenems
Nausea and vomiting (common)
Hypersensitivity reactions (uncommon)
Essentially the same as for penicillins,
exception is the monobactam
Cross-reactivity is possible, exception is the
monobactam