Cephalosporins

Dr.Maryam Mohammadzadeh Akın

• They are antibiotics with betalactamase ring like penicillins.

• They are bactericidal beta lactam antibiotics that inhibit transpeptidase enzyme in
cell wall synthesis.

• They are usually excreted through the kidneys and uricosuric drugs such as
probenecid reduce their tubular secretion.
• Cephalosparins such as cephalexin, cefaclor, cefadroxil, cephradine, cefprozil,
loracarbef, ceftibuten, cefuroxime axetil, cefixime and cefpodoxime are used
orally.
 Classification of Cephalosporins

First Generation second Generation. Third Generation Fourth Generation

Cephalothin Cefoxitin Ceftriaxone Cefepime

Cefazolin Cefaclor Ceftazidime Cefpirome
Cephalexin Cefamandol Cefaperazone
Cefradin Cefuroxime Cefataxime
Cefadroxyl Ceftibuten Cefprozil
Gram+ Ceftizoxime
Effect on skin and soft Gram+and - Antipsudomonas drugs Gram- and +
tissues Gram+ <-
 First generation cephalospares
• They are effective drugs against gram (+) cocci.
• Cefazolin and cephalothin, first-generation drugs, are used parenterally.

• Cefazolin is also preferred for surgical prophylaxis. Cephalothin is the shortest acting
cephalosporin.
• Cephalexin is often prescribed to outpatients
• Ceftriaxone is often used in the treatment of sexually transmitted diseases and pediatric
meningitis.
• cefepime is used in the treatment of psodomonas infections.
• Pseudomonas infections are diseases caused by a bacterium from the
genus Pseudomonas. The bacteria are found widely in the environment,
such as in soil, water, and plants.
 Second Generation Cephalosparins

• Their spectrum of action is a little wider than the first generation.They are more
effective against gram-negative bacteria.
• Cefoxitin is the most effective cephalosporin against anaerobic bacteria and is
used in intra-abdominal infections due to bacteroides fragilis.

• Bacteroides fragilis is an anaerobic, Gram-negative, pleomorphic to rod-shaped

bacterium. It is part of the normal microbiota of the human colon and is generally
commensal but can cause infection if displaced into the bloodstream or
surrounding tissue following surgery, disease, or trauma
 Third generation cephalosporins

• The most important differences from the second generation are that they are more
effective against pseudomanas and enterococci and pass more to central nervous
system.
• Their efficacy to gram positive cocci is lower than the first generation.
• Ceftriaxone has a long duration of action and can form bile sludge and is used in
meningitis prophylaxis.
• Ceftazidime is the most effective to pseudomanas, cefaperazone is the
cephalosporin that is excreted the most in bile. Ceftriaxone, ceftazidime and
cefotaxime pass into the cerebrospinal fluid at high rates.
 Fourth generation cephalosporins
• This group includes cefepime and cefpiroma. The most important difference from
the third generation is that they are more effective against enterococci and the
most resistant cephalosporins to beta lactamase enzyme
 Fifth Generation Cephalosporins

• This group includes drugs such as Ceftobiprole and ceftaroline.

• They are effective in the treatment of staphylococcus aureus.

• Staphylococcus aureus is the most dangerous of all of the many

common staphylococcal bacteria. These gr+, sphere-shaped (coccal)
bacteria (see figure ) often cause skin infections but can cause
pneumonia, heart valve infections, and bone infections and may be
resistant to treatment with some antibiotics.
 Important Properties of Cephalosporins
Cephalosporin Important Properties
Cefazolin Use in surgical prophylaxis
Cefoxitin / Cefotetan / Cefmetazol Use in B.fragilis infections
Cefaperazone Excretion with bile
Inability to pass the blood brain barrier sufficiently
Ceftriaxone Use in meningitis prophylaxis
cause bile sludge

Ceftazidime Showing efficacy against pseudomonas

Cefepime Being in the fourth generation
Moxalactam / Cefaperazone cuase Disulfiram reaction with alcohol
Ceftriaxone / Ceftazidime / Cefataxime Highly cross the blood brain barrier
Moxalactam Inhibition of the synthesis of coagulation factors due to vitamin K

Cefazolin / Cephalothin It is the first generation and use parenterally

Aminoglycosides
• Apart from streptomycin, they show bactericidal activity by irreversibly binding to
the 30S subunits in bacterial ribosomes.
• Streptomycin binds only to 305 subunits.
• Unlike other drugs that inhibit protein synthesis, aminoglycosides have a bactericidal
effect probably because of their irreversible binding to ribosomal subunits.
• Aminoglycosides are narrow-spectrum antibiotics that are effective only against
gram-negative aerobic bacilli (including pseudomonas) and tuberculosis bacilli, as
they require an oxygen-dependent oxygen-dependent Transport system.

• Not effective against gram negative and anaerobic bacteria

• Resistance develops to its effects by adenylation, acetylation and phosphorylation.
• Amikacin is the least resistant aminoglycoside group drug.

• They are absorbed very little from the gastrointestinal tract and, aminoglycosides
are polar drugs, they are given only parentally for systemic effect
• Neomycin is used orally to clean the intestines in colorectal surgeons.

• No aminoglycoside passes into the blood when administered orally.

• They kill bacteria in a concentration-dependent manner and have post antibiotic
activity.
• There is no significant difference in effect between single daily doses and multiple
doses.
• They cannot easily enter the cell and pass into the cerebrospinal fluid in patients
without meningitis.
• aminoglycosides are given intrathecally in meningitis, when aminoglycosides are
given intravenously they cannot pass into the CSF

• In cases of meningitis, their ratio in the cerebrospinal fluid is approximately 20%

of that in the blood.
• Since the safety indices are narrow, blood levels should be checked from the 3rd
day of treatment. They are excreted by the kidneys, their dose should be adjusted
in cases of renal failure.
• All of the drugs in the aminoglycoside group accumulate in the renal
cortex and inner ear, causing nephrotoxic and ototoxic side effects.
• Drugs in this group are eliminated by glomerular filtration by the
kidneys, without all being metabolized.
• Doses should be reduced in renal failure.
• All of the drugs in this group cross the placenta and are found in fetal
plasma and amniotic fluid, so cause hearing loss in the baby.
 Streptomycin
• It is one of the drugs in the treatment of tuberculosis.
• rapidly develops resistance to its effect with a single step ribosomal mutation
• Ribosomal resistance develops very rapidly to its effect.
• It is used in combination with tetracyclines in the treatment of plague, tularemia
and brucella.
• It is the aminoglycosic group antibiotic with the least nephrotoxic properties.
• without impairing the hearing function, disrupts the balance function.
• Those who are allergic to streptomycin are not given the oral polio vaccine.

• streptomycin is relatively contraindicated in pregnant women as it causes

deafness in the baby
• Plague is a disease that affects humans and other mammals. It is caused by
the bacterium, Yersinia pestis. Humans usually become infected through
the bite of an infected rodent flea or by handling an infected animal.

• Tularemia is a potentially serious illness caused by the

bacterium Francisella tularensis.
• People can become infected in several different ways, including tick and
deer fly bites, and contact with infected animals (especially rodents,
rabbits, and hares).
•
 Gentamicin
• It is used intrathecally in meningitis.
• It is used in combination with B-lactam antibiotics in sepsis and severe infections due
to gram-negative bacteria
• Aminoglycosides are not administered orally to achieve systemic effect and do not
affect anaerobic bacteria.
• For treating unknown cause sepsis: ampicillin + gentamicin is given.

• Sepsis is a serious condition in which the body responds improperly to an

infection. The infection-fighting processes turn on the body, causing the
organs to work poorly. Sepsis may progress to septic shock. This is a
dramatic drop in blood pressure that can damage the lungs, kidneys,
liver and other organs.
 Tobramycin
• It is similar to gentamicin in terms of spectrum of action.
• It is used by inhalation in the treatment of lower respiratory tract infections caused
by pseudomonas in patients with cystic fibrosis.
• cause hearing and balance disorders.
 Amikacin

• It is the aminoglycoside group antibiotics with the widest spectrum and the least
resistance. It is one of the second-line drugs in the treatment of tuberculosis.
Without disturbing the balance function, impairs hearing function.
 Paromomycin
• İt is an aminoglycoside antibiotic used locally in the treatment of
tapeworm and amoeba in the colon, and parenterally in the
treatment of visceral leishmaniasis.
 Netilmicin
• It is the least ototoxic aminoglycoside.
 Spectinomycin

• It is similar in structure to aminoglycoside antibiotics. It is used

intramuscularly in the treatment of penicillin-resistant gonorrhea.
• spectinomycin is excreted by the kidneys
• Spectinomycin, like aminoglycosides, is a drug that inhibits protein
synthesis by binding to the 30 S Ant unit of the ribosome.
 Neomycin
• It is the aminoglycoside with the most ototoxic, nephrotoxic and neuromuscular blocking
effects.
• It is used orally in the prophylaxis of colorectal surgery, in the treatment of hepatic
encephalopathy and in the treatment of hyperlipidemia by binding bile acids.

• Neomycin can be given to reduce the aerobic bacterial flora in colorectal surgeries and
hepatic coma.

• Hepatic encephalopathy, also called portosystemic encephalopathy,

happens when your liver isn’t filtering toxins as it should. These toxins build
up in your blood and affect your brain, causing confusion, disorientation
and other changes. Hepatic encephalopathy can get better with treatment,
but it can be life-threatening without.
 Side Effects of Aminoglycosides
• They accumulate in the kidneys and cause nephrotoxic side effects. Drugs such as
vancomycin, bacitracin, acyclovir, furosemide, amphotericin B and cyclosporine
increase the nephrotoxicity caused by aminoglycosides.
• They accumulate in the inner ear and cause ototoxic side effects, the first finding
is tinnitus.
• aminoglycosides reduce the secretion of acetylcholine and have a neurotoxic
effect. For this reason, they are not given in Myasthenia Gravis.
• They cause neuromuscular blockade by reducing acetylcholine secretion at the
neuromuscular junction and blocking calcium channels.
• They increase sensitivity to neuromuscular blocking drugs.
• Streptomycin can cause an optic nerve disorder called scotoma. They are not used
in pregnancy.
• all aminoglycosides are teratogenic and may cause irreversible hearing
loss in the fetus
• Since they do not affect anaerobic bacteria, they do not cause
psudomemberanous enterocolitis.