Cephalosporins

Jagir R. Patel
Asst Professor
Dept. Pharmacology
 Introduction
• The cephalosporins  are a class of β-lactam antibiotics originally
derived from the fungus Acremonium, which was previously known as
"Cephalosporium”
 Classification
• 1st Gen: Cephalothin, Cephalexin, Cefazolin Cephradine,
Cefadroxil

• 2nd Gen: Cefuroxime Cefaclor, Cefoxitin* Cefuroxime axetil

• 3rd Gen: Cefotaxime, Cefixime, Ceftizoxime Cefpodoxime

proxetil, Ceftriaxone Cefdinir, Ceftazidime Ceftibuten,
Cefoperazone Ceftametpivoxil

• 4th Gen: Cefepime, Cefpirome

• 5th Gen: Ceftaroline fosamil, Ceftolozane, Ceftobiprole

Mechanism of action
Mechanism of action
 Mechanism of resistance
• Acquired resistance to cephalosporins
could have the same basis as for
penicillins, i.e.:
• (a) alteration in target proteins (PBPs)
reducing affinity for the antibiotic.

• (b) impermeability to the antibiotic or its

efflux so that it does not reach its site of
action.

• elaboration of p-lactamases which

destroy specific cephalosporins
(cephalosporinase).
 1st Gen
• Spectrum
• Gram Positive Cocci, including MSSA (Does NOT cover Enterococcus)
• Gram Negative Rods
• No CNS penetration
• Coverage
• MSSA
• Streptococci Grp A,B,C,G
• Strep viridans
• S. pneumoniae
• H. influenzae
• E. coli
• Klebsiella pneumoniae
• Proteus mirabilis
 Cephalexin
• General information: administered orally may not cross the blood brain
• Barrier

• Side effects
• hypersensitivity reactions, leading to fever, skin rashes, angioedema
and/or anaphylactic shock consecutive hypersensitivity to penicillins (due
to cross reactivity) diarrhea (due to gastrointestinal overgrowth by
cephalosporin-resistant bacteria)

• Medical uses
• treatment of folliculitis, cellulitis and/or impetigo due to staphylococcus
and/or streptococcus infection treatment of pharyngitis due to
streptococcus infection
 2 Gen intermediate spectrum
nd

• Same as 1st Generation Plus:

• β-lactamase positive H. influenzae
• Moraxella catarrhalis
• Neisseria meningitidis
• E. coli
• Klebsiella pneumoniae
• Proteus
• Oral anaerobes
• Cefoxitin & Cefotetan cover B. fragilis
 Cefaclor & Cefuroxime
• General information: administered orally may not cross the blood brain
• Barrier

• Indications: treatment of pharyngitis due to streptococcus infection

• -Treatment of pneumonia due to streptococcus, enterobacter, klebsiella,
proteus and/or haemophilus infection.

• Side effects same as cephalexin

 3 broad spectrum
rd

• 3rd Generation Coverage

• Same as 1st Generation Plus:
• Expanded gram-negative coverage
• Oral anaerobes
• S. aureus (OSSA)
• Strep pneumoniae
• Strep Grp A,B,C,G
• Strep viridans
• Gram negative rods
• N. gonorrhea
• All cover B. fragilis EXCEPT cefotaxime & ceftazidime
• P. aeruginosa - ceftazidine only
 Cefotaxime
• Administered intramuscularly and/or IV may cross the blood-brain barrier

• Interactions: Cefotaxime + aminoglycosides = nephrotoxicity

• ADV: Clostridium difficile-associated diarrhoea and colitis, arrhythmias,

anaphylaxis.

• Medical uses
• Pharyngitis: due to streptococcus infection
• Meningitis due to streptococcus, haemophilus and/or neisseria infection
Gonorrhea due to neisseria infection
• Septicaemia
• Surgical prophylaxis
Dose: 1-2gm per day
 Ceftriaxone
• Administered intramuscularly and/or IV may cross the blood-brain barrier
exctred via urine and faeces

• ADV: Anaphylaxis, Clostridium difficile-associated diarrhoea and colitis,

hemolytic anemia.

• Indications: Uncomplicated Gonorrhoea, Prophylaxis of surgical

infections

• Contraindications: to hypersensitive to cephalosporins

 4 gen
th

• Spectrum

• Good gram-positive & gram-negative coverage

• Anti- Pseudomonal (including ceftazidime
resistant isolates)
• Penetrates CSF
• Limited anaerobic coverage
 Cefepime
• Absorption: Rapidly and almost completely absorbed on IM inj. Time to
peak plasma concentration: Approx 1.5 hr (IM); w/in 30 min (IV).
•
Distribution: Widely distributed in body tissues and fluids; high
concentrations in bile. Crosses the blood-brain barrier and enters breast
milk (low concentrations). Plasma protein binding: Approx 20%.
•
Metabolism: Minimally hepatic.
•
Excretion: Via urine (approx. 85% as unchanged drug). Plasma half-life:
Approx 2 hr.

• ADV: Neurotoxicity (e.g. encephalopathy, myoclonus, seizures, non-

convulsive status epilepticus); Clostridium difficile-associated diarrhoea;
anaphylaxis.
• Indications:
• Respiratory tract infections
• Skin and skin structure infections
• Urinary tract infections
• Abdominal infections
• Empiric therapy for febrile neutropenic patients

• Dose: 1-2gm daily

 Cefpirome
• Administration: i.v.

• Distribution: Widely distributed into body tissues and fluids; enters breast

milk. Protein-binding: 10%
•
Excretion: Mainly by the kidneys via the urine (80-90% as unchanged);
significantly removed by hemodialysis; 2 hrs (elimination half-life);
prolonged in renal impairment.

• Adv.: Pseudomembranous colitis.

• Indications: Susceptible infections

•  diarrhea, nausea, rash, electrolyte disturbances, and pain and inflammation
at injection site. vomiting, headache, dizziness,  pseudomembranous
colitis, superinfection, eosinophilia, nephrotoxicity, neutropenia,
thrombocytopenia, and fever.
•  hypoprothrombinemia and a disulfiram-like reaction with ethanol
• Hypersensitive reaactions
 General characteristics
• Bactericidal
• Bind to Penicillin Binding Proteins
• Resistant to Penicillinase, but not other classes of β-lactamases (e.g.
Extended Spectrum Beta-Lacatamases or ESBLs)
• Renal excretion
• Side Effects
• Hypersensitivity reactions (Cross-hypersensitivity with penicillins 1-3%)
• Superinfections: Enterococci, Enterobacter and Candida
 New drugs
• Ceftaroline fosamil
• is a fifth-generation]cephalosporin antibiotic.
• It is active against methicillin-resistant Staphylococcus aureus (MRSA)
and Gram-positive bacteria.
• It retains the activity of later-generation cephalosporins having broad-
spectrum activity against Gram-negative bacteria.
• It is currently being investigated for community-acquired
pneumonia and complicated skin and skin structure infection.
 Ceftolozane 
• Ceftolozane is a 5th generation cephalosporin antibiotic,
• developed for the treatment of infections with gram-negative bacteria
that have become resistant to conventional antibiotics.

•  It was studied for urinary tract infections, intra-abdominal infections and

ventilator-associated bacterial pneumonia. Ceftolozane is combined with
the β-lactamase inhibitor tazobactam, which protects ceftolozane from
degradation.
•  
• Ceftolozane-tazobactam is indicated for the treatment of
complicated urinary tract infections and complicated intra abdominal
infections.
 Ceftobiprole
• Ceftobiprole is a new 5th-generation cephalosporin for the treatment
of hospital-acquired pneumonia (HAP, excluding ventilator-associated
pneumonia, VAP) and community-acquired pneumonia (CAP).

• Ceftobiprole has high affinity for PBP2a  of methicillin

resistant Staphylococcus aureus (MRSA) strains