Cephalosporins: Four Generations of Beta-Lactam Antibiotics

Review literature: (Simon and Stille, 1997).

Four Generation of Cephalosporins

Cephalosporins are β-lactam antibiotics, which are grouped into four generations according to their antibiotic spectrum of activity. The first generation has mainly gram-positive activity. The second and third generation has more gram-negative activity with mostly decreased activity against gram-positive bacteria. The fourth generation of cephalosporins has a broad spectrum activity. The following list provides an overview over the generations of cephalosporins with major substances:

First Generation: cefazolin, cefalexin, cefadroxil
Second Generation: cefamandole, cefoxitin, cefaclor, cefuroxime, loracarbef, cefotetan
Third generation: cefotaxime, cefpodoxime, ceftizoxime, ceftriaxone, ceftazidime, cefoperazone
Fourth generation: cefepime, cefozopran, cefpirome, cefquinome

Cefazolin

Antibiotic Spectrum of Cefazolin

Cefazolin is a first-generation cephalosporin. Cefazolin has a comparable antibiotic spectrum as penicillin. In addition, cefazolin has activity against gram-negative bacteria (E. coli, Klebsiella) and staphylococci.

Urologic Indications for Cefazolin

Staphylococci infections
Wound infections
Perioperative antibiotic prophylaxis
Cefazolin can replace penicillin in a penicillin allergy. Patients with penicillin allergy have a low risk of cross-allergy (10%), which is even lower with cephalosporines of the second and third generation.

Pharmacokinetics of Cefazolin

Cefazolin is only for parenteral administration available. Elimination half life 1.5 h, 90% renal elimination.

Side Effects of Cefazolin

Allergy: 1–4%. Normally, there is a small risk for cross-allergy to penicillin (10%)
Allergic neutropenia
Positive direct Coombs test, very rarely hemolytic anemia.
Inhibiting the effect of anticoagulants or antiplatelet agents

Contraindications of Cefazolin

Cephalosporin allergy.

Dosage of Cefazolin

In adults, the dosage of cefazolin is 1 g 1-1-1 i.v. Children receive a daily dose of 60 mg/kg body weight, divided in three doses. Dose reduction is necessary in renal insufficiency.

Second Generation of Cephalosporins

Cefuroxime, cefotiam and cefaclor are important substances of the second generation of Cephalosporins.

Antibiotic Spectrum of Second Generation Cephalosporins

Good activity against streptococci, gonococci, meningococci, Haemophilus and staphylococci. High β-lactamase resistance. No efficacy against Pseudomonas, enterococci, mycoplasma, chlamydia.

Urologic Indications of Cefuroxime:

Urinary tract infections
Treatment of gonorrhea
Staphylococci infections
Wound infections
Perioperative antibiotic prophylaxis
Cefuroxime can replace penicillin in a penicillin allergy.

Pharmacokinetics of Cefuroxime and Cefotiam

Cefuroxime can be applied per os or intravenously. Elimination half life 1 h. 70–90% renal elimination.

Side Effects of Cefuroxime

Allergy: 1–4%. There is a minimal risk for cross-allergy to penicillin.
Allergic neutropenia
Positive direct Coombs test, very rarely hemolytic anemia.
Inhibiting the effect of anticoagulants or antiplatelet agents

Contraindications of Cefuroxime

Cephalosporin allergy.

Dosage of Cefuroxime and Cefotiam

In urinary tract infections: cefuroxime 250–500 mg 1-1-1 p.o., 750 mg 1-1-1 i.v. or 1 g cefotiam 1-1-1 i.v., depending on severity of infection Ovalle et al. 2000. Children receive 25 mg/kg i.v. 1-1-1. In severe infections the dosage is doubled. Dose reduction is necessary in renal insufficiency.

Third Generation of Cephalosporins

Important substances of third-generation cephalosporins are cefotaxime and ceftriaxone (cefotaxime-group).

Antibacterial Spectrum of cefotaxime and ceftriaxone

Cefotaxime and Ceftriaxone show good activity against streptococci, gonococci, meningococci, Haemophilus and staphylococci. High β-lactamase resistance. Weak activity against Pseudomonas. No activity against enterococci, mycoplasma, chlamydia and multidrug-resistant Staphylococcus aureus.

Urologic Indications for Third Generation Cephalosporins

Severe urinary tract infections, can be combined with gentamicin to include enterococci
Severe postoperative infections like peritonitis
Treatment of gonorrhea with a single dose of ceftriaxone i.m.

Pharmacokinetics of Cefotaxime and Ceftriaxone

Only parenteral administration of cefotaxime and ceftriaxone is possible. The elimination half life is 1 h for cefotaxime and 7–8 h for ceftriaxone. 50% renal elimination.

Side Effects of Cefotaxime and Ceftriaxone

Allergy: 1–4%. There is a minimal risk for cross-allergy to penicillin.
Allergic neutropenia
Positive direct Coombs test, very rarely hemolytic anemia.
Inhibition of the efficacy of anticoagulants or antiplatelet agents
Alcohol intolerance possible

Contraindications

Cephalosporin allergy.

Dosage of Cefotaxime and Ceftriaxone

Treatment of severe infection: the daily dosage of cefotaxime in adults amounts to 3–6 g (children 50–100 mg/kg), depending on the severity of the infection, and is divided into three doses. The daily dosage for ceftriaxone is 2–4 g in two doses. Dose reduction is necessary with a renal insufficiency below a glomerular filtration rate of 5 ml/min.

Single shot treatment of gonorrhea: 250 mg ceftriaxone i.m. [see Chapter gonorrhea].

Oral Cephalosporins

Ceftibuten

Ceftibuten is an oral cephalosporin which a high activity against Enterobacteriaceae and is suitable for the treatment of severe or complicated urinary tract infection in children Ho et al, 2001 Vilaichone et al, 2001.

Pharmacokinetics of Ceftibuten:

Elimination half life 2.5 h. 70% renal elimination.

Dosage of Ceftibuten:

400 mg 1-0-0 in adults, 9 mg/kg body weight 1-0-0 in children.

Cefixime

Cefixime is a derivative of cefotaxime, which can be given orally. Cefixime is suitable for the treatment of urinary tract infection in children Gok et al, 2001 Ho et al, 2001.

Pharmacokinetics of Cefixime:

Elimination half life 2.5 h, only 20% renal elimination, high biliary excretion.

Dosage of Cefixime:

Adults 200 mg 1-0-1 or 400 mg 1-0-0 p.o., children 4 mg/kg body weight 1-0-1 or 8 mg/kg 1-0-0.

Cefpodoxime

Cefpodoxime is a derivative of ceftizoxime. Cefpodoxime is suitable for the oral treatment of urinary tract infections.

Pharmacokinetics of cefpodoxime:

Elimination half life 2.5 h, 30–40% renal elimination.

Dosage of cefpodoxime:

Adults 200 mg 1-0-1 and children 4 mg/kg body weight 1-0-1.

Surgical management

Index

Pharmacology

Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

You did not find what you are looking for?

Search this site with Google:

Custom Search

References

Gok u.a. 2001 GOK, F. ; DUZOVA, A. ; BASKIN, E. ; OZEN, S. ; BESBAS, N. ; BAKKALOGLU, A.:: Comparative study of cefixime alone versus intramuscular ceftizoxime followed by cefixime in the treatment of urinary tract infections in children.
In: J Chemother
13 (2001), Nr. 3, S. 277–80
Ho u.a. 2001 HO, M. W. ; WANG, F. D. ; FUNG, C. P. ; LIU, C. Y.:: Comparative study of ceftibuten and cefixime in the treatment of complicated urinary tract infections.
In: J Microbiol Immunol Infect
34 (2001), Nr. 3, S. 185–9
Ovalle u.a. 2000 OVALLE, A. ; MARTINEZ, M. A. ; WOLFF, M. ; CONA, E. ; VALDERRAMA, O. ; VILLABLANCA, E. ; LOBOS, L.:: [Prospective, randomized, comparative study of the efficacy, safety and cost of cefuroxime versus cephradine in acute Pyelonephritis during pregnancy].
In: Rev Med Chil
128 (2000), Nr. 7, S. 749–57
Simon und Stille 1997 SIMON, C. ; STILLE, W.:: Antibiotika-Therapie in Klinik und Praxis.
9. Auflage.
Stuttgart New York : Schattauer, 1997
Vilaichone u.a. 2001 VILAICHONE, A. ; WATANA, D. ; CHAIWATANARAT, T.:: Oral ceftibuten switch therapy for acute pyelonephritis in children.
In: J Med Assoc Thai
84 Suppl 1 (2001), S. S61–7

Deutsche Version: Cephalosporine

Last update:

Dr. med. Dirk Manski (E-Mail)