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Cephalosporins and other Beta Lactams

The cephalosporins are broad spectrum antibiotics. Their pharmacology is similar to penicillins and they are mainly excreted by the kidney. They do not cross the blood brain barrier well, except when the meninges are inflamed. They are derived from fungus and work by inhibiting cell wall synthesis.1

Available treatments

Cephalosporins are divided into 3 generations:

  • 1st generation: cephalexin, cefadroxil, cephradine
  • 2nd generation: cefuroxime, cefaclor
  • 3rd generation: cefotaxime, ceftazidime, cefixime - these give the best CNS penetration

Other beta-lactams include:

  • Aztreonam: a monocytic beta-lactam, with an antibacterial spectrum which is active only against gram negative aerobes, including Pseudomonas aeruginosa. It is also active against Neisseria gonorrhoea.
  • Imipenem: a carbapenem with a broader spectrum of activity against gram positive and negative aerobes and anaerobes. Needs to be given with cilastatin, to prevent inactivation by the kidney.
  • Meropenem: similar to imipenem, but more stable, and not requiring cilastatin. Activity of this drug is monitored in the meropenem yearly susceptibility test information collection (MYSTIC) programme. The last report confirmed that it has sustained global potency against gram positive and negative organisms.2 It is an effective anti-pseudomonal treatment. In units where it is used often, there appears to be no increase in resistance.
  • Ertapenem: also has a broad spectrum of activity covering gram positive and negative, and anaerobes. Is not active against atypical respiratory infections, Pseudomonas or Acinebacter. It also has limited action against penicillin resistant Pneumococci.
  • Ceftobiprole is a new beta-lactam designed for bactericidal activity against methicillin-resistant staphylococci.3 It also has an extended broad spectrum of activity covering the most clinically important Gram-positive and Gram-negative pathogens.

Indications for use

Where possible treatment should be guided by sensitivities from a cultured specimen. Where empiric treatment is necessary consult your local antibiotic policy - based the HPA guidance adapted to take account of locally prevalent pathogens and resistance.4 Gram-negative bacteria resistance to cephalosporins is increasing.5

GI tract

  • Typhoid: cefotaxime
  • Biliary tract infection: cephalosporin
  • Peritonitis: cephalosporin with metronidazole
  • Peritoneal dialysis associated peritonitis: cephalosporin with metronidazole.

Respiratory tract

  • Throat infection: oral cephalosporin
  • Haemophilus influenzae epiglottitis: cefotaxime
  • Severe community acquired pneumonia of unknown aetiology: cefuroxime with erythromycin, or cefotaxime
  • Hospital acquired pneumonia: broad spectrum cephalosporin
  • Acute exacerbation of chronic bronchitis (AECB): second or third generation cephalosporins are more effective, but not less safe than amoxicillin6

CNS

  • Meningococcal meningitis: cefotaxime
  • Pneumococcal meningitis: cefotaxime
  • H. influenzae meningitis: cefotaxime

However, a recent Cochrane review shows no clinically important difference between cefotaxime and conventional antibiotics. In situations where availability or affordability is an issue, third generation cephalosporins, an amoxicillin-chloramphenicol combination, or chloramphenicol alone may be used as alternatives.7

Pelvis

NB: Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children.8

Blood-borne

  • Community acquired septicaemia: broad spectrum cephalosporin
  • Hospital acquired septicaemia: beropenem or imipenem
  • Meningococcal septicaemia: cefotaxime.

They are also commonly used for antibacterial prophylaxis in surgery.

  • Stomach/ oesophagus/ gallbladder: IV cefuroxime, single dose
  • Colon or rectum: IV cefuroxime with metronidazole, single dose
  • Pelvis: IV cefuroxime with metronidazole, single dose
Cautions and contraindications
  • Known hypersensitivity to penicillin or cephalosporins. The cross-reactivity with penicillins varies according to which type of cephalosporin is prescribed. It is greatest with first and second generation cephalosporins, (30%), or with cephalosporins containing an amino-benzyl ring (27%).9 It may be as low as 4-5% with a 3rd generation/ no benzyl ring cephalosporin.
  • Diabetics should be informed they may have a false positive test for glucose on urine testing, whilst taking cephalosporins.
  • They are excreted renally, so patients with renal impairment may have higher circulating concentrations and be more prone to adverse effects. They may require a lower dose.
  • It should be used with caution where the patient also has porphyria.
Adverse effects
  • Hypersensitivity reactions may be seen.
  • Diarrhoea and, rarely, antibiotic associated colitis are found. This occurs more commonly with very high doses.
  • Increased bleeding tendency may occur.
  • Interacting with other medications:
    • Combined oral contraceptive pill efficacy is reduced.
      Extra precautions should be used for the duration of the course and 7 subsequent days.
    • Diuretics increase plasma concentrations of cephalosporins and their toxicity.
    • Warfarins anticoagulant effect is enhanced by cefamandole.
    • Antacids reduce the absorption of cefaclor.
  • Cefamandole gives a disulfiram reaction with alcohol.



Document references
  1. Wellcome Trust - how antibiotics work
  2. Jones RN, Mendes C, Turner PJ, et al; An overview of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program: 1997-2004.; Diagn Microbiol Infect Dis. 2005 Dec;53(4):247-56. [abstract]
  3. Rossolini GM; Redesigning beta-lactams to combat resistance: summary and conclusions. Clin Microbiol Infect. 2007 Jun;13 Suppl 2:30-3. [abstract]
  4. HPA; Management of infection guidance for Primary Care - for consultation and local adaption.; Health Protection Agency
  5. Livermore D; The zeitgeist of resistance. J Antimicrob Chemother. 2007 Aug;60 Suppl 1:i59-61. [abstract]
  6. Dimopoulos G, Siempos II, Korbila IP, et al; Comparison of first-line with second-line antibiotics for acute exacerbations of chronic bronchitis: a metaanalysis of randomized controlled trials. Chest. 2007 Aug;132(2):447-55. Epub 2007 Jun 15. [abstract]
  7. Prasad K, Kumar A, Gupta P, et al; Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001832. [abstract]
  8. Montini G, Toffolo A, Zucchetta P, et al; Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial. BMJ. 2007 Aug 25;335(7616):386. Epub 2007 Jul 4. [abstract]
  9. Fonacier L, Hirschberg R, Gerson S; Adverse drug reactions to a cephalosporins in hospitalized patients with a history of penicillin allergy.; Allergy Asthma Proc. 2005 Mar-Apr;26(2):135-41. [abstract]

Internet and further reading AcknowledgementsEMIS is grateful to Dr Hayley Willacy for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2008.
DocID: 299
Document Version: 2
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Last Updated: 6 Dec 2007
Review Date: 5 Dec 2008




















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