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Cephalosporins are broad spectrum antibiotics similar to penicillins. They have a beta-lactam ring which interferes
with bacterial cell wall synthesis by binding to penicillin-binding proteins, eventually leading to cell lysis and death.1 Like
amoxicillin clavulanate, cephalosporins should be avoided when a narrower spectrum antibiotic would be effective because
they increase the risk of Clostridium difficile, MRSA and other resistant infections.
Cephalosporins mainly used in general practice are; cefaclor, cephalexin and ceftriaxone (injection). Other cephalosporins
available on the Pharmaceutical Schedule are; cefazolin, cefoxitin and cefuroxime – these medicines are usually
prescribed for patients undergoing dialysis and for patients with cystic fibrosis.
Cephalosporins are grouped based on their antibacterial properties and when they were introduced:2
- First generation cephalosporins include cephalexin and cefazolin. They have good activity against a wide spectrum
of Gram-positive bacteria including penicillinase-producing staphylococci. However, they are not active against methicillin-resistant
staphylococci (MRSA). Enterococci are resistant.2
- Second generation cephalosporins include cefaclor, cefuroxime and cefoxitin. They are more stable to hydrolysis by
beta-lactamases produced by Gram-negative bacteria and therefore have enhanced activity against many of the Enterobacteriaceae,
e.g. Escherichia coli, Salmonella.2
- Ceftriaxone is a third generation cephalosporin. They have the widest spectrum of activity compared to other generations
of cephalosporins and are active against Gram-negative organisms, including many of the significant Enterobacteriaceae.
They are also very active against streptococci.2
- There are few infections where cephalosporins are the antibiotics of first choice and their use should be avoided
when other more narrow spectrum antibiotics remain effective
- Ceftriaxone is an appropriate first line treatment for gonorrhoea, pelvic inflammatory disease and epididymo-orchitis
- Ceftriaxone may also be used for suspected meningitis in patients allergic to penicillin (benzylpenicillin is first-line)
- Cefaclor may be considered as a second-line treatment for otitis media, sinusitis, cellulitis, diabetic foot infection
- Cephalexin is a third-line alternative for the treatment of urinary tract infection in pregnant women (after nitrofurantoin
Indications for the use of cephalosporins
There are few infections where cephalosporins are the antibiotics of first choice (Table 1). Ceftriaxone may be used
first-line for some genital tract infections such as gonorrhoea, pelvic inflammatory disease (PID) and epididymo-orchitis
(if sexually transmitted pathogens are suspected). Ceftriaxone is also appropriate empiric treatment for suspected meningitis
in people allergic to penicillin.
: First and second-line indications for cephalosporins
Sexually transmitted infections
Gonorrhoea – ceftriaxone in combination with azithromycin
Pelvic inflammatory disease – ceftriaxone in combination with doxycycline and metronidazole
Epididymo-orchitis – ceftriaxone in combination with doxycycline
Respiratory tract infections
Otitis media – first-line amoxicillin, second-line erythromycin, co-trimoxazole or cefaclor
Sinusitis – first-line amoxicillin, second-line doxycycline, co-trimoxazole or cefaclor
Meningitis – ceftriaxone is an alternative to benzylpenicillin
Cellulitis – first-line flucloxacillin, second-line erythromycin, roxithromycin, co-trimoxazole or cefaclor
Diabetic foot infections – first-line amoxicillin clavulanate, second-line co-trimoxazole or cefaclor in combination
Mastitis – first-line flucloxacillin, second-line erythromycin or cefaclor
Urinary tract infections in pregnancy
First-line nitrofurantoin, second-line trimethoprim, third-line cephalexin
Norfloxacin is now used in place of cephalexin for third-line treatment of UTIs in pregnancy;
cephalexin is also now recommended in place of cefaclor. For more information on this and other conditions treated with cephalosporins, see the latest edition of our handbook, "Antibiotics: Choices for common infections", bpacnz.
First line indications for cephalosporins
A single dose of ceftriaxone 250 mg given intramuscularly is the treatment of choice for gonorrhoea. N.B.
Ceftriaxone is subsidised if prescribed for the treatment of confirmed ciprofloxacin-resistant gonorrhoea, and the prescription
or MPSO is endorsed accordingly.
Research shows that ceftriaxone attains the optimal concentrations to prevent the development of step-wise mutations
and resistance in Neisseria gonorrhoea.3 Standard treatment with ceftriaxone has been shown to be greater than
95% effective.4 Therefore a repeat test to ensure cure is not usually required as long as the patient is asymptomatic
after treatment. Azithromycin (oral) is also routinely given when treating gonorrhoea, because co-infection with chlamydia
Ciprofloxacin (500 g stat) is an alternative to ceftriaxone if cephalosporins are contraindicated (most often due to
a documented allergy to beta-lactam antibiotics) or if the isolate is known to be sensitive to ciprofloxacin.Ciprofloxacin
resistance is becoming increasingly common, with a prevalence of approximately 30% across New Zealand, varying by location.5
Pelvic inflammatory disease
Broad-spectrum treatment is justified in pelvic inflammatory disease (PID) because the consequences of untreated
infection can be serious, e.g. infertility, ectopic pregnancy. The recommended treatment which covers N. gonorrhoea,
Chlamydia trachomatis and anaerobes is ceftriaxone 250 mg IM stat and doxycycline 100 mg, twice daily, and metronidazole
400 mg, twice daily, for two weeks.
Ceftriaxone is included in the regimen primarily to cover N. gonorrhoeae. Patients should be advised to inform sexual
partners that they need to be screened and treated if positive for gonorrhoea and chlamydia.
Epididymo-orchitis if STI pathogens are suspected
Ceftriaxone 250 mg IM stat in combination with doxycycline 100 mg, twice daily, for two weeks is recommended
for epididymo-orchitis if sexually transmitted infections (mostly chlamydia or gonorrhoea) are the suspected cause. Most
guidelines recommend this regimen in men aged less than 35 years.6 Other risk factors for sexually transmitted
infection include urethral discharge and more than one sexual partner in the last 12 months.7
Ceftriaxone is an alternative to benzylpenicillin for suspected meningitis
Any patients with suspected meningitis should be immediately transferred to hospital. IV or IM benzylpenicillin
should be given while transfer to hospital is being arranged. Ceftriaxone is an alternative to benzylpenicillin for people
with suspected meningitis who have a history of immediate allergic reaction to penicillin. Although there is some cross-reactivity
between penicillin and cephalosporin allergy, it is appropriate to use ceftriaxone given the seriousness of the infection
Second-line indications for cephalosporins
Cefaclor is used as a second-line alternative for some respiratory tract infections
Cefaclor is a second-line alternative to amoxicillin for suspected acute bacterial sinusitis. Other second-line
alternatives are doxycycline or co-trimoxazole. However, in most cases antibiotics are not necessary at all. Eighty percent
of sinusitis cases resolve in 14 days without antibiotics. In addition, antibiotics only offer marginal benefit after
seven days.8 Analgesics (e.g. paracetamol or NSAIDs) are the primary treatment for sinusitis.9 Other
treatments that may increase drainage of exudate and improve symptoms include: intranasal corticosteroids, sodium chloride
0.9% sprays and drops, steam inhalations and decongestants.1 Purulent nasal discharge persisting for more
than seven days, facial pain or maxillary tooth ache, unilateral sinus tenderness or fever suggest that bacterial infection
is more likely and antibiotics may be appropriate in people with these symptoms and signs.
Cefaclor is also a second-line alternative (as are erythromycin or co-trimoxazole) to amoxicillin for acute otitis media,
however, again antibiotic treatment is usually unnecessary. Most cases of acute otitis media can be treated symptomatically
(e.g. with paracetamol) and arrangements for a follow-up appointment and antibiotic prescription can be made if no improvement
occurs in the next 24 hours. Antibiotics can be considered earlier for those with systemic symptoms, children aged under
six months or children under aged two years with severe or bilateral disease.
Cephalexin is appropriate as a third-line option for UTI in pregnant women
Norfloxacin is now used in place of cephalexin for third-line treatment of UTIs in pregnancy. For more information on this and other conditions treated with cephalosporins, see the latest edition of our handbook, "Antibiotics: Choices for common infections", bpacnz.
Cephalosporins are not associated with an increased risk of congenital malformations when used in pregnancy and are
therefore considered safe to use.1 However, it is recommended that cephalexin is reserved as a third-line option
after nitrofurantoin (avoid at 36+ weeks) and trimethoprim (avoid during first trimester) for the treatment of UTI in
pregnant women because it is a broad spectrum antibiotic and increases the risk of C. difficile. C. difficile infection
can be life-threatening in pregnant women, with case reports of both maternal deaths and stillborn infants.10
Cefaclor may be used as a second-line option for mastitis, cellulitis and diabetic foot infections
Cephalexin is now recommended over cefaclor for many conditions. For more information, see the latest edition of our handbook, "Antibiotics: Choices for common infections", bpacnz.
Cefaclor has good activity against a wide spectrum of Gram-positive bacteria and also has activity against Gram-negative
bacteria, particularly Haemophilus influenzae. This makes it suitable as a second-line option for treating mastitis (first-line
flucloxacillin, other second-line option erythromycin) and cellulitis (first-line flucloxacillin, other second-line options
erythromycin, roxithromycin or co-trimoxazole). It may also be used as a second-line alternative to amoxicillin clavulanate
to treat diabetic foot infections (in combination with metronidazole). Co-trimoxazole plus metronidazole is another second-line
Serum sickness type syndrome with cefaclor
Cefaclor has been associated with serum sickness-like reactions, especially in young children, and
typically after several courses. Symptoms include skin reactions, arthralgia and lymphadenopathy, which may last for
six to twelve days. A full recovery usually occurs after stopping cefaclor.1
Probenecid increases the activity of cephalosporins
Probenecid reduces renal and gut secretion of cephalosporins (excluding ceftriaxone), increasing
their half-life and prolonging their activity. Probenecid 250–500 mg can be given orally three to four times
daily to increase serum and tissue antibiotic levels. Monitor for adverse effects of cephalosporins and halve doses
of NSAIDs if taken concomitantly.1,6
Issues associated with cephalosporins
Cross-reactivity with penicillin allergy is often over-estimated
Penicillin allergy is reported by up to 10% of people, however, many do not have a true (IgE mediated) allergy. True
allergy is recognisable by clinical features such as urticaria, laryngeal oedema, bronchospasm, hypotension or local swelling
within 72 hours of administration or a pruritic rash, developing even after 72 hours.11
Cross-reactivity between penicillins and cephalosporins of 10% is widely quoted, however, this is now believed to be
an overestimate. This estimation was largely based on reviews in the 1970s which included the following limitations:11
- Up until 1982, compounds relating to penicillin had been produced commercially using the cephalosporin mould and the
cephalosporins used in these reviews were contaminated with penicillin
- The fact that people with penicillin allergy are three times more likely to have adverse reactions to other drugs
was not accounted for
- The definition of allergy was imprecise and differed between studies
A more recent review suggests that the cross-reactivity between first generation cephalosporins and penicillins is closer
to 0.5% than 10% and that second and third generation cephalosporins (e.g. ceftriaxone) are unlikely to be associated
with cross-reactivity as they have different side chains to penicillin.11
It is still considered appropriate to avoid cephalosporins in patients who have a history of an immediate hypersensitivity
(Type I allergy) to penicillins for mild to moderate infections when a suitable alternative antibiotic exists. However,
in life-threatening cases (e.g. suspected meningitis) where a cephalosporin is essential because a suitable alternative
is not available then a second or third generation cephalosporin (such as ceftriaxone, but excluding cefaclor) can be
used with caution.12
Gonorrhoea shows potential signs of resistance to cephalosporins
Cephalosporins are now widely used for the treatment of gonorrhoea, following the development of resistance to fluoroquinolones.
In New Zealand the recommended treatment is IM ceftriaxone which is the same advice given by the United States Centres
for Disease Control and Prevention (CDC). United States data is now showing that the percentage of isolates with elevated
mean inhibitory concentrations (the lowest concentration that will inhibit the growth of a microorganism) to cephalosporins
(cefixime and ceftriaxone) has increased during the last ten years. These trends are concerning because the emergence
of resistance to fluoroquinolones followed a similar pattern in the United States as what is now being seen with ceftriaxone.
Cephalosporin treatment failures have also been reported in Europe and Asia.13
Although cephalosporins are still effective, the CDC is advising health-care providers to be vigilant for gonorrhoea
treatment failures after using a cephalosporin (shown by persistent symptoms or a positive follow-up test despite treatment).13
Extended-spectrum beta lactamases
Extended spectrum beta lactamases (ESBLs) are produced by some bacteria and confer resistance to all penicillins and
cephalosporins, including the extended spectrum cephalosporins (e.g. ceftriaxone, cefuroxime) that were originally designed
to resist the action of older beta-lactamases. Many of these organisms producing ESBLs may also be resistant to other
antibiotic classes, e.g., aminoglycosides, sulphonamides and fluoroquinolones, limiting treatment options for patients
infected with ESBL-producing organisms.14 ESBLs are most common in Escherichia coli and Klebsiella pneumoniae.
The most typical type of infection they cause is urinary tract infections, however, they can cause serious infections
in the blood stream, in which case they are likely to be resistant to many of the empirical antibiotics used for these
Infections with ESBL-producers are most common amongst elderly people or those who have recently been in hospital, received
antibiotic treatment or travelled overseas. The incidence of these infections has been increasing in New Zealand and globally
and is of concern because these organisms are resistant to many commonly used antibiotics. As with other types of antibiotic
resistance, minimising the spread of resistant organisms relies in part on only using antibiotics when necessary and at
appropriate doses for the correct duration in both the community and inpatient settings.14
Thank you to Dr Rosemary Ikram, Clinical Microbiologist, Medlab South, Christchurch for expert guidance
in developing this article.
- Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd, 2011.
- Sweetman S, editor. Martindale: The Complete Drug Reference. London: Pharmaceutical Press, 2011.
- Ison C, Mouton J, Jones K. Which cephalosporin for gonorrhoea? Sex Transm Infect 2004;80:386-8.
- Moran J, Levine W. Drugs of choice for the treatment of uncomplicated gonococcal infection Clin Infect Dis 1995;20(Suppl
- Institute of Environmental Science and Research (ESR). Antimicrobial resistance data from hospital and community
laboratories. ESR, 2009. Available from: www.surv.esr.cri.nz (Accessed
- Everts R. Antibiotic guidelines for primary care. Nelson and Marlborough 2010-2. 2010. Available from: www.nmdhb.govt.nz (Accessed
- Clinical Knowledge Summaries (CKS). Scrotal swellings. CKS, 2010. Available from: www.cks.nhs.uk (Accessed
- Health Protection Agency (HPA). Management of infection guidance for primary care for consultation and local adaptation.
HPA, 2010. Available from: www.hpa.org.uk (Accessed Nov, 2011).
- Ah-See KW, Evans AS. Sinusitis and its management. BMJ 2007;334:358-61.
- Clinical Knowledge Summaries (CKS). Urinary tract infection (lower) - women. CKS, 2009. Available from: www.cks.nhs.uk (Accessed
- Pegler S, Healy B. In patients allergic to penicillin, consider second and third generation cephalosporins for life
threatening infections. BMJ 2007;335:991.
- British National Formulary (BNF) 62. London: Pharmaceutical Press, 2011.
- Centres for Disease Control and Prevention (CDC). Cephalosporin susceptibility among Neisseria gonorrhoeae isolates
- United States, 2000-2010. Morbidity and Mortality Weekly Report 2011;60(26):873-7.
- Drug and Therapeutics Bulletin. Risks of extended-spectrum beta-lactamases. Drug and Therapeutics Bulletin 2008;46(3):21-4.