In this commodity

  • What are macrolides and how do they work?
  • Which infections should macrolides be used for?
  • First-line indications for macrolides
  • Campylobacteriosis
  • Second-line indications for macrolides
  • Agin furnishings of macrolides
  • References

In this commodity

View / Download pdf version of this article

What are macrolides and how do they work?

Macrolides are a class of antibiotic that includes erythromycin, roxithromycin, azithromycin and clarithromycin. They are useful in treating respiratory, skin, soft tissue, sexually transmitted, H. pylori and singular mycobacterial infections. Macrolides share a similar spectrum of antimicrobial activity with benzylpenicillin making them useful alternatives for people with a history of penicillin (and cephalosporin) allergy. Bacteria oft display cross-resistance between the macrolides.

Macrolides interfere with bacterial poly peptide synthesis and, depending on concentration and bacterial species, are either bactericidal (kill bacteria), or bacteriostatic (inhibit growth of leaner). Macrolides as well have immunomodulatory and anti-inflammatory effects, which tin be benign in some situations, east.yard. when they are used in the treatment of cystic fibrosis.1

Which infections should macrolides exist used for?

Macrolides are constructive against gram-positive (excluding enterococci) and some gram-negative bacteria. They are also agile against Mycoplasma pneumoniae, Treponema pallidum, Bordetella pertussis, Chlamydia trachomatis, Chlamydophila pneumoniae, Legionella spp., Campylobacter spp. and Borrelia spp.i

Showtime-line indications for macrolides for common infections are listed in Tabular array 1. There are numerous infections in which macrolides would be considered for second-line treatment.

Table 1: Common outset-line indications for macrolides
Infection Kickoff-line handling Second-line treatment
Pertussis Erythromycin -
Community acquired pneumonia Amoxicillin alone
or
Amoxicillin + erythromycin (for atypical infections)		 Erythromycin, roxithromycin, doxycycline or co-trimoxazole
H. pylori Amoxicillin + clarithromycin + omeprazole Metronidazole + clarithromycin + omeprazole
Chlamydia Azithromycin Doxycycline, amoxicillin, erythromycin
Astute not-specific urethritis Azithromycin
Vancomycin (Doxycycline treatment)
For further information see "Antibiotic choices for common infections", available from: world wide web.bpac.org.nz

First-line indications for macrolides

Pertussis

Erythromycin 10 mg/kg (400 mg for adults), four times daily, for 14 days

Cases of pertussis (whooping cough) persist in New Zealand, despite the vaccine existence part of the National Immunisation Schedule. Antibiotics are ineffective at reducing the elapsing or severity of symptoms if given more vii days after the infection begins. All the same, antibiotics are notwithstanding useful, if started inside three to four weeks of infection, to prevent transmission to others. Women diagnosed with pertussis in the tertiary trimester of pregnancy, should be given antibiotic treatment regardless of the time of onset of infection.4

Prophylactic antibody handling should be offered to household contacts of a person with pertussis, if the household includes a kid who has non completed a grade of pertussis vaccination.four

Erythromycin is considered the medicine of choice for treatment and prophylaxis of pertussis as information technology is active against the causative organism - Bordetella pertussis. Infants aged under three months treated with erythromycin are at increased gamble of developing pyloric stenosis. As the risk associated with pertussis in a young babe is considerably greater, erythromycin is even so indicated, but the infant should be monitored for complications for four weeks after completion of treatment.4

Prescribing erythromycin

Erythromycin is available in New Zealand as erythromycin ethyl succinate (fully subsidised), erythromycin lactobionate (fully subsidised, injection only) and erythromycin stearate (partially subsidised).

The usual oral adult dose of erythromycin is one - 2 g daily, in ii to iv divided doses. The dose may be increased up to 4 g per mean solar day co-ordinate to the severity of the infection. As erythromycin ethyl succinate is now the only fully subsidised oral option, dosing recommendations in this article are altered to take into business relationship the tablet dosages bachelor.

Erythromycin ethyl succinate is available in 400 mg tablets, and two strengths of liquid conception - 200 mg/5 mL and 400 mg/five mL. The usual adult dose is 400 mg, 4 times daily. Alternatively, 800 mg, twice daily, may exist a more convenient dose regimen for some patients. In severe infections, the dose may be increased up to a maximum of 4 g per twenty-four hours. Tablets may be taken with or without food.

The usual dose for infants and children is ten mg/kg, iv times daily, although this may be doubled in severe infections. The daily dose may be divided into twice daily or three times daily dosing if desired. Children aged over eight years may be given the usual adult dose.2

The erythromycin doses expressed in this article refer to prescribing of erythromycin ethyl succinate. Therefore, some dosing recommendations may differ slightly from those listed in the bpacnz antibody guide.

Community-acquired pneumonia: atypical infection

Amoxicillin 500 - one thousand mg, three times daily, for seven days + erythromycin 400 mg, four times daily (or 800 mg, twice daily), for seven days

Severe cases of pneumonia require hospitalisation. The first-line treatment choice for pneumonia treated in the customs is amoxicillin (to cover Streptococcus pneumoniae). Erythromycin (or roxithromycin) should exist added to the treatment regimen when singular infection is known to be circulating in the community. Erythromycin and roxithromycin provide coverage for Mycoplasma pneumoniae, Legionella spp. and Chlamydophilia pneumoniae.

Resistance of Southward. pneumoniae to macrolides is a worldwide problem. In 2010, resistance of S. pneumonia (not-invasive illness) to erythromycin in New Zealand was nineteen%.v

Prescribing roxithromycin

Roxithromycin may exist considered as an culling to erythromycin. All the same, its use is generally reserved for mild to moderate respiratory infections, such as mild to moderate atypical community acquired pneumonia (in combination with amoxicillin). Roxithromycin is by and large well tolerated, only does not have any major advantages over erythromycin.iii The usual dose of roxithromycin is 150 mg, twice daily or 300 mg, once daily. Roxithromycin tablets (150 mg, 300 mg) are fully subsidised. A liquid form is non available in New Zealand.

Pneumonia in children

Amoxicillin (25 mg/kg, three times daily, for seven days) is the first-line antibody for the treatment of pneumonia in children managed in the community. Erythromycin (10 mg/kg, four times daily, for seven days) may exist used instead of amoxicillin in children aged over v years, if treatment fails or if atypical infection is known to exist circulating in the community. Atypical infection is unlikely in children anile less than five years.6

If there is no response to treatment within 24 - 48 hours, review the diagnosis and consider referral to hospital.

Erythromycin may also be used as an alternative to amoxicillin in whatsoever kid with an allergy to penicillin.

Helicobacter pylori infection

Clarithromycin 500 mg, amoxicillin 1 g and omeprazole 20 mg, twice daily, for seven days

The rate of eradication of H. pylori with "triple therapy" (amoxicillin, clarithromycin and omeprazole) is over 85%.vii Postal service-treatment "test of cure" is not required unless the patient has a peptic ulcer, significant co-morbidities or non-resolution of symptoms.vii

Resistance to clarithromycin is increasing worldwide, therefore it is recommended that clarithromycin should non exist used as part of "triple therapy" if it has been used in the last yr for any other infection.8

Chlamydia

Azithromycin one thousand stat

Azithromycin is the treatment of choice for Chlamydia trachomatis infection. Alternatives include doxycycline (100 mg, twice daily, for 7 days), amoxicillin (500 mg, three times daily, for vii days) or erythromycin (800 mg, iv times daily, for vii days).9

A "exam of cure" should be requested four to five weeks later on handling with azithromycin if the patient is pregnant, has a rectal infection or if amoxicillin or erythromycin have been used for handling.ix

Sexual contacts from the by two months of a symptomatic person and from the by six months of an asymptomatic person who has tested positive for chlamydia should likewise exist treated.9 Patients should be advised not to take unprotected sex for one calendar week after treatment and until partners have completed treatment.9

Resistance of Chlamydia trachomatis to azithromycin is increasing, although the extent to which this is occurring is unknown.x Some guidance suggests that doxycycline should exist considered get-go-line instead of azithromycin, in order to avert overuse.10

Azithromycin is also added to the treatment regimen for gonorrhoea (ceftriaxone 250 mg IM + azithromycin ane g stat) considering co-infection with chlamydia is common. Monotherapy with azithromycin ane g is not adequate handling for both pathogens.

Astute not-specific urethritis

Azithromycin 1 g stat

Not-specific urethritis is a diagnosis of exclusion. Symptoms include erythema, discomfort and pain in the urethra and penile discharge.

A showtime void urine sample and urethral swab* should be taken to test for gonorrhoea and chlamydia. Empirical treatment with azithromycin is given on the presumption that the patient has unproblematic urethritis, due to Chlamydia trachomatis. If a purulent discharge is present, treat equally for gonorrhoea (i.due east. add ceftriaxone 250 mg IM stat).

Sexual contacts from the past two months should as well exist treated and tested. This is still necessary if chlamydia and gonorrhoea tests are negative every bit simulated negative results are possible and treating the female partner reduces the chance of recurrence in affected males.9

*Cheque with your local laboratory, a swab may not exist necessary depending on urinanalysis method

Campylobacteriosis

In the bulk of cases of campylobacteriosis, antibiotic treatment is not required equally diarrhoea will resolve with symptomatic treatment only. Antibiotics have limited effect on the elapsing and severity of infection, but tin remove the infection from the stool and therefore reduce transmission to others. Treatment with erythromycin 400 mg (children 10 mg/kg), four times daily, for five days, is indicated for people with severe or prolonged infection, in pregnant women nearing term and may be considered for food handlers, childcare workers and people caring for patients who are immuno-compromised.

Second-line indications for macrolides

Erythromycin is an culling antibody for people with a history of penicillin allergy in the treatment of otitis media, pharyngitis and boils (when treatment is indicated for these conditions), cellulitis, mastitis and syphilis.

Azithromycin (1 g stat or 500 mg, once daily, for iii days) tin can exist used instead of ciprofloxacin as a second-line handling for severe traveller's diarrhoea, when antibiotics are required. Azithromycin is recommended for pregnant women (ciprofloxacin is contraindicated) or in areas where in that location is quinolone resistance, e.k. South E Asia. Azithromycin (10 mg/kg, once daily for three days) is too recommended for immature children with traveller's diarrhoea (ciprofloxacin is not recommended in children), but a liquid formulation is not available in New Zealand. Erythromycin is an alternative. Due north.B. Azithromycin is not funded for this indication.

Azithromycin 1 g stat can be used instead of doxycycline to treat pelvic inflammatory disease (plus ceftriaxone 250 mg, IM stat and metronidazole 400 mg, twice daily, for two weeks), when chlamydia is present, especially if compliance is likely to be a problem.

Agin furnishings of macrolides

The most mutual agin effects associated with macrolides are gastrointestinal, such as abdominal discomfort and balk, nausea, vomiting and diarrhoea. Symptoms are dose dependent and are more common in children.1 Erythromycin is associated with a higher incidence of gastrointestinal adverse furnishings than other macrolides, with five - 30% of patients reporting symptoms.ii Erythromycin ethyl succinate has a lower incidence of gastrointestinal adverse effects compared to other forms of erythromycin. More frequent daily dosing may convalesce gastrointestinal effects.

Endorsement is required when prescribing azithromycin or clarithromycin

Prescriptions for azithromycin must exist endorsed to qualify for a full subsidy. An endorsement requires the prescriber to write "certified condition" on the prescription, to bespeak that the patient meets the criteria for subsidy. Azithryomycin is fully-subsidised for people with unproblematic urethritis or cervicitis proven or presumed to exist due to chlamydia infection, and their sexual contacts. Azithromycin is likewise bachelor via Practitioners Supply Society, which must exist endorsed.

Clarithromycin is fully subsidised with endorsement for H. pylori eradication. Endorsement occurs automatically if clarithromycin, amoxicillin (or metronidazole) and a proton pump inhibitor are concurrently prescribed as "triple therapy". A maximum of 14 tablets per prescription is allowed. Special Authority criteria also applies for relevant practitioners to prescribe clarithromycin for mycobacterial infections.

Come across pharmaceutical schedule for full details www.pharmac.govt.nz

Macrolides, peculiarly erythromycin and clarithromycin, have been associated with prolongation of the QT interval and should be used cautiously in patients at risk of developing arrhythmias.1,3 The risk of prolongation of the QT interval may also be increased when macrolides are taken with other medicines that may affect cardiac function or reduce the rate of macrolide clearance (come across "Medicines interactions").

Macrolides should exist avoided in people with astringent liver damage.

Other rare adverse furnishings include hypersensitivity (eastward.k. anaphylaxis, stock-still drug eruptions, Stevens-Johnson syndrome and interstitial nephritis), cholestatic hepatitis, pancreatitis, Clostridium difficile-associated infection, blood dyscrasias (e.g. blood thrombocytopenia), psychiatric disturbances and ototoxicity.1,two,3

Safe in pregnancy and breast feeding

Erythromycin - Category A*; condom to use, merely consider an alternative in the first trimester (unconfirmed reports of an association with congenital cardiac malformations)

Roxithromycin - Category B1; considered safe to use

Azithromycin - Category B1; considered safe to use

Clarithromycin - Category B3; uncertain prophylactic in pregnancy, consider an alternative

Erythromycin, roxithromycin and azithromycin are safe to utilise while breast feeding, clarithromycin is considered safe to use while breast feeding.1

* Australian Therapeutic Appurtenances Administration Pregnancy Categories

Medicines interactions

Macrolides are potent hepatic cytochrome P450 enzyme inhibitors. They also take an inhibitory effect on transporter proteins, too as affecting gastrointestinal flora and gastric emptying.1,ii These actions take the potential to crusade adverse interactions with other medicines. Erythromycin and clarithromycin are more commonly associated with medicine interactions than other macrolides. Elderly people and those with renal or liver damage are more likely to be affected by medicines interacting with macrolides. If possible, it is recommended that the interacting medicine exist withheld, or the dose reduced during the course of antibiotics while monitoring for signs of toxicity.

Calcium channel blockers taken at the same time as erythromycin or clarithromycin have been shown to increment the short-term risk of hypotension or shock amongst elderly people.11 Verapamil may increase the concentration of erythromycin, resulting in a increased risk of QT interval prolongation.i Other medicines that may increase the take a chance of QT prolongation include; amiodarone, methadone, lithium, amitriptyline and citalopram.ane

For a total listing of medicines that increase QT prolongation run across: world wide web.azcert.org/alphabetize.cfm

N.B. this is a US based reference so may not include all medicines bachelor in New Zealand

Warfarin and dabigatran may have increased anticoagulant properties when taken with clarithromycin and erythromycin.12 If possible, an alternative antibiotic should be used. Warfarin may demand to be temporarily stopped or the dose reduced if in that location is no alternative. The INR should be monitored if warfarin and macrolides are taken at the same time. Picayune information is available on interactions with dabigatran, just patients should be monitored for signs of bleeding. This effect may be more pronounced in elderly people, or when renal function is reduced.

Statin metabolism, in particular simvastatin and atorvastatin, may exist affected past macrolides inhibiting CYP3A4 enzymes. This can result in an increased chance of statin-induced rhabdomyolysis. Azithromycin interacts less with CYP3A4 enzymes, notwithstanding, at that place take also been occasional reports of rhabdomyolysis in patients taking azithromycin.13 Patients can be brash not to accept simvastatin or atorvastatin while completing a class of a macrolide antibiotic. Pravastatin is not significantly metabolised by CYP3A4, therefore is less likely to be affected by concurrent macrolide use.

Digoxin is known to interact with clarithromycin, which can lead to digoxin toxicity.14 When these medicines are taken in combination the digoxin dose should be reduced by half and the patient monitored for symptoms of toxicity.xv

Other medicines that may have significant interactions with macrolides in elderly people or those with significant co-morbidities include; benzodiazepines, carbamazepine, cimetidine, clozapine, colchicine and theophylline.14

ACKNOWLEDGEMENT: Thank you to Dr Rosemary Ikram, Clinical Microbiologist, Christchurch for practiced guidance in developing this commodity.

References

  1. Australian medicines handbook. Adelaide: Australian Medicines Handbook Pty Ltd, 2011.
  2. Sweetman S, editor. The complete drug reference. London: Pharmaceutical Press, 2011.
  3. Grayson M. Kucers' the use of antibiotics. 6th ed. Credo; 2010. Available from: world wide web.medicinescomplete.com (Accessed May, 2012).
  4. Ministry of Health. Immunisation Handbook 2011. Wellington: Ministry of Health.
  5. Ecology Scientific discipline and Enquiry (ESR). Antimicrobial resistance data from hospital and community laboratories, 2010. Available from: www.surv.esr.cri.nz (Accessed May, 2012).
  6. Clinical Knowledge Summaries (CKS). Cough - acute with chest signs in children. Customs-caused pneumonia. 2007. Bachelor from: http://cks.library.nhs.uk (Accessed May, 2012).
  7. New Zealand Guidelines Grouping (NZGG). Direction of dyspepsia and heartburn. NZGG, 2004 Available from: www.nzgg.org.nz/search?search=Dyspepsia (Accessed May, 2012).
  8. National Institute for Health and Clinical Excellence (NICE). Dyspepsia. Prissy, 2004. Available from: www.overnice.org.united kingdom of great britain and northern ireland (Accessed May, 2012).
  9. The New Zealand Sexual Health Lodge Inc (NZSHS). All-time exercise guidelines. NZSHS, 2009. Available from: world wide web.nzshs.org.guidelines.html (Accessed May, 2012).
  10. Ison CA. Antimicrobial resistance in sexually transmitted infections in the developed world: implications for rational handling. Curr Opin Infect Dis 2012;25(ane):73-8.
  11. Wright AJ, Gomes T, Mamdani MM, et al. The risk of hypotension following co-prescription of macrolide antibiotics and calcium-aqueduct blockers. CMAJ 2011;183(iii):303-seven.
  12. British National Formulary (BNF). BNF 62. London: BMJ Publishing Group and Royal Pharmaceutical Society of Bully Britain, 2011.
  13. Strandell J, Bate A, Hägg S, Edwards IR. Rhabdomyolysis a result of azithromycin and statins: an unrecognized interaction. Br J Clin Pharmacol 2009;68(3):427-34.
  14. Westphal JF. Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin. Br J Clin Pharmacol 2000. 50(4):285-95.
  15. Lee CYW, Marcotte F, Giraldeau G, et al. Digoxin toxicity precipitated by clarithromycin use: case presentation and curtailed review of the literature. Can J Cardiol 2011;27(6):870.e15-16.