In this commodity

  • What are sulfonamides and how do they work?
  • Prescribing co-trimoxazole
  • Adverse effects of co-trimoxazole
  • Medicine interactions with co-trimoxazole
  • References

In this article

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Advisable use of sulfonamide antibiotics

What are sulfonamides and how do they work?

Sulfonamides are a grouping of synthetic medicines that contain the sulfonamide chemic group. As well as antibiotics,* this group includes thiazide diuretics, furosemide, acetazolamide, sulfonylureas and some COX-2 inhibitors.

By definition sulfonamides are antimicrobials rather than antibiotics, i.east. an antibiotic is a substance produced by leaner or fungi which have antimicrobial activity, whereas sulfonamides are synthetic.

The only antibody medicine containing a sulfonamide routinely available, and subsidised, in New Zealand is sulfamethoxazole with trimethoprim (co-trimoxazole). Sulfadiazine (unsubsidised, Department 29 medicine) is occasionally used in a hospital setting.

Sulfonamide antibiotics work by interfering with folic acrid synthesis in susceptible organisms, due to their structural similarity to para-aminobenzoic acid (PABA) in bacterial cells. Folic acrid is essential for nucleic acrid synthesis. When used lonely, sulfonamide antibiotics are bacteriostatic to susceptible organisms. Withal, sulfamethoxazole in combination with trimethoprim (co-trimoxazole), which acts at a unlike enzyme in the pathway of folic acid synthesis, is idea to be synergistic and may be bactericidal in certain cellular conditions.

Which infections should sulfonamide antibiotics be used for?

In that location are limited uses for sulfonamide antibiotics due to increasing bacterial resistance, potential for adverse furnishings and the availability of more active antibiotics.ane In most cases, they are used in primary care only when first-line recommended antibiotics take been ineffective or are contraindicated.

Start-line indications for sulfonamide antibiotics

Co-trimoxazole is normally used in general practise, merely in about circumstances, information technology is indicated as a showtime-line antibody in hospital settings only, such equally for the handling of pneumocystis pneumonia and nocardiosis (rare bacterial infection affecting lungs, brain or peel) in immunocompromised people. Toxoplasmosis is commonly treated with a combination of sulfadiazine and pyrimethamine (both unapproved Section 29 medicines), as well in a specialist setting.

A first-line indication where co-trimoxazole may be considered in a primary care setting would be for the treatment of mild, lower urinary tract infection in a kid. However, it is the trimethoprim component, rather than sulfamethoxazole, which is important. Trimethoprim is only bachelor in tablets of 300 mg, therefore unsuitable for use in children. As co-trimoxazole is available in a liquid formulation, and contains trimethoprim, this is an advisable choice.

For farther information see: Managing urinary tract infections in children , BPJ 44 (May, 2012).

Second-line indications for sulfonamide antibiotics

Co-trimoxazole is not recommended outset-line for the majority of patients in primary care with infections. Yet, it tin be considered when first-line choices have been ineffective, are contraindicated, or antibiotic sensitivities indicate that co-trimoxazole is the appropriate choice. Antibiotics are not always indicated in the first instance for some of these infections, due east.1000. otitis media, sinusitis, salmonellosis, and other 2nd-line antibiotics may be preferable to co-trimoxazole (Table i).

N.B. Second-line antibiotics commonly have less predictable susceptibility against the likely pathogens causing a clinical syndrome, due east.yard. Streptococcus pneumoniae susceptibility to co-trimoxazole is unpredictable; in 2011 resistance was 29% across New Zealand.4

Table 1: Second-line indications for the use of co-trimoxazole

Infection First-line antibiotic Other second-line antibiotics Notes for using co-trimoxazole
Acute exacerbations of chronic bronchitis Amoxicillin Doxycycline Only if evidence of sensitivity to co-trimoxazole
Pneumonia in adults Amoxicillin Erythromycin, roxithromycin, doxycycline Can be used every bit monotherapy if a history of penicillin allergy
Otitis media in children Amoxicillin Cefaclor, erythromycin Only if antibiotics are required
Sinusitis Amoxicillin Doxycycline, cefaclor Only if bacterial infection suspected
Cellulitis Flucloxacillin Erythromycin, roxithromycin, cefaclor If a history of penicillin allergy
Diabetic pes complications Amoxicillin + clavulanic acrid Cefaclor Utilize with metronidazole to cover polymicrobial infection
Salmonellosis Ciprofloxacin - Antibiotic treatment unremarkably unnecessary, treat only if severe symptoms
Acute pyelonephritis Ciprofloxacin Amoxicillin + clavulanic acid Refer to hospital if moderate to astringent symptoms

Prescribing co-trimoxazole

Co-trimoxazole (trimethoprim and sulfamethoxazole in fixed ratio 1:5) is available every bit:

  • Tablets - 80/400 mg (trimethoprim lxxx mg + sulfamethoxazole 400 mg)
  • Oral liquid - 40/200 mg/5 mL (trimethoprim twoscore mg + sulfamethoxazole 200 mg in five mL)
  • Injection (non subsidised) - 80/400 mg/5 mL (trimethoprim 80 mg + sulfamethoxazole 400 mg in 5 mL)

For treatment of an infection the following doses are suitable:i

  • Child aged six weeks - v months - 20/100 mg (ii.5 mL), twice daily
  • Child aged 6 months - five years - 40/200 mg (five mL), twice daily
  • Kid aged half dozen - 12 years - lxxx/400 mg (ten mL or one tablet), twice daily
  • Child aged over 12 years and adults and -160/800 mg (two tablets), twice daily

Alternatively, the co-trimoxazole dose for children can be calculated by body weight:five

  • Child aged 6 weeks - 12 years - 0.5 mL/kg oral liquid, twice daily

Co-trimoxazole should be avoided in infants aged under six weeks, due to the risk of hyperbilirubinaemia.

Co-trimoxazole is contraindicated in people with a previous hypersensitivity reaction or severe hepatic harm. Severe renal harm, bone marrow depression and agranulocytosis are also contraindications to utilise of co-trimoxazole, unless these can be closely monitored for and the clinical need outweighs the risk.

If co-trimoxazole is existence taken long-term, a full blood count is recommended monthly, peculiarly in patients who are poorly nourished or who may exist folate scarce.6

Co-trimoxazole for MRSA

The charge per unit of methicillin-resistant Staphylococcus aureus (MRSA) is increasing in New Zealand, and at to the lowest degree one-half of the cases are now thought to exist customs acquired.

At that place is show that co-trimoxazole is constructive against MRSA, although further clinical trials are needed.ii

Patients with a not-healing wound or an infected surgical wound that is not responding to kickoff-line antibiotics should have a wound swab taken to check for the presence of MRSA and to guide antibiotic pick. Depending on susceptibility, appropriate treatments in the community include co-trimoxazole, clindamycin (requires specialist endorsement) and tetrayclines.

Silver sulfadiazine for burns: no longer recommended

In the by, topical silver sulfadiazine one% foam was a common treatment for superficial and mid-dermal burns treated in primary care. It is still an effective treatment, withal, newer occlusive dressings are associated with faster healing, decreased hurting, fewer dressing changes and improved patient satisfaction.iii

Double-check and prescribe conspicuously: is it mg of trimethoprim, or mg of co-trimoxazole?

Dosing recommendations of co-trimoxazole vary, especially in paediatric references, with some using milligrams of the trimethoprim component alone and other using milligrams of both components combined. Administration errors tin can hands occur, and most often effect in significant nether-dosing of co-trimoxazole.

Adverse effects of co-trimoxazole

Adverse furnishings with sulfonamide antibiotics are relatively common, occurring in approximately 3% of people taking a course of treatment.vii Nausea, airsickness, anorexia, diarrhoea and hyperkalaemia are the nearly commonly reported agin furnishings, but co-trimoxazole is also rarely associated with serious hypersensitivity reactions and blood dyscrasias (bone marrow depression and agranulocytosis) especially in elderly people.one

Hypersensitivity reactions

Information technology is estimated that 0.09% of people experience a hypersensitivity reaction after taking a sulfonamide antibiotic, although the frequency is much college among people with HIV and AIDS.eight Reactions include; anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, serum sickness-like syndrome, lupus-similar syndrome, multi-organ hypersensitivity syndrome, pneumonitis, hepatitis, interstitial nephritis, systemic vasculitis and pancytopaenia.nine

Patients with a hypersensitivity reaction may present with fever, painful macropapular rash, lesions in mucous membranes, cough, sore throat or difficulty animate. A "hypersensitivity" syndrome characterised past hypotension, fever, rash and pulmonary infiltrates has too been associated with sulfonamides.8 Hypersensitivity symptoms usually develop inside 1 to iii weeks after starting handling, and resolve within i to 2 weeks afterward ceasing treatment.8,x

Anaphylaxis typically occurs inside thirty minutes of the offset dose, but is more mutual with parenteral administration.8 Urticaria or isolated angioedema tin occur within minutes to days after the first dose.8

Hypersensitivity reactions to sulfonamide antibiotics are not completely understood merely are thought to be related to the drugs' sulphur moiety (the sulphur part of the drug molecule) and the presence of an arylamine group.8 At that place is no well-validated diagnostic exam for sulfonamide sensitivity. If a hypersensitivity reaction occurs, sulfonamide antibiotics should be avoided, unless the benefit outweighs the adventure. A history of Stevens-Johnson syndrome, toxic epidermal necrolysis or anaphylaxis would be a contraindication to using a sulfonamide antibiotic.8

Chance of cross-reactivity with other sulfonamides is low

Other sulfonamide medicines, such as thiazide diuretics, do non incorporate the arylamine grouping and are less likely to cause severe hypersensitivity reactions.eight Cantankerous-reactivity betwixt sulfonamide antibiotics and other sulfonamide medicines is too unlikely.7

Despite this low take chances, many practitioners have a cautious approach, and avoid prescribing all sulphur-containing medicines in a patient who has had a reaction subsequently taking a sulfonamide antibiotic. In that location are a express number of case reports which support this advice. Nevertheless, a big cohort study constitute that allergy to a sulfonamide antibiotic was a chance factor for allergy to medicines in general, rather than cross-reactivity to other sulfonamides. The authors concluded that patients with a history of allergic reaction subsequently taking sulfonamides (or penicillins) should exist considered at increased risk for allergy to any medicine.11

Applied advice would be to avoid prescribing other sulfonamide medicines (and sulphur-containing products) in patients with serious allergic reactions to sulfonamide antibiotics. Sulfonamide medicines could be prescribed in patients with only balmy reactions if there was no other culling, and the patient was monitored for signs of an adverse reaction.seven

Older people are more at chance of agin effects

Older people are generally more susceptible to adverse reactions when taking any medicine, and these effects are more probable to have serious consequences. This is compounded by multiple medicine use and the presence of dumb renal or hepatic function.

Although a rare agin effect, at that place appears to be an increased take a chance of thrombocytopenia (with or without purpura) in older people who are prescribed co-trimoxazole and who are currently taking a diuretic such as a thiazide.six

Avoid co-trimoxazole in early and late pregnancy

Co-trimoxazole is a folate antagonist. Although its inhibitory effect is more selective for leaner, co-trimoxazole should be avoided in women who are in the first trimester of pregnancy (equally folate is essential during this menstruum). Co-trimoxazole should besides be avoided in women later 32 weeks gestation, as it is associated with an increased risk of neonatal haemolysis and methaemoglobinaemia.i

Co-trimoxazole may exist used in women who are breast feeding, but just if the infant is aged ane month or older.1

Medicine interactions with co-trimoxazole

Several clinically of import medicine interactions tin can occur with co-trimoxazole (Table two), which are more than significant in elderly people and those taking multiple medicines.

Tabular array two: Known drug interactions involving co-trimoxazole1,12

Drug Mechanism of interaction Complexity Management
Warfarin CYP450 2C9 inhibition Increased INR and bleeding Monitor INR a few days later starting co-trimoxazole, and once again later stopping
Sulfonylureas e.g. gliclazide, glipizide CYP450 2C9 inhibition, CYP450 2C8 inhibition, and a direct outcome on pancreatic jail cell release of insulin Hypoglycaemia, which will take longer to resolve in renally impaired people Consider reducing dose of gliclazide or glipizide when starting co-trimoxazole if creatinine clearance is less than 30 mL/min; increase blood glucose monitoring
Methotrexate Organic anion transporter inhibition in the renal tubule, anti-folate effect Methotrexate toxicity (cytopenia, hepatotoxicity, mucositis) Monitor total claret count; may need to reduce dose of methotrexate (with specialist advice)
ACE inhibitors, ARBs, Spironolactone Trimethoprim-induced antikaliuretic effect due to chemical structure similarities Hyperkalaemia Monitor potassium levels a few days after starting co-trimoxazole if person is elderly, or has impaired renal role; review any potassium supplementation
Phenytoin CYP450 2C9 and 2C8 inhibition (too metabolized by 2C19) Phenytoin toxicity Monitor for clinical signs of phenytoin toxicity; fever, rash, bradycardia, gingival hyperplasia, neurological effects, and monitor FBC, LFT, electrolytes
Clozapine Condiment effect of bone marrow supression Blood dyscrasias and potentially fatal agranulocytosis Increased frequency of monitoring white cell count

For farther information virtually drug interactions, see Stockley's alerts, accessed from the New Zealand Formulary: www.nzf.org.nz

References

  1. New Zealand Formulary (NZF). NZF v6. NZF; 2012. Available from: www.nzf.org.nz (Accessed Dec, 2012).
  2. Goldberg Due east, Bishara J. Contemporary unconventional clinical use of co-trimoxazole. Clin Microbiol Infect 2012;18:8-17.
  3. Lloyd E, Rodgers B, Michener M, Williams Chiliad. Outpatient burns: prevention and care. Am Fam Physician 2012;85(one):25-32.
  4. Environmental Science and Enquiry (ESR). Antibiotic resistance data from hospital and community laboratories, 2011. ESR: Wellington; 2012.
  5. BMJ Group. British National Formulary for Children. The Royal Pharmaceutical Society of Great Britain and RCPCH Publications Ltd; 2012.
  6. Mylan New Zealand Ltd. Trisul Medicine Datasheet. Medsafe; 2011. Available from: www.medsafe.govt.nz (Accessed Nov, 2012).
  7. Sweetman S, editor. The consummate drug reference. London: Pharmaceutical Press, 2011.
  8. Slatore CG, Tilles SA. Sulfonamide hypersensitivity. Immunol Allergy Clin N Am 2004;24(3):477-490.
  9. Adelaide: Australian Medicines Handbook Pty Ltd, 2011. Australian medicines handbook.
  10. Cairns B, Rich G. Fever, rash and peeling peel. J Fam Pract 2011;60(11):ix-12.
  11. Strom B, Schinnar R, Apter A, et al. Absence of cantankerous-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Eng J Med 2003;349(17):1628-35.
  12. Ho J, Juurlink D. Considerations when prescribing trimethoprim-sulfamethoxazole. CMAJ 2011;183(16):1851-8.