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Antimicrobials

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Co-trimoxazole (Trimethoprim + Sulfamethoxazole)

Guidelines for use

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1. Spectrum of Activity

Active against:

  • Gram-positive bacteria (including some strains of MRSA) – however, activity is variable (consider C&S prior to treating streptococcal or staphylococcal infections)
  • Gram-negative aerobic bacteria (including enterotoxigenic E. coli)
  • Many strains of Burkholderia cepacia, Stenotrophomonas maltophilia, Nocardia species
  • Listeria monocytogenes
  • Pneumocystis jiroveci (carinii)
  • Toxoplasma gondii
  • Isospora and Cyclospora species

Not active against:

  • Enterococcus spp.
  • Oral anaerobes
  • Campylobacter
  • Pseudomonas aeruginosa
  • Bacteroides fragilis
  • Mycobacterium tuberculosis

2. Clinical Use

Appropriate Uses:

  • Prevention and treatment of Pneumocystis jiroveci (carinii) pneumonia (PCP)
  • Prevention of infection caused by Toxoplasma gondii
  • Treatment of infections caused by unusual pathogens not susceptible to other agents (see above)

Inappropriate Uses:

  • Treatment of infections for which other more effective and reliable agents are available

3. Precautions

  • A hypersensitivity reaction to co-trimoxazole is likely in patients with a history of allergy to other sulfonamide antibiotics. Drug desensitization should be considered when use of co-trimoxazole is deemed essential (contact Pharmacy for protocol).
  • Hemolysis may occur in patients with G6PD deficiency
  • Caution in patients at high risk of folate deficiency (monitor CBC)
  • Co-trimoxazole can inhibit the hepatic metabolism of other drugs via the CYP 450 enzyme system; screen for drug interactions.
  • Pregnancy:
    •  Case control studies suggest an association with neural tube defects (NTDs), cardiovascular malformations and facial clefting as a result of antifolate effect.
    • During 1st trimester, use of an alternate agent would be preferable where feasible.
    • If use during the 1st trimester cannot be avoided, high dose folic acid (4 – 5 mg/day) should be given to minimize the risk of NTDs.
    • Sulfamethoxazole should be avoided near term due to potential toxicity to the newborn (hemolytic anemia and kernicterus).
  • Breastfeeding:
    • Trimethoprim is present at low levels in breast milk and is not expected to cause adverse effects in healthy, full term infants.
    • Sulfamethoxazole use during breastfeeding is not expected to cause adverse effects in healthy, full term infants.
    • Sulfamethoxazole should be used with caution while breastfeeding premature infants or neonates with hyperbilirubinemia.
    • Sulfamethoxazole should be avoided while breastfeeding an infant with G6PD deficiency.
    • Monitor nursing infant for GI symptoms

4. Adverse Effects

  • Nausea, anorexia, vomiting, diarrhea
  • Trimethoprim inhibits renal tubular secretion of potassium and creatinine
    • Hyperkalemia is dose-related; monitor serum K; higher risk patients with renal insufficiency and those taking potassium-sparing diuretics.
    • Hyponatremia is not as common as hyperkalemia, risk factors may be similar to those of hyperkalemia; monitor serum Na.
    • Serum creatinine elevation is clinically insignificant (no reduction in GFR)
  • Hypoglycemia may occur, especially in patients taking a sulfonylurea (e.g., glyburide)
  • Dermatologic reactions include rash, urticaria, and photosensitivity. Rarely, severe or fatal reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis may occur.
  • Hypersensitivity reactions (fever, rash) are more common in HIV-positive patients.
  • Rarely: blood dyscrasias, aseptic meningitis, fulminant hepatic failure

5. Dosage

Content of trimethoprim & sulfamethoxazole in various dosage forms Tablet Oral suspension Injection

Trimethoprim 80 mg
+
Sulfamethoxazole 400 mg

 1 single strength (SS) 10 mL 5 mL vial (dilute each 4 mL in D5W 50 mL)

Bacterial Infections

  • Urinary tract infections (cystitis, pyelonephritis):
    • Oral Dosage: 2 tablets (or 1 DS tablet) PO BID
    • IV Dosage: 10 mL IV q12h

  • All other sites of infection:
    • 10 mg/kg per day of TMP component given in 3 to 4 divided doses. For specific dosage, refer to the appropriate weight-based dosing table (10 mg/kg) below.

Pneumocystis jiroveci (carinii) Pneumonia (PCP)

  • Prophylaxis: 1 SS tablet PO once daily or 1 DS tablet PO qMWF (3 times per week)
  • Treatment: 15 or 20 mg/kg per day of TMP component given in 3 or 4 divided doses. For specific dosage, refer to the appropriate weight-based dosing table (15 mg/kg or 20 mg/kg) below.

Dosage in renal insufficiency

Creatinine Clearance (mL/min) Bacterial Infection PCP Infection
10 – 29

75% of usual dose:
7.5 mg/kg/day TMP* given in 3 or 4 divided doses q8h or q6h

75% of usual dose:
12 or 15 mg/kg/day TMP* given in 3 or 4 divided doses q8h or q6h
< 10 (ESRD; PD)

Not recommended in ESRD

If used: 50% of usual dose:
5 mg/kg/day TMP* given in 3 or 4 divided doses q8h or q6h

PD: Schedule one of the day’s doses post-PD.

Not recommended in ESRD

If used: 50% of usual dose:
7.5 or 10 mg/kg/day TMP* given in 3 or 4 divided doses q8h or q6h

PD: Schedule one of the day’s doses post-PD.
Hemodialysis (HD)

50% of usual dose:
5 mg/kg/day TMP* given in 3 or 4 divided doses q8h or q6h

On dialysis days, give one of the day’s doses towards the end of HD

50% of usual dose:
7.5 or 10 mg/kg/day TMP* given in 3 or 4 divided doses q8h or q6h

On dialysis days, give one of the day’s doses towards the end of HD
Continuous Renal Replacement Therapy (CRRT) 7.5 mg/kg/day TMP* 15 mg/kg/day TMP*

*For specific dosage, refer to the appropriate weight-based dosing table below.

Weight-based dosing tables for IV and oral therapy

5 mg/kg TMP per day

Body weight (kg) IV Dosage PO Dosage TMP Dose per day (mg)
40 – 54 5 mL q8h 1 SS tab q8h 240
55 – 79 5 mL q6h 1 SS tab q6h 320
80 – 109 10 mL q8h 2 SS tabs q8h 480
110 – 129 10 mL q6h 2 SS tabs q6h 640

7.5 mg/kg TMP per day

Body weight (kg) IV Dosage PO Dosage TMP Dose per day (mg)
40 – 49 5 mL q6h 1 SS tab q6h 320
50 – 69 10 mL q8h 2 SS tabs q8h 480
70 – 89 10 mL q6h 2 SS tabs q6h 640
90 – 109 15 mL q8h 3 SS tabs q8h 720
110 – 129 15 mL q6h 3 SS tabs q6h 960

10 mg/kg TMP per day

Body weight (kg) IV Dosage PO Dosage TMP Dose per day (mg)
40 – 49 10 mL q8h 2 SS tabs q8h 480
50 – 64 10 mL q6h 2 SS tabs q6h 640
65 – 74 15 mL q8h 3 SS tabs q8h 720
75 – 99 15 mL q6h 3 SS tabs q6h 960
100 – 129 20 mL q6h 4 SS tabs q6h 1280

12 mg/kg TMP per day

Body weight (kg) IV Dosage PO Dosage TMP Dose per day (mg)
40 – 49 10 mL q8h 2 SS tabs q8h 480
50 – 59 10 mL q6h 2 SS tabs q6h 640
60 – 69 15 mL q8h 3 SS tabs q8h 720
70 – 94 15 mL q6h 3 SS tabs q6h 960
95 – 114 20 mL q6h 4 SS tabs q6h 1280
115 – 129 30 mL q8h 6 SS tabs q8h 1440

15 mg/kg TMP per day

Body weight (kg) IV Dosage PO Dosage TMP Dose per day (mg)
40 – 44 10 mL q6h 2 SS tabs q6h 640
45 – 49 15 mL q8h 3 SS tabs q8h 720
50 – 69 15 mL q6h 3 SS tabs q6h 960
70 – 79 25 mL q8h 5 SS tabs q8h 1200
80 – 89 20 mL q6h 4 SS tabs q6h 1280
90 – 99 30 mL q8h 6 SS tabs q8h 1440
100 – 109 25 mL q6h 5 SS tabs q6h 1600
110 – 119 35 mL q8h 7 SS tabs q8h 1680
120 – 129 30 mL q6h 6 SS tabs q6h 1920

20 mg/kg TMP per day

Body weight (kg) IV Dosage PO Dosage TMP Dose per day (mg)
40 – 54 15 mL q6h 3 SS tabs q6h 960
55 – 69 20 mL q6h 4 SS tabs q6h 1280
70 – 79 30 mL q8h 6 SS tabs q8h 1440
80 – 89 25 mL q6h 5 SS tabs q6h 1600
90 – 104 30 mL q6h 6 SS tabs q6h 1920
105 – 119 35 mL q6h 7 SS tabs q8h 2240
120 – 134 40 mL q6h 8 SS tabs q6h 2560

6. Intravenous Administration

For preparation/administration, see IV drug monograph

Last updated: March 10, 2023