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.

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*

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

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

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

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

Antimicrobials

Co-trimoxazole (Trimethoprim + Sulfamethoxazole)

Guidelines for use

1. Spectrum of Activity

2. Clinical Use

3. Precautions

4. Adverse Effects

5. Dosage

Bacterial Infections

Pneumocystis jiroveci (carinii) Pneumonia (PCP)

Dosage in renal insufficiency

Weight-based dosing tables for IV and oral therapy

5 mg/kg TMP per day

7.5 mg/kg TMP per day

10 mg/kg TMP per day

12 mg/kg TMP per day

15 mg/kg TMP per day

20 mg/kg TMP per day

6. Intravenous Administration

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