trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS, Cotrim, cotrimoxazole, Sulfatrim)
Classes: Sulfonamides; Antibiotics, Combos
Dosing and uses of Bactrim, Bactrim DS (trimethoprim/sulfamethoxazole)
Adult dosage forms and strengths
trimethoprim/sulfamethoxazole
injected solution
- (16mg/80mg)/mL
oral suspension
- (40mg/200mg)/5mL
tablet
- 80mg/400mg
- 160mg/800mg
Dosing Guidelines for Infections
1-2 DS tablets PO q12-24hr
8-20 mg TMP/kg/day IV q6-12hr
Chronic Bronchitis
Acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae
DS tablet: 1 PO q12h for 10-14 days
Meningitis, Bacterial
10-20 mg TMP/kg/day IV divided q6-12hr
Pneumocystis (Carinii) Jiroveci Pneumonia
Documented Pneumocystis jiroveci pneumonia (PCP); also, prophylaxis against PCP in individuals who are immunosuppressed
Prophylaxis
- Tablet: 80-160 mg TMP PO qDay or 160 mg TMP 3 times/week on consecutive or alternate days
Treatment
- 15-20 mg TMP/kg/day PO/IV divided q6-8hr
Sepsis
20 mg TMP/kg/day IV divided q6hr
Shigellosis
Enteritis caused by susceptible strains of Shigella flexneri and S sonnei
DS tablet: 1 tab PO q12hr for 5 days
Alternatively, 8-10 mg TMP/kg/day IV divided q6-12hr for up to 5 days
Traveler's Diarrhea
Traveler's diarrhea due to susceptible strains of enterotoxigenic Escherichia coli
DS tablet: 1 tab PO q12hr for 5 days
Urinary Tract Infections
UTIs caused by susceptible strains of Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis, and Proteus vulgaris
Pyelonephritis: 1 DS tab or 2 regular-strength tabs PO q12hr x 14 days
Prostatitis: 1 DS tab or 2 regular-strength tabs PO q12hr x 14 days or 2-3 months if chronic infection
A 3 to 5 day course may be used for acute, uncomplicated cystitis
Prophylaxis (off-label): Various regimens exist; may use regular-strength tablet once/twice per week
Acne Vulgaris (Off-label)
1 DS tab or 1 regular-strength tab PO qDay or q12hr for up to 18 weeks
Community Acquired Pneumonia (Off-label)
1 DS tab PO q12hr for 10-14 days
Dosing Considerations
Susceptible organisms
- Acinetobacter baumannii, Actinobacillus actinomycetemcomitans, Aeromonas hydrophila, Alcaligenes xylosoxidans, Bartonella henselae, Bordetella pertussis, Brucella spp, Burkholderia pseudomallei, Burkholderia cepacia, Chryseobacterium meningosepticum, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus aphrophilus, Haemophilus influenzae, Hafnia alvei, Kingella spp, Klebsiella pneumoniae, Klebsiella granulomatis, Legionella spp, Listeria monocytogenes, Moraxella catarrhalis, Morganella morganii, MRSA, MSSA, Nocardia asteroides, Plesiomonas shigelloides, Pneumocystis jiroveci (PCP), Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Salmonella typhi, Serratia spp, Shigella spp, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus pneumoniae, Tropheryma whippelii, Vibrio cholerae, Yersinia enterocolitica, Yersinia pseudotuberculosis, various Mycobacteria
Dosing Modifications
Renal impairment
- CrCl >30 mL/min: Dose adjustment not necessary
- CrCl 15-30 mL/min: Decrease dose by 50%
- CrCl <15 mL/min: Do not use
Pediatric dosage forms and strengths
trimethoprim/sulfamethoxazole
injected solution
- (16mg/80mg)/mL
oral solution
- (40mg/200mg)/5mL
tablet
- 80mg/400mg
- 160mg/800mg
Mild to Moderate Infections
<2 months: Contraindicated
>2 months
- 8 mg TMP/kg/day PO divided q12hr
Serious Infections
<2 months: Contraindicated
>2 months
- 15-20 mg TMP/kg qDay PO divided q6hr
- 8-12 mg TMP/kg/day IV divided q6-12hr
Acute Otitis Media
Acute otitis media in pediatric patients due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae
<2 months: Contraindicated
>2 months: 6-10 mg TMP/kg/day PO divided q12hr for 10 days
Pneumocystis (Carinii) Jiroveci Pneumonia
<2 months: Contraindicated
>2 months
- Treatment: 15-20 mg TMP/kg/day PO/IV divided q6-8hr for 21 days
- Prophylaxis: 150 mg TMP/m²/day PO divided q12 hr for 3 days/week on consecutive or alternate days
Shigellosis
<2 months: Contraindicated
>2 months
- 8 mg TMP/kg/day PO divided q12hr for 5 days
- 8-10 mg TMP/kg/day IV divided q6-12hr for 5 days
Urinary Tract Infection
<2 months: Contraindicated
>2 months
- 8 mg TMP/kg/day PO divided q12hr for 7-14 days if serious infection
- 8-10 mg TMP/kg/day IV divided q6-12hr for 14 days if serious infection
- Prophylaxis: 2 mg TMP/kg/dose PO qDay or 5 mg TMP/kg/dose twice daily
Skin/soft Tissue Infection Due to Community Acquired MRSA (Off-label)
8-12 mg TMP/kg/dose PO q12hr for 5-10 days; add beta-lactam antibiotic to regimen if beta-hemolytic Streptococcuts spp also suspected
Bactrim, Bactrim DS (trimethoprim/sulfamethoxazole) adverse (side) effects
Frequency not defined
Anorexia
Nausea
Vomiting
Vertigo
Seizure
Peripheral neuritis
Erythema multiforme
Hyperkalemia
Rash
Urticaria
Immune hypersensitivity reaction
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Agranulocytosis
Aplastic anemia
Hyponatremia
Disorder of hematopoietic structure
Fulminant hepatic necrosis
Postmarketing Reports
Thrombotic thrombocytopenia purpura
Idiopathic thrombocytopenic purpura
QT prolongation resulting in ventricular tachycardia and torsade de pointes
Warnings
Contraindications
Known hypersensitivity
Age <2 months
CrCl <15 mL/min when renal function status cannot be monitored
Documented megaloblastic or folate deficiency anemia
Significan hepatic impairment
Contraindicated in pregnant patients at term and in nursing mothers, because sulfonamides, which pass the placenta and are excreted in the milk, may cause kernicterus
History of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides
Cautions
Not for use in areas with resistance rates >10%
Trimethoprim decreases urinary potassium excretion; may cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia
Severe and symptomatic hyponatremia reported with high dose trimethoprim
Rare fatalities reported with sulfonamides due to Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias
Caution when used in elderly individuals; risk of bone marrow suppression
PCP prophylaxis with AIDS: Rash, fever, leukopenia, and elevated transaminase values reported; hyperkalemia and hyponatremia also appear to be increased
Severe cases (including fatalities) of immune-mediated thrombocytopenia reported
Sulfonamides should not be used to treat group A beta-hemolytic streptococcal infections; they will not eradicate streptococcus or prevent rheumatic fever
Clostridium difficile-associated diarrhea reported
Coadministration with leucovorin for the treatment of HIV-positive patients with PCP resulted in treatment failure and excess mortality in a randomized, placebo-controlled trial; avoid coadministration
Development of drug-resistant bacteria may occur when prescribed in absence of strongly suspected bacterial infection or prophylactic indication
Prolonged use may result in fungal or bacterial superinfection
Caution with impaired renal or hepatic function, patients with possible folate deficiency (eg, the elderly, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome, and patients in malnutrition states), and patients with severe allergies or bronchial asthma
Hemolysis may occur if administered to patients with G6PD deficiency
Hypoglycemia (rare) reported in nondiabetic patients; patients with renal dysfunction, liver disease, or malnutrition or those receiving high doses at particular risk
Trimethoprim may impair phenylalanine metabolism
Caution with porphyria or thyroid dysfunction
Pregnancy and lactation
Pregnancy category: D; avoid near term due to risk of kernicterus in the newborn (see Contraindications)
Some epidemiologic studies suggest that exposure to sulfamethoxazole/trimethoprim during pregnancy may be associated with an increased risk of congenital malformations, particularly neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, and club foot
Lactation: Excreted in breast milk; use caution; contraindicated by some sources (AAP Committee states compatible with nursing)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Bactrim, Bactrim DS (trimethoprim/sulfamethoxazole)
Mechanism of action
Blocks 2 consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria
Trimethoprim: Inhibits dihydrofolate reductase, thereby blocking production of tetrahydrofolic acid from dihydrofolic acid
Sulfamethoxazole: Inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid
Absorption
Time to peak: 1-4 hours
Distribution
Protein bound: TMP (44%); SMX (70%)
Metabolism
Hepatic
Enzymes inhibited: Hepatic CYP2C9
Elimination
Half-life: TMP (8-10 hr); SMX (10 hr)
Excretion: Urine (as unchanged drug)
Administration
IV Incompatibilities
Additive: Fluconazole, linezolid, verapamiL
Y-site: Cisatracurium (incompatible at 2 mg/mL cisatra; may be compatible at much lower concs), fluconazole, foscarnet (may be compatible at very low TMP/SMX concs), midazolam, vinorelbine
IV Preparation
Do not use NS as diluent
Injection vehicle contains benzyl alcohol and sodium metabisulfite
Stability of parenteral admixture at room temperature (25°C)
- 5 mL/125 mL D5W: 6 hr
- 5 mL/100 mL D5W: 4 hr
- 5 mL/75 mL D5W: 2 hr
IV Administration
Infuse over 60-90 min; give q6hr, 8hr, or 12hr
Must be diluted welL
May be given less diluted in a central line
Not for Im
Maintain adequate fluid intake to prevent crystalluria
Storage
Do not refrigerate injection
Less soluble in more alkaline pH
Protect from light