trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS, Cotrim, cotrimoxazole, Sulfatrim)

Dosing and uses of Bactrim, Bactrim DS (trimethoprim/sulfamethoxazole)

• Adult
• Pediatric

 

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