What is the appropriate dose of Bactrim orally for purulent cellulitis? Should a different dose be used based on patient weight or BSA?

What is the appropriate dose of Bactrim orally for purulent cellulitis? Should a different dose be used based on patient weight or BSA?

Comment by InpharmD Researcher

Clinical guidelines recommend an oral Bactrim dose of 1 to 2 double-strength tablets twice daily for adults with purulent cellulitis. However, the recommended oral dose in pediatric patients is based on patient weight (4-6 mg/kg/dose of trimethoprim and 20-30 mg/kg/dose of sulfamethoxazole every 12 hours). Data to support dosing based on body surface area for purulent cellulitis was not identified. Of note, one randomized, controlled trial used dosing tiers for Bactrim in adults based on weight (see Table 2).

Background

According to the Infectious Diseases Society of America (IDSA) guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections, the recommended oral dose of trimethoprim-sulfamethoxazole (TMP-SMX) for purulent cellulitis is 1 to 2 double-strength tablets twice daily in adults. In pediatric patients with purulent cellulitis, the recommended oral TMP-SMX dose is 4-6 mg/kg/dose TMP and 20-30 mg/kg/dose SMX every 12 hours. Similarly, IDSA guidelines for the management of skin and soft tissue infections recommend 1 to 2 double-strength tablets twice daily in adults, or 8-12 mg/kg (based on the trimethoprim component) in 2 divided oral doses. [1], [2]

In patients with purulent cellulitis, the recommended dose of trimethoprim-sulfamethoxazole to cover for MRSA is 800 mg/160 mg twice daily for 5 days in addition to cephalexin 500 mg every 6 hours. Different dosing regimens based on patient weight or body surface area are not provided. [3]

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

What is the appropriate dose of Bactrim orally for purulent cellulitis? Should a different dose be used based on patient weight or BSA?

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Tables 1-3 for your response.

Dose of Trimethoprim-Sulfamethoxazole To Treat Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus
Design	Prospective observational cohort with nested case-control study N= 291
Objective	To investigate whether treatment with a higher dose of trimethoprim-sulfamethoxazole (TMP/SMX) led to greater clinical resolution in patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA)
Study Groups	High dose TMP/SMX (n= 121) Standard dose TMP/SMX (n= 170)
Inclusion Criteria	Presence of signs and symptoms of skin and soft tissue infection, age ≥18 years, and occurrence of the episode of SSTI for the first time during the study period
Exclusion Criteria	Recurrent episodes of MRSA SSTIs during the study period, occurrence of folliculitis only, or presence of complicated infection involving deep tissues
Methods	Patients with MRSA SSTIs were treated with either a high dose of TMP/SMX (320 mg/1,600 mg twice daily) or a standard dose (160 mg/800 mg twice daily) for 7 to 15 days. Clinical characteristics and outcomes were compared between the two groups. MRSA identification was done using MRSA CHROMagar medium, and susceptibility was tested by the disk diffusion method
Duration	May 2008 to September 2008
Outcome Measures	Primary: Clinical resolution of infection Secondary: Not specified
Baseline Characteristics		160/800 mg twice daily (n= 170)	320/1,600 mg twice daily (n= 121)	p-Value
	Age, years	38 (24–52)	40 (28–52)	0.433
	Female	51.2%	43.0%	0.19
	Body weight, kg	77 (44.5–156)	86 (42–141)	0.553
	Body mass index	28 (16.8–54)	30 (18–58.8)	0.454
	% of patients with: Diabetes mellitus HIV Injection drug use	18.8% 1.2% 7.1%	19.0% 4.1% 10.7%	0.968 0.13 0.269
	History of MRSA colonization or infection within previous 1 year	10.0%	9.9%	0.981
	SSSI characteristics Abscess Receipt of incision and drainage Hospitalization for SSSI management	79.4% 48.2% 5.3%	84.3% 63.6% 3.3%	0.291 0.009 0.568
	Abbreviations: HIV, human immunodeficiency virus; MRSA, methicillin-resistant Staphylococcus aureus; SSSI, skin and skin structure infections
Results		160/800 mg twice daily (n= 170)	320/1,600 mg twice daily (n= 121)	p-Value
Results	Clinical resolution	127 (74.7%)	88 (72.7%)	0.79
Adverse Events	None of the patients in either group had documented adverse events due to therapy with TMP/SMX.
Study Author Conclusions	Patients with MRSA SSTIs treated with a higher dose of TMP/SMX had similar clinical resolution rates as those treated with the standard dose. A higher dose may not be necessary for treating skin and soft tissue infections caused by MRSA.
Critique	The study's prospective design and focus on a specific patient population are strengths. However, limitations include the lack of randomization, potential clinician bias in dosing decisions, absence of pharmacokinetic and pharmacodynamic evaluations, and an imbalance in the rate of incision and drainage between groups. The study is also limited by its single-institution setting and reliance on medical record reviews, which may affect the generalizability of the findings.

References:

Cadena J, Nair S, Henao-Martinez AF, Jorgensen JH, Patterson JE, Sreeramoju PV. Dose of trimethoprim-sulfamethoxazole to treat skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2011;55(12):5430-5432. doi:10.1128/AAC.00706-11

Comparative Effectiveness of Cephalexin Plus Trimethoprim-Sulfamethoxazole Versus Cephalexin Alone for Treatment of Uncomplicated Cellulitis: A Randomized Controlled Trial
Design	Randomized, multicenter, double-blind, placebo-controlled trial N= 153
Objective	To test the hypothesis that antibiotics targeting community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are beneficial in the treatment of cellulitis
Study Groups	Trimethoprim-sulfamethoxazole (TMP/SMX; n= 73) Placebo (n= 73)
Inclusion Criteria	Must have cellulitis as defined by recent onset of soft tissue erythema or color change, considered bacterial in origin, with signs of infection; agreement from clinical attending physician for treatment with cephalexin; patient understanding and consent; commitment to follow-up appointments
Exclusion Criteria	Age <12 months or weight <15 kg, current skin infection already treated, allergy to sulfa drugs, severe allergic reaction to penicillin, current use of any antibiotic, diabetes mellitus, cellulitis complicated by peripheral vascular disease, renal insufficiency, hospital admission required, purulent discharge >1 cc, cellulitis involving indwelling catheter, immunocompromise, pregnancy, breastfeeding, facial cellulitis, cellulitis associated with marine or freshwater injury or animal/human bite, history of glucose-6-phosphate dehydrogenase deficiency, taking certain medications, known megaloblastic anemia due to folate deficiency
Methods	Participants received cephalexin and were randomized to receive either trimethoprim-sulfamethoxazole (TMP-SMX) or placebo. Antibiotics were provided for 14 days, with instructions to continue for at least 1 week and stop 3 days after feeling cured. Main outcome was treatment success at 2 weeks, confirmed at 1 month. The following dosing scheme was used for cephalexin and trimethoprim-sulfmethoxazole (based on mg trimethoprim): Children <30 kg 15-19 kg: cephalexin 300 mg 4 times daily; TMP-SMX 40/200 mg 4 times daily 20-24 kg: cephalexin 400 mg 4 times daily; TMP-SMX 60/300 mg 4 times daily 25-29 kg: cephalexin 500 mg 4 times daily; TMP-SMX 72/360 mg 4 times daily Adults and children ≥30 kg: <60 kg: cephalexin 500 mg 4 times daily; TMP-SMX 80/400 mg 4 times daily 60-80 kg: cephalexin 1,000 mg 3 times daily; TMP-SMX 160/800 mg 3 times daily >80 kg: cephalexin 1,000 mg 4 times daily; TMP-SMX 160/800 mg 4 times daily
Duration	June 2007 to December 2011
Outcome Measures	Primary: Risk difference for treatment success Secondary: Association of nasal MRSA colonization with treatment response
Baseline Characteristics		All Participants (N = 146)	Trimethoprim-Sulfamethoxazole (n= 73)	Placebo (n= 73)
	Age (median [range, interquartile range])	29 (3–74, 23–43)	31 (12–71, 25–47)	27 (3–74, 22–40)
	Race - White	88 (60)	44 (60)	44 (60)
	Race - Black	24 (16)	13 (18)	11 (15)
	Race - Asian	3 (2)	1 (1.4)	2 (2.7)
	Race - Other	1 (0.68)	0 (0)	1 (1.4)
	Hispanic	38 (26)	19 (26)	19 (26)
	Antibiotics in the past year	57 (39)	24 (33)	33 (45)
	Past history of skin infection	50 (34)	25 (34)	25 (34)
	Ever diagnosed with MRSA	3 (2.1)	2 (2.7)	1 (1.4)
	Physical contact with someone with MRSA	17 (12)	10 (14)	7 (9.7)
	Nasal MRSA colonization	7 (4.9)	4 (5.6)	3 (4.2)
	Infection Characteristics - Purulence	19 (13)	8 (11)	11 (15)
	Infection Characteristics - Warmth	136 (94)	69 (96)	67 (92)
	Infection Characteristics - Fever	19 (13)	9 (12)	10 (14)
	Infection Characteristics - Lymphangitis	16 (12)	8 (13)	8 (12)
	Infection Characteristics - Induration	65 (46)	33 (47)	32 (44)
	Infection Characteristics - Ulceration	18 (13)	11 (15)	7 (10)
	Infection Characteristics - Pain	138 (95)	69 (95)	69 (95)
	Infection Characteristics - Edema	106 (74)	58 (81)	48 (68)
	Varying Events - Received up to 24 h of intravenous therapy	40 (27)	18 (25)	22 (30)
Results		Trimethoprim-Sulfamethoxazole (n= 73)	Placebo (n= 73)	Risk Difference (95% CI)	p-value
	Cure (no failure by final follow-up at 30 d) (%)	62 (85)	60 (82)	2.7 (−9.3% to 15%)	.66
	Progression to abscess (%)	5 (6.8)	5 (6.8)	0 (−8.2% to 8.2%)	1.0
	Any adverse event (%)	36 (49)	39 (53)	−4.1 (−20% to 12%)	.62
	Diarrhea (%)	21 (29)	25 (34)	−5.5 (−21% to 10%)	.48
	Nausea (%)	15 (21)	13 (18)	2.7 (−10% to 16%)	.67
	Vomiting (%)	5 (6.9)	8 (11)	−4.1 (−13% to 5.1%)	.38
	Rash (%)	4 (5.5)	3 (4.1)	1.4 (−5.6% to 8.3%)	.70
	Pruritus (%)	5 (6.9)	3 (4.1)	2.7 (−4.6% to 10%)	.47
	Candidiasis (%)	1 (1.4)	3 (4.1)	−2.7 (−8.0% to 2.5%)	.31
	Clostridium difficile colitis (%)	0 (0)	1 (1.4)	−1.4 (−4.0% to 1.3%)	.32
	Other adverse events (%)	3 (4.1)	3 (4.1)	0 (−6.4% to 6.4%)	1.0
	CI, confidence interval
Adverse Events	Any adverse event: 49% in trimethoprim-sulfamethoxazole group vs 53% in placebo group. Common adverse events included diarrhea, nausea, vomiting, rash, pruritus, candidiasis, and Clostridium difficile colitis
Study Author Conclusions	The addition of trimethoprim-sulfamethoxazole to cephalexin did not improve outcomes in the treatment of cellulitis without abscess. This supports IDSA guidelines against targeting CA-MRSA for nonpurulent cellulitis
Critique	The study provides valuable experimental evidence supporting IDSA guidelines, but its limitations include the inability to make an etiologic diagnosis of cellulitis and its restriction to outpatient settings. The study's modest size and exclusion of certain patient populations, such as those with complicated skin infections, limit its generalizability.

References:

Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial. Clin Infect Dis. 2013;56(12):1754-1762. doi:10.1093/cid/cit122

Trimethoprim–Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess
Design	Multicenter, double-blind, randomized trial N= 1265
Objective	To determine whether trimethoprim–sulfamethoxazole (TMP-SMX) is superior to placebo in patients with a drained uncomplicated skin abscess
Study Groups	Trimethoprim–sulfamethoxazole (n= 630) Placebo group (n= 617)
Inclusion Criteria	Patients older than 12 years with a cutaneous lesion suspected to be an abscess, present for less than 1 week, measuring at least 2.0 cm in diameter, found to have purulent material, and intended for outpatient treatment
Exclusion Criteria	Described in the Supplementary Appendix
Methods	Participants were randomly assigned to receive trimethoprim–sulfamethoxazole (320 mg and 1600 mg, respectively, twice daily) or placebo for 7 days.
Duration	April 2009 to April 2013
Outcome Measures	Primary: Clinical cure of the abscess Secondary: Rates of subsequent surgical drainage procedures, skin infections at new sites, infections in household members
Baseline Characteristics		TMP-SMX (n= 630)	Placebo (n= 617)
	Median age, years (range)	35 (14 to 73)	35 (14 to 73)
	Male	58.2%	58.2%
	History of MRSA infection	7.6%	7.6%
	MRSA positive wound cultures	45.3%	45.3%
Results		TMP-SMX (n= 630)	Placebo (n= 617)	Difference (95% CI)	p-value
	Clinical cure (mITT-1)	80.5%	73.6%	6.9 (2.1 to 11.7)	0.005
	Clinical cure (per-protocol)	92.9%	85.7%	7.2 (3.2 to 11.2)	<0.001
	Subsequent surgical drainage	3.4%	8.6%	-5.2 (-8.2 to -2.2)	N/A
	Skin infections at new sites	3.1%	10.3%	-7.2 (-10.4 to -4.1)	N/A
	mITT, modified intention-to-treat population
Adverse Events	Trimethoprim–sulfamethoxazole was associated with slightly more gastrointestinal side effects (mostly mild) than placebo. No treatment-associated serious or life-threatening adverse events occurred.
Study Author Conclusions	Trimethoprim–sulfamethoxazole treatment resulted in a higher cure rate among patients with a drained cutaneous abscess than placebo, with better secondary outcomes and only slightly more mild gastrointestinal side effects.
Critique	The study was well-designed with a large sample size, allowing for detection of small differences in cure rates. However, the exclusion criteria and potential bias in patient selection may limit generalizability. The study's reliance on self-reported adherence and the potential for incomplete abscess drainage could also affect the results.

References:

Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N Engl J Med. 2016;374(9):823-832. doi:10.1056/NEJMoa1507476