MMRSA Guide
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Reference · Staph infection · Antibiotics

Antibiotics for a staph skin infection

Which drug is right depends on one question: is the strain MRSA or not. This page sets out what is normally prescribed for a staph skin infection, what changes when MRSA is involved, and why some antibiotics never work against staph at all.

Written by David Roberts, editor · Updated

Checked against current CDC and IDSA guidance. Not medically reviewed. How we source this

Drainage first, antibiotics second

For a boil or abscess, the decisive treatment is incision and drainage. Antibiotics struggle to penetrate a walled-off pocket of pus, which is why a lesion can keep growing on day three of a prescription. A randomised trial published in 2017 found that adding an antibiotic after drainage of a small abscess improved cure rates, so most clinicians now do both — but the drainage still does the heavy lifting.

Cellulitis, by contrast, has nothing to drain: a spreading, flat red area is treated with antibiotics alone. Working out which of the two you have changes the whole plan, and the boil and cellulitis pages describe both.

Does this antibiotic cover staph?

MSSA is ordinary methicillin-sensitive staph. MRSA is the same bacterium with resistance to the whole penicillin and cephalosporin family. Almost every prescribing mistake comes from treating the second as if it were the first.

AntibioticMSSAMRSANotes
Flucloxacillin / dicloxacillinYesNoFirst choice for ordinary staph in the UK and US respectively.
Cephalexin (Keflex)YesNoCommon first prescription for cellulitis; useless against MRSA.
AmoxicillinNoNoDestroyed by staph penicillinase. Amoxicillin-clavulanate covers MSSA only.
DoxycyclineYesYesOral MRSA option. Avoid in pregnancy and young children.
Trimethoprim-sulfamethoxazole (Bactrim)YesYesWidely used for MRSA skin infection; weaker on streptococci.
ClindamycinYesOftenLocal resistance varies; carries a Clostridioides difficile risk.
LinezolidYesYesReserved oral or IV option for difficult or deeper infection.
Vancomycin (IV)YesYesThe hospital backbone for serious MRSA infection.

The full list of drugs used against resistant staph, with routes and roles, is on every MRSA antibiotic.

What is usually prescribed, by situation

SituationUsual approach
Small abscess, person otherwise wellDrainage; an oral antibiotic often added afterwards
Cellulitis, no abscess, MRSA unlikelyFlucloxacillin, dicloxacillin or cephalexin
Skin infection with MRSA suspected or culturedDoxycycline, trimethoprim-sulfamethoxazole or clindamycin
Penicillin allergyClindamycin, doxycycline or a macrolide depending on the reaction and local resistance
Extensive infection, fever, or not improving on tabletsHospital assessment and intravenous therapy
Bloodstream, bone or joint involvementIntravenous vancomycin or an alternative for weeks, with specialist input

Choices and names vary between countries and change with local resistance patterns. This page describes published guidance; it is not a prescription, and it deliberately avoids doses.

Why the first prescription sometimes fails

  • The abscess was never drained.
  • The strain is MRSA and the drug was a beta-lactam such as cephalexin, amoxicillin or flucloxacillin.
  • Local clindamycin resistance is high, and no culture was taken.
  • The lesion is not infected at all — a cyst, an inflamed follicle or an inflammatory condition.
  • The course was stopped as soon as it looked better.

A swab or wound culture resolves most of this. See MRSA testing for what is involved and how long results take.

When to be seen urgently

  • Fever or chills alongside the skin lesion
  • Redness spreading by the hour, or red streaks tracking away from it
  • Pain out of proportion to how the skin looks
  • Any significant infection in a baby, or in someone with diabetes, cancer treatment or a weakened immune system
  • Confusion, breathlessness or feeling profoundly unwell — see when staph becomes dangerous

After treatment

Keep the wound covered until it is dry and healing, wash hands after dressing changes, and do not share towels or razors. If infections keep returning, ask about decolonisation and read why staph and MRSA come back. For the wider treatment path, see treating skin and soft-tissue infection.

Frequently asked questions

What is the best antibiotic for a staph skin infection?
There is no single best drug — it depends on whether the strain is MSSA or MRSA. For ordinary methicillin-sensitive staph, guidelines point to flucloxacillin (UK), dicloxacillin or cephalexin. If MRSA is suspected or confirmed, those drugs do not work and treatment moves to doxycycline, trimethoprim-sulfamethoxazole (Bactrim) or clindamycin. A culture and sensitivity result is what settles it.
Does doxycycline cover staph and MRSA?
Yes. Doxycycline is one of the standard oral options for community MRSA skin infection and also covers most MSSA. It is avoided in pregnancy and in young children, and it can cause sun sensitivity and stomach upset.
Does Bactrim treat a staph infection?
Trimethoprim-sulfamethoxazole (Bactrim, co-trimoxazole) is widely used for MRSA skin and soft-tissue infection and covers most staph. It is less reliable against streptococci, so a clinician may pair or switch it when cellulitis without an abscess is the main problem.
Does amoxicillin treat a staph infection?
Plain amoxicillin is a poor choice — most Staphylococcus aureus produces penicillinase, which destroys it. Amoxicillin-clavulanate does cover MSSA, but neither covers MRSA. This is a common reason a first prescription fails to work.
Does cephalexin cover MRSA?
No. Cephalexin (Keflex) is a good MSSA drug and a common first prescription for cellulitis, but MRSA is resistant to it and to the whole beta-lactam family. If a skin infection is not improving on cephalexin after two to three days, MRSA is one of the reasons to re-swab.
How long do you take antibiotics for a staph skin infection?
Typically five to ten days for an uncomplicated skin or soft-tissue infection, extended if the response is slow or the infection is extensive. Deeper infections, bone or joint involvement and bloodstream infection need weeks, usually starting intravenously in hospital.
Can a staph skin infection be treated without antibiotics?
Sometimes. For a small, well-defined abscess in an otherwise healthy person, incision and drainage is the key treatment; a trial showed antibiotics after drainage improve cure rates modestly, so many clinicians now add them, but drainage does the heavy lifting. Antibiotics alone rarely clear a walled-off collection of pus.
Why is my staph infection not responding to antibiotics?
The usual reasons are an undrained abscess, a resistant strain (MRSA treated with a beta-lactam), the wrong diagnosis — a cyst, an inflamed hair follicle or a non-infectious inflammatory lesion — or a course stopped early. Any spreading redness, fever or worsening pain on treatment should be reviewed the same day.
What antibiotics are used for a serious staph infection in hospital?
Intravenous flucloxacillin or cefazolin for MSSA, and intravenous vancomycin, daptomycin, linezolid, ceftaroline or teicoplanin for MRSA, chosen by infection site and kidney function. Bloodstream and bone infections need prolonged courses with specialist input.

Symptoms hub

Overview of MRSA symptoms and day-by-day progression.

What does MRSA look like?

Bumps, boils, abscesses and cellulitis — every visual form.

MRSA rash

Does MRSA cause a rash? Look-alikes and how to tell them apart.

MRSA in the nose

Nasal carriage vs infection, swab testing and mupirocin treatment.

MRSA skin infection

Types, diagnosis, treatment, and when skin MRSA becomes dangerous.

MRSA boil

Deep, painful, pus-filled lumps and how they are drained.

MRSA cellulitis

Spreading deeper-skin infection and urgent warning signs.

MRSA folliculitis

Small pus-filled bumps around hair follicles and prevention.

MRSA pneumonia

Hospital, ventilator-associated and necrotising lung infection.

MRSA bacteremia

MRSA in the bloodstream — how it gets there and how it's treated.

MRSA sepsis

Can MRSA cause sepsis? Warning signs and survival rates.

Invasive MRSA

How MRSA reaches the bloodstream, lungs and bone.

MRSA test

PCR nasal swab, wound culture and susceptibility testing.

MSSA vs MRSA

Same bacterium, different antibiotic susceptibility.

Staph infection vs pimple

How to tell a normal pimple from a staph or MRSA skin lesion.

MRSA colonization

Carriers, nasal swabs, how long carriage lasts and when it is treated.

MRSA UTI

MRSA in the urinary tract — catheters, symptoms and treatment.

MRSA ICD-10 codes

B95.62, A49.02, Z22.322 and the sequencing rules for coders.

Scalded skin syndrome

The staph toxin illness that makes a child's skin blister and peel.

Can MRSA kill you?

Death rates by infection type, who is at risk and the warning signs.

Staph infection

Staphylococcus aureus infection overall — symptoms, spread and treatment.

What does a staph infection look like?

Every form on the skin, stage by stage, and the look-alikes.

Is a staph infection contagious?

How it spreads, how long for, and the school, work and sport rules.

References
  1. Stevens D.L. et al., IDSA. Practice guidelines for the diagnosis and management of skin and soft tissue infections (2014)
  2. Liu C. et al., IDSA. Clinical practice guidelines for the treatment of MRSA infections in adults and children (2011)
  3. CDC. Staphylococcus aureus and MRSA: treatment information for clinicians (2024)
  4. NICE. Cellulitis and erysipelas: antimicrobial prescribing (NG141) (2019)
  5. Daum R.S. et al., New England Journal of Medicine. A placebo-controlled trial of antibiotics for smaller skin abscesses (2017)
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