Skin and Soft-Tissue Infection

Cellulitis

Definition, pathobiology and microbiology

Cellulitis is an acute, spreading bacterial infection of the dermis and subcutaneous tissues, classically presenting with unilateral erythema, warmth, swelling and tenderness. Erysipelas is a more superficial lymphatic dermal infection with a sharply demarcated, raised edge; in practice the distinction rarely alters empirical therapy. Pathogenesis usually requires a breach in the cutaneous barrier—tinea pedis, ulceration, eczema, trauma, venous disease or lymphoedema—followed by bacterial proliferation and a host neutrophilic inflammatory response. Lymphatic injury predisposes to recurrence because impaired lymph drainage reduces local immune trafficking and increases interstitial protein-rich oedema.

The dominant pathogens in non-purulent cellulitis are β-haemolytic streptococci, especially Streptococcus pyogenes groups A, C and G. Staphylococcus aureus is more likely with penetrating trauma, abscess, purulence, injection drug use or previous colonisation. Gram-negative and anaerobic pathogens become relevant in immunocompromise, animal/human bites, water exposure, perineal infection or diabetic foot disease. Blood cultures are positive in only approximately 2–5% of uncomplicated cases and should not be routine.

Clinical assessment and differential diagnosis

Diagnosis is clinical. Typical cellulitis is unilateral; bilateral lower-leg erythema should prompt consideration of mimics. Fever, rigors, tachycardia, hypotension, rapidly progressive pain, bullae, skin necrosis or anaesthesia indicate severe infection and mandate senior review. The key examination is not merely the red area: assess portal of entry, interdigital tinea, peripheral pulses, venous disease, lymphoedema, joint involvement and whether there is a drainable abscess.

Feature	Cellulitis	Common mimic
Distribution	Usually unilateral, expanding erythema	Bilateral chronic erythema suggests venous eczema/lipodermatosclerosis
Pain	Tender, proportionate to visible inflammation	Pain out of proportion suggests deep infection or compartment process
Systemic features	May have fever, rigors, raised CRP/WCC	DVT may cause swelling and pain but usually less cutaneous heat/erythema
Surface change	Warm, oedematous; lymphangitis possible	Scaling, pruritus, hemosiderin staining favour dermatitis/venous disease

Severity classification and investigations

UK practice commonly uses the CREST/Eron classification, useful for deciding oral versus parenteral therapy and admission. It is not a mortality score, but it provides an exam-relevant framework.

Class	Clinical description	Usual management implication
I	No systemic toxicity; no uncontrolled comorbidity	Oral antibiotics as outpatient
II	Systemically unwell or significant comorbidity such as peripheral vascular disease, morbid obesity or chronic oedema	Consider admission or outpatient parenteral antimicrobial therapy
III	Marked systemic upset, acute confusion, tachycardia, tachypnoea, hypotension, or unstable comorbidity	Hospital admission, intravenous therapy
IV	Sepsis syndrome or suspected necrotising/deep infection	Urgent surgical assessment and broad-spectrum intravenous therapy

FBC and CRP support diagnosis and trend response but are non-specific; CRP may remain elevated for 48–72 hours despite adequate therapy. Renal and hepatic function guide dosing. Swabs are useful only from pus, ulcers or breaches in skin; intact-skin swabs are unhelpful. Blood cultures are indicated with sepsis, immunosuppression, lymphoedema-associated severe infection, unusual exposures or admission-level illness. Ultrasound is appropriate when abscess or DVT is clinically suspected, but indiscriminate D-dimer testing is often misleading because cellulitis itself raises D-dimer.

Antimicrobial treatment

NICE NG141 and IDSA guidance emphasise streptococcal cover for non-purulent disease, with anti-staphylococcal cover when clinically indicated. Usual duration is 5–7 days; extend to 10–14 days if slow response, severe lymphoedema, immunocompromise or inadequate source control. Mark the skin edge and reassess at 24–48 hours; early apparent extension may reflect inflammatory evolution rather than failure.

Scenario	Preferred regimen	Notes
Uncomplicated non-purulent cellulitis	Flucloxacillin 500 mg–1 g orally QDS	UK first-line; targets streptococci and MSSA
Penicillin allergy	Clarithromycin 500 mg BD or doxycycline 100 mg BD	Doxycycline has weaker streptococcal reliability; consider local resistance
Severe infection requiring IV therapy	Flucloxacillin 1–2 g IV QDS	Switch to oral when afebrile, improving and able to absorb
Facial cellulitis or suspected polymicrobial source	Co-amoxiclav 625 mg orally TDS or 1.2 g IV TDS	Provides anaerobic and broader Gram-negative cover
MRSA risk or confirmed MRSA	Vancomycin 15–20 mg/kg IV every 8–12 h adjusted to renal function; alternative linezolid 600 mg BD	Vancomycin target AUC/MIC 400–600; trough-only targets are less favoured

Clindamycin 300–450 mg orally QDS or 600–900 mg IV every 8 hours is useful when toxin-mediated streptococcal disease is suspected because it inhibits protein synthesis and toxin production; monitor for Clostridioides difficile. Incision and drainage, not antibiotics alone, is essential for abscess.

Adjunctive management and recurrence prevention

Elevation, analgesia, hydration and treatment of portals of entry are core management. Compression should generally be deferred during acute painful inflammation but instituted after recovery for chronic oedema/venous disease. Recurrent cellulitis is defined pragmatically as two or more episodes per year; address tinea pedis, obesity, oedema and skin disease before prophylaxis.

The PATCH I randomised trial showed that penicillin V 250 mg BD for 12 months reduced recurrence during prophylaxis in patients with recurrent leg cellulitis, although benefit waned after stopping. Guidelines therefore consider prophylactic phenoxymethylpenicillin 250 mg BD for recurrent disease, increased to 500 mg BD in high body weight, with erythromycin 250 mg BD if penicillin-allergic. Review need at 6–12 months and ensure the original diagnosis was not a mimic.

Diabetic Foot

Pathophysiology and microbiology

Diabetic foot infection (DFI) is infection of tissue below the malleoli, usually arising in an ulcer created by the triad of peripheral neuropathy, peripheral arterial disease and repetitive mechanical trauma. Loss of protective sensation permits unrecognised pressure injury; motor neuropathy produces claw toes and high plantar pressures; autonomic neuropathy causes dry, fissured skin. Hyperglycaemia impairs neutrophil chemotaxis, phagocytosis and oxidative burst, while microvascular dysfunction and macrovascular disease reduce antibiotic and leukocyte delivery. Clinically, infection must be diagnosed by local or systemic inflammatory signs, not by culture positivity alone: all chronic ulcers are colonised.

Microbiology depends on chronicity and prior antibiotics. Acute, superficial, antibiotic-naïve infection is usually Staphylococcus aureus and β-haemolytic streptococci. Chronic, deep, ischaemic, necrotic or previously treated ulcers are often polymicrobial, including Enterobacterales, enterococci and anaerobes. Pseudomonas aeruginosa is uncommon in temperate climates unless there is maceration, soaking, warm-climate exposure or previous isolation. MRSA risk is increased by previous MRSA, recent hospitalisation, residence in long-term care, haemodialysis and repeated antibiotics.

Classification and severity assessment

The IWGDF/IDSA scheme is exam-relevant because it directly determines route of therapy, breadth of cover and need for admission. Infection requires purulence or at least two of erythema, warmth, tenderness, pain or induration. Erythema diameter is measured from the ulcer edge after excluding mimics such as Charcot neuroarthropathy, gout and venous dermatitis.

IWGDF/IDSA grade	Clinical definition	Implication
Uninfected	No local or systemic inflammatory signs	No antibiotics; optimise off-loading, debridement, perfusion and glycaemia
Mild	Local infection involving skin/subcutaneous tissue only; erythema >0.5 cm to ≤2 cm	Usually oral therapy targeting Gram-positive cocci
Moderate	Erythema >2 cm or involvement deeper than skin/subcutaneous tissue, without systemic inflammatory response	Often admission if limb-threatening; broader cover and imaging
Severe	Any foot infection with systemic inflammatory response syndrome: temperature >38°C or <36°C, heart rate >90/min, respiratory rate >20/min or PaCO2 <4.3 kPa, WCC >12 or <4 ×109/L or >10% bands	Urgent admission, IV antibiotics, source control and vascular/surgical review

Ulcer systems such as Wagner and University of Texas add anatomical and prognostic information. The University of Texas classification grades depth 0–3 and stages A–D for absence/presence of infection and/or ischaemia; stage D lesions, combining infection and ischaemia, have the highest amputation risk. Objective vascular assessment is mandatory because palpable pulses do not exclude disease. An ankle–brachial pressure index <0.9 suggests peripheral arterial disease, but medial arterial calcification may give falsely high values; toe pressure <30 mmHg, transcutaneous oxygen pressure <25 mmHg or ankle pressure <50 mmHg indicates severe ischaemia and poor healing probability.

Diagnosis, cultures and osteomyelitis

Swabs from ulcer surface are low value. After cleansing and debridement, obtain a deep tissue specimen or aspirate for culture before antibiotics if this does not delay treatment. Plain radiographs assess gas, foreign body, deformity and cortical destruction; bony changes may lag by 2–3 weeks. MRI is the preferred imaging test for diabetic foot osteomyelitis, with typical sensitivity about 90% and specificity about 80%; false positives occur in Charcot arthropathy and recent surgery. A positive probe-to-bone test is most useful in high-prevalence settings: pooled sensitivity is approximately 0.87 and specificity 0.83. ESR >70 mm/h substantially increases suspicion of osteomyelitis, whereas a normal CRP and ESR make extensive bone infection less likely. Bone biopsy for histology and culture remains the diagnostic gold standard, particularly when prolonged therapy is planned or resistant organisms are suspected.

Management

DFI management is multidisciplinary: diabetology, microbiology, podiatry, vascular surgery, orthopaedics and tissue viability. Key principles are source control, appropriate antibiotics, off-loading, revascularisation where indicated and metabolic optimisation. NICE NG19 and IWGDF/IDSA guidance emphasise that antibiotics alone rarely cure an infected ulcer if necrotic tissue, abscess, compartmental infection or critical ischaemia persists. Urgent surgical assessment is required for suspected necrosis, abscess, deep space infection, wet gangrene, crepitus, rapidly progressive infection or systemic toxicity.

Scenario	Typical regimen in adults with normal renal function	Usual duration
Mild DFI, low MRSA risk	Flucloxacillin 500 mg–1 g orally every 6 h; alternatives include doxycycline 100 mg orally every 12 h or clarithromycin 500 mg every 12 h if β-lactam allergy	1–2 weeks
Mild infection where mixed flora suspected	Co-amoxiclav 625 mg orally every 8 h	1–2 weeks
Moderate/severe DFI	Co-amoxiclav 1.2 g IV every 8 h, or piperacillin–tazobactam 4.5 g IV every 6–8 h if severe, necrotic or broad Gram-negative/anaerobic cover required	2–4 weeks for soft tissue, guided by response
MRSA risk or proven MRSA	Add vancomycin IV 15–20 mg/kg every 8–12 h, targeting trough 15–20 mg/L for serious infection, or linezolid 600 mg orally/IV every 12 h	Individualised; monitor toxicity
Osteomyelitis without complete bone resection	Culture-directed therapy; high-bioavailability agents may be oral if susceptible	Usually 6 weeks; up to 3 weeks after minor amputation with positive bone margin

Empirical therapy should be narrowed once cultures and clinical response are available. Linezolid has excellent oral bioavailability but risks thrombocytopenia, neuropathy and serotonin toxicity; monitor full blood count at least weekly beyond 10–14 days. Vancomycin requires renal function and therapeutic drug monitoring. Avoid unnecessary antipseudomonal or anaerobic cover in mild acute infection.

Off-loading is therapeutic, not ancillary: non-removable knee-high devices are most effective for neuropathic plantar forefoot/midfoot ulcers when infection and ischaemia are not severe. Glycaemic control should be improved while avoiding hypoglycaemia; severe infection may precipitate hyperosmolar crisis or ketoacidosis. Revascularisation should be considered urgently when perfusion thresholds are poor or an ulcer fails to improve after 4–6 weeks of optimal care. The exam trap is to treat a positive culture from an uninfected ulcer: this selects resistance without improving healing.

Necrotising Fasciitis

Necrotising fasciitis (NF) is a fulminant infection of the deep fascia and subcutaneous tissues, characterised by rapidly progressive fascial necrosis, microvascular thrombosis, systemic toxicity and high mortality. Muscle is initially spared, distinguishing NF from clostridial myonecrosis, although late involvement may occur. Mortality remains approximately 20–30%, rising to >50% with streptococcal toxic shock, delayed debridement, renal failure, or shock at presentation. For MRCP, the key discriminator is that pain out of proportion to cutaneous signs is an early, high-yield clue.

Pathogenesis and microbiological classification

Necrosis results from bacterial invasion along relatively avascular fascial planes, exotoxin-mediated tissue injury, neutrophil activation, endothelial damage and thrombosis of perforating vessels, producing ischaemia that limits antibiotic penetration. Systemic toxicity reflects cytokine release, superantigen effects and septic shock physiology.

Type	Microbiology	Typical setting	Exam-relevant points
Type I	Polymicrobial: streptococci, Staphylococcus aureus, Enterobacterales, anaerobes including Bacteroides and Clostridium	Diabetes, peripheral vascular disease, postoperative wounds, perineal infection, immunosuppression	Most common overall; gas more likely; includes Fournier gangrene
Type II	Group A streptococcus, often with S. aureus	Minor trauma, varicella, injection drug use, previously healthy host	Severe pain, toxic shock; clindamycin essential for toxin suppression
Type III	Marine Gram-negatives: Vibrio vulnificus, Aeromonas hydrophila	Seawater exposure, seafood injury, liver disease, iron overload	Rapid bullae and shock; use doxycycline plus third-generation cephalosporin
Type IV	Fungal, e.g. mucormycosis, Candida	Neutropenia, burns, transplant, profound immunosuppression	Rare; requires surgical debridement and antifungal therapy

Clinical recognition

Early skin findings may be deceptively mild: erythema, oedema and warmth resemble cellulitis. Red flags include disproportionate pain, rapidly advancing margins, woody induration, anaesthesia from cutaneous nerve infarction, haemorrhagic bullae, ecchymosis, skin necrosis, crepitus, severe tenderness beyond erythema, fever, confusion, hypotension or organ dysfunction. Fournier gangrene involves perineal, genital or perianal fascia; risk factors include diabetes, alcoholism, malignancy and colorectal or urogenital sources.

Investigation, scoring and imaging

NF is a clinical and surgical diagnosis; investigations must not delay theatre. Blood tests often show neutrophilia, hyponatraemia, raised CRP, metabolic acidosis, lactataemia, acute kidney injury, coagulopathy and high creatine kinase if muscle involvement develops. Blood cultures are positive in a minority but should be taken before antibiotics if this does not delay treatment.

LRINEC component	Scoring thresholds
CRP	<150 mg/L = 0; ≥150 mg/L = 4
WCC	<15 × 109/L = 0; 15–25 = 1; >25 = 2
Hb	>13.5 g/dL = 0; 11–13.5 = 1; <11 = 2
Sodium	≥135 mmol/L = 0; <135 = 2
Creatinine	≤141 µmol/L = 0; >141 = 2
Glucose	≤10 mmol/L = 0; >10 = 1

The LRINEC score classifies risk as low <6, intermediate 6–7 and high ≥8. Original derivation reported positive predictive value 92% for ≥6 and 93% for ≥8, but later external validation shows poor sensitivity, often ~40–70%; therefore a low score does not exclude NF. CT may show fascial thickening, fluid tracking, non-enhancement and gas; MRI is sensitive for fascial oedema but time-consuming and non-specific. Plain radiographs detect gas but have low sensitivity. Imaging is appropriate only when diagnosis is uncertain and the patient is stable.

Management

Management is simultaneous resuscitation, broad-spectrum antimicrobials and urgent surgical source control. Guidelines from IDSA and UK sepsis practice emphasise immediate senior surgical review and debridement ideally within 6 hours; delay beyond 12–24 hours markedly increases mortality. At operation, “dishwater” grey fluid, lack of fascial resistance to blunt dissection, non-bleeding fascia and necrotic subcutaneous tissue are characteristic. Repeat debridement every 24–48 hours is commonly required until viable tissue is reached; amputation may be lifesaving.

Clinical context	Empirical antimicrobial regimen	Rationale
Community or healthcare-associated NF	Piperacillin-tazobactam 4.5 g IV 6-hourly plus clindamycin 600–900 mg IV 6–8-hourly plus MRSA cover if risk: vancomycin 15–20 mg/kg IV 8–12-hourly, adjusted to renal function and trough/AUC monitoring	Broad Gram-positive, Gram-negative and anaerobic cover; clindamycin suppresses streptococcal toxin and is active in stationary-phase inocula
Severe penicillin allergy	Meropenem 1 g IV 8-hourly if tolerated, or specialist regimen with aztreonam plus metronidazole plus vancomycin; add clindamycin	Maintain broad-spectrum and antitoxin coverage
Suspected Vibrio vulnificus	Doxycycline 100 mg IV/PO 12-hourly plus ceftazidime 2 g IV 8-hourly or ceftriaxone 2 g IV daily	Marine exposure, liver disease, haemorrhagic bullae

Clindamycin has a half-life of approximately 2–3 hours and inhibits the 50S ribosomal subunit, reducing streptococcal pyrogenic exotoxin and staphylococcal toxin synthesis; this is why it is used even when isolates are beta-lactam susceptible. Once cultures identify group A streptococcus, narrow to high-dose benzylpenicillin, for example 2.4 g IV 4-hourly, plus clindamycin. Duration is individualised, commonly continued until no further debridement is required and the patient has been afebrile and haemodynamically stable for 48–72 hours.

Adjunctive intravenous immunoglobulin may be considered in streptococcal toxic shock with refractory shock or organ failure; typical dosing is 1 g/kg on day 1 then 0.5 g/kg on days 2–3. Evidence is limited: small randomised and observational studies suggest toxin neutralisation and possible mortality reduction, but certainty is low. Hyperbaric oxygen may inhibit anaerobes and improve oxygen-dependent neutrophil killing, but evidence is weak and it must never delay debridement. Supportive care follows sepsis principles: early broad-spectrum antibiotics, crystalloid resuscitation, vasopressors to maintain MAP ≥65 mmHg, lactate reassessment, renal support and glycaemic control.

Bacterial Skin Infection

Clinical syndromes and microbiology

Bacterial skin infections are best approached anatomically: epidermal infections such as impetigo; follicular infections such as folliculitis, furunculosis and carbuncle; toxin-mediated disease such as staphylococcal scalded skin syndrome; and special exposure-related syndromes. The dominant pathogens are Staphylococcus aureus and Streptococcus pyogenes, with community-associated MRSA increasingly relevant in recurrent abscesses, contact-sport outbreaks, prisons and intravenous drug use. Gram-negative, anaerobic or water-associated organisms should be suspected when the history dictates: Pasteurella multocida after cat/dog bites, Eikenella corrodens after human bites, Vibrio vulnificus after seawater exposure, Aeromonas hydrophila after freshwater exposure, and Erysipelothrix rhusiopathiae in fish handlers or butchers.

Syndrome	Key features	Usual organisms	Exam-relevant management
Non-bullous impetigo	Honey-coloured crusts, often perioral/nasal; highly contagious	S. aureus, S. pyogenes	Topical therapy if localised; oral antibiotics if extensive, outbreaks or systemic features
Bullous impetigo	Flaccid bullae, minimal surrounding erythema; neonates/children	Toxin-producing S. aureus	Anti-staphylococcal therapy; culture if recurrent or treatment failure
Ecthyma	Ulcerative “punched-out” impetigo extending into dermis	S. pyogenes, S. aureus	Usually requires oral therapy; consider immunosuppression/poor hygiene
Folliculitis/furuncles/carbuncles	Pustules centred on hair follicles; boils; carbuncles have multiple draining sinuses	S. aureus; hot-tub folliculitis: Pseudomonas aeruginosa	Incision and drainage for fluctuant lesions; antibiotics only if indicated
Erythrasma	Brown-red intertriginous patches; coral-red fluorescence under Wood lamp	Corynebacterium minutissimum	Topical azole or erythromycin; oral macrolide if extensive

Impetigo, ecthyma and toxin-mediated staphylococcal disease

Impetigo is diagnosed clinically. Swabs are not routinely required but are useful in recurrent disease, outbreaks, suspected MRSA, treatment failure or when the diagnosis is uncertain. NICE guidance favours topical hydrogen peroxide 1% cream for localised non-bullous impetigo; if unsuitable, topical fusidic acid 2% or mupirocin 2% may be used, typically three times daily for 5 days. Topical antibiotics should be used sparingly because fusidic-acid resistance in S. aureus is selected rapidly, particularly with repeated monotherapy.

Oral treatment is appropriate for widespread lesions, bullous impetigo, ecthyma, systemic features, high-risk patients or failure of topical treatment. Standard adult regimens include flucloxacillin 500 mg orally four times daily for 5–7 days. In immediate penicillin allergy, clarithromycin 500 mg twice daily for 5 days is commonly used; erythromycin is preferred in pregnancy. Where MRSA is proven or strongly suspected, options guided by susceptibility include doxycycline 100 mg twice daily, co-trimoxazole 960 mg twice daily, or clindamycin 300–450 mg four times daily; doxycycline is avoided in pregnancy and children under 12 years.

Bullous impetigo and staphylococcal scalded skin syndrome reflect exfoliative toxins A/B targeting desmoglein-1, causing superficial intraepidermal cleavage. In scalded skin syndrome, mucous membranes are typically spared, helping distinguish it from Stevens–Johnson syndrome/toxic epidermal necrolysis. Severe disease requires intravenous anti-staphylococcal therapy, fluid and temperature management, analgesia and specialist dermatology/paediatric input.

Purulent infections: abscess, furunculosis and MRSA

For a fluctuant cutaneous abscess, incision and drainage is the definitive treatment; antibiotics alone penetrate poorly because the abscess cavity is acidic, hypoxic and has impaired vascular access. Send pus for culture when infection is recurrent, severe, associated with systemic inflammatory response, immunosuppression, healthcare exposure or suspected MRSA. Antibiotics are indicated with fever, surrounding cellulitis, multiple lesions, extremes of age, immunocompromise, prosthetic material, difficult-to-drain sites, or failure of drainage alone.

Randomised trial evidence supports adjunctive anti-MRSA therapy in selected drained abscesses. In the NEJM trial by Talan et al. 2016, trimethoprim-sulfamethoxazole after drainage improved clinical cure compared with placebo, approximately 80.5% versus 73.6% in the modified intention-to-treat population. Daum et al. 2017 similarly showed higher cure rates with clindamycin or trimethoprim-sulfamethoxazole than placebo for small abscesses, at the cost of more adverse events with clindamycin. These data underpin IDSA guidance: drainage for all purulent collections, with antibiotics added according to systemic severity and host risk.

Situation	Typical adult regimen	Important cautions
MSSA skin infection	Flucloxacillin 500 mg orally QDS; severe infection 1–2 g IV every 6 h	Cholestatic hepatitis risk, especially age >55 years or prolonged courses
Community MRSA, mild-moderate	Doxycycline 100 mg BD, co-trimoxazole 960 mg BD, or clindamycin 300–450 mg QDS	Clindamycin: check D-test for inducible erm-mediated resistance; risk of C. difficile
Severe MRSA	Vancomycin 15–20 mg/kg IV every 8–12 h, adjusted to renal function; linezolid 600 mg BD IV/oral alternative	Vancomycin nephrotoxicity; linezolid thrombocytopenia, serotonin syndrome, MAOI effect

Recurrent infection and decolonisation

Recurrent furunculosis should prompt assessment for nasal/perineal S. aureus carriage, household transmission, eczema, diabetes, HIV risk, neutrophil dysfunction if unusually severe from childhood, and PVL-producing S. aureus when boils are recurrent, necrotic or clustered. Panton–Valentine leukocidin is a bicomponent cytotoxin associated with recurrent abscesses and, rarely, severe necrotising pneumonia after influenza-like illness.

Decolonisation is considered after active infection is treated and household hygiene measures have been optimised. A common regimen is mupirocin 2% nasal ointment three times daily for 5 days plus daily chlorhexidine 4% body wash for 5 days, with laundering of towels, bedding and clothing. Treating colonised household contacts may be necessary in repeated transmission. Avoid repeated unsupervised decolonisation because mupirocin resistance compromises a key infection-control agent.