Pharmaceutical Journal Article SSTI

8/14/2019 Pharmaceutical Journal Article SSTI

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Vol 1 January 2009 Clinical Pharmacist 13

By R A Seaton, DTM&H, FRCP(Edin)

Skin and soft tissue infections (SSTIs) comprise an

important and diverse group of anatomically and

aetiologically distinct infections. In UK hospitals,

34% of patients receive treatment for SSTI. Of these,

47% receive intravenous (IV) therapy, accountingfor 16% of all IV antibiotic-treated patients.1 Infections of

the skin and subcutaneous tissues account for around 176

admission per 100,000 of the UK population.2

Since the anatomical site, severity, associated co-

morbidity and aetiology vary, the clinical team managing

patients in hospital is likely to include a variety of

healthcare professionals in both medical and surgical

specialties. This review focuses on important bacterial

SSTIs seen in UK hospital practice.

In terms of clinical features and classification, SSTIs

may be defined by their involvement of deep structures, by

associated risk factors and by their microbiology (see Box

1, p15).

Superficial SSTIsFor people who develop superficial SSTIs, the causative

organisms are usually Staphylococcus aureusand Streptococcus

pyogenes.

Impetigo is a superficial SSTI rarely associated withsystemic upset or extensive skin involvement and more

commonly seen in children and young adults. Discrete,

multiple lesions usually occur on the face or extremities

that are either vesicular-purulent bullous or papular in

appearance. Yellow or brown crusting is characteristic.

Occasionally, secondary cellulitis can occur.

Folliculitis, furuncles and carbuncles comprise arange of superficial infections involving hair follicles.

Folliculitis consists of superficial epidermal inflammation

around the follicles; furuncles are small abscesses which

may coalesce to form larger carbuncles, usually on the

neck.

Cellulitis and erysipelas are pathologically distinctdermal infections comprising the most common SSTIs

that require admission to hospital and IV antibiotic

therapy. Both are diffuse, spreading, superficial infections

without underlying suppurative foci in muscle or fascia

and without associated necrosis.Characterised by heat, erythema, induration and

localised tenderness, there may also be an orange skin

appearance, due to superficial oedema surrounding hair

follicles which remain tethered to underlying dermis.

Blisters or bullae may also occur (Figure 1, p15).

Erysipelas involves the upper dermis and is raised

above surrounding skin with a well demarcated edge

There is a wide range of skin and soft tissue infections with a variety of risk factors and causes. This

article focuses on the diagnosis and treatment of some of these infections

Skin and soft tissue infectiond iagno s is and m anag em ent

Staphylococcus aureusbacteria (coloured scanning electron micrograph)

Andrew Seaton is consultant in infectious diseasesand general medicine at the Brownlee Centre,

Gartnavel General Hospital, Glasgow.

E: [email protected]

Skin and soft tissue infections (SSTIs) encompass a broad range of

infections with a variety of risk factors and causes. Careful assessment of

risk factors, severity markers and co-morbidities will inform the most

appropriate therapy.

Key clinical decisions include route of administration of therapy,switching from IV to oral therapy, adjunctive measures and suitability for

outpatient management. Outpatient parenteral therapy is a viable option

for ambulant patients with moderate SSTI requiring IV therapy and without

risk factors for severe disease or unstable co-morbidities.

GopalM

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SUMMARY

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Vol 1 January 2009 Clinical Pharmacist 15

(Figure 2). Cellulitis involves deeper dermis and

subcutaneous fat, is not raised and is without a well

demarcated edge (Figure 3). Each may be accompanied by

a systemic inflammatory response and regional

lymphadenopathy is common. Infection occurs following

a minor skin breach, for example an insect bite (morecommon in the summer months). It may also complicate

Tinea pedisor paronychia. Risk of infection is increased in

immunocompromised patients, following trauma or

surgery, in those with diabetes mellitus or lymphoedema,

and in the morbidly obese (Figure 4, p16).

Necrotising SSTIsNecrotising infection of the skin and soft tissue is severe

and life-threatening, with a systemic inflammatory

response, involvement of deep tissues, including

underlying fascia or muscle, and associated tissue

destruction.

Necrotising infections can be distinguished from moresuperficial infections by the presence of a combination of

the following clinical signs: severe, constant pain;

blistering and bruising; oedema beyond the margin of the

erythema; localised skin anaesthesia; gas in the tissues;

systemic inflammatory response and multi-organ failure;

and rapidly evolving and spreading infection.

Necrotising fasciitis involves the tissues deep to thedermis and superficial to the muscle. Infection moves

along these planes, extending well beyond the superficial

signs of infection, and usually occurs as a direct

consequence of more superficial infection.

Underlying tissues often feel wooden and there maybe a dusky discoloration to the skin (Figures 5a and 5b,

p16).

Myositis involves muscle and two distinct groups arerecognised: anaerobic streptococcal myositis, usually

occurring following surgery or open trauma and involving

muscles and fascial planes; and pyomyositis, which is pus

within an individual muscle group, usually presenting

with localised pain, muscle spasm and fever.

Synergistic necrotising cellulitis is a necrotising softtissue infection involving muscle groups, in addition to

superficial skin and fascia (Figure 6, p17).

Fournier gangrene involves the perineum and genitalia,usually in patients with underlying disease, particularly

diabetes mellitus. Onset is usually sudden but can be

insidious. An initial superficial focus of infection becomes

necrotic and spreads to deep tissues and along fascial

planes.

Clostridial myonecrosis (gas gangrene) is

characterised by severe localised pain, systemicinflammatory response and rapidly evolving skin changes

within 24 hours of trauma. Affected areas become tense,

fluid-filled blisters develop and gas is visible on plain

radiographs.

Spontaneous gangrene can complicate malignancy and

neutropenia, is usually blood-borne from a colonic focus

and occurs in the absence of trauma.

Microbiology and associated risk factorsIrrespective of site or severity, SSTIs are predominantly

caused by aerobic gram-positive cocci, in particular the

beta-haemolytic streptococci (notably S pyogenes) and S

aureus.3

Other micro-organisms are variably implicated

ure 1: Skin blistering in cellulitis. Typically seen

beta-haemolytic streptococcal infections

Figure 2: Facial erysipelas. Typical of

Streptococcus pyogenesinfection

Figure 3: Facial cellulitis with periorbital oedema

Box 1: Microbial causes of SSTI

CLINICAL PRESENTATION CAUSATIVE ORGANISMS

Impetigo, folliculitis, furunculosis, Staphylococcus aureusand Streptococcus

carbuncles, cellulitis and erysipelas pyogenes

Necrotising infections S aureus, S pyogenes, clostridial species, gram-negative organisms and polymicrobial species

Infections following human or S aureus, aerobic and anaerobic streptococci,

animal bites Fusobacteriumand Pasteurella spp;

capnocytophaga (in animals)

Surgical site infections S aureus, beta-haemolytic streptococci; genital

tract or abdominal surgery consider gram-

negatives and anaerobes

Infections in immunocompromised S aureus, S pyogenes, gram-negatives including

patients Pseudomonas aeroginosa, mycobacteria and fungi

Infections in parenteral drug users S aureus, beta-haemolytic streptococci, and

clostridial species

SSTI due to water exposure Vibrio vulnificus, Aeromonas hydrophiliaand

Mycobacterium marinum

Travel-related SSTI S aureus, S pyogenes, endemeic mycoses,

Mycobacterium ulcerans, Leishmaniaspp, and others


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depending on the nature of the SSTI and whether it is

healthcare-associated or community-acquired.

Surgical site infection usually occurs more than 48hours after an incision and is characterised by localised

wound-related erythema, heat, induration and purulentdischarge.

Involvement of deep structures should always be

considered and management depends on the surgical site.

In hospitals, S aureusdominates as a cause of surgical-site

infection4 (Figure 7, p17), with variable rates of meticillin

resistance (see accompanying article, p23).

Animal or human bites can result in infection, and thedepth and site of the bite is critical. Hand injuries are

common so attention should be paid to potential tendon

involvement and the maintenance of function. Therapy is

often pre-emptive in view of the high risks of loss of

function. Infections are polymicrobial, reflecting oralflora: S aureus, aerobic and anaerobic streptococci,

clostridial species, fusobacteria and gram-negative

bacteria. With animal bites Pasteurella spp and

capnocytophaga are also important.

Water exposure refers to water-related trauma (eg,coral or rock laceration) or contamination with water of

an open wound or sore. Both fresh and salinated water

harbour micro-organisms and individuals are at potential

risk of SSTI following such exposure. Vibrio vulnificus and

Aeromonas hydrophiliaare frequently responsible.

In hospitals some hydrophilic organisms such as

pseudomonas and stenotrophomonas can also causeSSTIs, particularly in compromised, post-operative

patients. Mycobacterium marinum infection (or fish tank

granuloma) most frequently occurs following a laceration

incurred when cleaning tropical fish tanks. Systemic

infection is unusual.

Parenteral drug users are an at-risk group for SSTIs.The full range of infections ranging from simple

injection-site abscesses to necrotising infections can be

seen in inner-city hospitals and clinics. Concomitant

blood-stream infection and venous thromboembolism is

not uncommon (Figure 8, p17).

Individuals are at risk through translocation ofcommensal skin organisms into the blood stream directly,

by use of contaminated heroin (usually with heat-resistant

organisms), or via contamination during drug preparation.

Gram-positive organisms, particularly S aureusand beta-

haemolytic streptococci, are usually implicated.

Clostridial species, particularly C perfringensand C novyi,

can cause devastating, rapidly progressive infections

associated with marked leucocytosis and systemic

inflammatory response.

Immunocompromised patients may develop SSTIs,with S aureus and S pyogenesas the predominant organisms

in this diverse patient group. Gram-negative organisms,including Pseudomonas aeroginosa, should be considered in

the context of neutropenia and line-related SSTI.

Fungal infections (eg, with Fusarium, Aspergillus or

Sporothrixspp) are less frequently seen, but may occur in

Figure 4: Progressive cellulitis due to group B streptococcus, complicating

lymphoedema and morbid obesity

Figure 5a: Necrotising fasciitis due to Streptococcus

pyogenesshowing blistering in lower leg

Figure 5b: Dusky skin discoloration extending over buttock

and flank indicating progressive infection

association with neutropenia, organ transplant or long-

term immunosuppressive therapy. Their presentation is

variable but may consist of papullar, erythematous or

purple eruptions with lymphatic spread or erythema and

skin ulceration. Fungal infections can occur either as a

primary complication or in the context of disseminated

infection with multi-organ involvement.Mycobacterial infections are uncommon and can be

indistinguishable from fungal infections but should be

considered in the same population.

Travel-related or tropical skin infections are notuncommon in migrants or people returning from abroad.


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resuscitation and appropriate imaging, to delineate the

extent and nature of the infection. Frequent clinical

review and early surgical review are essential. For

patients with necrotising fasciitis, aggressive surgical

debridement akin to radical tumour resection, with wide

margins of excision of affected tissues, can be life saving although limb amputation or extensive skin and tissue

loss is frequent and mortality high (>60%). Normal

human immunoglobulin infusion for 72 hours is used

by many infectious diseases physicians in these

circumstances in an attempt to neutralise streptococcal

toxic shock protein.7

Surgical review should also be sought for SSTIs

occurring from a surgical procedure and for all patients

with a significant bite or trauma. Careful attention should

be paid towards the potential for involvement of deep

structures and prosthetic implants.

Outpatient parenteral antibiotic therapyOutpatient parenteral antibiotic therapy (OPAT) is ameans to facilitate safe and effective delivery of parenteral

antimicrobial therapy, in a non-inpatient setting, to

patients for whom IV treatment is the most appropriate

choice (Box 2). For greatest efficiency, OPAT should be

available soon after presentation to avoid admission or

plan early discharge.

Different models exist: an integrated healthcare at

home service can manage SSTIs in conjunction with

other non-infectious conditions, including deep-vein

thrombosis, and takes place via acute admissions unit; a

comprehensive infection service utilises infection

specialists (usually infectious diseases physicians),

overseeing the management of a range of infectious

conditions in the hospital outpatient setting.8 In the US,

OPAT is often delivered in the community, usually by a

contracted private healthcare provider in an infusion

centre, overseen by an infection specialist.9 There are

advantages and disadvantages to each model and they can

be adapted to local economics and strategies.Contraindications to OPAT include uncontrolled local

infection or sepsis syndrome, unstable co-morbidities,

unsuitability for self-care or lack of appropriate home

Box 2: Advantages of OPAT services for SSTI

Development of an outpatient parenteral antibiotic therapy (OPAT) service

for patients with skin and soft tissue infections has the potential to:

Provide patients with choice in how and where their care is delivered

Promote more rapid return to normal activities (including work) for

patients

Simplify the patient journey by

a) avoiding admission to hospital for some

b) reducing the duration of hospital stay for others

Improve and streamline infection management in a broad population

of patients dispersed across many clinical areas

Reduce bed-occupancy pressures in acute clinical areas

Promote early discharge to accommodate increasing numbers of acute

admissions and elective surgery patients

Published guidance is deliberately non-prescriptive

with respect to antibiotic choice, in part reflecting these

complexities, but also because SSTI clinical trials

typically exclude the most severely ill patients and are

powered only to show non-inferiority between agents.5,6

For patients admitted to hospital requiring IVtreatment and where fully sensitive organisms are

isolated or suspected and there is no history of penicillin

allergy narrow-spectrum beta-lactam antibiotics such

as benzylpenicillin (for beta-haemolytic streptococci) and

flucloxacillin (for both beta-haemolytic streptococci and

staphylococci) remain the antibiotics of choice. It is the

authors practice to use flucloxacillin monotherapy as

first-line treatment for non-allergic patients unless MRSA

or polymicrobial infection is suspected following

assessment (see Box 1, p15).

When oral therapy is indicated flucloxacillin is

appropriate, and for the beta-lactam-sensitive patient

erythromycin or clarithromycin, clindamycin, ordoxycycline (except during pregnancy or lactation and for

children) are efficacious. For patients with beta-lactam

sensitivity requiring IV therapy, vancomycin or

clindamycin is usually selected.

For adults with severe SSTIs requiring IV therapy, it is

the authors practice, following administration of an initial

IV dose, to use a continuous infusion of either

flucloxacillin (eg, 12g/24h) or vancomycin (eg, 2g/24h), to

provide the maximum time for the antibiotic to be above

the minimum inhibitory concentration for the suspected

organism. Therapeutic drug monitoring should be

performed for patients receiving vancomycin, aiming for a

random-level concentration of 1015mg/L, with higherconcentrations appropriate for patients with MRSA

bacteraemia.

For patients with necrotising or rapidly progressive

infections, IV clindamycin at a dose of 900mg eight-

hourly is added to enhance cover against toxigenic S

pyogenes. Clindamycin reduces the production of

streptococcal toxic shock protein by its action on bacterial

mitochondria. It is also active when beta-lactams are

rendered ineffective, which occurs during the static

growth phase of streptococci when penicillin binding

protein production is halted.

If polymicrobial infection is suspected the spectrum of

antibiotic cover should be expanded. Typically, forinfected bites co-amoxiclav (IV or oral) is appropriate.

Doxycyline is a suitable oral alternative if the patient is

allergic to beta-lactams. Gentamicin, vancomycin and

metronidazole can be considered as alternatives, but

specialist advice should be sought and therapy adjusted

depending on microbiological results.

Adjunctive measuresAll patients with lower-limb SSTI should be assessed for

signs of T pedis, which should be treated with topical

imidazole antifungal (eg, miconazole) or terbinafine. For

severe tinea infections oral terbinafine may be required.

Rest and leg elevation are also important in speedingrecovery from lower-limb SSTI.

Severe SSTIs should be managed in a high-

dependency setting with broad antibiotic therapy, fluid


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Antibiotic prophylaxis should be considered for patients

requiring repeated IV treatment or hospital admission.

Because streptococcal species are the most frequently

recurring organisms, twice-daily phenoxymethylpenicillin

prophylaxis could be considered. Other options include

doxycycline, co-trimoxazole and erythromycin. For patientswith recurrent, rapidly progressive, severe infections it is

the authors practice to give (with counselling) take-home

antibiotics for use at the earliest sign of infection.

ACKNOWLEDGEMENT The author would like to thank Kirsty

Lattka from medical illustration services at Gartnavel General

Hospital, Glasgow, for arranging the photographs published.

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antibiotic use in Scottish hospitals utilising the Glasgow Antimicrobial

Audit Tool (GAAT). International Journal of Antimicrobial Agents

2007;29:6939.

2 ISD Scotland. Scottish inpatient, day case and outpatient statistics.

www.isdscotland.org/isd/4334.html (accessed 9 December 2008).

3 Carratal J, Rosn B, Fernndez-Sab N, et al. Factors associated with

complications and mortality in adult patients hospitalized for infectious

cellulitis. European Journal of Clinical Microbiology & Infectious

Diseases 2003;22:1517.

4 Kirkland KB, Briggs JP, Trivette SL, et al. The impact of surgical site

infections in the 1990s: attributable mortality, excess length of

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5 Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for thediagnosis and management of skin and soft tissue infections. Clinical

Infectious Diseases 2005;41:1373406.

6 Eron LJ, Lipsky BA, Low DE, et al. Managing skin and soft tissue

infections: expert panel recommendations on key decision points. Journal

of Antimicrobial Chemotherapy 2003;52(s1):i317.

7 Darenberg J, Ihendyane N, Sjlin J, et al. Intravenous immunoglobulin G

therapy in streptococcal toxic shock syndrome: a European randomized,

double-blind, placebo-controlled trial. Clinical Infectious Diseases

2003;37:33340.

8 Seaton RA, Bell, E, Gourlay Y, et al. Nurse-led management of

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9 Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient

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Pharmaceutical Journal Article SSTI