Vol 1
January 2009
Clinical Pharmacist
By R A Seaton, DTM&H, FRCP(Edin)
kin and soft tissue infections (SSTIs) comprise an
important and diverse group of anatomically and
aetiologically distinct infections. In UK hospitals,
3–4% of patients receive treatment for SSTI. Of these,
47% receive intravenous (IV) therapy, accounting
for 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 comorbidity 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).
S
Superficial SSTIs
For people who develop superficial SSTIs, the causative
organisms are usually Staphylococcus aureus and Streptococcus
pyogenes.
Impetigo is a superficial SSTI rarely associated with
systemic 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 a
range 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.
Andrew Seaton is consultant in infectious diseases
and general medicine at the Brownlee Centre,
Gartnavel General Hospital, Glasgow.
E: andrew.seaton@ggc.scot.nhs.uk
SUMMARY
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.
Cellulitis and erysipelas are pathologically distinct
dermal 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
Staphylococcus aureus bacteria (coloured scanning electron micrograph)
Gopal Murti | SPL
For personal use only. Not to be reproduced without permission of the editor (permissions@pharmj.org.uk)
Skin and soft tissue infection
diagnosis and management
CLINICAL FOCUS
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
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Vol 1
Box 1: Microbial causes of SSTI
CLINICAL PRESENTATION
CAUSATIVE ORGANISMS
Impetigo, folliculitis, furunculosis,
carbuncles, cellulitis and erysipelas
Staphylococcus aureus and Streptococcus
pyogenes
Necrotising infections
S aureus, S pyogenes, clostridial species, gramnegative organisms and polymicrobial species
Infections following human or
animal bites
S aureus, aerobic and anaerobic streptococci,
Fusobacterium and Pasteurella spp;
capnocytophaga (in animals)
Surgical site infections
S aureus, beta-haemolytic streptococci; genital
tract or abdominal surgery consider gramnegatives and anaerobes
Infections in immunocompromised
patients
S aureus, S pyogenes, gram-negatives including
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 hydrophilia and
Mycobacterium marinum
Travel-related SSTI
S aureus, S pyogenes, endemeic mycoses,
Mycobacterium ulcerans, Leishmania spp, and others
Necrotising SSTIs
Necrotising 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 more
superficial 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 the
dermis 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 may
be a dusky discoloration to the skin (Figures 5a and 5b,
p16).
Myositis involves muscle and two distinct groups are
recognised: 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 soft
tissue infection involving muscle groups, in addition to
superficial skin and fascia (Figure 6, p17).
Figure 1: Skin blistering in cellulitis. Typically seen
in beta-haemolytic streptococcal infections
Clinical Pharmacist
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, systemic
inflammatory 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 factors
Irrespective 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
Figure 2: Facial erysipelas. Typical of
Streptococcus pyogenes infection
Figure 3: Facial cellulitis with periorbital oedema
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CLINICAL FOCUS
(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 (more
common in the summer months). It may also complicate
Tinea pedis or 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).
January 2009
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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 48
hours after an incision and is characterised by localised
wound-related erythema, heat, induration and purulent
discharge.
Involvement of deep structures should always be
considered and management depends on the surgical site.
In hospitals, S aureus dominates 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 the
depth 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 oral
flora: S aureus, aerobic and anaerobic streptococci,
clostridial species, fusobacteria and gram-negative
bacteria. With animal bites Pasteurella spp and
capnocytophaga are also important.
Figure 4: Progressive cellulitis due to group B streptococcus, complicating
lymphoedema and morbid obesity
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 hydrophilia are frequently responsible.
In hospitals some hydrophilic organisms such as
pseudomonas and stenotrophomonas can also cause
SSTIs, 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.
association with neutropenia, organ transplant or longterm 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 not
uncommon in migrants or people returning from abroad.
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 of
commensal 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 aureus and betahaemolytic streptococci, are usually implicated.
Clostridial species, particularly C perfringens and 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 pyogenes as 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
Sporothrix spp) are less frequently seen, but may occur in
Figure 5a: Necrotising fasciitis due to Streptococcus
pyogenes showing blistering in lower leg
Figure 5b: Dusky skin discoloration extending over buttock
and flank indicating progressive infection
Vol 1
Clinical Pharmacist
Figure 6: Healthcare-associated synergistic necrotising
cellulitis due to Stenotrophomonas maltophilia
Investigation and management of SSTIs
Severity of SSTI can be determined by several clinical
factors: extent and intensity of inflammation; distribution
and depth of infection; presence of systemic inflammatory
response; and significant co-morbidities. These markers
will help clinicians decide a patient’s suitability for
treatment in the community or hospital and whether
parenteral or oral therapy is appropriate (Figure 9, p21).
Consideration of these factors will direct the
antimicrobial therapy.
Folliculitis and furuncles are usually treated by GPs
using topical antibiotic treatment, or short-course oral
therapy if the infection fails to respond. Imprudent and
prolonged topical therapy is not advised due to the risk of
promotion of bacterial resistance. More extensive SSTIs
— such as localised and limited cellulitis with no systemic
inflammatory response or significant co-morbidities, and
with no compounding microbiological risk factors — can
be safely managed with oral antibiotic therapy in the
community and without hospital admission.
If signs of localised inflammation persist or worsen
then parenteral therapy either as an outpatient or
inpatient is indicated. Patients with cellulitis or erysipelas,
with significant heat, erythema and induration, generally
require parenteral therapy. Deep-seated and necrotising
infections always require hospital admission for parenteral
therapy and surgical intervention. Patients with postoperative wound infections, particularly following joint or
abdominal (or perineal) surgery, should also be admitted
for surgical assessment.
For all patients treated with parenteral therapy or
managed in the hospital environment, attempts should be
made to establish a microbiological diagnosis. In almost all
patients with cellulitis or erysipelas there is no exudate
and therapy is empiric. Swabs in these circumstances may
give misleading results, although evidence of meticillinresistant S aureus (MRSA) carriage does influence
empirical choice. Blood cultures are rarely positive.
Nevertheless, they are important prognostically and in
directing route and duration of therapy, and, therefore,
form part of the severity assessment.
Patients with a discharging wound should have a swab
performed. However, results should be interpreted with
some caution as they may reflect commensal flora. Ideal
specimens are obtained aseptically in theatre from the
inflamed tissues. In the case of severe SSTI, it is not
appropriate to delay antibiotics in order to obtain
microbiological specimens and, therefore, specimens are
usually obtained after starting parenteral therapy.
Other useful investigations include full blood count,
renal function and C reactive protein (CRP). The latter is
often normal in patients with cellulitis and erysipelas but
is raised in those with severe infections where there is a
systemic inflammatory response. CRP can also be useful
in the monitoring of more severe infections, particularly
when the microbial cause is uncertain. Plain radiographs
are useful to assess for subcutaneous gas and soft-tissue
Figure 7: Staphylococcus aureus infection following
saphenous vein harvesting for coronary artery bypass graft
❝
IN THE CASE OF
SEVERE SSTI, IT IS
NOT APPROPRIATE
TO DELAY
ANTIBIOTICS IN
ORDER TO OBTAIN
MICROBIOLOGICAL
SPECIMENS
Figure 8: Staphylococcus aureus infection with deep venous
thrombosis in a groin-injecting drug user
❞
oedema. Radiographs are less useful in assessing for acute
bony involvement. Computerised tomography and
ultrasound examination are used to assess for deep-tissue,
bone and joint involvement and for abscess formation. In
rapidly progressive necrotising infections, surgical
management may be both diagnostic and therapeutic —
exploring and debriding fascial planes and muscle
compartments to determine the extent and severity of the
infection.
Antibiotic therapy
Antibiotic choices for SSTI vary between specialties and
institutions, reflecting differing patient populations,
anatomical site, resistance patterns, MRSA risk (see
accompanying article, p23) and local policy.
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CLINICAL FOCUS
In addition to the usual bacterial species, infection with a
variety of endemic mycoses, mycobacteria (eg, M
tuberculosis and M ulcerans) and parasites (eg, Leishmania
spp) are possible, depending on the source of exposure.
January 2009
CLINICAL FOCUS
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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 IV
treatment — 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
author’s 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, or
doxycycline (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 author’s 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 10–15mg/L, with higher
concentrations appropriate for patients with MRSA
bacteraemia.
For patients with necrotising or rapidly progressive
infections, IV clindamycin at a dose of 900mg eighthourly 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, for
infected 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 measures
All 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 speeding
recovery from lower-limb SSTI.
Severe SSTIs should be managed in a highdependency setting with broad antibiotic therapy, fluid
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 therapy
Outpatient parenteral antibiotic therapy (OPAT) is a
means 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.
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
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
Vol 1
January 2009
Clinical Pharmacist
CLINICAL FOCUS
Figure 9: Clinical decisions for skin and soft tissue infection — IV versus oral therapy and hospital versus home care
• Significant localised heat, erythema and induration
• Unable to tolerate oral therapy
• Failure with previous oral therapy
IV therapy for SSTI
Hospital admission
for non-SSTI
factors
Hospital admission
for specific
SSTI/sepsis
management
•
•
•
•
•
Active substance misuse
Uncontrolled co-morbidity
Mental incapacity and lack of appropriate carer
Unable to travel to hospital for therapy
No telephone
•
•
•
•
•
Severe localised pain
New onset of confusion
Rapidly evolving skin lesions or skin blistering
Systolic blood pressure <100mmHg
Sepsis syndrome (any two of: heart rate >100 beats/min,
respiratory rate >20 breaths/min, temperature >38C or <36C,
white cell count >12 or <4 x109 cells/L)
support (Figure 9, above). When infection is non-severe
and rapidly improving, and when there is an appropriate
oral agent and swallowing and absorption are not
compromised, OPAT is not appropriate — unless the
infecting organism is resistant to the available oral
therapies. An OPAT antibiotic should be appropriate for
the suspected infecting organism, have proven efficacy in
SSTI and have a predictable and non-life-threatening
toxicity profile. Because OPAT is usually of short
duration, once-daily treatment is preferred, combined
with clinical review to ensure timely consideration of
simplification to oral therapy. For those without true
penicillin allergy and at low risk of MRSA, IV or IM
ceftriaxone is used.8
Ceftriaxone is bactericidal against both streptococci
and meticillin-sensitive staphylococci, with activity
against community-acquired enterobacteriaceae. The
drug’s half-life is seven to eight hours and serum
concentrations suitable to clear most meticillin-sensitive S
aureus and streptococcal species are maintained
throughout most of the once-daily dosing interval.10
Ertapenem has broad cover (with additional sensitivity
against anaerobes), its half-life is long (hence once-daily
dosing) and it is suitable for polymicrobial infections,
particularly infected bites. Ceftriaxone is preferred for
OPAT because of its lower cost and long-term experience
with its use.
Teicoplanin is highly protein-bound, has a long halflife and has a good tolerability profile with a sound track
record in SSTI. It is, therefore, a suitable alternative to
ceftriaxone for patients with true beta-lactam allergy.
Intravenous-to-oral antibiotic switch
Switching antibiotics from IV to oral should occur after a
significant reduction in heat, erythema and induration, and
with resolution of the systemic inflammatory response.
The median duration of IV therapy is three to five days
and it is unusual for patients to require IV antibiotics for
more than 10 days. Oral treatment following IV therapy
should be as for initial oral therapy (as above) and
continued for a further five to seven days. Guidelines have
been developed by some NHS organisations for suitably
trained and experienced non-medical prescribers to
facilitate rapid, streamlined IV-to-oral switching in OPAT
without the need for scheduled medical input.8
Prevention of recurrent SSTI
Lymphoedema, obesity, diabetes and chronic recurrent T
pedis predispose individuals to recurrent SSTI. In frequent
recurrences, underlying bony involvement should be
considered. Patients with lower-limb SSTI should be
counselled on suitable footwear and on prevention of
tinea recurrence by regular cleaning and drying of the
web spaces and early antifungal therapy.
21
❝
THE MEDIAN
DURATION OF IV
THERAPY IS THREE
TO FIVE DAYS AND IT
IS UNUSUAL FOR
PATIENTS TO
REQUIRE IV
ANTIBIOTICS FOR
MORE THAN 10 DAYS
❞
CLINICAL FOCUS
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January 2009
Vol 1
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 patients
with recurrent, rapidly progressive, severe infections it is
the author’s 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.
3
Carratalà J, Rosón B, Fernández-Sabé N, et al. Factors associated with
complications and mortality in adult patients hospitalized for infectious
cellulitis. European Journal of Clinical Microbiology & Infectious
Diseases 2003;22:151–7.
4
Kirkland KB, Briggs JP, Trivette SL, et al. The impact of surgical site
infections in the 1990s: attributable mortality, excess length of
hospitalization and extra costs. Infection Control and Hospital
Epidemiology 1999;20:725–30.
5
Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the
diagnosis and management of skin and soft tissue infections. Clinical
Infectious Diseases 2005;41:1373–406.
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):i3–17.
7
Darenberg J, Ihendyane N, Sjölin J, et al. Intravenous immunoglobulin G
therapy in streptococcal toxic shock syndrome: a European randomized,
double-blind, placebo-controlled trial. Clinical Infectious Diseases
2003;37:333–40.
8
Seaton RA, Bell, E, Gourlay Y, et al. Nurse-led management of
uncomplicated cellulitis in the community; evaluation of a protocol
incorporating intravenous ceftriaxone. Journal of Antimicrobial
Chemotherapy 2005;55:764–7.
9
Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient
parenteral antimicrobial therapy. Clinical Infectious Diseases
2004;38:1651–72.
References
1
Seaton RA, Nathwani D, Burton P, et al. Point prevalence survey of
antibiotic use in Scottish hospitals utilising the Glasgow Antimicrobial
Audit Tool (GAAT). International Journal of Antimicrobial Agents
2007;29:693–9.
2
ISD Scotland. Scottish inpatient, day case and outpatient statistics.
www.isdscotland.org/isd/4334.html (accessed 9 December 2008).
10 Scully BE, Fu KP, Neu HC. Pharmacokinetics of ceftriaxone after
intravenous infusion and intramuscular injection. American Journal of
Medicine 1984;77:112–6.