burns 37 (2011) 16–26

available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/burns

Review

Antibiotics and the burn patient

François Ravat a,*, Ronan Le-Floch b, Christophe Vinsonneau c, Pierre Ainaud d,

Marc Bertin-Maghit e, Hervé Carsin f, Gérard Perro g
the Société Française d’Etude et de Traitement des Brûlures (SFETB)
a
Centre des brûlés, Centre hospitalier St Joseph et St Luc, 20 quai Claude Bernard, 69007 Lyon, France
b
Centre des brûlés, Centre hospitalo-universitaire, Nantes, France
c
Centre des brûlés, Groupe hospitalier Cochin, Paris, France
d
Centre des brûlés, Hôpital de la Conception, Marseille, France
e
Centre des brûlés, Hôpital Edouard Herriot, Lyon, France
f
Centre des brûlés, Hôpital d’Instruction des Armées Percy, Clamart, France
g
Centre des brûlés, Hôpital Pellegrin-Tripode, Bordeaux, France

article info abstract

Article history: Infection is a major problem in burn care and especially when it is due to bacteria with
Accepted 13 October 2009 hospital-acquired multi-resistance to antibiotics. Moreover, when these bacteria are Gram-
negative organisms, the most effective molecules are 20 years old and there is little hope of
Keywords: any new product available even in the distant future. Therefore, it is obvious that currently
Antibiotics available antibiotics should not be misused. With this aim in mind, the following review was
Antibiotic therapy conducted by a group of experts from the French Society for Burn Injuries (SFETB). It
Burn examined key points addressing the management of antibiotics for burn patients: when
Burn patient to use or not, time of onset, bactericidia, combination, adaptation, de-escalation, treatment
Bacterial resistance duration and regimen based on pharmacokinetic and pharmacodynamic characteristics of
Pharmacokinetics these compounds. The authors also considered antibioprophylaxis and some other key
Pharmacodynamics points such as: infection diagnosis criteria, bacterial inoculae and local treatment. French
Dosage guidelines for the use of antibiotics in burn patients have been designed up from this work.
# 2009 Elsevier Ltd and ISBI. All rights reserved.

Contents

1. General considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.2. Infection criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.3. Dealing with local infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.4. Role of bacterial population (inoculum) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2. Time for onset of antibiotic therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
3. Bactericidal or bacteriostatic molecules? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
4. Association or monotherapy? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
5. Adaptation of antibiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

* Corresponding author. Tel.: +33 478 61 89 25; fax: +33 478 61 88 77.
E-mail address: fravat@ch-stjoseph-stluc-lyon.fr (F. Ravat).
0305-4179/$36.00 # 2009 Elsevier Ltd and ISBI. All rights reserved.
doi:10.1016/j.burns.2009.10.006
 burns 37 (2011) 16–26 17

6. Duration of antibiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
7. Administration methods (dosage and rhythm of injection) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
7.1. Notions of pharmacokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
7.2. Notions of pharmacodynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
7.3. Regimen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8. Monitoring antibiotic concentrations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
9. Perioperative antibiotic prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
10. Guidelines from the French Society for Burn Injuries (SFETB) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
10.1. Guidelines for antibiotic therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
10.2. Guidelines for antibiotics prophylaxis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
10.3. Practical use. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

A study conducted in the French burns centres during the
summer 2006 pointed out that 19% of inpatients developed
an infection. Although these facts are comparable to those
observed in intensive care units, infection is a major problem
in burn care and especially when it is due to bacteria
with hospital-acquired multi-resistance to antibiotics,
which has been proved to be directly related to the
consumption of antibiotics. Moreover, when these bacteria
are Gram-negative organisms, the most effective molecules
are 20 years old and there is no hope to see any new molecule
available even in the far future. Therefore, it is obvious that
current antibiotics – still active – should not be overused or
misused.
Thus, the French Society for Burn Injuries (SFETB) has
published guidelines for the use of antibiotics in the burn
patient. These guidelines were drawn up by a group of
experts from the SFETB. Analysis of the literature, synthesis
of the relevant items and drafting the guidelines were led by
three members of the group. The changes, definitive draft
and validation were approved collectively by all the experts,
according to the levels of evidence-based medicine [1,2]. The
following text is the review of literature conducted by
the French group of experts prior to the elaboration of
guidelines.
1. General considerations
1.1. Introduction
 Antibiotics should be used by keeping mind that they target
not the patient but the bacteria: the clinician should select
the molecule or molecules with the greatest antibacterial
efficacy and attempt to supply a concentration at the
infection site high enough to kill targeted pathogens
(bactericidia).
 Antibiotics should not allow bacterial resistance to arise by
lowering the selection pressure and thereby limiting the
consequences of antibiotics use in terms of bacterial
ecology. Controlling the prescription of antibiotics, espe-
cially by avoiding useless antibiotic therapy, is an excellent
means to decrease emergence of bacterial resistance [3–5].
 Antibiotics are only one of the means to fight infection.
Antibiotic therapy is part of global hospital strategy as well
as hygiene, and others.
1.2. Infection criteria
Diagnosis of infection in burn patient is not easy because
clinical (hyperthermia) and biological (hyperleukocytosis,
increased CRP levels, etc.) infection criteria are poorly
relevant, especially in heavier-burn patients. Actually, a
serious burn triggers a systemic inflammatory response
syndrome (SIRS), which mimics usual clinical and biological
signs of infection [6–9]. Therefore, deciding an antibiotic
therapy based on such usual infection criteria may lead to the
prescription of useless antibiotics. This has led experts to
define the criteria of infection in burn patient. The retained
criteria are based on those validated for intensive care patients
with two particular characteristics, namely the general criteria
of infection and criteria for burn wound infection. Differenti-
ation between skin infection and colonisation should be
pointed out, as the presence of germs on the wound does not
necessarily mean that it is infected (see Appendix 1).
1.3. Dealing with local infection
Antibiotic therapy prescribed to prevent infection of burned
skin does not actually prevent it and even facilitates the
emergence of multi-resistant bacteria [10]. Diffusion of
antibiotic in the burned skin is questionable and cannot
achieve bactericidal concentrations so that bacteria can grow
and develop resistances. However, local topical agents are
known to be efficient in preventing and treating burned skin
infections [7]. For these two reasons, local infection – that is,
without general symptoms of sepsis – should require only
local treatment.
1.4. Role of bacterial population (inoculum)
The probability of antibiotic-resistant mutant strains appear-
ing within a bacterial population is not void. For example, with
Pseudomonas aeruginosa, the probability of a fluoroquinolone-
resistant strain appearing is estimated at 10 6. The risk of
appearance of resistant strains is therefore directly related to
the size of the bacterial population (inoculum). With P.
aeruginosa, if the size of the bacterial population exceeds
106, the probability of a fluoroquinolone-resistant strain
appearing becomes higher. One of the means of limiting this
probability is to reduce the inoculum [11]. For some infectious
diseases, the reduction of inoculum alone ensures recovery
18 burns 37 (2011) 16–26
without antibiotic therapy or becomes the main treatment
(this is especially the case of skin and soft-tissue infections
[12]). In burn patients, very significant inocula may be
observed during pneumonias and/or infection of burned skin.
In these cases, reducing the inoculum has tremendous impact,
by clearing for pneumonia and debridement (or removal) of
infected burned tissues, respectively.
During bacterial colonisation of tissue, the shift from
colonisation to infection depends on three parameters,
namely the level of the bacterial inoculum, host defences
and bacterial virulence [13–15]. Reducing the inoculum may
therefore contribute to preventing infections.
2. Time for onset of antibiotic therapy
In case of serious infection (i.e., poorly tolerated and/or life
threatening), antibiotic therapy should be started within 6 h
following the diagnosis of infection [16,17] as delayed
antibiotic therapy increases mortality [17–19]. When the
infection is not very serious (i.e., well-tolerated and without
organ failure), initiation of antibiotic therapy can be delayed
until microbiological documentation. In serious undocument-
ed infection, bacteriological sampling should be performed
before starting antibiotic therapy [20], but without delaying it.
As long as the infection is not documented, antibiotic
therapy is empiric. Therefore, broad-spectrum molecules
should be chosen for maximum efficacy. Nevertheless, the
choice for empiric treatment depends on patient ecology,
ward ecology, length of stay, previous antibiotic therapy,
patient condition, and so on.
3. Bactericidal or bacteriostatic molecules?
Burn patients exhibit immune deficiency, which is still
incompletely understood, and mainly affects cell-mediated
immunity (lymphocytes, macrophages and neutrophils) [21].
In these conditions, antibiotic therapy will, by itself, probably
need to be effective, that is, without the help of host defences
[22]. Moreover, the infections observed are often with heavy
inoculae (lung, wound). Bactericidal antibiotics will there help
to reduce inoculum. Lastly, in case of serious infection,
antibiotic therapy will need to be effective quickly. For all
these reasons, bactericidal molecules should be preferred.
4. Association or monotherapy?
The literature does not provide powerful enough data to
recommend combination therapy rather than monotherapy
[23,24] except in particular cases. Nevertheless, combination
therapy has a number of theoretical advantages, namely
broader spectrum (useful in situations of empiric antibiotic
therapy), enhanced bactericidia (more important and with the
quickest bactericidal activity) and prevention of emergence of
resistant strains (especially when inoculum is heavy). The
probability of bacterial resistance to a combination of two
molecules is the product of probability for each molecule (if
each molecule presents with a probability of 10 6, the
probability of the combination is 10 12, which exceeds the
usual inoculae sizes).
Some antibiotics should not be used in monotherapy due
to their high selection risk (fosfomycin, fusidic acid, rifampi-
cin and fluoroquinolones) [11]. Combination therapy is also
recommended against multi-resistant hospital bacteria to
avoid acquisition of new resistances, thereby maintaining
their sensitivity profile [11]. One should remember that the
burn patient is immunocompromised and expresses a
number of factors altering the pharmacokinetics of anti-
biotics [25]; this means that the regimen of antibiotics should
be altered when compared with that recommended in the
healthy volunteer [26]. Antibiotic therapy should be started
immediately and should be effective from the beginning
[11,12,16,17,19].
All these arguments are in favour of the use of antibiotic
combinations for the management of serious bacterial
infections in burn patients.
5. Adaptation of antibiotherapy
Adaptation is a two-stage strategy [19,27,28]:
 Initial clinical approach: start of empirical treatment when
infection is suspected.
 Subsequent bacteriological approach: assessment of initial
treatment based on bacteriological documentation.
Antibiotic therapy should be started immediately [16,17].
Consequently, it is often started though bacteriological
documentation is lacking (empiric antibiotic therapy). This
empiric antibiotic therapy may be inappropriate, and is known
to increase mortality [17,29]. The antibiotic usually chosen has
a broad-spectrum activity (with multi-drug resistant strains
selection risk) although bacteria involved are sensitive to
narrower-spectrum antibiotics [30,31]. In these conditions,
any antibiotic therapy should be assessed after 48–72 h
[12,16,20], as soon as bacteriological results are available.
Antibiotic therapy will have to be adapted to the germ(s)
actually responsible for the infection.
Shifting from broad-spectrum empiric antibiotic therapy to
a narrow-spectrum adapted strategy (guided by the antibio-
gram) is called de-escalation. It should be performed whenev-
er possible [16,20,27,28,32]. De-escalation has two aims,
namely individual benefit (recovery of a patient) and collective
benefit (reducing selective pressure and source of bacterial
resistance).
Three conditions are mandatory for de-escalation.
 Bacteriological documentation available.
 Antibiogram available (bacterial sensitivity to antibiotics
established).
 Improvement of clinical status after 72 h.
There are understandable limits:
 Reliability of bacteriological data (e.g., in the case of
ventilator-associated pneumonia, what type of sample
should be chosen to confirm diagnosis?).
 burns 37 (2011) 16–26
 How to assess the clinical evolution (e.g., which elements
should be used in pneumonia: hyperthermia? arterial blood
gases? imaging?)?
Discontinuation of antibiotic therapy considered useless
may be likened to de-escalation [33].
6. Duration of antibiotherapy
Excepted in few particular situations related to the microor-
ganism and/or severe immune failure, a well-conducted
antibiotic therapy enables a quick inoculum decrease [34].
Prolonged administration of antibiotics is often unjustified
and leads to an increase in selective pressure. Following
several prospective randomised studies conducted in ventila-
tor-associated pneumonia [32,35,36], antibiotic therapy lasting
7–8 days is recommended unless treatment provided initially
was adequate. However, in P. aeruginosa-related infections, a
longer duration is probably necessary [35]. In that case, it is
recommended not to exceed 15 days of antibiotic therapy [37]
or discontinue it after 48–72 h of apyrexia (or disappearance of
signs that led to diagnosis of infection).
7. Administration methods (dosage and
rhythm of injection)
7.1. Notions of pharmacokinetics
In intensive care and burn patients, all pharmacokinetics
parameters (absorption, distribution, metabolism and excre-
tion) of many classes of drugs, including antimicrobials, are
altered, with significant intra-individual variations, and have
been documented over the past 30 years [26,38–44]. The main
clinical consequence is a drop in tissue concentrations. It has
also been demonstrated that low serum concentrations of
antibiotics may lead to both therapeutic failures and emergence
of resistant strains [45]. In addition, the resistance mechanisms
developed by bacteria lead to reduced efficacy of usual dosages
of antibiotic (increase in minimum inhibitory concentration),
and the combination of these factors brings about therapeutic
failures [46]. Consequently, the usually recommended regimen,
suitable for a healthy volunteer, is not recommended and both
daily dosage and regimen should be altered in burn patients.
7.2. Notions of pharmacodynamics
Bactericidal antibiotics may be divided into two groups,
depending on their bactericidal activity profile [47,48]:
 Concentration-related antibiotics. Bactericidal activity is
proportional to the concentration obtained, that is, to the
administered dose: the higher the dose, the stronger the
bactericidal activity. The targeted pharmacokinetic objec-
tive is therefore the highest possible concentration, the only
limit being side effects.
 Time-related antibiotics. Bactericidal activity increases with
the dose but reaches a plateau over which it does not
19
increase further (maximum bactericidal activity). With
these antibiotics, the determining factor is how long does
the concentration surpass the MIC.
7.3. Regimen
The regimen depends on the pharmacodynamic character-
istics of the molecules [47,49]:
 Concentration-related antibiotics (aminoglycosides, fluoroqui-
nolones and fosfomycin) [34,50–54]. The parameter to
consider is the inhibitory quotient (IQ), defined as the ratio
between the maximum concentration (Cmax) and the MIC.
Administration is intermittent; the interval between two
administrations depends on the elimination half-life of the
molecule; it should not exceed 3 times this half-life [55].
Consequently, regimen of aminoglycosides is a single daily
dose (SDD) while, with fluoroquinolones, it consists of
several daily injections (ciprofloxacin 3–4 daily, ofloxacin 3
daily, pefloxacin 2 daily and levofloxacin 2–3 daily).
 Time-related antibiotics (beta-lactams, glycopeptides) [45,56–
58]. Bactericidal activity is slow and poorly related to
concentration. The predictive parameter of therapeutic
success is the time during which the antibiotic serum
concentrations are above the MIC. The aim is therefore to
reach serum concentrations exceeding the MIC 100% of the
time. There are several methods to achieve this, namely
using molecules with a long half-life, shortening the time
period between the two injections or using continuous
intravenous infusion. Continuous infusion regimen seems
to be the optimal choice because it appears to provide more
stable serum levels in burn patients [59–61]. Continuous
infusion needs the injection of a loading dose to achieve
levels above MIC within a reasonable time period. The
loading dose depends on the molecules used [12,16].
8. Monitoring antibiotic concentrations
Historically, antibiotic monitoring was suggested to prevent
toxicity. Nowadays, there is no doubt on its relevance in
guaranteeing, as soon as possible, the efficacy of the molecules
used [38,56,62–64]. A new concept has been defined, based on
the interactions between the pharmacokinetics and pharma-
codynamics of the drug, in which the key factors are serum
levels. The following two situations occur, depending on the
bactericidal activity of the antibiotic considered:
 Concentration-related activity: Achieving an IQ above 10 in
most cases [34,50] and above 20 for P. aeruginosa (or similar
germ)-related infection is recommended. To determine the
IQ, both Cmax and MIC values are requested. MIC of targeted
bacteria can be found by the bacteriology laboratory (E-test
or other technique [65]). When MIC is unknown, the highest
MIC in sensitive bacteria (low critical concentration (LCC))
can be found by local scientific societies or CDC and should
be the value used to calculate IQ.
To measure the maximum concentration (Cmax), sam-
pling should proceed 30 min after the end of the injection,
20 burns 37 (2011) 16–26
with the exception of ciprofloxacin, where a sample must be
taken as soon as infusion is completed, due to the fast
diffusion of the molecule. With aminoglycosides, concen-
tration measurement just before the second injection
(through concentration) is recommended. It will help assess
the risk of toxicity.
 Time-related antibiotics: When the continuous infusion regi-
men is chosen, monitoring blood concentrations by steady
state (Css) is mandatory. The experts recommend a Css
between 4 and 5 times the MIC [59]. In some particular cases,
such as Pseudomonas infections, targeted Css could be 10
times the MIC [57]. The half-life of most (except for
ceftriaxone, ertapénème, doripenem, céfépime and teico-
planin) is short. Provided that the steady state is reached
after 5 T1/2b, samples for Css monitoring can be obtained by
the day following onset of the compound [59]. The steady
state is more quickly achieved after the administration of a
loading dose. Furthermore, with time-related antimicro-
bials, initiating continuous infusion without loading dose
will probably lead to initial low concentrations, when
inoculum and thereby risk of resistance selection is higher.
In the continuous infusion regimen, the sample can be
obtained for monitoring at any moment when the steady
state is thought to be achieved.
9. Perioperative antibiotic prophylaxis
In burn patients, antibiotic prophylaxis is only relevant during
the perioperative period as discussed above [10]. It aims to
fulfil three objectives [66,67]:
 Reduce local inoculum and enhance grafts intake.
 Decrease wound-borne bacteraemia.
 Do not increase selection pressure.
Antibiotic prophylaxis rules had been defined and spread
worldwide by several consensus conferences driven by other
scientific societies [68]. These are:
 Antibiotic prophylaxis should be started early enough before
surgery (approximately 1 h 30 min, usually just before
anaesthesia induction).
 Half of the initial dose should be re-injected every 2 half-
lives of the molecule (for oxacillin, the re-injection should be
practised every 4 h).
 Antibiotic prophylaxis lasts at least 24 h and should never
exceed 48 h.
 If repeated injections are likely, continuous infusion after
loading dose is possible, provided pharmacodynamics of the
molecule is suitable (time-related bactericidal molecules).
10. Guidelines from the French Society for
Burn Injuries (SFETB)
The following guidelines have been established according to
the levels of evidence-based medicine [1,2]. They have been
validated by Société Française d’Etude et de Traitement des
Brûlures in June 2008. They are available at www.sfetb.org or
www.brulure.org.
10.1. Guidelines for antibiotic therapy
 No antibiotics without proven infections (level 1)
 A local infection requires a local treatment (level 1)
However, when the local infection is associated with
general signs of infection, experts consider that the
infectious process is no longer purely local and that use
of an antibiotic may be indicated.
 Attempt to reduce the bacterial inoculum (level 5)
 Antibiotics in serious infections is an emergency (level 1)
 Use bactericidal antibiotics (level 5)
 Know how to combine antibiotics (level 5)
Experts recommend the use of antibiotic combinations
for the management of serious bacterial infections
during, at least, the first 72 h of the infection.
 Adapt antibiotic therapy (level 1)
Any antibiotic therapy should be assessed within 48–
72 h, as soon as bacteriology is available. Antibiotic
therapy should be adapted to the germ(s) responsible of
the infection.
 Practise de-escalation (level 5)
Anytime possible, shift broad-spectrum antibiotic for
narrow-spectrum one guided by the antibiogram.
 When to stop antibiotics therapy (level 5)
Antibiotic therapy lasting 7–8 days is recommended,
provided initial treatment was accurate.
In P. aeruginosa infections antibiotherapy should not
exceed 15 days.
 Respect the regimen (level 1)
With concentration-related antibiotics, administration is
intermittent and the interval between two injections
should not exceed 3 times its half-life.
With time-related antibiotics, continuous infusion after
the loading dose should be used.
In any burn patient, but those with kidney and/or liver
failure, higher dosage than usually recommended is
needed.
 Antibiotic monitoring is mandatory (level 2)
With concentration-related antibiotics, IQ over 10 should
be achieved (20 in P. aeuginosa infections).
With time-related antibiotics, experts recommend to
achieve a concentration at steady state between 4 and 5
times the MIC.
10.2. Guidelines for antibiotics prophylaxis
In burn patients, antibiotic prophylaxis could be used in
patients needing invasive surgery (excisions, flaps, etc.) but
not in dressing changes. The experts recommend [68] (level 5):
 No identified local infection and undefined bacterial target.
Target methicillin-sensitive Staphylococcus, that is, oxa-
cillin or cloxacillin (30 mg kg 1) or first-generation ceph-
alosporin (30 mg kg 1). In case of allergy, clindamycin
should be used (10 mg kg 1).
 No identified local infection but isolation of a pathogen on
skin samples.
 burns 37 (2011) 16–26 21

Target this one.  To the burns

 Documented or non-documented local infection. - Presence of pus
This is no longer prophylaxis, as the infection is ongoing. - Rapid cleansing and detachment
Administration should follow the usual rules about - Appearance of blackish marks (necrosis or haemor-
curative treatment and consider the identified or rhage)
presumed pathogen. - Unexplained conversion of a lesion from superficial to
 Application of inert skin substitute such as artificial dermis. deep (>48th hour)
In the absence of guidelines in the literature, the experts  To the donor graft sites
suggest if bacteria are isolated from skin samples, target - Presence of pus
them. Otherwise, target Staphylococcus. - Unexplained delayed healing
- Scab
10.3. Practical use  To the recipient grafts
- Presence of pus
For examples of regimen for some antibiotics in burn patients, - Lysis of grafts
see Appendix 2. - Necrosis of fat located under the graft
 To the healed areas
- Impetigo
Conflict of interest statement - Lysis of healed areas
(2) Bacteriological skin samples:
The authors have no financial interests to declare. They are used to find out the germ(s) involved.
More often, a simple swab is enough.
The biopsy is never systematic. It might be performed in
Appendix A difficult cases, followed by

General definitions  Microbiology examination

- Direct microscope examination with staining and
No predictive value of infection semi-quantitative measurement of germs
 In adults, presence of SIRS: two or more criteria of the four - Quantification of germs present per gram of tissue
below: after homogenate status: threshold of 105 CFU g 1 is
T (8C)>38.5 8C or <36 8C, retained as significant of the risk of haematogenous
Heart rate >90 bpm, dissemination
RR >20 per minute or capnia <25 mmHg,  An extemporaneous pathology examination after
Leucocytes >12 G or <4 G or >10% of immature forms. freezing enabling one to appreciate the level of
 Any burn patient >20% BSA and/or with smoke inhalation invasivity
injury is likely to present with SIRS criteria in any infectious - Colonisation: germs in the non-vascularised tissue
process. - Infection: germs in the living tissue and in contact with
vessels
(3) Summary:
Predictive values of infection Skin infection with general signs is considered as a
 Appearance of SIRS criteria in an adult whose lesions are systemic infection originated from skin.
<15% or 20% BSA and without any smoke inhalation injury.
 Two or more of the four criteria below in an adult with a burn
General signs + + + +
>BSA and/or with smoke inhalation injury:
Local signs + + + +
- T (8C) >39.5 8C or <35.5 8C,
Skin culture + + + +
- 50% basal HR, Skin infection + S + S + ? +
- 50% basal RR,
- or 100% of number of leucocytes,
- Haemodynamic failure with onset or enhancement of Fungal skin infection
catecholamine treatment. The diagnosis may be confirmed with a biopsy.

Herpes skin infection

Definitions of infection criteria for burned skin The diagnosis is clinical and may be confirmed with the
onset of a serology conversion and the presence of the virus in
The diagnosis of a skin infection is clinical. local samples.

Bacterial infection
(1) Positive local signs: Definitions of infection criteria for the other sites
 Presence of a local or loco-regional inflammatory
reaction Definitions per site (below) originate from those main-
 Unfavourable and unexpected local evolution tained by the CCLIN (French Central Comity for Struggle
22 burns 37 (2011) 16–26
Against Nosocomial Infections), the survey of the REA-
REACAT/RAISIN 2006 monitoring network. These definitions
are taken up in the ‘Guide de définition des infections
nosocomiales’ – of the CCLIN Paris-Nord (1995), itself adapted
from 1988 CDC definitions (CDC definitions for nosocomial
infections, Gardner JS, Jarvis WR, Emori TG, et al., Am J Infect
Contl 1988;16:128–40.) and the 1992 CSHPF (100 recommanda-
tions pour la surveillance et la prévention des infections, BEH
June 1992) (100 guidelines for the monitoring and prevention of
infections).
Lung infection
Pneumonia
General signs + specific organ signs  microbiological cri-
teria:
 At least two chest X-rays, with new image of pneumonia or a
change of a previous image
 At least one of the following signs (two in the absence of
microbiological criteria):
- Appearance of purulent secretions or change in their
characteristics (colour, smell, consistency and
quantity)
- Dyspnoea, tachypnoea or cough (if not ventilated)
- Recent onset or worsened hypoxemia
 Microbiological diagnosis (one of the following criteria):
- BAL with a threshold of 104 CFU ml 1 or 5% of cells with
direct bacterial inclusion
- Wimberley brush technique with a threshold of
103 CFU ml 1
- PDP with threshold of 103 CFU ml 1
- Quantitative bronchial aspiration with a threshold of
106 CFU ml 1
- Blood culture or positive sample of bronchial tissue
(histology) or pleural fluid in the absence of any other
source of infection
- Specific examinations for viral pneumonia or pneumonia
due to particular microorganisms (Ag or Ac in bronchial
secretions, direct examinations or positive cultures of
bronchial secretions, urinary antigens or serology con-
versions)
Bronchitis
General signs, cough, recent change in expectorations or
bronchial aspirations, bronchial crepitations + isolation of
germ(s) in bronchial aspirations + no radiological sign of
infection.
Bacteraemia
General signs + positive blood culture(s):
 At least one blood culture (sample taken during a tempera-
ture peak) positive to a germ known to be a pathogen
 Two blood cultures in a maximum interval of 48 h
(sample taken during a temperature peak) positive to one
of the following germs: coagulase-negative Staphylococcus,
Bacillus sp., Corynebacterium sp., Propionibacterium sp., Micro-
coccus sp. and Acinetobacter sp.
 If bacteraemia is the consequence of another infection or is
responsible for secondary localisations, local signs of
infection will be associated.
 In case of central venous catheter (CVC)-associated bacter-
aemia, the following will be necessary:
- Positive blood culture in presence of a CVC (or withdrawn
within 48 h) in the absence of any other infection to the
same germ
- AND one of the following criteria:
- 103 CFU ml 1 of the same germ in quantitative culture of
the catheter
- Differential blood cultures with CVC/periph 5 or positiv-
ity time period CVC/periph 2 h to the same germ.
Infection of central catheter
Local or general infection signs with all the following
criteria:
 No blood culture to the same germ
 CVC culture 103 CFU ml 1
 Regression of the infectious syndrome within 48 h following
catheter withdrawal
Urinary tract infection
 Positive urine cytology (104 leucocytes ml 1)
 Asymptomatic (without general signs):
- Bladder catheter within past 7 days: urine culture
105 CFU ml 1 if the patient has had urinary catheter
insertion within the previous 7 days.
- In the absence of urinary catheterisation, no bladder
catheter: two consecutive urine cultures 105 CFU ml 1 to
the same germ(s) without the presence of more than two
species (no more than two different species)
 Symptomatic (general signs):
- Urine culture 105 CFU ml 1 (at maximum of two species)
or
- or 103 CFU ml 1 with 104 leukocytes ml 1 and general
signs
Appendix B
Methods of administration of some antibiotics in burn
patients.
Beta-lactams
Beta-lactams are time-related bactericidal antibiotics.
They should be administered by continuous infusion
whenever possible [55,69–73].
Continuous perfusion is immediately preceded by a
loading dose, depending on the molecule [12,16], and is
usually equal to a single dose in repeated administration
regimen.
Continuous administration is sometimes rendered difficult
by poor stability of the molecule along time (clavulanic acid
and imipenem), physical and chemical incompatibility of
molecules and differences in the pharmacokinetics of a
molecule and its co-factor (amoxicillin–clavulanic acid/imi-
penem–cilastatin).
 burns 37 (2011) 16–26 23

Penicillins Iimipenem
Continuous infusion
Cloxacillin and oxacillin 50–100 mg kg 1 daily
Continuous infusion Loading dose 10 mg kg 1
150–200 mg kg 1 daily Stability: 3 h 30 min at 25 8C
Loading dose 50 mg 1 kg 1 Targeted steady-state concentration is at 16–20 mg l 1 or 4–5 times
1
Targeted steady-state concentration is at 8–10 mg l or 4–5 times MIC. For germs at risk (specifically Acinetobacter baumanii) it is 32–
the MIC. 40 mg l 1 or 8–10 times MIC

Amoxicillin, amoxicillin + clavulanate Fluoroquinolones

Continuous infusion
150–200 mg kg 1 daily
Concentration-related bactericidal antibiotics active on
Loading dose 50 mg 1 kg 1
Targeted steady-state concentration is at 64–80 mg l 1 or 4–5 times
Gram-negative and Gram-positive bacteria [74]. These pro-
the MIC. ducts should be administered repeatedly. The frequency of
Amoxicillin: stable 6 h at 25 8C in NaCl solvent. In case of electric injections is determined by the half-life of the molecules [74].
syringe administration, replace the syringe every 6 h. Only few data about pharmacokinetics of fluoroquinolones
Amoxicillin–clavulanate: clavulanate tends to accumulate because such as ciprofloxacin being available, the experts can only
its half-life is longer than amoxicillin’s. In continuous infusion
provide guidelines for ciprofloxacin.
regimen, mix 50% amoxicillin and 50% as amoxicillin–clavulanate
and change syringe every 6 h. In repeated injections regimen, the
Ciprofloxacin [26,75]
recommended targeted concentration (16–20 mg l 1) is a trough
Repeated administration
concentration.
3–4 injections daily
10–20 mg kg 1 per injection (total dose 30–80 mg kg 1 daily)
Carboxy- and Ureidopenicillins Infuse for 30 min. Sample for Cmax immediately at the end of the
injection (due to the very quick diffusion time of the molecule)
Ticarcillin, ticarcillin + clavulanic acid Target (Cmax): >30 mg l 1 (optimal = 40 mg l 1) or >10 times the
Continuous infusion MIC
150–200 mg kg 1 daily Beware of occult water administration (0.5 ml per mg ciproflox-
Loading dose 50 mg 1 kg 1 acin)
Targeted steady-state concentration 64–80 mg l 1 or 4–5 times the
MIC
Ticarcillin: stable for 24 h at 25 8C Aminoglycosides
Ticarcillin–clavulanic acid: stable for 6 h at 25 8C. Clavulanate tends to
accumulate because its half-life is longer than ticarcillin’s. In Concentration-related bactericidal antibiotics.
continuous infusion regimen, mix 50% ticarcillin and 50% ticarcil-
Single daily dose (SDD).
lin–clavulanate and change syringe every 6 h. In repeated injections
The dosage should be increased in burn patients [42].
regimen, the recommended target concentration (16–20 mg l 1) is a
trough concentration
Amikacin
30 mg kg 1 once a day
Piperacillin, piperacillin + tazobactam
Infuse for 60 min
Continuous infusion
Sample for peak concentration 30 min after the end of infusion
At least 200 mg kg 1 daily
Targeted peak value: >80 mg l 1 or >10 times the MIC
Loading dose 50 mg kg 1
Sample for trough concentration immediately before the second
There are no stability or accumulation problems. Targeted steady-
infusion
state concentration is reached at 64–80 mg l 1 or 4–5 times the MIC
Trough concentration < 5 mg l 1

Cephalosporins
Gentamicin, tobramycin and netilmicin
10 mg kg 1 once a day
Cefotaxime
Infuse for 60 min
Continuous infusion
Sample for peak concentration 30 min after the end of infusion
100–150 mg kg 1 daily
Targeted peak value: >20 mg l 1 or >10 times the MIC
Loading dose 25 mg kg 1
Sample for trough concentration immediately before the second
Stability: 3 h 30 min at 25 8C
1 infusion
Targeted steady-state concentration is at 16–20 mg l or 4–5 times
Trough concentration < 2 mg l 1
MIC

Ceftazidime
Continuous infusion Glycopeptides
100–150 mg kg 1 daily
Loading dose 25 mg kg 1
Administration in soft bags with volumetric pump is preferred due Vancomycin
to the risk of gas release, but continuous administration with electric Continuous infusion
syringe is possible 30 mg kg 1 per day
Targeted steady-state concentration is at 16–20 mg l 1 or 4–5 times Loading dose = 5 mg kg 1
MIC. For germs at risk (specifically ticarcillin-R P. aeruginosa), the Concentration at steady state: 20–30 mg l 1. Sample can be taken
targeted steady-state concentration is 32–40 mg l 1 or 8–10 times MIC any time, more than 12 h after infusion onset
24 burns 37 (2011) 16–26
Oxazolidinones
[17]
a et al. Duration of hypotension before initiation of effective
Linezolide
Spectrum limited to Gram-positive cocci. Bactericidal activity
limited to streptococci [76].
[18]
Continuous infusion (time-related bactericidal activity)
1200 mg daily in adults
Loading dose = 5 mg kg 1
Target concentration is 10 mg l 1 or 5 times the MIC
a [19]
Few data available by this day [77–79].
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