Iranian Red Crescent Medical Journal

REVIEW ARTICLE

Pseudomonas aeruginosa: Burn Infection, Treatment

and Antibacterial Resistance

A Japoni1*, S Farshad1, A Alborzi1

1
Prof Alborzi Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of
Medical Sciences, Shiraz, Iran

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen causing severe, acute and chronic nosocomial infections
in immunocompromised, catheterized or burn patients. Various types of virulent factors have been identified in P.
aeruginosa, suggesting their contribution to the pathogenesis of the disease. The organism is generally resistant
to numerous antimicrobial agents due to natural resistance in particular impermeability or mutations and acquisi-
tion of resistant determinants. Plasmid and integron have a crucial role in acquisition of mobile elements. Most
treatment failures are related to inappropriate initial antibiotic therapy with insufficient coverage of multidrug
resistant (MDR) pathogens, the rationale for using combinations of antibiotics to cover MDR gram-negatives.
However, clinical data supporting this strategy are limited. In fact, systematic combination therapy may have
contributed to the overuse of antibiotics and to the emergence of MDR microorganisms. Nevertheless, combina-
tion therapy is the best strategy to treat severe infections due to suspected MDR Pseudomonas. Optimally,
therapeutic strategies should be sufficiently broad to cover relevant pathogens while minimizing the risk for
emergence of antimicrobial resistance. Polymyxin E (colistin) and carbapenems are the most effective antibiotics
against MDR isolates.
Keywords: Pseudomonas aeruginosa; Multidrug-resistance; plasmid; Integron

Introduction host defense such as burn patients. While many

cases of P. aeruginosa infection can be attributed to
Pseudomonas aeruginosa is a gram-negative rod general immunosuppression (e.g. AIDS patients),3,4
measuring 0.5 to 0.8 µm by 1.5 to 3.0 µm. Almost in neutropenic patients undergoing chemotherapy,5
all strains are motile by means of a single polar fla- such scenarios predispose the host to a variety of
gellum. It is a free-living bacterium, commonly bacterial and fungal infections, and therefore do not
found in soil and water. This bacterium, a member yield information which is specific to the pathogene-
of the gamma proteobacteria, is a gram-negative, sis of P. aeruginosa. In this respect, three of the
aerobic rod belonging to the bacterial family pseu- more informative human diseases caused by P.
domonadaceae.1 Based on conserved macromole- aeruginosa are: 1) bacteremia in severe burn vic-
cules (e.g. 16S ribosomal RNA), the family includes tims; 2) chronic lung infection in cystic fibrosis pa-
only members of the genus Pseudomonas which are tients; and 3) acute ulcerative keratitis in users of
cleaved into eight groups. P. aeruginosa is a typical extended-wear soft contact lenses. Observations and
species of its group which contains 12 other mem- experimental evaluation of various bacterial viru-
bers.2 Almost all the clinical cases of P. aeruginosa lence factors have shed a great deal of light on how
infection can be associated with the compromise of P. aeruginosa is able to cause disease in a wide va-
riety of organs, secondary to disruption of the nor-
*Correspondence: Aziz Japoni, PhD, Professor Alborzi Clinical mal physiologic function. Such insights provide an
Microbiology Research Center, Nemazee Hospital, Shiraz understanding at the molecular and cellular level of
University of Medical Sciences, Shiraz, Iran. Tel: +98-711-6474264, how and why P. aeruginosa has become such an
Fax: +98-711- 6474303, e-mail: [email protected]
Received: February 05, 2009 Accepted: April 10, 2009 important pathogen in human infection.

IRCMJ 2009; 11(3):244-253 ©Iranian Red Crescent Medical Journal

 Burn infections with P. aeruginosa

P. aeruginosa Bacteremia in Severe Burn tion of bacterial elastase and other proteases.12 Elas-
Victims tase has been shown to degrade collagen and non-
collagen host proteins, and to disrupt the integrity of
Bacterial infection following severe thermal injury the host basement membrane.13 Proteases can have
can be most simplistically attributed to extensive adverse effects on several aspects of the innate and
breaches in the skin barrier. The fact that P. aerugi- acquired host immune response. For example, elas-
nosa occurs so commonly in the environment makes tase inhibits monocyte chemotaxis,14 which could ad-
it extremely likely that an individual suffering severe versely affect early clearance of P. aeruginosa from
burns will be challenged with this microorganism be- wound sites by phagocytosis, as well as subsequent
fore the burns can heal. Burn hospitals often harbor presentation of bacterial antigens to the host immune
multidrug-resistant P. aeruginosa that can serve as system.15 The lasR gene encodes a protein critical for
the source of infection. P. aeruginosa has been found initiation of the quorum sensing response involved in
to contaminate the floors, bed rails, and sinks of hos- virulence factor production and biofilm formation,
pitals, and has also been cultured from the hands of indicating that other factors controlled by lasR are
nurses.6 Besides transmission through fomites and critical determinants of P. aeruginosa pathogenesis in
vectors, bacterial flora can be carried into a hospital burn wound infection.16 Other P. aeruginosa viru-
by the patient and can be an important source of in- lence factors reported to be involved in pathogenesis
fection for the same individual after injury.7 Regard- of burn wound infection include phospholipase C, 17
ing multidrug resistance, Hsueh et al. 8 reported single the ferripyochelin-binding protein,18 lipopolysaccha-
multidrug-resistant strain of P. aeruginosa over a pe- ride (LPS),19 and exoproducts secreted by type III se-
riod of several years, and concluded that the strain cretion apparatus.20 While the loss of the skin's barrier
was carried by some patients asymptomatically function is certainly an important factor in burn
through several rounds of antibiotic treatment which wound infection, its compromise fails to explain the
were administered to treat Pseudomonas and non- relatively narrow range of bacterial pathogens which
Pseudomonas infections. This scenario can be worse are typically cultured from infected burn wounds.21 It
during the spread of P. aeruginosa from one patient is, therefore, likely that additional host defense
to another; the persistence of this strain takes place in mechanisms specific to some pathogens are more
patients throughout several courses of antibiotic compromised in severe burns. A reduction in infec-
treatment. It has been proved that during admission of tion following local application of polyclonal human
patients in burn centers, a limited number of common antibody to burn sites has been reported,22 suggesting
strains cross-contaminate burn victims mostly when that in the untreated burn wound, immunoglobulin
their lesions scrubbed in the bathroom.9 exists at subprotective levels. The possibility of a lo-
cal deficiency of antibody-mediated immunity in burn
wounds is further supported by an earlier report23 stat-
P. aeruginosa Virulence Factors in Burn ing that Fc receptor expression by polymorphonuclear
Infection leukocytes (PMNs) decreases by the fifth day post-
injury in burn victims. Complement has also been
Numerous P. aeruginosa virulence factors contribute shown to be depleted in burn wounds,24 probably due
to the pathogenesis of burn wound infection. Rahme to local consumption of complement components.
et al. highlighted the occurrence of virulence factors Local deficiencies in protective antibody complement
of P. aeruginosa contributing to pathogenesis in burn proteins, and PMN Fc receptors may explain the de-
wound infection of rodents.10 A significant role has fects in random migration and chemotaxis of PMNs
also been established for P. aeruginosa pili and fla- observed at burn wound sites. Taken together, these
gella. Experiments comparing infection of burn data suggest that the ability to colonize a burn wound
wounds by pilus and flagellum deficient P. aerugi- depends upon the concerted impairment of several
nosa strains clearly demonstrate that the bacteria de- host immune mechanisms, and that the importance of
ficient in either of these structures have reduced viru- P. aeruginosa in such infections is due to its ability to
lence, both in their ability to persist at the wound site, take advantage of the host immune compromise and
and in their ability to disseminate throughout the host secrete a variety of important virulence factors.
organism.11 Dissemination of P. aeruginosa through- P. aeruginosa produces two extracellular protein tox-
out the host is also partially dependent upon produc- ins, exoenzyme S and exotoxin A. Exoenzyme S has

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Japoni et al.

the characteristic subunit structure of the A- candidate vaccines are under first to third stage of ex-
component of a bacterial toxin, and it has ADP- perimental clinical trials.40
ribosylating activities.25 Exoenzyme S is produced by
the bacteria growing in the burned tissue and may be Table 1: Summary of the virulence determinants of
detected in the blood before the bacteria are present. It pathogenic Pseudomonas aeruginosa
has led to the suggestion that exoenzyme S may act to Adhesins
impair the function of phagocytic cells in the blood- pili (N-methyl-phenylalanine pili)
stream and internal organs as a preparation for invasion polysaccharide capsule (glycocalyx)
by P. aeruginosa.26 Exotoxin A has exactly the same alginate slime (biofilm)
mechanism of action as the diphtheria toxin; it causes Invasins
elastase
the ADP ribosylation of eucaryotic elongation factor 2,
alkaline protease
resulting in inhibition of protein synthesis in the af- hemolysins (phospholipase and lecithinase)
fected cell.27 Although it is partially-identical to diphthe- cytotoxin (leukocidin)
ria toxin, it is antigenically distinct. It utilizes a different siderophores and siderophore uptake systems
receptor on host cells than diphtheria toxin does; oth- pyocyanin diffusible pigment
erwise, it enters the cells in the same manner and has Motility/chemotaxis
the exact enzymatic mechanism. The production of flagella
exotoxin A is regulated by exogenous iron, but the de- pili
tails of the regulatory process are distinctly different in Toxins
C. diphtheriae and P. aeruginosa.28 Exotoxin A appears Exoenzyme S
Exotoxin A
to mediate both local and systemic disease processes Lipopolysaccharide
caused by P. aeruginosa. It has necrotizing activity at Antiphagocytic surface properties
the site of bacterial colonization and is therefore thought capsules, slime layers
to contribute to the colonization process.29,30 Table 1 is a LPS (Lipopolysaccharide)
summary of the virulence determinants of Biofilm construction
P. aeruginosa. Defense against serum bactericidal reaction
slime layers, capsules, biofilm
LPS
Candidate Vaccines for High Risk People protease enzymes
Genetic attributes
genetic exchange by transduction and conjugation
Although antibiotic therapy has considerably improved
inherent (natural) drug resistance
the management of infectious diseases in general, R factors and drug resistance plasmids
many P. aeruginosa infections are not fully treated or Ecological criteria
eradicated by the application of anti-pseudomonal adaptability to minimal nutritional requirements
drugs and can, thus, become chronic infections. For metabolic diversity
instance, burn patients that survive the initial burn widespread occurrence in a variety of habitats
trauma can become colonized with antibiotic-resistant,
hospital-derived P. aeruginosa strains that are not eas- Treatment of Infections
ily eradicated with antibiotic therapy. 31,32 In cystic fi-
brosis patients, when the strains are eventually selected Topical antimicrobial therapy
out by antibiotic therapy to become multiply-resistant, It has been proved that an effective topical antim-
an increase in the rate of decline in lung function is icrobial agent substantially reduces the microbial load
seen when compared to patients infected with antibi- on the open burn wound surface and reduces the risk
otic susceptible strains.33-35 Several P. aeruginosa anti- of infection.41,42 Selection of topical antimicrobial
gens are used for vaccine development including therapy should be based on the agent’s ability to in-
lipopolysaccharide alone, polysaccharides alginate, hibit the microorganisms recovered from burn wound
extracellular proteins, exotoxin A, and killed whole surveillance cultures and monitoring of the nosoco-
cell.36-39 However, none of them are clinically available mial infections acquired in the burn unit. Prescription
to use for people who are at risk such as firefighters or is also based on the individual preparation of the topi-
infected patients (Immunocompromised and cystic fi- cal agent (e.g., ointment or cream versus solution or
brosis patients). Nevertheless, at the present time some dressing) and its pharmacokinetic properties. Burn

246 WWW.irmj.ir Vol 11 July 2009

 Burn infections with P. aeruginosa

units may rotate the use of various topical antimicro- microbe.46 It is easy to use and painless when applied
bial preparations on a regular basis to decrease the and can be used with or without a dressing. Limited
potential for development of antibiotic resistance. 43-45 systemic toxicity with repeated daily or twice-daily
Topical antibiotic agents should first be applied di- application has occurred aside from the development
rectly to the patient’s dressings before application to of leukopenia.60,61 Silver sulfadiazine has excellent
the burn wound to prevent contamination of the broad-spectrum antibacterial coverage against P.
agent’s container by burn wound flora. The inhibitory aeruginosa and other gram-negative enteric bacteria,
action of silver is due to its strong interaction with although some resistance has recently been re-
thiol groups present in the respiratory enzymes in the ported.41,62 In addition, this agent has some activity
bacterial cell.46,47 Silver has also been shown to inter- against Candida albicans, but enhanced antifungal
act with structural proteins and preferentially bind activity can be achieved by using nystatin in combi-
with DNA nucleic acid bases to inhibit replica- nation with silver sulfadiazine.58 Although silver sul-
tion.48,46 For this reason, silver has recently been fadiazine dissociates more slowly than silver nitrate,
shown to be highly toxic to keratinocytes and fibro- there is still poor penetration into the wound.54,55 Sil-
blasts and may delay burn wound healing if applied ver sulfadiazine is only absorbed within the surface
indiscriminately to debrided healing tissue areas.48-50 epidermal layer, which limits its effectiveness in
Moist exposure therapy, using a moisture-retentive, some patients with severe injuries. In Europe, a com-
has been shown to act as an effective antibacterial bination of cerium nitrate and silver sulfadiazine has
agent while promoting rapid autolysis debridement been used to combat this problem. 63,64 It has been
and optimal moist wound healing in partial-thickness shown to reduce the inflammatory response to burn
injury.51,52 Moisture-retentive ointment also resulted injury, decrease bacterial colonization, and provide a
in earlier recovery of keratinocytes with improved firm eschar for easier wound management.64
wound healing and decreased scar formation. 53 Silver
nitrate is most effective before the burn wound be-
comes colonized. The burn wound needs to be Mafenide Acetate
cleansed of emollients and other debris before a mul-
tilayered dressing is applied to the burn wound and Topical mafenide acetate cream allows open burn
subsequently saturated with silver nitrate solution. wound therapy and regular examination of the burn
Effective use of this preparation, therefore, requires wound surface because it is used without dressings.
continuous application with secondary occlusive Mafenide acetate is applied a minimum of twice daily
dressings, making examination of the wound difficult. and has been shown to penetrate the burn eschar. 54
The silver ion in AgNO3 also quickly binds to ele- The 5% solution must be applied to saturate gauze
mental chlorine ions so that repeated or large-surface dressings, and these need to be changed every 8 hours
application of this solution may lead to electrolyte for maximal effect. Mafenide acetate solution appears
imbalance (e.g., hyponatremia and hypochlore- to be as effective as the cream preparation when used
mia).40,54 Silver nitrate antibacterial activity is limited in this way.41,65 Mafenide acetate (Sulfamylon) cream
to the burn wound surface.55,56 This agent demon- has a broad spectrum of activity against gram-
strates the bacteriostatic activity against gram- negative bacteria, particularly P. aeruginosa, but it
negative aerobic bacteria such as P. aeruginosa and has little activity against gram-positive aerobic bacte-
E. coli, but it is not active against other genera, in- ria such as Staphylococcus aureus.41 This agent also
cluding Klebsiella, providencia, and Enterobacter.40,57 inhibits anaerobes such as Clostridium spp. Because
Silver nitrate also has limited antifungal activity so protracted use of mafenide acetate favors the over-
that nystatin should be used concomitantly. 58,59 growth of C. albicans and other fungi, this agent
should be used in combination with nystatin to pre-
vent this complication due to its limited antifungal
Silver Sulfadiazine activity.58,59 This compound is converted to p-
sulfamylvanzoic acid by monoamide oxidase, a car-
This agent is a combination of sodium sulfadiazine bonic anhydrase inhibitor, causing metabolic acidosis
and silver nitrate. The silver ion binds to the microor- in the burn patient.41,42 In burn patients with inhalation
ganism’s nucleic acid, releasing the sulfadiazine, injury and a concomitant respiratory acidosis, the use
which then interferes with the metabolism of the of mafenide acetate over a large burn surface area or

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Japoni et al.

the repeated application of this compound can be fatal. sulfadiazine resistant strains of Entrobacter cloace in a
Mafenide acetate also decreases the breaking strength burn unit where silver sulfadiazine was in use. These
of healed wounds and delays healing.66 strains showed high resistance to silver sulfadiazine
(MIC= 400 μg/ml) and were cross-resistant to silver
benzoate but not to silver nitrate.75 Recently we also
Acticoat AB Dressing demonstrated that P. aeruginosa isolated from burned
patients were resistant to silver sulfadiazine while most
This product is a specialized dressing, consisting of of them were sensitive to silver nitrate solution.76
two sheets of high-density polyethylene mesh coated
with nanocrystalline silver (e.g., ionic silver with a
rayon-polyester core).67-69 The more controlled and Resistance to Antibiotics
prolonged release of nanocrystalline silver to the burn
wound area allows less-frequent dressing changes, Resistance due to mutations
reducing the risk of tissue damage, nosocomial infec- Various penicillins, cephalosporins, carbapenems,
tion, patient discomfort, and the overall cost of topi- monobactams, aminoglycosides, fluoroquinolones,
cal therapy. 67,70 Acticoat AB provides the most com- and polymyxins have been used to treat patients in-
prehensive broad-spectrum bactericidal coverage fected with P. aeruginosa and are active against most
against important burn wound pathogens of any topi- isolates. All, however, are prone to being compro-
cal antimicrobial preparation currently marketed.67,70 mised by mutational resistance. Mutations to topoi-
These dressings have a potent antibacterial activity somerases II and IV confer fluoroquinolone resis-
against most aerobic gram negatives, including P. tance more readily in P. aeruginosa than in Entero-
aeruginosa and antibiotic resistant members of the bacteriaceae, because P. aeruginosa has a poorer in-
family Enterobacteriaceae as well as aerobic gram- herent susceptibility.77 Derepression of the chromo-
positive bacteria, including MRSA and vancomycin somal AmpC β-lactamase reduces susceptibility to
resistant Enterococci.67,69,70 If the burn wound surface penicillins and cephalosporins although the level of
has minimal exudates, these specialized dressings can resistance depends on the degree of derepression,
remain in place for several days and retain antibacte- which is more variable than that in Enterobactermu-
rial activity.70 tants.78 The up-regulation of MexAB-OprM compro-
mises the fluoroquinolones, penicillins, cepha-
losporins, and, to some extent, meropenem (although
Resistance to Antimicrobial Agents not imipenem), and it also enhances resistance to
many other drugs that lack useful antipseudomonal ac-
Resistance to topical antimicrobial agents tivity.78-79 Up-regulation of other efflux systems, for ex-
Although resistance to silver sulfadiazine in P. ample MexCD-OprJ and MexEF-OprN confers resis-
aeruginosa was reported, its resistance mechanism tance to fluoroquinolones and some β-lactams; up-
has not been determined.62 It is suggested that resis- regulation of MexXY-OprM also affects aminoglyco-
tance of Pseudomonas to silver based topical antim- sides.80 There is better evidence that increased imperme-
icrobials in part is based on the mutation of outer ability is a mechanism of aminoglycoside resistance, for
membrane proteins that transport ions including silver example in the “small-colony variants” which are some-
across bacterial membrane.71,72 Gentamicin-resistant times selected during gentamycin therapy and in isolates
strains of P. aeruginosa which were isolated from with reduced susceptibility to all aminoglycosides, car-
burned patients have been reported.73 These stains bapenems and fluoroquinolones.81-84
showed cross-resistance to silver sulfadiazine but
their resistance was unstable and did not persist on
subculture media. According to a report in USA, an Multidrug Resistance due to Mutations
epidemic sepsis of Enterobacter cloacae in burned
patients occurred and resulted into 13 deaths. 74 The No single mutation compromises every antipseudo-
MIC values of silver sulfadiazine for these strains monal drug. Nevertheless, up-regulated efflux can si-
were 3200 μg/ml whilst the strains isolated from non- multaneously compromise fluoroquinolones and most
burned patients were all sensitive to silver sulfadiaz- β-lactams, leaving only the aminoglycosides (which
ine. Similarly, Rosenkranz et al. isolated two silver lack reliable efficacy as antipseudomonal monother-

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 Burn infections with P. aeruginosa

apy) and imipenem (to which mutational resistance to a survey conducted in Ghotbeddin Burn hospital
evolves at high frequency). A combination of upregu- (Shiraz, Iran) almost all P. aeurginosa isolated from
lated efflux, loss of OprD and impermeability to ami- burn patients were resistant to all tested anti-
noglycosides compromises every drug class except the Pseudomonal antibiotics except carbapenems
polymyxins. Each of the necessary mutations arises in (meropenem and imipenem ).96 Moreover, several
1 cell per 107 to 109 cells, and, although simultaneous reports from Iran confirmed multidrug resistance of
emergence is mathematically and biologically improb- burn’s isolates.97-99 It seems likely that most of this
able, sequential emergence is all too likely because multidrug resistance reflects the accumulation of mul-
infections resistant to the first antibiotic administered tiple mutations, although this surmise remains to be
are likely to be treated with a second antibiotic, and so confirmed by molecular studies, and although reports
on. Mutations that up-regulate efflux may act addi- from other parts of the world document extreme mul-
tively with those effecting permeability, β-lactamase tidrug resistance associated with acquired resistance
expression, or topoisomerase susceptibility so as to genes. In a hospital in Thessaloniki, Greece, a sero-
exacerbate resistance. 85 Accumulation of sequential type with cross-resistance to aztreonam, aminoglyco-
mutations may be facilitated by hypermutators, which sides, and ciprofloxacin persisted for 3 years, with
either lack the ability to perform DNA proofreading or 1211 isolates of this strain recovered. 100 In South Ko-
mismatch repair, or which use DNA polymerases with rea, resistant isolates of P. aeurginosa, with the hy-
a reduced copying fidelity. Because resistance is most drolyzing enzyme being found in organisms at 9 out
likely to emerge in hypermutators, antibiotics may se- of 29 hospitals were surveyed. Moreover, a detailed
lect for hypermutators, thereby increasing the probabil- study at one Korean Hospital revealed dissemination
ity that further resistance will emerge.86 in multiple P. aeruginosa lineages.

Acquisition of Genes and Multidrug Resistance Prevention and Management of Multi-Drug

Resistance
Many acquired β-lactamases and aminoglycoside-
modifying enzymes have been noted in P. aerugi- The selection of resistant mutants, a risk associated
nosa.87-89 Resistance to oxyimino-aminothiazolyl with any antipseudomonal therapy, varies with the
cephalosporins, monobactams, and penicillins but not type and dosage of antibiotic used and the infection
to carbapenems has been reported as a result of expres- site. It revealed a 2-fold greater risk of selection for
sion of potent aminoglycoside-modifying enzymes.90 resistance when imipenem, rather than ciprofloxacin,
Metallo-β-lactamases enzyme rapidly hydrolyzes peni- ceftazidime, or piperacillin, was used.101,102 It is often
cillins, cephalosporins, and carbapenems but not az- assumed that combination therapy prevents the selec-
treonam. 91 Resistance to penicillins and cephalosporins tion of mutational resistance, but evidence for this is
usually accompanies production. A variety of enzymes scanty. In addition, single efflux mutations may affect
have been identified from Japan, Taiwan, France, both the β-lactams and the fluoroquinolones, thereby
Greece, South Korea, Italy and Canada.91-93 The genes undermining the use of combinations of these drugs.
for resistance are often carried as cassettes within inte- The original emergence of multi-drug resistance in
grons, which are natural recombination systems that association with plasmids and integrons is less pre-
assemble series of acquired genes behind a single pro- dictable than mutational resistance because it depends
moter. This organization facilitates gene recombina- on the random escape of genes to mobile DNA. How-
tion. Critically, the β-lactamase genes are often adja- ever, once such resistance emerges, either the host
cent to aminoglycoside 6-N acetyltransferase [aac(6)- strain can spread among patients or the resistance can
1b] determinants.91,94,95 disseminate among strains. When strains have multi-
ple mutational or acquired resistance, the choice of
therapy is often frighteningly limited, especially be-
Prevalence of Multidrug Resistance cause most clinicians would prefer to use a synergis-
tic combination for serious Pseudomonal infections.
P. aeurginosa isolated from patients in burn center No new fluoroquinolone offers better antiPseudo-
were resistant to most classes of antibiotics. According monal activity than ciprofloxacin, and none retains
activity against ciprofloxacin-resistant isolates.

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Japoni et al.

Where resistance is mutational, tobramycin and Conclusion

meropenem are the drugs most likely to retain activ-
ity, because they are the aminoglycoside and the β- P. aeruginosa infections identify those of a pathogen
lactam with the best inherent activity against P. with many potentially virulent factors that allow it to
aeruginosa. Isolates with efflux-mediated resistance colonize and infect essentially any mammalian tissue.
to meropenem, penicillins, and cephalosporins The organism possesses a multitude of factors that
might, however, retain susceptibility to imipenem. promote adherence to host cells and mucins, damage
Although meropenem is usually a more active car- host tissue, elicit inflammation and disrupt defense
bapenem, this possibility should always be consid- mechanisms. Due to impairment of the skin barrier in
ered. In instances in which all chances of β-lactam, burn patients and frequent scrubbing, debridement
aminoglycoside, and quinolone use are lost, the po- and manipulation of the burn site, cross-
lymyxins remain the drugs of last resort. Despite contamination of MRD strains of Pseudomonas and
their significant toxicity, they have been used with colonizing of MDR strains is more likely. In spite of
some success. Levin et al. 103 reported that the use of the ubiquitous nature of this microorganism and the
intravenous polymyxin E (colistin) was successful in frequency with which it is encountered, most human
35 (58%) out of 60 patients treated for multidrug- hosts counteract the infectious process effectively via
resistant Pseudomonas and acinetobacter infections the innate immune system. A more detailed molecular
although it was associated with a failure rate of 75% and cellular understanding of the bacterial and host
when used for the treatment of pneumonias. Perhaps factors is crucial to an overall comprehension of the
most disturbing is the dearth of new drug options. pathogenic process of Pseudomonas, and will be of
Clinafloxacin was slightly more active than cipro- increasing importance to the development of preven-
floxacin, but its development has been suspended, tative strategies to be sought for this major human
and no other antiPseudomonal antibiotic is in ad- pathogen. Selection of multi-drug resistant Pseudo-
vanced development. For the long term, multi-drug monas in burn centers can be facilitated through
efflux inhibitors are promising for use with fluoro- transmission from person to person as well as exten-
quinolones or β-lactams104, and metallo-β-lactamase sive applications of antipseudomonal antibiotics. To
inhibitors105 are the focus of laboratory investiga- overcome inappropriate treatment of burn patients
tion. Unless new drugs are developed, it is hard to infected with P. aeruginosa, periodical antibacterial
escape the conclusion that multi-drug-resistant susceptibility surveys for the bacteria isolated from
Pseudomonas strains will be an increasing reality burn patient are warranted.
and that the use of polymyxins will increase, despite
their toxicity. Conflict of interest: None declared.

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