Annals of Burns and Fire Disasters - vol. XII - n° 2 - June 1999

GRAM-NEGATIVE BACTERIAL SURVEILLANCE IN BURN PATIENTS

Department Of Plastic And Reconstructive Surgery and Burn Unit, Çukurova University Medical School, Adana, Turkey

SUMMARY. A retrospective study of gram-negative bacterial surveillance from the wound swab cultures of burn patients treated in a major burn unit in Adana, Turkey, was performed. Over a 17-month period, 232 swab cultures from 114 patients were evaluated and 176 gram-negative micro-organisms were isolated. Pseudomonas aeruginosa was the organism most frequently isolated (53.97%). Imipenern-cilastatin was the most active antibiotic to P. aeruginosa (44%) and to all species (58%). The results showed a very serious antibiotic resistance of micro-organisms isolated from burn wounds. Surgical excision in order to remove infected and necrotic tissues from the body is thus confirmed as a routine basic procedure for the management of burn wounds, and antibiotics should be regarded as supportive agents.

The burn wound represents a susceptible site for opportunistic colonization by organisms of endogenous and exogenous origin. Patient factors such as age, extent of injury, and depth of burn in combination with microbial factors such as type and number of organisms, enzyme and toxin production, and motility determine the likelihood of invasive burn wound infection. Wound infection cannot be avoided, particularly in large burn wounds, and this may cause morbidity and mortality. Wound infection may be a source of sepsis and if it occurs, mortality is never far away. Also, an infected wound sometimes complicates the procedures of defect closure, such as grafting. This increases the length of hospital stay and treatment expenses. The most important process is surgical debridement for removing infected and necrotic tissues from the body. Antibiotic administration before, during and after surgery is an important part of survival and appropriate antibiotic treatment is vital. Both facultative and aerobic gramnegative bacilli and aerobic gram-positive cocci can be isolated in burn wound cultures. Nearly all these microorganisms are hospital-acquired agents that are resistant to antibiotics to varying degrees.
In this study, we aimed to study the dissociation and antibiotic susceptibilities of gram-negative microorganisms isolated in the burn wounds of patients treated in our burn unit.

When antibiotic susceptibility for P. aeruginosa was evaluated, in 18 samples all 12 antibiotics showed resistance to P. aeruginosa (19%); these were defined as pan-resistant P. aeruginosa. In 24 samples, only one antibiotic was susceptible to P. aeruginosa (25%); these were defined as multi-resistant P. aeruginosa. In 53 other samples, at least two antibiotics were susceptible to P. aeruginosa (55%). In multi-resistant samples, imipenemcilastatin was susceptible in 17 samples (70.83%), ceftazidime in four samples (16.66%), and cyprofloxacin, amikasin, and ticarcillin/clavulanate in one sample (4.16%). When P. aeruginosa samples were considered in general, imipenem-cilastatin was the antibiotic most susceptible to P. aeruginosa, with a ratio of 42/95 (44.21 %). Ceftazidime was the second most susceptible, with a ratio of 29/95 (30.52%), and cyprofloxacin third, with a ratio of 28/95 (29.47%).
Proteus mirabilis, with a 10.22% ratio, was the second most frequently isolated micro-organism in burn wounds. Cyprofloxacin was found to be the most susceptible antibiotic to this micro-organism, with a ratio of 94.44%. Imipenem-cilastatin and ticarcillin-clavulanate were second in line with the same ratio of 77.77%. The third most frequently isolated micro-organism was Providencia stuartfl with 9.09%. Cyprotloxacin and ticarcillinclavulanate were the most susceptible antibiotics, with 75%. imipenem-cilastatin followed, with 68.75%.
Citrobacter freundii was isolated in one sample and imipenem-cilastatin was the only susceptible antibiotic.
Providencia rettgeri was isolated in one sample and was resistant to imipenem-cilastatin.
Overall, imipenem-cilastatin (58%), cyprofloxacin (52%), and ticarcillin/clavulanate (35%) demonstrated the best activity against the gram-negative bacterial isolates. Many bacteria that were resistant to ceftazidime demonstrated cross-resistance to other third-generation cephalosporins. The micro-organisms isolated and antibiotic susceptibilities are shown in Table III.

Our study mainly depends on surface swab cultures. Quantitative microbiology has recently become popular and many reports deal with it. Comparing the two methods, it can be said that the use of quantitative microbiology in burns is limited by the unreliability of a single surface swab or biopsy for the representation of the whole burn wound, and it is suggested that quantitative bacteriology by burn wound biopsy or surface swab does not aid the in prediction of sepsis or graft loss The surface swab culture method cannot be ignored and still has its importance, particularly in routine practice.
From a review of the literature it would seem that our study is one of the widest reports of the prevalence and antimicrobial susceptibilities of gram-negative bacteria isolated from infected burn wounds. In the population studied, P. aeruginosa, P. mirabilis and P. stuartii were the most frequent isolates. Together they accounted for 72% of the gram-negative organisms collected. Susceptibility studies showed that imipenem-cilastatin, cyprofloxacin, and ticarcillin-clavulanate exerted the best activity against almost all the micro-organisms that were susceptible to antibiotics. The gram-negative bacilli that were resistant to ceftazidime frequently demonstrated crossresistance to other cephalosporins. However these organisms remained susceptible to imipenem-cilastatin.
Of the microbial population, P. aeruginosa was the most frequently cultured organism, representing 53% of all the isolates collected. The reasons for this high prevalence are as follows: factors associated with the acquisition of nosocomial pathogens in patients with recurrent or longterm hospitalization, complicating illnesses, prior administration of antimicrobial agents, the immunesuppressive effects of burn trauma, and other factors as yet unknown.Of great interest to us was the finding that nearly 74% of the gram-negative isolates were organisms associated with the production of inducible RichmondSykes type 1 cephalosporinase. These organisms produce large quantities of type 1 cephalosporinase when exposed to first-generation cephalosporins, ampicillin, and penicillin G. As these antimicrobials are also readily hydrolysed by this enzyme, inducible organisms are intrinsically resistant to these agents.
Our in vitro data suggest that ceftazidime, a thirdgeneration cephalosporin, is not active against organisms that produce inducible type I cephalosporinase, except P. aeruginosa. This may demonstrate some other properties of P. aeruginosa different from this mechanism.
Sanders and Sanders reported that resistance emerged in 14 to 56% of organisms when cephalosporins were used to treat infections caused by type I cephalosporinaseinducible bacteria. Importantly, treatment with a combination of a cephalosporin and an aminoglycoside did not appear to decrease the emergence of beta-lactarn resistance Studies have shown that broad-spectrum activity of imipenem-cilastatin monotherapy is as efficacious as combination antimicrobial regimens in the treatment of serious polymicrobial infections. Moreover, the combination of imipenem-cilastatin with amino glycoside does not appear to reduce the incidence of resistance acquisition.
Milatovic and Braveny reviewed the literature and found that as many as 24.5% of P. aeruginosa isolates may become resistant to imipenem-cilastatin during therapy.
These observations, together with our finding that bacteria associated with inducible type I cephalosporinase account for nearly 74% of the organisms in our study population, suggest that empirical use of cephalosporins or penicillins to treat burn wound infections should be performed with caution.
In our study, imipenem-cilastatin, a carbapenem beta-lactam antimicrobial with broad-spectrum activity against gram-positive cocci, gram-negative bacilli, and obligate anaerobes, demonstrated the best activity against gram-negative micro-organisms. However, in our series P. aeruginosa became resistant to imipenem-cilastatin with a rate of nearly 56%. This was the highest resistance rate of P. aeruginosa to imipenem-cilastatin. Also, it was seen that monotherapy with imipenem-cilastatin would not be suitable for adequate management of P. aeruginosa isolated in burn wounds. A combination of imipenem-cilastatin with an aminoglycoside appeared to be needed.
A basic procedure such as surgical excision must be correctly performed and antimicrobial agents should then be applied. Surgical excision is the recommended procedure for the management of infected burn wounds, as proposed by Pruitt.

Conclusions

Our study shows, once again, that antibiotics alone can never be sufficient in the management of infected burn wounds. In addition, it can easily be seen that as time goes on we may expect that antibiotics will come to mean less than they do today. As a supportive agent they are today still significant. On the basis of this consideration, a combination of imipenem-cilastatin with an aminoglycoside should be administered together in order to widen the spectrum, particularly in the case of P. aeruginosa.

RESUME. Les Auteurs ont effectué une étude rétrospective de la surveillance bactérienne à Gram négatif des cultures des tampons des lésions des patients traités dans une importante unité des brûlures à Adana, Turquie. Pendant une période de 17 mois, ils ont évalué 232 cultures de tampons provenant de 114 patients et 176 micro-organismes à Gram négatif ont été isolés. L'organisme isolé le plus fréquemment était Pseudomonas - aeruginosa (53,9711/o). L'imipenem-cilastatin s'est démontré l'antibiotique le plus actif contre P. aeruginosa (44%) et à toutes les espèces (58%). Les résultats indiquaient une importante résistance antibiotique des micro organismes isolés dans les lésions. Les Auteurs ont donc confirmé que l'excision chirurgicale pour l'élimination des tissus infectés et nécrosés du corps reste une procédure de base de routine dans le traitement des brûlures, et qu'il faut considérer les antibiotiques comme des agents de support.