Fungal Infections in Major Burns - 2 Years Overview

Infections are the most severe and the most frequent complication in major burns requiring adequate diagnosis and treatment. Extensive burned areas, impaired immune system and antibiotic therapy contribute to the development of opportunistic fungal infections. An important aspect is the increased level of antimicrobial resistance in
our country. We present a two years study on the burn patients hospitalized in our institution. A total of 355 burned patients were hospitalized during this period, 210 (59%) of them being addmited in Critical Care Burn Unit. We noted the main infectious complications and established a dinamic microbian mapping during patient hospitalization. Fungal infections were noted. We performed microbiological screening: testing at admission and once a week or in case of clinical signs from all potential sites. For the clinical therapy of mycoses, it is mandatory to know whether a fungal colonization or a fungal infection is involved. Unfortunately, often in severe burned patients, clinical presentation is unspecifi c and sensitivity of diagnostic results may be unreliable. Invasive fungal infections due to Candida species and Aspergillus species are important emerging causes of morbidity and mortality. The systemic use of antifungal agents is conducted depending on the general condition of the burn patient, the fungal species
involved and the confi rmation of fungemia. In conclusion, specifi c treatment of infectious complications has to be conducted according to the characteristics of the patients in order to reduce morbidity and mortality and avoid the development of antimicrobial resistance.

Fungal infection types have been assessed and a dynamic fungal mapping has been established during patient hospitalization. Microbiological screening was based on patient testing at admission in the hospital and once a week or in case of clinical signs from all potential sites during hospitalization.

RESULTS
From a total of 355 patients with burn lesions, 59% were admitted to the Critical Burn Care Unit with severe burns and 41% were treated in the Postcritical Care Unit (Figure 1).
In our two years study, from the Critical Care Burn Unit patients, we have found that 26 severely burnt patients have had positive determinations for Candida spp. and 5 patients have had present determinations for Aspergillus spp. Assessing the fungal distribution for the studied patients, we have obtained the following data: most determinations for Candida spp have been diagnosed in the fi rst day postadmission, while most determinations for Aspergillus spp have been diagnosed seven days after the admission in the Critical Care Unit ( Figure 2).

Patients with identifi ed Candida spp:
Th e statistics evaluating age and sex distribution in patients with the presence of Candida Spp. revealed 9 female and 17 males with ages ranging between 23 and 88 years old, with an average of 55 years old ( Figure 3).
In what concerns the associated pathologies in Candida burnt patients, 7 out of 26 patients had some of the following pathologies associated: HTA, Diabetes mellitus type II, COPD, VHC, stroke, obesity, depression, mental retard and chronic ethanol consume.
Regarding the evaluation of the association between

INTRODUCTION
Th e natural protective barriers (skin, respiratory tract and digestive tract) are usually aff ected in case of severe burns, getting to the the activation of the pro-infl ammatory cascade that causes a complex disorder of the immune system, cumulating both cellular and humoral responses. Immune alterations determine high susceptibility for infectious complications that are a rule in the evolution of severe burns, usually marked by the presence of opportunistic germs [1][2][3][4][5] . Fungal wound colonization and infection became progressively prevalent by introducing topical antibacterials and through empiric use of broad-spectrum antibiotics. Invasive fungal infection is correlated to higher death rates, regardless of the surface of the burn, associated inhalation burn lesions, or patient's age 3,4 .
Candida spp. are the most typical fungal colonizers of the burn lesion, although fungi like Aspergillus spp., Penicillium spp., Rhizopus spp., Mucor spp., Rhizomucor spp., Fusarium spp., and Curvularia spp. can also be responsible for colonization, and these may develop signifi cant invasive potential with increased mortality 6 .
A correct diagnoses is often diffi cult, due to unspeciffi c clinical symptoms which frequently imitate lowgrade bacterial infections and requirement for specifi c laboratory assesment. An important strategy for improving patient outcome is to prevent infectious complications 1,3 .
sented by: the burn wound, respiratory, urinary and systemic; the predominant site of infection being the urinary tract ( Figure 5). As revealed by antibiograms comparison, the highest sensibility of the fungi has been shown to appear when exposed to the following antifungals: Voriconazol, Fluconazol and Amphotericin B. Anidulafungin was also very eff ective in treatment of candidiasis in our patients. Figures 6 and 7 the severity of the burn, a large body area with burn lesions and a high percentage of third degree burns, with Candida exposure, it has been shown that most of the patients had around 40-50% TBSA, with an average of 47% TBSA and an average of 22% of third degree lesions ( Figure 4). Th ere have been airway burns in two of the Candida presenting patients.
Eight of the 26 patients (30.76%) were noted as having infections with Candida spp and needed systemic antifungal therapy. Th e sites of infection were repre-      tients presented also burn lesion of the airway ( Figure  9).
Aspergillus spp was detected on the burn wound in 3 patients, in ear cavity in one patient and in respiratory tract of one patient ( Figure 10). All those fi ve patients received antifungal treatment. As revealed by antibiograms, the highest sensibility of the Aspergillus has been shown to appear when exposed to the antifungal Voriconazol. Figures 11 and 12 shows the aspect of burnt lesions tested positive for Aspergillus spp.
Regarding the evolution of Aspergillus aff ected burnt patients, four of the fi ve have died and one patient was discharged from the Burn Unit in healing process.

DISCUSSION
Infections are the most common complications in our burn unit, requiring proper diagnosis and treat-illustrates the clinical aspect of Candida presence on burned wound in two severely burnt patients.
Regarding the outcome of the patients tested positive for Candida, it results that there have been 9 patients discharged from our hospital in healing process, 16 deaths and 1 transfer to homeland for a foreign patient.

Patients with identifi ed Aspergillus spp:
Th e distribution by sex and age in Aspergillus spp patients revealed a number of 4 males and 1 female with ages ranging between 48 and 59 years old, with an average of 53 years (Figure 8).
Concerning associated illnesses, hypertension, diabetes mellitus type II and chronic alcohol consumption have been associated in three patients out of fi ve.
By assesing the distribution of TBSA and third degree burns percentage, we have reached the following results: the average TBSA was 72%, third degree burns were present in an average of 45% of the burn lesions for the fi ve Aspergillus aff ected burn patients. Two pa-    Patient-specifi c risk factors for fungal infections after burn injury include high age groups, large burns >40% burned TBSA and inhalation lesions. Additional contributing elements are neutropenia, uncontrolled Diabetes mellitus and the need for central venous catheters 1,11 .
Patients tested positive for fungi in our group were around the sixth decade of life and presented predominantly extensive burns, over 40% TBSA and full thickness burns, characteristics well known as negative prognostic factors leading to increased morbidity and mortality 12,13 .
Ten patients out of 31 (one third) in which we identifi ed fungi, presented signifi cant comorbidities which altered their survival prognosis.
Th e most critical target in burn patients that have a high infection risk is a quick achievement of adequate immune competence. Th is objective may be facilitated by prompt enteral nutrition, precocious and entire burn wound excision and grafting, restrictive utilization of blood transfusion, early detachment from mechanical ventilation, restraint from broad spectrum antibiotic prophylaxis, targeted antibiotic therapy, recurrent reevaluation, as well as limited utilization of invasive catheterization if possible 1 .
Specifi c treatment includes topical antifungal agents and systemic treatment in severe cases. For burn wound site fungal localization, topical treatment may be applied and eff orts to obtain burn wound closure as fast as possible are made, but if invasive infection is considered, systemic antifungals are then administered as fi rst line treatment. Th e systemic administration of antifungals is conditioned by the general status of the burned patient, the type of fungus involved and the laboratory clear diagnostic for mycosis or confi rmation of fungemia. Th e antifungal agent is selected according with the appropriate antimicrobial susceptibility. Invasive ment. We perform microbiological screening: at time of patient admission, than once a week or in case of clinical signs of infection from aff ected site and from all potential sites in undetermined sepsis. Antibiotic therapy is administered according to the antibiogram, but if necessary, when clinical and paraclinical signs are suggestive of infection, antibiotic therapy is started empirically, with a broad spectrum, and immediately after receiving the antibiogram, targeted antibiotics are administered. Th e principle of de-escalation is applied in order to administer the drug eff ective on the germ, but with a narrow spectrum and, if possible, to avoid reserve antibiotics.
An important aspect to consider is the high microbial resistance present in our country, requiring stronger antibiotics and predisposing to growth of opportunistic organisms like fungi and viruses 2,7 .
Diagnosis of fungal infections is diffi cult, with clinical alert signs which are nonspecifi c and not particularly diff erent from bacterial infections, also sensitivity of diagnostic results may be inaccurate. Direct evidence of positive fungal cultures from burn sites is the main diagnostic approach but it may be correlated with latency and species-dependent diagnostic requirements 1,8 . Diff erentiation between fungal infection and colonization in burn wounds is also very challenging.
We observed in our group that 50% determinations for Candida spp have been diagnosed in the fi rst day postadmission.
According to literature, previous Candida colonization is a critical risk factor for Candida presence, and the risk rises considerably along with the number of colonized sites. After burn lesions, ubiquitary Candida colonization of the skin and mucosal components of the nose, throat and digestive tract is prone to represent a latent cause of infection, particularly in patients with a defi cient immune system 1,4,9,10 .  Regarding the mycoses clinical therapy, it is mandatory to dissociate between fungal colonization and fungal infection. Unfortunately, frequently in the case of a burn patient, the presence of clinical signs is nonspecifi c and the sensibility of the diagnostic results is variable.
Th e systemic support of the patient allowing recovery of immune competence and adequate early surgical excision of burn eschar and coverage of the defects, are key factors in reducing the risk determined by fungal infections in major burns.
Compliance with ethics requirements: Th e authors declare no confl ict of interest regarding this article. Th e authors declare that all the procedures and experiments of this study respect the ethical standards in the Helsinki Declaration of 1975, as revised in 2008 (5), as well as the national law. Informed consent was obtained from all the patients included in the study.
fungal infections of the burn wounds require prompt, extensive, surgical debridement, even limb amputation if necessary to obtain local infectious control 1,14 . After effi cient control of wound infection( negative cultures must be obtained) and there is no evidence for sepsis with fungi, defi nitive coverage of the burn area must be performed as soon as possible using skin grafts or skin substitutes 5 .
As important principle, infection control protocols are mandatory in a burn unit and must be carefully respected, microbiological surveillance is useful in determine the characteristics of local fl ora, as fungal infections are diffi cult to identify and the treatment is specifi c and expensive 5 .

CONCLUSIONS
Fungal infections in burns are prone to appear in patients with large burn surfaces, defi cient immune system, advanced age and irrational use of broad-spectrum antibiotic therapy.