Prescription Pattern of Empirical Antibiotic Therapy in the Burn Unit of a Tertiary Care Setting in the Kingdom of Saudi Arabia.

BACKGROUND: It is crucial to follow rational prescribing practices while prescribing antibiotics for burn patients, thus leading to better patient outcomes. The objective of this study was to assess the initiation of empirical antibiotics in the burn unit.
METHODS: A prospective cross-sectional study was conducted in a large tertiary care setting of the Kingdom of Saudi Arabia between August 2016 and December 2018.
RESULTS: A total of 102 hospitalized burn patients were included in this study, of whom 84 (82.4%) were males. Burns were classified as first degree, second degree, third degree, or fourth degree depending on their severity and extent of penetration into the skin. The majority (81.3%) of the patients suffered from flame burn, followed by scald (9.85), chemical (6.9%), and electrical (2%) types of burns. Broad-spectrum antibiotic such as piperacillin/tazobactam (40.57%) was the most common empirically prescribed antibiotic. In 35 patients (34.3%), there was a change in antibiotic after culture findings.
CONCLUSION: This study demonstrated that 40% of antibiotic therapy decisions followed the recommended clinical guidelines. This study also found that Gram-negative microorganisms such as Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus were ubiquitous in our burn unit. The study results will facilitate to develop antibiogram for our study setting, thus reducing antibiotic resistance. Further studies are needed to explore the extent and consequences of irrational antibiotic prescriptions in critically ill burn patients. Copyright:

INTRODUCTION

Burns are the fifth most common cause of nonfatal childhood injuries. In countries such as Bangladesh, Colombia, Egypt, and Pakistan, 17% of children with burns suffer from a temporary disability, whereas 18% suffer from a permanent disability.[1] Nonfatal burns are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability and are associated with resulting stigma and rejection. Infection in burn patients is a leading cause of morbidity and mortality and remains one of the most challenging concerns for the burn team in clinics or hospitals. The importance of preventing infection has been recognized in organized burn care since its inception, and recurring themes have been followed through the years. These themes include strict aseptic technique, use of sterile gloves and dressing materials, wearing masks for dressing changes, and routine use of prophylactic antibiotics.[2]

Antibiotic resistance of bacteria is an increasing worldwide problem[3] and is mainly caused due to the frequent use of antibiotics.[4] It is well known that a large proportion of administered antibiotics are prescribed without proper indication, and the published rates of inappropriate antibiotic use are as high as 41%–91%.[2] Thus, it is essential to thoughtfully consider systemic antimicrobial treatment for the treatment of burn patients to prevent the emergence of resistant organisms. The burn wound is colonized with organisms until wound closure is observed, and the administration of systemic antimicrobials promotes the emergence of resistant organisms instead of eliminating the colonization. Systemic antimicrobials are indicated to treat documented infections such as pneumonia, bacteremia, wound infection, and urinary tract infection.[2] Antimicrobial therapy should be tailored to the specific susceptibility patterns of the organisms as soon as this information is available. In addition, antibacterial treatment should precede with a heightened awareness of the possibility of superinfection with resistant organisms, yeasts, or fungi. Empirical antimicrobial therapy for treating fever should be strongly discouraged as burn patients often experience fever secondary to the systemic inflammatory response to burn injury. Prophylactic antimicrobial therapy is only recommended during the immediate preoperative period surrounding excision or grafting of the burn wound, which eventually reduces the risk of transient bacteremia. Treatment should be started immediately before the procedure and generally discontinued within 24 h, assuming restoration of normal cardiovascular hemodynamics.[5] However, there is no standard treatment guideline for treating patients admitted in burn intensive care unit (ICU). There is no antibiogram and specific guideline for the initiation of empirical antibiotics in our ICU for burn patients. Given this background, the objective of the present study was to assess the initiation of empirical antibiotics in the burn unit. This study will facilitate the development of such guidelines and antibiogram for burn patients admitted in ICU, thus preventing the emergence of multiresistant microorganisms and reduce morbidity and mortality rates in burn patients.

METHODS

Design, setting, and population

A prospective cross-sectional study was conducted at King Saud Medical City, Ministry of Health, Riyadh, Kingdom of Saudi Arabia (KSA). Patients diagnosed for any degree of burn and admitted to our burn unit were included in this study. These patients were observed by an experienced clinical pharmacist from August 2016 to December 2018. We only recruited eligible subjects based on inclusion and exclusion criteria during the study period. This study was approved by the Institutional Review Board (Reference number: H1RI-11-Aug16-01) of King Saud Medical City.

Inclusion criteria

Patients of either gender who have been provisionally diagnosed with burn (any degree burn)

Patients aged between 18 and 60 years.

Exclusion criteria

Patients aged <18 years

Patients suffering from immunodeficiency diseases

Patients without burns

Pregnant women and incarcerate patients.

Procedure for taking informed consent form:

Consent was obtained from conscious burn patients and some patients on empirical antibiotics for 1 h (septic shock) after explaining that there was no harm in participating

For the majority of unconscious patients (inhalation injury and on ventilator), consent was obtained from the family members, close relatives, and friends. In case of unconscious expatriates, consent was obtained from their family members, relatives, company supervisors, and friends of the same country of origin.

Patients’ data for characteristics such as age, sex, body weights, vital signs (e.g., fever, blood pressure), drug name, dosage form, route and duration of therapy, empirically or definitely, culture reports (wounds, peripheral, tissue, and urine), laboratory reports, biochemistry, and hematology results were included, patient's empirical antibiotics documented, was followed up until the culture result and adjusted antibiotic therapy. The empirical antibiotic therapy was defined as the initial antibiotic regimen started within 24 h of admission. The adjusted antibiotic therapy was the antibiotic regimen after the change of the first antibiotic substance. The appropriateness of antibiotic prescriptions was judged against evidence-based guidelines. All antibiotics were administered through intravenous route.

Statistical analysis

The study assumed that approximately 50% of antibiotic therapy decisions follow the recommended clinical guidelines. The estimated minimum required sample size was 78 with 10% margin of error, 95% confidence level, and an alpha error of 5%. Descriptive statistics were applied on collected data. The values within parentheses represent percentages.

RESULTS

This study included 102 hospitalized burn patients, 84 males (82.4%) and 18 females (17.6%), and their ages ranged from 18 years to 60 years. The mean age of patients was 38.3 ± 2.0 years, and the mean weight was 74.4 ± 21.8 kg. Burns were classified as first degree, second degree, third degree, or fourth degree depending on their severity and extent of penetration into the skin. The most commonly encountered degrees of burn were fourth degree (38.3%), followed by second degree (35.5%) and third degree (26.5%) [Table 1]. Of the 102 burn patients, flame burn was found to be the most common type of burn that occurred in 83 (81.3%) patients. Scald, chemical, and electrical types of burns were reported in 10 (9.8%), 7 (6.9%), and 2 (2%) patients, respectively [Table 1]. Albumin count was lower in more than two-thirds (72.5%) of the hospitalized burn patients.

Table 1

Characteristics of burn cases

Variables	n (%)
Sex
Male	84 (82.4)
Female	18 (17.6)
Mean age (years)	38.3±2.0*
Mean weight (kg)	74.4±21.8*
Degree of burn
Second degree	36 (35.3)
Third degree	27 (26.5)
Fourth degree	39 (38.3)
Type of burn
Chemical burn	7 (6.9)
Flame burn	83 (81.3)
Scald	10 (9.8)
Electrical	2 (2.0)
WBC count
Low	4 (3.9)
Normal	14 (13.7)
High	84 (82.4)
Albumin count
Low	74 (72.5)
Normal	27 (26.5)
High	1 (1.0)

Second-degree (partial thickness) burns - Second-degree burns involve the epidermis and part of the lower layer of skin, the dermis. Third-degree (full thickness) burns - Third-degree burns destroy the epidermis and dermis. Fourth-degree burns - Fourth-degree burns go through both layers of the skin and underlying tissue as well as deeper tissue, possibly involving muscle and bone. *Mean±SD. WBC: White blood cell, SD: Standard deviation

The majority (82.4%) of the burn patients had higher white blood cell (WBC) count. Wound culture was positive in 39 (38.2%) patients, whereas tissue culture was merely positive in 9 (8.8%) burn patients [Table 2]. Table 2 also shows that Gram-negative microorganisms were mostly observed in the burn tissue samples. In 35 patients, there was a change in antibiotic after culture findings [Table 2]. Figure 1 illustrates that broad-spectrum antibiotics were predominant. The most prescribed empirical antibiotics were piperacillin/tazobactam (40.57%), vancomycin (20.28%), ceftriaxone (20.28%), imipenem/cilastatin (15.94%), meropenem (15.94%), cefazolin (14.49%), and cefuroxime (10.14%) [Figure 1]. The least commonly prescribed antibiotics for burn patients were metronidazole (1.44%), doxycycline (1.44%), colistimethate sodium (1.44%), and clarithromycin (1.44%). Thirty-four percent of prescriptions had a single empirical antibiotic, whereas 33.3% of prescriptions had combination antibiotic therapy [Figure 2].

Table 2

Culture findings

Culture	n (%)
Blood culture
Positive (+ve)	9 (8.8)
Negative (−ve)	93 (91.2)
Organisms (positive culture)
A. baumannii MDRO	3
MRSA	3
Enterococcus	2
Mixed: E. coli+K. pneumonia	1
Wound culture
Positive (+ve)	39 (38.2)
Negative (−ve)	63 (61.7)
Organisms (positive culture)
P. aeruginosa MDRO	20
MRSA	8
A. baumannii MDRO	6
Enterococcus	5
Tissue culture
Positive	9 (8.8)
Negative	93 (91.17)
Organisms (positive culture): MRSA	4
A. baumanni MDRO	3
Mixed +ve cocci and −ve E. coli	2
Sputum culture
Positive	10 (9.8)
Negative	92 (90.2)
Organisms (positive culture)
−ve A. baumanni MDRO	4
MRSA	3
K. pneumonia	2
Mixed−ve K. pneumoniae+MRSA	1
Change of antibiotics after culture result	35 (34.3)

MRSA: Methicillin-resistant Staphylococcus aureus; MDRO: Multidrug-resistant organisms, A. baumannii: Acinetobacter baumannii, E. coli: Escherichia coli, K. pneumonia: Klebsiella pneumonia, P. aeruginosa: Pseudomonas aeruginosa

Figure 1

Prescription pattern of empirical intravenous antibiotics in burn patients (%)

Figure 2

Number of antibiotics (%)

DISCUSSION

To the best of our knowledge, this is the first study assessing the initiation of empirical antibiotics for hospitalized patients admitted to the burn ICU. Previous studies primarily focused on prophylactic treatment for burn infections.[6] The present study revealed several important findings regarding the initiation of empirical antibiotics at the burn unit of the largest tertiary care setting in the KSA. This study demonstrated that 67.6% of patients admitted to the burn unit received either single or combination antibiotic therapy empirically, whereas one-third of the admitted patients were treated with other antibiotics such as metronidazole, doxycycline, colistimethate sodium, and clarithromycin. These antibiotics were the least preferred choices as an empirical treatment. Similarly, all the patients started on antibiotics in the present study received them in an intravenous form as systemic antibiotics when used judiciously as one of the important therapeutic modalities to treat infections in burn patients.[7]

In this study, Gram-negative bacteria such as Pseudomonas aeruginosa were predominant among the wound culture findings. P. aeruginosa is recognized as the most ubiquitous burn wound pathogen responsible for sepsis, leading to burn-linked death.[8] P. aeruginosa poses several challenges while treating severely burned patients because of its multiple-drug resistant ability.[8] Piperacillin/tazobactam is the treatment of choice for P. aeruginosa infection, and this antibiotic was also frequently prescribed (40.57%) in our study setting.[8] Methicillin-resistant Staphylococcus aureus (MRSA) was the second most common microorganism in our burn unit as burn wound infections mainly occur due to S. aureus.[9] MRSA has become the predominant pathogen in ICU owing to the irrational prescription of broad-spectrum antimicrobials.[8] These findings are consistent with the findings of studies conducted in North American burn centers.[10] Moreover, these pathogens should be considered during the initiation of empirical antibiotic therapy as inappropriate empirical antibiotic therapy may lead to progressive deterioration of the burns and development of complications or mortality.[111213]

It is imperative to follow rational prescribing practice as the selection of an antibiotic regimen should depend on an inhibitory activity against bacteria isolated from the burn wound and periodic bacterial cultures.[14] Moreover, diagnostics uncertainty promotes antibiotic overuse. This study revealed that treating physicians prescribed antibiotics to 13.7% burn patients having normal WBC count. It is crucial to consider the total count of WBC when prescribing antibiotics to prevent the unnecessary use of antibiotics.[15] Similarly, a low or normal WBC level signal viral infection, while leukocytosis, an increase in the total number of WBCs, is usually associated with bacterial infection.[15]

The study data may facilitate the development of guidelines and alleged susceptible strains of pathogens to a variety of antibiotics among burn patients those admitted in burn ICUs. Thus, the study data may suggest the preventing rise of multidrug resistant and diminish the morbidity and mortality rates in burn patients. As this was a prospective observational study, there were inevitably some limitations. First, we could not collect the data pertinent to mortality after initiating the empirical antibiotic treatment for burn patients. Furthermore, this study was conducted at a single tertiary care institution in the KSA, and hence, the results cannot be generalized to the entire population of the country. Therefore, these findings should be validated by a multicenter longitudinal study across KSA tertiary care settings.

CONCLUSION

This study demonstrated that 40% of antibiotic therapy decisions followed the recommended clinical guidelines. The majority of the burn patients in this study were treated empirically with piperacillin/tazobactam, while metronidazole, doxycycline, colistimethate sodium, and clarithromycin were the least preferred choices as an empirical treatment. This study also found that Gram-negative microorganisms such as P. aeruginosa and MRSA were ubiquitous in our burn unit. The study results will facilitate to develop antibiogram for our study setting, thus reducing antibiotic resistance. Further studies are needed to explore the extent and consequences of irrational antibiotic prescriptions in critically ill burn patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.