Efficacy of antibiotic regimens used in severe burn patients – Nguyen Thi Hong Tham

Journal of military pharmaco-medicine 188 EFFICACY OF ANTIBIOTIC REGIMENS USED IN SEVERE BURN PATIENTS Nguyen Thi Hong Tham*; Luong Quang Anh* Nguyen Nhu Lam*; Nguyen Gia Tien SUMMARY Objectives: To conduct efficacy trials of various antibiotic regimens that had been used at the Intensive Care Unit, National Institute of Burns. Subjects and methods: A retrospective study was conducted on 101 medical records of severe burn patients admitted to the Intensive Care Unit, National Institute of Burns. The data were analysed by calculating and comparing the outcomes among three antibiotic regimens. Results: The prophylactic-antibiotic regimens succeeced in 17.56% of cases. Among the antibiotic regimens, the combination between cephalosporin and fosfomycin had 19.23% of successful cases. The replaced-antibiotic regimens succeeded in 50% of patients with majority of two-antibiotic regimens (68.49%). Among two-antibiotic regimens, the combination between carbapenem and other antibiotics was predominant (54.84%). Conclusions: Effectiveness of different antibiotic regimens was different for severe burn patients. Further research should be conducted to clarify the indications and effects of antibiotics for severe burn patients. * Keywords: Severe burn; Antibiotic regimen; Effectiveness. INTRODUCTION Treatment of severe-burn patients still has encountered challenges because of complication, especially multi-organ dysfunction, sepsis [4, 5, 6]. Antibiotics are currently prescribed for prevention as well as treatment of infection post burn. However, two subsequence problems including inappropriate antibiotics and uneffectiveness can affect the efficacy of antibiotics. The aim of this study is: To evaluate the efficacy of several antibiotic regimens using in severe-burn patients at Intensive Care Unit, National Institute of Burns. SUBJECTS AND METHODS 1. Subjects. Medical records of 101 patients with severe burn treated at the Intensive Care Unit, National Institute of Burns from 01 - 2014 to 12 - 2014 with the following selected criteria: patients aged in the range of 16 - 65 years old, admitted within 72 hours after burn with total burned surface area (TBSA) from 20% to 70% and full thickness burn area was not more than 50% TBSA. Patients who died within the first three days post burn were excluded. * National Institute of Burn Corresponding author: Luong Quang Anh (luongquanganh@yahoo.com) Date received: 26/06/2017 Date accepted: 11/08/2017 Journal of military pharmaco-medicine 189 2. Methods. A retrospective study was conducted to evaluate the effect of three antibiotic regimens by the following criteria: - Prophylatic-antibiotic regimens were used if patients still had not been infected yet: the effect was evaluated by two classifications as follows: + Effective: Patients did not show the symptoms of systemic infection during hospital stay, and clinical developments were positive without changed antibiotics. + Ineffective: Patients showed the symptoms of systemic infection and other infectious complications as pneumonia, urinary infection, etc. Antibiotics had to change during the treatment. - Therapy-antibiotic regimens were used if patients had been infected or prophylactic-antibiotic regimens were failed. The effect was evaluated by two classifications as follows: + Effective: Symptoms of infection were reduced or disappeared. Burn wound was healing, and functions of human body’s organs were altering to normal. Culture of bacterial blood was negative. + Ineffective: Symptoms of infection were not reduced or worsen, and shock sepsis was becoming a threatened factor to the patient’s life. Culture of bacterial blood was negative or positive, but culture of bacteria on burn wound was positive. - Replaced-antibiotic regimens were used when/if treatment antibiotic regimens failed and its effect was assessed similarly to that of treatment antibiotic regimens. * Analytical data: The data were obtained, subgrouped to the subjects of study, and compared with research criteria. The data were analyzed by the use of Microsoft Excel and SPSS version 16.0 software and p value ≤ 0.05 was considered as significant level. RESULTS AND DISCUSSION 1. Effect of prophylactic and therapy antibitotic regimens. Table 1: Results of prophylactic antibiotic regimens and therapy antibiotic regimens. Results Patient (n) Percentage (%) Effective 13 17.56 Ineffective 61 82.44 Prophylactic- antibiotic regimen Total 74 100 Effective 3 11.11 Ineffective 24 88.89 Therapy- antibiotic regimen Total 27 100 The result showed that patients used the prophylactic-antibiotic regimen were unsuccessful and then had to tranfer to the next therapy-antibiotic regimen. There were 27 patients used the therapy- antibiotic regimen, and 24/27 cases (88.89%) were failed. During the treatment, antibiotic regimens were frequently changed in order to increase the effect and to reduce the resistance of bacteria. The changing times and duration of antibiotic regimens were shown in table 2. Journal of military pharmaco-medicine 190 Table 2: Changing times of antibiotic regimens. Changing antibiotic regimens (times) Patients (n = 101) Percentage (%) Time (days) 0 16 15.84 7.03 ± 2.21 1 24 23.76 4.70 ± 2.92 2 21 20.79 4.52 ± 2.70 3 18 17.82 4.74 ± 3.12 4 8 7.92 4.78 ± 2.76 5 8 7.92 4.52 ± 2.91 6 4 3.96 4.14 ± 2.92 7 2 1.99 3.91 ± 2.83 Average of day in treatment 15.04 ± 8.62 Average of antibiotic regimen per patient 3.34 ± 1.82 Antibiotic regimens changed many times during the treatment. The antibiotic regimens were ranged from one to eight times with average of approximately three regimes per patient. The average time of each regimen used was in the range from four to seven days. 2. First time use and effect of prophylactic and therapy antibitotic regimens relating with time-intervals. Table 3: Antibiotic regimens used at first time relating with time-intervals. Time (hours) 240 Total Patient (n, %) 41 (100) 32 (100) 1 (100) 74 Effective (n, %) 0 12 (37.50) 1 (100) 13 Prophylactic antibiotic regimen Ineffective (n, %) 41 (100) 20 (62.50) 0 61 Patient (n, %) 8 (100) 18 (100) 1 (100) 27 Effective (n, %) 0 2 (11.11) 1 (100) 3 Therapy antibiotic regimen Ineffective (n, %) 8 (100) 16 (88.89) 0 24 Total (n, %) 49 (48.51) 50 (49.50) 2 (1.99) 101 (100) Journal of military pharmaco-medicine 191 On the one hand, if administered into the hospital within 72 hours after being burned, all two antibiotic regimens had been failed (49/101 patients). On the other hand, 28% of patients (14/50 cases) used antibiotic regimens from 72 hours to 240 hours was successful. Fundamentally, using antibiotics in patients within three days after being burned at once was not suitable for the practical guidelines of burn care launched by French Burns Association in 2007 [7]. However, due to hot and wet weather in the tropical countries as Vietnam, infection from medicine centers was becoming an high risk factor. The dangerous factor increased in case of severe-burn wounds, loss of covered skin, drain of body fluid, and immunosuppression. Thus, using antibiotics to prevent infection within three days after burn was necessary. The antibiotic regimens including prophylactic-antibiotic regimens and therapy-antibiotic regimens consisted of one, or two, or three antibiotics. The effect of the regimens was depicted in table 4. Table 4: Effect and details of antibiotic regimens. Prophylactic-antibiotic regimen (n, %) (n = 74) Therapy-antibiotic regimen (n, %) (n = 27) Number of antibiotics per regimen Patients Effective regimen Ineffective regimen Patients Effective regimen Ineffective regimen One antibiotic 7 0 7 P2 1 0 1 0 0 0 C 3 0 3 0 0 0 F 3 0 3 0 0 0 Two antibiotics 67 (100) 13(19.40) 54 (80.60) 23 (100) 3 (13.04) 19 (86.96) C + F 43 (64.17) 7 (16.27) 36 (83.73) 9 (39.13) 3 (33.33) 6 (66.67) C + A/Q 8 (11.94) 3 ( 37.50) 5 (62.50) 4 (17.39) 0 4 (100) F + C/Q 3 2 1 2 0 2 F + P3 7 0 7 5 0 5 Q + P3 6 1 5 3 0 3 Three antibiotics 0 0 0 4 (14.81) 0 4 (100) P4 + F + Q 0 0 0 4 0 4 (Notes: A: Aminoside; C: Cephalosporin; F: Fosfomycin; P2: Peniciline& with β- lactamase inhibitors; P3: Uredo cephalosporin; P4: Carbapenem; Q: Quinolone) Journal of military pharmaco-medicine 192 Figure 1: Percentage of prophylactic- antibiotic regimens. Figure 2: Percentage of therapy-antibiotic regimens. In the prophylactic-antibiotic regimens, the percentage of regimens having only one antibiotic was 9.46% (7/74 patients), and the outcome was completely unsuccessful. Meanwhile, 67/74 patients used two antibiotics per regimen (19.40% successful percentage) in which the combination between C and F was major ratio (64.17%) and resulted in 16.27% successfully. Next, there was the combination between C and A or Q (11.94%) with 37.5% results in success. Among the therapy-antibiotic regimens, there were not regimens consisting of one antibiotic. Nevertheless, there were 23/27 patients used the regimens in combination of two antibiotics, in which the outcome was 13.04% successful. The combination between C and F was 39.13%, and its result was 33.33% successful. Four patients were used three antibiotic regimens (P4 and F and Q), but percentage of success was zero. The combination between C and F was 52 cases, in which the effective result was 19.23% (10/52 cases). The combination between C and A/Q was 13.33% (12/90 cases) in total of two antibiotic regimens, in which its effective result was 25% (3/12 cases). As a result, using prophylactic- antibiotic regimens and initial therapy- antibiotic regimens was similar to the practical guidelines for burn care of the French Burns Association in 2007 [7] as well as the results in an earlier study [3]. In many guidelines, selection the class of broad-spectrum beta-lactam antibiotics before gathering microbiological tests was prior [7, 8]. On the contrary, the effect of prophylactic- and therapy-antibiotic regimens in combination between F or Q and P3 were negative (only one case was successful in total of five cases used preventive regimens, and no successful case was found after using infective regimens). It suggested that using antibiotics in combination was very difficult to achieve the optimal effect towards prevention and, or treatment of infection in patients with severe burn. Journal of military pharmaco-medicine 193 Table 5: Relationship between burn severity and effect of antibiotic regimens. Prevention Treatment Characteristics Effective (n, %) Ineffective (n, %) Effective (n, %) Ineffective (n, %) Total (n, %) 20 - 40 8 (15.09) 32 (60.37) 3 (5.66) 10 (18.88) 53 (100) 41 - 60 5 (12.5) 24 (60) 0 11 (27.5) 40 (100) > 60 0 5 (62.5) 0 3 (37.5) 8 (100) Burn surface area (%) Total 13 61 3 24 101 0 - 19 12 (14.81) 51 (62.96) 2 (2.46) 16 (19.77) 81 (100) 20 - 39 1 (5.88) 10 (58.82) 1 (5.88) 5 (29.42) 17 (100) ≥ 40 0 0 0 3 (100) 3 (100) Fullthickness burn area (%) Total 13 61 3 24 The results in table 5 revealed that both prophylactic and therapy antibiotic regimens were only effective in patients with burn surface area from 20% to 40% and/or full thickness burn area under 20% TBSA. It seemed that the positive trend in prevention and treatment by using antibiotic regimens was inversely proportional to the increasing burn area also burn area in depth. 3. Effect of replaced-antibiotic regimens. Table 6: Replaced-antibiotic regimens and effect. Results Number of antibiotics per regimen Patient Effective (n, %) Ineffective (n, %) One antibiotic 17 (100) 8 (47.06) 9 (52.94) P2 3 2 1 C 5 2 3 P4 4 1 3 Q 5 3 2 Two antibiotics 163 (100) 80 (49.08) 83 (50.92) P2 + F 1 0 1 C + A/F/G/Q 42 (25.77) 15 (35.71) 27 (64.29) P3 + A/F/G/Q 18 (11.04) 8 (44.44) 10 (55.56) P4 + A/F/G/Q 93 (57.06) 51 (54.84) 42 (45.16) Journal of military pharmaco-medicine 194 A + F/G/Q 8 6 2 Others 1 0 1 Three antibiotics 57 (100) 31 (54.38) 26 (45.62) P4 + A + Q/G/P 10 9 1 P4 + F + G/Q/A 27 (47.36) 15 (55.55) 12 (44.45) C + F + A/G/Q 10 3 7 P3 + Q + A/G 6 4 2 Others 4 0 4 Four antibiotics 1 0 1 C + F + A + Q 1 1 Total 238 (Notes: G: Glycopeptide; P: Polypeptide). 7.14 68.49 23.95 0.42 1 antibiotic 2 antibiotics 3 antibiotics 4 antibiotics Figure 3: Percentage of replaced-antibiotic regimens. In the replaced-antibiotic regimens, there were 7.14% of regimens containing only one antibiotic, and its effective percentage was 47.06%. Among the regimens containing one antibiotic, C/Q were popular administrations, and brought more positive effect than that of the others. The priority of the replaced-antibiotic regimens was the regimen containing two antibiotics (163/238 in total = 68.49%), in which the effective outcome was 49.08%. There were many antibiotic combinations in two antibiotic regimens. The combination between P4 and other antibiotics was prior (57.06%) with 54.84% in success. By calculating in sum of two antibiotic regimens, the effective percentage of P4 regimens was 31.29% (51/163 cases). The next widespread combination was C or P3 and other antibiotics, and the outcome was positive. When comparing with the result of a recent survey [3], the two antibiotic regimens were also common among the replaced-antibiotic regimens. There were 57 patients used three antibiotic regimens, and the combination between P4 plus F with other antibiotics was prior (47.36%) with its effective treatment percentage was 55.55%. Journal of military pharmaco-medicine 195 4. Relation between burn injuries and effects. Table 7: Relation between burn injuries and effects. Results (n, %) Levels of burn injuries Effective (1) Ineffective (2) Percentage (1)/(2) (times) 20 - 40 50 (54.95) 3 (30) 16.67 41 - 60 35 (38.46) 5 (50) 7.0 > 60 6 (6.59) 2 (20) 3.0 Burn area (%) Total 91 (100) 10 (100) 9.1 0 - 19 77 (84.61) 4 (40) 19.25 20 - 39 12 (13.18) 5 (50) 2.40 ≥ 40 2 (2.21) 1 (10) 2.0 Depth of burn area (%) Total 91 (100) 10 (100) 9.10 Yes 16 (17.58) 8 (80) 2.0 No 75 (82.42) 2 (20) 37.50 Inhalation injury (%) Total 91 (100) 10 (100) 9.10 The result showed that if the patients underwent more severe burn wounds, especially with combination of inhalation injuries, the percentage of successful treatment was trending towards decrease. Conversely, it was clear that the percentage of successful treatment was increasing in tendency in case of patients suffered from less serious burn states (shallow and small burn wound without inhalation injuries). CONCLUSION Effectiveness of different antibiotic regimens was different for severe burn patients. The prophylactic-antibiotic regimens succeeded in 17.56% of cases. Among the therapy-antibiotic regimens, the combination between C and F was 19.23% in success, the next was the combination between C and A/Q with the effective percentage was 25%. Among replaced-antibiotics regimens, the Journal of military pharmaco-medicine 196 combination of two antibiotic was common (68.49%). Both prophylactic- and therapy-antibiotic regimens were only effective in patients with burn surface area from 20% to 40% and/or full thickness burn area under 20% total body surface area. 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