Intraoperative bacteraemia has been used as an indicator of the efficacy of prophylactic antibiotics. Two clinical isolates of Staphylococcus aureus in nutrient broth, with or without human serum, were exposed to teicoplanin (50 mg/L) and, either immediately or after 30 min, inoculated into blood culture bottles. Bottles with and without resin were used and the experiment was repeated five times with one strain. In the absence of teicoplanin, an inoculum of 10 cfu/mL produced growth in both resin and non-resin bottles. In the presence of teicoplanin, an inoculum of at least 10(5) cfu/mL was required in non-resin bottles to obtain growth, but this was reduced to 10(2)-10(3) cfu/mL for resin bottles. Intraoperative blood cultures overestimate the efficacy of bacterial killing by prophylactic antibiotics during surgery.
Background Burn wound surgery or change of dressings commonly causes bacteraemia. The use of antibiotic prophylaxis has not been tested adequately in a controlled trial.Methods A randomized double-blind placebo-controlled study was performed to determine the effect on Gram-positive bacteraemia and clinical outcome of a single dose of teicoplanin (12 mg/kg intravenously) given at burns surgery or change of dressings.Results A total of 134 patients were entered into the study, representing 220 episodes of dressing or debridement (110 episodes in each group). There was a significant difference between the groups with respect to perioperative Gram-positive bacteraemia: eight episodes (7 per cent) in the teicoplanin group versus 51 (46 per cent) in the placebo group (P < 0.001). However, good clinical outcome was similar in both groups (80 of 110 versus 77 of 110 respectively, P = 0.7), Only eleven patients had bacteraemia caused by Gram-negative species alone. Bacteriological response in terms of wound culture showed no significant difference between the groups: 63 (57 per cent) of 110 episodes versus 58 (53 per cent) of 110 respectively respectively.Conclusion Prevention of Gram-positive bacteraemia did not affect postoperative recovery.
The bactericidal activities of teicoplanin and flucloxacillin in a 50:50 mixture of human serum and Iso-sensitest broth were compared in an in-vitro pharmacokinetic model, at serum concentrations present during surgical prophylaxis. The bactericidal activity of teicoplanin with and without serum was also compared. Six strains of Staphylococcus aureus were tested. The bactericidal rate of teicoplanin in serum was significantly lower than the rate in broth alone. However, there was no significant difference in the bactericidal rates in serum of teicoplanin compared with flucloxacillin, an antibiotic which is commonly used as prophylaxis for certain surgical procedures.
Attachment of coagulase-negative staphylococci to plastic surfaces by means of hydrophobic interaction and slime production may be important in producing catheter associated infections. In continuous ambulatory peritoneal dialysis (CAPD), the relationship between these properties and disease is unclear and the effect of dialysate fluid is not considered. For a collection of coagulase-negative staphylococci from CAPD patients, slime production and adherence were measured by colorimetric methods and hydrophobicity was determined by autoaggregation in ammonium sulphate solution. Comparison of 73 nasal isolates with 69 isolates from peritonitis showed no significant differences with respect to three properties, with the exception of a greater adherence of peritoneal isolates in dialysate because of a greater proportion of staphylococcal species other than Staphylococcus epidermidis. Fewer strains showed adherence in dialysate (12/142 8.5%) than in broth (94/142 66%) but the proportion of strains producing slime was similar. The milieu of the bacteria rather than the organisms themselves may be of greater importance in the establishment of infection.
BACKGROUND:Clinical deterioration after burn wound manipulation may be related to the release of cytokines including tumour necrosis factor-alpha (TNF) and interleukin-6 (IL-6).METHODS:The two cytokines were assayed by immunoenzymetric assay in blood samples taken before and during manipulation of the burn wound. An antibiotic, teicoplanin, was administered to half the patients at the start of the procedure in a randomized fashion as part of a separate trial.FINDINGS:Sixty patients with a median burn size of 8% (range 1-56%) were studied during dressing change (n = 40) or burn excision (n = 20). There was little change in TNF levels between preoperative and recovery samples but IL-6 concentrations increased three-fold, particularly in those with large recent burns or bacteraemia, and were correlated with poor clinical outcome. The presence of teicoplanin did not significantly affect the levels of either cytokine.INTERPRETATION:The systemic cytokine response to burn wound dressing or debridement is predominantly that of IL-6 and it is not significantly reduced by preventing Gram-positive bacteraemia during the procedure.
Antibiotic treatment of patients developing infection after burns is principally based on experience with other surgical patients. Few comparative trials have been performed in burns patients despite the altered pharmacokinetics of antibiotics and the high incidence of Gram-positive infection in the first week. A randomized trial was performed to compare the cure rates of presumed Gram-positive infection in burns patients given teicoplanin (6 mg/kg every 12 h for three doses then daily) or flucloxacillin (1 g every 6 h i.v./p.o.). Both groups received gentamicin if additional Gram-negative infection was thought likely. A total of 64 patients were entered into the study representing 65 episodes of treatment of which 55 were completed. Clinical success was achieved in 22 (73%) of 30 evaluable patients given teicoplanin and in 21 (68%) of 31 evaluable patients given flucloxacillin (not significant). Of 51 patients assessable for bacteriological efficacy, clearance was achieved in 15 (63%) of 24 patients given teicoplanin and in 15 (56%) of 27 patients given flucloxacillin (not significant). Serum trough concentrations of teicoplanin were 9 mg/L in five patients at the steady state. Adverse events were recorded in 15 (48%) of episodes in the teicoplanin group and in 14 (41%) of episodes in the flucloxacillin group. Teicoplanin demonstrated similar efficacy and safety to flucloxacillin with or without gentamicin.
Patients with severe burns are susceptible to infection with Gram-positive organisms including methicillin-resistant Staphylococcus aureus, and often require higher antibiotic dosages compared with other patients. This study examined the pharmacokinetics of a single iv dose of teicoplanin (12 mg/kg) in 15 adults and five children with severe burns. Adults were aged 21-82 years with a median total body surface area (TBSA) burn of 30% (range 15-60%). Children were aged 10 months-l0 years with median TBSA burn of 15% (10-30%). At 12 h, the median serum teicoplanin concentration was 12.8 mg/L (9.027.1 mg/L) in adults and 7.6 mg/L (6.6-l0.8 mg/L) in children, (P < 0.01); at 24 h, the corresponding values were 8.3 mg/L (4.6-l2.9 mg/L) and 5.2 mg/L (4.2-6.0 mg/L). Using a three-compartment model, the median terminal half life in adults was 114 h (47-278 h). Children fitted a two-compartment model with a terminal half-life of 38 h (2l-41 h). The median concentration of teicoplanin in fluid from the burn wound was 60% of the serum antibiotic concentration. A single iv dose of 12 mg/kg of teicoplanin was sufficient to produce therapeutic serum concentrations in burn patients for 24 h, but monitoring of antibiotic levels in serum may be advisable in those with high total clearance, especially children.
The diagnosis and treatment of burn wound infection is commonly determined by clinical impression and the qualitative results of surface swabs. It has been suggested that quantitative bacteriology from burn wound biopsies confirms burn wound infection and improves patient management. Methods for quantitating surface flora have been described, but comparisons with biopsy specimens have been contradictory. The quantitative and qualitative results of 141 pairs of biopsies and surface swabs, from 74 burn patients, were compared. Staph. aureus was the commonest organism isolated (29 per cent of biopsies and 35 per cent of swabs). Recovery of the same set of species from biopsy and swab occurred in 54 per cent of pairs. There was a significant correlation between the bacterial count obtained by biopsy and by surface swab (P < 0.001), but using various threshold values, the predictive value of the counts obtained by one method to predict the counts obtained by the other was poor. Parallel cultures taken on 18 occasions, showed a significant correlation between bacterial counts obtained from two biopsies or two swabs taken simultaneously (P < 0.002), but there was wide variation in bacterial densities from the same burn wound at the same time. Recovery of the same set of species from both biopsies occurred in 56 per cent of pairs, and from both swabs in 50 per cent of pairs. The use of quantitative microbiology in burns is limited by the unreliability of a single surface swab or biopsy to represent the whole burn wound.
The use of quantitative bacteriology in the burns unit has been thought to be efficient in predicting sepsis or graft loss. To examine the relationship between clinical outcome and bacterial densities on and in the burn wound, 69 biopsy/surface swab pairs were collected from 47 patients on 64 occasions, either immediately prior to excision and grafting, or at routine change of dressings. The mean per cent TBSA burn was 16 (range 1–65). There was a significant correlation between log total bacterial count by biopsy with total white cell count and age (P = 0.028), and a significant negative correlation between total bacterial count by swab with per cent TBSA (P = 0.006). There was no significant difference in bacterial counts between patients judged to be a clinical success or clinical failure (72h follow-up), either after undergoing excision and grafting, or change of dressings, and no difference in counts between patients with perioperative bacteraemia and those without. With burns > 15 per cent TBSA, a relationship between bacterial counts and subsequent sepsis or graft loss still was not demonstrated. It is suggested that quantitative bacteriology by burn wound biopsy or surface swab does not aid the prediction of sepsis or graft loss.
Infection remains a common cause of death in burned patients. A recent survey of UK burns units showed a range of opinion on the timing of burn wound excision and the use of therapeutic and prophylactic antibiotics. The same questionnaire was sent to other European burns units to assess their practice. Answers were obtained from 96 of the 164 units contacted. A written policy on antibiotic treatment was used by 35 (36%) units, imipenem being the single most popular antibiotic, but courses often lasted more than 10 days. Excisions were covered routinely by prophylactic antibiotics in 44 (45%) units, and 10 of these covered all procedures where the wound was manipulated. All units took surface swab cultures, and 26 (27%) took punch biopsies of the wounds. Silver sulphadiazine was used in 66 (69%) of the units while others preferred sulfamylon, povidone iodine or flamacerium. In 40 hospitals (42%) reporting proven cases of toxic shock syndrome, the median number was only six cases in two years. Nineteen (20%) excised burns within 48 hours of admission. The use of very broad spectrum antibiotics for prolonged courses was the most marked difference from the UK.
Polymorphonuclear leucocyte (PMN) function is suppressed for several weeks after burn injury, rendering patients susceptible to infection, commonly with Staphylococcus aureus. A study was performed to determine the effects of surgery to the burn wound and antimicrobial prophylaxis with teicoplanin on killing of S. aureus by PMNs taken from burn patients. The bactericidal rate was significantly reduced before surgery compared to controls (P<0.01 Mann Whitney), but neither surgery nor teicoplanin had any significant additional effect on the bactericidal rate. The bactericidal rate of PMNs did not have any significant effect on clinical outcome following surgery.
Despite advances in the use of topical and parenteral antimicrobial therapy, and the practice of early tangential excision, infection of the burn wound remains a leading cause of morbidity and mortality. The aim of this study was to survey and compare wound management and antibiotic usage in burn surgery in all UK burn centres. A postal questionnaire was used, followed up by telephone. Answers were obtained from all 39 units treating burns in the UK. A written policy on antibiotic usage was used by 13 centres. Excisions were covered routinely by prophylactic antibiotic therapy in 18 units, and three of these used antibiotic cover during all procedures in which the wound was manipulated. No routine antibiotic cover was given in 21 units. All units obtained surface swab cultures, but only two performed punch biopsy of the wounds. Quantitative bacteriology (counting colony forming units) was employed by three centres. Most units cleaned the burn with saline (17 of 39) or chlorhexidine (eight of 39) but combinations of these and other agents were also used. Nearly half (17 of 37) of those who replied had not seen any cases of proven or suspected toxic shock syndrome in the past 2 years. Four units gave prophylaxis against Staphylococcus aureus, and four gave antibiotics against Streptococcus pyogenes, despite recommendations in the literature. Twenty-nine units gave no prophylaxis. This study has revealed that there is no consensus on antibiotic usage amongst centres treating burns in the UK and that most units rely on surface swab cultures to monitor infection.