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A prospective study of infections in burn patients
Burns 28 (2002) 39–46
A prospective study of infections in burn patients Pia Appelgren a , Viveca Björnhagen b,∗ , Katarina Bragderyd b , Carl Evert Jonsson b , Ulrika Ransjö c b
a Department of Infectious Diseases, Karolinska Hospital, SE-171 76 Stockholm, Sweden Burns Unit, Department of Surgical Sciences, Section of Reconstructive Plastic Surgery, Karolinska Hospital, SE-171 76 Stockholm, Sweden c Department of Clinical Microbiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden
Accepted 17 April 2001
Abstract In a 3-year prospective study, all infections presenting in the burns unit of a university hospital were registered in a specially designed database. Two-hundred and thirty adult patients were included. Eighty-three patients had in all 176 infections, giving an infection rate of 48 per 1000 patient days including both nosocomial and community-acquired infections. Thirty-five blood-stream infections (BSI) occurred in 22 patients; most common micro-organisms were coagulase-negative staphylococci and methicillin-sensitive Staphylococcus aureus. The device-specific BSI rate was 6 per 1000 central venous catheter days, which is low compared to other burn units. The pneumonia rate was 41 per 1000 ventilator days. Seventy-two patients had 107 burn wound infections. Antibiotics were given to only 50% of the burn patients, including 96% of the patients with infection and 26% of those without infection. Most frequently used antimicrobials were cloxacillin, penicillin and gentamicin. The antibiotic resistance rates were low, and multi-resistant bacteria or fungi were rare. The database can be used to evaluate the effects of changes in burn treatment, staffing and design of burn units, and antimicrobial resistance development in relation to antibiotic usage. © 2002 Elsevier Science Ltd and ISBI. All rights reserved. Keywords: Burn; Infection; Prospective; Database; Antibiotic
1. Introduction Measures to prevent and treat infections are essential for the survival of patients with extensive burns. Many studies indicate that infection is correlated to mortality [1]. In patients with less extensive burns, infections may increase morbidity and hospital stay. Infection is one indicator of outcome in the field of quality assurance in burn management [2]. To assess the quality of care and to identify risk factors for infection an other complications, a prospective monitoring system is necessary. The structure of burn care: personnel resources, isolation room standards and recording system must be known. The process of patient care must be monitored, and all procedures recorded. The outcome should be defined, monitored, and correlated to injury severity and to procedures undertaken. The diagnosis of infection in burn patients is based on clinical and laboratory parameters. The collection of information for diagnosis and treatment by paper files may well work in the clinical routine, but the retrieval of such a vast ∗ Corresponding author. Tel.: +46-8-5177-2345; fax: +46-8-5177-3404. E-mail address: [email protected] (V. Björnhagen).
amount of data for analysis is at best erratic. A systematic filing of data by means of a computer system is necessary for scientific analysis. In this prospective study we describe a specially designed computer system for the analysis of data, and report the results from the first 3 years of using the system for routine registration of infection in a consecutive series of burn patients.
2. Material and methods 2.1. Patients Burn patients consecutively admitted to the burn unit of Karolinska Hospital during 1993–1995 were included in this prospective study. The patients were followed to discharge or death. During the same period 67 patients not included in the study were treated in the unit due to other diseases. For the estimation of burn area, the Lund & Bowder chart was used [3]. The total body surface area burned (TBSAB) was calculated by adding percentages of dermal and subdermal burns. To assess the injury severity for each patient, the Abbreviated Burn Severity Index (ABBSI) was used [4].
0305-4179/02/$22.00 © 2002 Elsevier Science Ltd and ISBI. All rights reserved. PII: S 0 3 0 5 - 4 1 7 9 ( 0 1 ) 0 0 0 7 0 - 5
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This index is a scoring system based on sex, age group, presence of inhalation injury and full thickness burn, and total body surface burn area in per cent.
Statistical methods used were Fisher’s exact test, Chi-square analysis with Yates’ correction and logistic regression analysis (statistica 1995, for Windows, StatSoft, Inc., Tulsa, OK).
2.2. Burn treatment 2.4. Laboratory investigations The Karolinska Hospital Burn Unit with an average of 75 burn admissions annually, consisted of six one-patient rooms with ante-rooms but no separate ventilation. At direct patient contact a protective gown and disposable gloves were used [5]. Hands were washed with conventional soap when necessary, and disinfected with 70% ethanol/glycerol before and after every patient contact. Fluid replacement was given according to a modified Parkland formula [6]. Plasma was given from the second day. Intravenous supplement with amino acids and lipids was given from the third day. Enteral feeding was started as soon as gastrointestinal function allowed. Pain relief [7] and ventilatory support was given when needed. Sucralfate was given as stress ulcer prophylaxis. Central venous catheters were placed in the subclavian or jugular vein at the discretion of the anaesthesiologist. The catheters were removed on clinical grounds, i.e. no further indication, mechanical failure or suspected catheter infection. Catheters were not changed routinely. Exposure to dry, warm air, regular wound cleansing and hydrotherapy was the routine for treatment of burned areas [8]. Dressings with nitrofurazone [9] were used until mid 1995, but since then no other topical chemotherapy has been used. Early excision and skin grafting was performed within the first 5 days in full thickness burns when the patients condition permitted [10]. Gentle removal of the burn eschar started 7–10 days after injury and was repeated every second or third day, allowing granulation tissue to be formed. Grafted areas were usually left exposed. 2.3. Data registration and statistical analysis Since 1993, we have used a computerised recording system for all patients, built in the relational data base system OMNIS 7 (Software Ltd., Brackwell, Berkshire, UK) and linked to a statistical programme (jmp, statistical software for the Macintosh 1994, SAS Institute Inc, Cary, NC). The system consisted of nine main files, all of which were linked to the patient file, namely: infections, background pain and temperature, antibiotics, operations, dialysis, other treatments, laboratory, complications, diagnosis. Besides personal data, relevant data about the injury were registered: sex, vital status, date of accident, date of admission, reason for admission, underlying diagnoses, site of injury, depth and width of burn, type of injury, smoke inhalation and ABBSI. The procedures were recorded, such as operations, intubation, mechanical ventilation and vascular accesses, as well as outcome in terms of date of discharge and length of stay, time to infection, and other complications. For readmissions only the ward days were registered.
Cultures were taken on admission from throat, urine, and burned areas, and then routinely twice a week from nasopharynx, urine (if indwelling catheter), tracheal aspirate (ventilated patients), and burn wounds one swab from every 5% of burned surface [11]. All catheter tips were cultured when removed [12]. On suspicion of blood stream infection (BSI), two to three sets of blood cultures were drawn by syringe from a peripheral vein and one culture from any suspected focus of infection. On suspicion of pneumonia culture specimens from protected brush or bronchoalveolar lavage via fiberoptic bronchoscopy were taken as often as was practically possible. Microbial cultures and serology were processed according to current methods [13]. Bronchial specimens were also examined for viruses in the herpes group. Fungal surveillance was performed in patients at risk of contracting disseminated candida infection, that is patients exposed to three or more antibiotics, patients with prolonged central line and bladder catheterisation together with parenteral nutrition. Surveillance fungal cultures from urine, stool, oropharynx, throat, gastric aspirate, intravascular sites were in such patients taken weekly. Haematological and biochemical tests were performed once daily in mechanically ventilated patients, every third day in others. 2.5. Infection and antimicrobial therapy Infections in all patients, admitted and treated for burn injury, have been registered prospectively, according to previously defined criteria. Prophylactic antimicrobial therapy was not given. Patients colonised with candida in three or more body orifices received antifungal prophylactic treatment with oral fluconazol. Antimicrobial therapy was instituted with the help of an infectious disease consultant from the Department of Infectious Diseases (mostly author PA) who visited the unit regularly. All infections were registered, starting at the day of admittance. Only burn wound infections already present on admission were excluded. Data on infections were recorded daily on a paper form, and fed into the computer by the same nurse (author KB). Infections were grouped in four major classes: blood stream infection, pneumonia, burn wound infection, and urinary tract infection. The criteria for infections, except those for wound infections, were mainly based on those given by the Centre for Disease Control, Atlanta, USA [14]. These criteria are shown in Appendix A. If there was any doubt about the diagnosis, a final decision was reached by consensus between the infectious disease consultant (author PA) and the burn surgeon directly in
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charge of the patient (author VB). In patients with infection caused by a known micro-organism, the appearance of another microbe was required in order to classify subsequent symptoms as a new infection. Whenever we found positive blood cultures a BSI was registered even if the patient at the same time had pneumonia and/or wound infection, which were also registered.
3. Results Two-hundred and thirty patients with burn injuries, consecutively admitted to the Burn Unit of Karolinska Hospital during 1993–1995, were included in the study. Most patients admitted were 16 years or older. Eighty-six female and 144 male patients were included in the study. Median age for the 230 patients was 44 years (range 5–90), 49 (range 16–90) in women and 40 (range 5–88) in men. Median TBSAB was for women 5% (range 1–60%, mean 9%) and for men 4% (range 1–82%, mean 8%). Median ABBSI was for women 6 (range 3–12, mean 6,1) and for men 4 (range 2–14, mean 4.4), all patients 5 (2–14). 193 patients had up to 20% TBSAB, 28 21–40%, 3 41–60% and 6 >60%. 140 of the patients had flame injuries or fire in clothes; 53 were scald injuries, 17 contact injuries and 6 electrical injuries. Twelve patients had smoke inhalation injury. One-hundred and sixty four patients stayed >72 h in the unit. The median length of stay was 10 days (range 1–92 days). One-hundred and fifty eight patients were admitted on the day of injury and 43 had been treated in another hospital before admission. Twenty patients were infected on admission. Of these, 18 had wound infections. Ten came from home and eight from other hospitals. Thirteen patients (eight women and five men) died during their stay in the burns unit: seven in 1993, none in 1994 and six in 1995. Median age for those patients was 75 years
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(range 29–90). TBSAB was median 30% (range 2–82%) and burn score median 9 (range 7–14). Seven patients had signs of severe infections at the time of death. The main contributing factors to death in patients without infection were pulmonary and cardiac failure. 3.1. Comparison between infected and uninfected patients Eighty-three patients had in total 176 infections, whereas 147 patients were not infected. Comparison between infected and not infected patients are given in Table 1. One-hundred and seventy six infections in 230 burn patients is equivalent to an infection ratio of 76.5 infections per 100 patients, or an incidence density of 48 infections per 1000 patient days [15]. The TBSAB for the infected patients was median 10% (1–82%). Fifty-one of the 83 patients (61%) with infection and 36 of 147 (24%) patients without infection were subjected to surgery and skin grafting (P<0.001). Twenty-four infected and 11 non-infected (P=0.007) patients were intubated, for median 11 (range 1–45) and 3 (1–11) days, respectively (P=0.004). Patients with infection were older and had larger burns. Infected patients were submitted to more procedures such as ventilator therapy, central venous catheters and arterial catheters. Patients with infections stayed longer in the unit. 3.2. Bloodstream infection (BSI) and intravascular accesses Twenty-two of 67 blood-cultured patients (33%) had 35 verified BSI episodes. Their median age was 53 (range 23–90) years. Their median TBSAB was 25% (4–82%) and burn score 8 (3–14). All BSI patients but one had full thickness burns. The median time to first BSI was 5 days (range 1–50). Their median length of stay was 52 days (range 3–92).
Table 1 Comparison between infected and uninfected patients
Patients (n) Women Men Age (years, median, range) TBSAB% (median, range) total Women Men ABBSI (median, range) Mortality Intubation Ventilator days median No. of central venous catheters/in no. of patients Central venous catheter days median (range) No. of arterial catheters/in no. of pat Arterial catheter days median (range) Length of stay median (range)
Infected
Uninfected
83 38 45 50 (11–90) 10 (1–82) 10 (1–38) 9 (1–82) 6 (3–14) 8 24 11 66/33 9 (1–23) 62/31 5 (1–36) 30 (1–92)
147 48 99 38 (5–89) 5 (1–92) 5 (1–60) 4 (1–92) 4 (2–14) 5 11 3 4/4 6.5 (2–9) 7/6 4 (1–5) 3 (1–53)
P 0.048 <0.001 <0.001 <0.001 0.09 0.007 0.004 <0.001 <0.001 <0.001
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Table 2 Micro-organisms that caused wound and bloodstream infection Micro-organisms
Wound
Bloodstream
Coagulase-negative staphylococci Staphylococcus aureus Streptococci group A, B, G Streptococcus pneumoniae Enterococcus faecalis Lactobacillus Bacillus Clostridium species Propionebacterium acnes Pseudomonas aeruginosa Acinetobacter Sphingotrophomonas maltophilia Escherichia coli Enterobacter Citrobacter Klebsiella Morganella morganii Candida
17 61 26 1 0 0 2 1 0 27 3 2 0 10 0 8 0 1
10 8 3 0 2 1 0 0 1 4 0 0 1 1 2 4 2 2
The micro-organisms causing BSI are listed in Table 2. Coagulase-negative staphylococci (CoNS) were the most common micro-organisms causing BSI (n = 9), and next in frequency were methicillin sensitive Staphylococcus aureus (MSSA) (n = 5), Klebsiella (n = 5), Enterococcus (n = 2), Pseudomonas aeruginosa (n = 2), Lactobacillus (n = 2) and Streptococcus species (n = 2). Among the nine patients with CoNS BSI, seven had more than one positive blood culture. In 26/35 blood stream infections the same micro-organism was identified in burn wounds. Six patients had more than one micro-organism in one BSI episode: the four patients who died had group A streptococci and S. aureus, group B streptococci and S. aureus, P. aeruginosa and enterococci or klebsiella and citrobacter bacteremia, whereas the two survivors had CoNS and S. aureus or CoNS and propionebacteria. Six patients had more than one episode of BSI. One patient belonged to both groups. The mortality rate for patients with verified and strongly suspected BSI (27%, 6/22) was nine times greater than for the non septic patients (3%, 7/208) (OR 10.8, CI 2.9–42, P < 0.0001). The mortality in polymicrobial bacteremia was 4/6 and in monomicrobial bacteremia 0/14 (P = 0.003). Seventy central venous catheters were inserted in 37 patients, and 69 arterial catheters were inserted in 37 patients. Two patients had central venous but no arterial catheter and two patients had arterial but no central venous catheter. Five patients had a catheter-associated blood stream infection and four patients had a suspected catheter-related blood stream infection. The device-specific bloodstream infection rate [16,17] was 6 catheter-associated blood stream infections per 1000 central venous catheter days and 7 catheter-associated blood stream infections per 1000 arterial catheter days. Most frequently found micro-organism
in catheter-associated blood stream infection was S. aureus (n = 6). 3.3. Pneumonia and smoke inhalation Fourteen patients developed 17 pneumonia episodes. Besides positive radiology, the diagnosis of pneumonia was verified by bronchoscopy and culture from protected brush in 12 episodes, culture from tracheal aspirates in two and BSI in two episodes. Median age was 52 years (range 29–87). Median TBSAB was 18% (2–45%) and median burn score 8 (range 4–10). All patients except two had full thickness burns. The median time to first pneumonia was 3 days (range 2–51). The median length of stay was 40.5 days (6–92). The device-specific rate of pneumonia [16,17] was 41 pneumonias per 1000 ventilator days. Thirteen pneumonias were caused by bacteria, one by herpes simplex, one by influenza A, one by influenza B and one causative agent was never found. The most common micro-organisms causing pneumonia were pneumococci (n = 6) and MSSA (n = 3). Four of 14 patients died with pneumonia (TBSAB 2, 13, 30 and 45%, burn score 8, 7, 10 and 8, respectively). Twelve of 230 patients had been exposed to smoke inhalation, and 11 of these were intubated. Median TBSAB was 17% (1–82%) and median burn score 7 (range 4–14). The risk of pneumonia was higher in patients with smoke inhalation (7/12, TBSAB median 16%, range 2–35) than in other burn patients (7/218, TBSAB median 30%, range 2–45) (P<0.001). Two of the patients died (TBSAB 30% and 82%). There was no significant difference in mortality between patients with or without smoke inhalation (2/12 against 11/218, P = 0.9). 3.4. Burn wound infection Seventy-two patients had 107 registered burn wound infections. Their median age was 50 years (range 10–85). TBSAB was median 10% (0.5–45%) and burn score median 6 (range 3–10). All except ten patients had full thickness burns. The median time to first wound infection was 5 days (range 2–33). Their median length of stay was 30 days (1–92). Fourty-five patients had one, 21 patients two, four patients three and two patients had four wound infections. The micro-organisms causing burn wound infection are listed in Table 2. The most frequent organism causing wound infection was MSSA (n = 61), and next in frequency were P. aeruginosa (27), -haemolytic streptococcus spp (n = 26), coagulase-negative staphylococci (n = 17), Enterococcus (n = 13) and Enterobacter (n = 10). 3.5. Urinary tract infections Seventeen patients, six men and 11 women, had 17 urinary tract infections. Their median age was 65 years (range 21–90). TBSAB was median 12% (1–35%) and burn score median 7 (range 6–9). In 14 of these 17 patients a urinary
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tract catheter had been used. All patients had full thickness burns. Median time to first urinary tract infection was 22 days (range 1–49). Their median length of stay was 50 days (range 1–92). The most common micro-organism causing urinary tract infection was E. coli (n = 9), and second in frequency was P. aeruginosa (n = 3). 3.6. Antibiotic usage and antimicrobial resistance About 1300 cultures were taken per year, with 54–61% positive. All S. aureus isolates were sensitive to isoxazolylpenicillins. Coagulase-negative staphylococci were resistant to isoxazolylpenicillins in 57% and to gentamicin in 53% of isolates tested. Enterococci were sensitivity tested in 45 patients, of which six carried gentamicin-resistant strains. Stenotrophomonas maltophilia was found in seven patients (no blood cultures), two of which were gentamicin resistant. P. aeruginosa in 126 patients (no blood cultures), none were resistant to gentamicin or cephtazidim. K. pneumoniae in 19 patients (three blood) and K. oxytoca in 29 patients (two blood), none resistant to ceftazidime. Enterobacter aerogenes 7 (no blood) and Enterobacter cloacae 45 (no blood), one resistant to cephtazidim. Two patients had a candida BSI and one patient had a wound infection caused by candida. Seven patients were colonised with candida in three or more body orifices and underwent antifungal prophylactic treatment with oral fluconazol. In all, ten patients were treated in 11 periods with antifungal therapy, and median length of treatment was 16 days (range 3–34 days), TBSAB in these ten patients was median 34% (range 15–45%), median length of stay 55 days (range 10–92 days). One-hundred and fifteen of the 230 patients (50%) received antibiotics during their stay in the burns unit. Three-hundred and seventy-two courses of antibiotics were given for proven infection, with a median duration of 5 days (range 0–45). Seventy-seven out of 83 patients (94%) with infection were treated with antibiotics. Most commonly used antibiotics were cloxacillin, penicillin and gentamicin. All antibiotic courses are shown in Fig. 1.
Fig. 1. Number of courses of antibiotics given to patients.
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Thirteen of 176 infections were not treated with antibiotics. These were four urinary tract infections and nine burn wound infections. Thirty-eight out of 147 patients (26%) without infection were given antibiotics. Median TBSAB was 4% (range 1–32%), median length of stay was 13 days (range 1–53 days), none of these patients died. Antimicrobials were given for median 6 days (range 2–34 days). Most frequently used antimicrobial was isoxazolypenicillin (n = 31), penicillin (n = 14), clindamycin (n = 5) and cefuroxim (n = 3). 4. Discussion In Europe, this is the first prospective study of long-term incidence of infection in a burns unit. The number of patients is large compared to many other studies. Our patients were adults, with very few exceptions. The mean patient age was at least 10 years higher than in other prospective studies [18,19]. Median burn size in our patients was comparatively small. Median age is given as this is more adequate than means in non-normally distributed populations. In other studies burn sizes are usually given as means, and mean burn sizes are often 25–45% [18], i.e. three to five times higher than in our study. The mortality rate in our study of burn patients is consistent with those reported from other studies when these differences in patient materials are taken into account [18,20–22]. The patients who died without signs of infection were very old and suffered from chronic heart or lung disease. These patients did not survive long enough to contract a nosocomial infection. Large burns, late primary excisions, old age and polymicrobial bacteremias are well recognised risk factors for mortality in burn patients [22–24]. The non-survivors in our study were older and had larger burns as well as a higher incidence of inhalation injury (23%, 3/13) than the survivors (4%, 9/217). Polymicrobial BSI has been described in burn patients from USA [25] as associated with a high mortality. In agreement, we found that four out of six patients that died from BSI had polymicrobial blood stream infection. Candida infections were not a great problem in our burn unit. Two patients died with Candida infections; one with a mixed blood culture of bacteria and Candida, and the other with a clinical suspicion of disseminated Candida infection and where no post mortem investigation was performed. We believe our strict antibiotic policy, avoiding systemic prophylaxis and topical antibiotic agents which promotes proliferation of yeast and fungi in burn wounds, is one of the reasons [26,27]. In all patients, we registered all infections not present on admission [19]. Infected patients were older, had larger burns, higher burn score, longer stay in hospital, more operations, and a larger number of central venous catheters and arterial catheters, compared to uninfected patients.
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Prospective studies of infection in burn patients are few, and comparisons between units are problematical. In a 6-month study Wurtz et al. [18] registered only signs and symptoms of infection starting 72 h or more after admission to the burns unit. In that study, tracheal intubation and central venous catheterisation were seen as risk factors for infection, but the severity of burn injury was not considered. Taylor 1992 [19] is a 1-year study using the CDC criteria, and starting to register from the time of admission. In Taylor 1992 [19] the average burn size was not given. They used topical antimicrobial therapy and antimicrobial prophylaxis but no hydrotherapy. Their main infecting microorganisms were staphylococci. Other risk factors for infection were not analysed. Wurtz et al. [18] had 90 nosocomial infections per 100 discharges and deaths, whereas we had 77 infections per 100 patients and Taylor [19] 78. The patients in these studies were not equivalent, however. Our patients were older, had smaller burns as expressed by TBSA and a shorter average length of stay. Old age has been found to lead to a higher incidence of infections. BSI figures in our study contains both primary septicemia and positive blood cultures originating from localized infections such as pneumonia. Wurz [18] excluded early septicemias and Taylor [19] counted only first primary septicemias, which accounts for their lower figures. Our device-specific BSI rates were low compared to other reports [28]. S. aureus was our main BSI organism, indicating that the patients were infected with strains from their wounds [24]. The diagnosis of pneumonia is notoriously difficult [29]. Our incidence of pneumonia is much lower than in other studies [18,19]. Our injuries were smaller and the inhalation injuries fewer. Nearly all our pneumonias were diagnosed by positive protected brush culture, which is not often used in other studies. The majority of our infections were wound infections. Wound infection rates varies greatly between studies [18,19]. These differences seem to be related to differences in criteria, but might also describe differences regarding the use of topical antimicrobials and frequent swab cultures contra burn biopsy specimens. There is a great need for better definitions of burn wound infection [30]. Antimicrobial therapy can cause severe problems with resistance mainly against cephalosporins and other betalactams as well as quinolones in intensive care units [31]. A strict antibiotic policy is of importance in the control of antibiotic resistance [32]. In particular, broad-spectrum betalactam antibiotics have been shown to cause gram-negative problems in areas of the hospital with a high number of courses of empirical treatment. Antibiotic prophylaxis has been shown to be of little use [33], and has not been practised in our unit for several years. Our strict criteria for infection have helped us to keep the number of patients empirically treated with antibiotics low. We have shown that it is possible to reserve antibiotics for
proven infection and to limit the use of broad-spectrum drugs without increasing mortality and other complication rates. We believe that this is the reason for the favourable situation concerning antimicrobial resistance rates in the unit, both against betalactams and aminoglycosides. Infection rates in burns units have been reported to be high, compared to other intensive care units [28]. The burn patient is infection-prone and very contagious when infected [34]. Isolation care of the burn patient consists of barrier nursing in single rooms, and also of control of airborne infection [34]. Transmission of MRSA in burn units is common [35]. We have managed to prevent transmission of MRSA and other multiresistant micro-organisms in the unit through successful barrier nursing, despite repeated introduction of these bacteria from other centra. That isolation care in general is important in the prevention of nosocomial transmission of infection has long been known, and detailed guidelines are available [36]. Cross-transmission of multi-resistant micro-organisms is common in intensive care units [37]. If transmission occurs, this is an indicator of poor quality of nursing care—nursing overload and patient crowding are the most important factors [38]. Simple barrier nursing using gloves and gown at patient contact is more effective than elaborate isolation care with gowning, sterile gloves, cap etc on every patient visit [39]. 4.1. Conclusion Careful surveillance of infection, good isolation techniques and procedure routines, and a restrictive antimicrobial policy can keep antimicrobial resistance rates and infection rates low in infection-prone burn patients.
Acknowledgements The authors are indebted to Anneli Holmsten, BSc, and Ove Tullberg, MD, for the design and development of the computerised medical record system.
Appendix A. Criteria for nosocomial infection A.1. Blood stream infection 1. Verified blood stream infection One or several positive blood cultures and at least one sign from the list below 2. Suspected blood stream infection No positive blood culture but sign (f) and at least another two signs and antimicrobial therapy instituted 3. Catheter-associated blood stream infection
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Positive catheter tip culture and blood culture obtained by separate venipuncture with the same micro-organism and at least one sign 4. Suspected catheter-associated blood stream infection No positive blood culture but positive catheter tip culture >1000 colony forming units and at least two signs
4. Positive swab culture from burn wound and at least two signs from the list below. 5. Pus and/or foul smelling discharge from wound, abscess, drain or fistula beneath fascia.
A.1.1. Clinical and laboratory signs of BSI
(a) temperature >38.5 ◦ C or <36 ◦ C during at least 12 h or ongoing antipyretic therapy (b) leucocyte count <4 or >12×109 /l in blood (c) C-reactive protein >50 mg/l
<36 ◦ C
(a) temperature >38.5 or during at least 12 h or ongoing antipyretic therapy (b) pulse rate >100/min (c) mean arterial pressure <75 mmHg (d) respiratory rate >28/min or FiO2 >0.21 (e) septic emboli (f) disturbance of mental orientation or level of consciousness (g) hypotension <90 mmHg or inotropic drugs (h) C-reactive protein >100 mg/l (i) platelet count <100×109 /l (j) leucocyte count <4 or >12×109 /l A.2. Pneumonia Positive chest radiography (new or progressive infiltrates where circulatory reasons or ARDS can be excluded) and one of the following criteria: 1. positive quantitative culture with protected brush (threshold 103 cfu/ml) and at least one sign from the list below 2. broncho-alveolar lavage (threshold 104 cfu/ml) and at least one sign 3. purulent sputum or tracheal secretion and at least two signs 4. positive blood culture and at least one sign 5. positive virus isolation/antigen test via bronchoscopy and/or serological or cytological signs of virus infection
A.3.1. Clinical and laboratory signs of burn wound infection
A.4. Urinary tract infection 1. In patients with indwelling catheter: 1.1. two urinary cultures>100 000 cfu/ml with the same micro-organism and at least two signs from the list below 2. in patients without indwelling catheter: 2.1. one urinary culture >100 000 cfu/ml and at least one sign 2.2. two urinary cultures >10 000 cfu/ml with the same micro-organism and at least two signs A.4.1. Clinical and laboratory signs of urinary tract infection (a) temperature >38.5 ◦ C or <36 ◦ C during at least 12 h or ongoing antipyretic therapy (b) suprapubic tenderness (c) frequent micturition (d) dysuria (e) C-reactive protein >50 mg/l (f) leukocyte count <4<12×109 /l in blood
References
A.2.1. Clinical and laboratory signs of pneumonia (a) temperature >38.5 ◦ C or <36 ◦ C during at least 12 h or ongoing antipyretic therapy (b) leucocyte count <4 or >12×109 /l in blood (c) C-reactive protein >100 mg/l A.3. Burn wound infection 1. Pus and/or foul smelling discharge from skin, wound, blister, abscess, drain, fistula or vascular insertion site above fascia. 2. Change in burn wound appearance or character, such as dark discoloration of the eschar, increased bleeding tendency, signs of inflammation in or around the wound or vascular insertion site and positive swab culture 3. Skin graft detached more than 2 days after grafting and positive swab culture.
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[10] Jonsson CE, Dalsgaard CJ. Early excision and skin grafting of selected burns of the face and neck. Plast Reconstr Surg 1991;88:83– 92. [11] Ransjö U, Malm M, Hambraeus A, Arturson G, Hedlund A. Multiresistant Staphylococcus aureus in burn units, its clinical significance and epidemiological control. J Hosp Infect 1989;13:355– 65. [12] Aufwerber E, Ringertz S, Ransjö U. Routine semiquantitative cultures and central venous catheter related bacteremia. Acta Pathol Microbiol Scand 1991;99:627–30. [13] Murray PR, editor. Manual of Clinical Microbiology. 6th ed. Washington, DC: ASM Press, 1995. [14] Garner JS, Jarvis WR, Emori TG, Horan TC, Hoghes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control 1988;16:128–40. [15] Haley RW, Gaynes RP, Aber RC, et al. Surveillance of nosocomial infections. In: Bennett JV, Brachman PS, editors. Hospital Infections. Boston, MA: Little, Brown and Co., 1992:91–5. [16] Gaynes RP, Culver DH, Emori TG, et al. The national nosocomial infections surveillance system: plans for the 1990s and beyond. Am J Med 1991;91(Suppl 3B):116–20. [17] Martin MA. Nosocomial infections in intensive care units: an overview of their epidemiology, outcome, and prevention. New Horizons 1993;1:162–71. [18] Wurtz R, Karajovic M, Dacumos E, Jovanovic B, Hanumadass M. Nosocomial infections in a burn intensive care unit. Burns 1995;21:181–4. [19] Taylor GD, Kibsey P, Kirkland T, Burroughs E, Tredget E. Predominance of staphylococcal organisms in infections occurring in a burns intensive care unit. Burns 1992;18:332–5. [20] El Danaf A. Burn variables influencing survival: a study of 144 patients. Burns 1995;21:517–20. [21] Wong MK, Ngim RCK. Burns mortality and hospitalization time— a prospective statistical study of 352 patients in an Asian National Burn Centre. Burns 1995;21:39–46. [22] Ryan CM, Schoenfeld DA, Thorpe WP, Sheridan RL, Cassem EH, Tompkins RG. Objective estimates of the probability of death from burn injuries. New Engl J Med 1998;338:362–6. [23] Thompson PB, Herndon DN, Traber DL, Abston S. Effect on mortality of inhalation injury. J Trauma 1986;26:163–5.
[24] Still JM, Law E, Thiruvaiyaru D, Belcher K, Donker K. Central line-related sepsis in acute burn patients. Am Surg 1998;64: 165–70. [25] Still JM, Belcher K, Law EJ. Experience with polymicrobial sepsis in a regional burn unit. Burns 1993;19:434–6. [26] Prasad JK, Feller I, Thomson PD. A ten-year review of candida sepsis and mortality in burn patients. Surgery 1987;101:213–6. [27] Becker WK, Cioffi WG, McManus AT, et al. Fungal burn wound infection. A 10-year experience. Arch Surg 1991;126:44–8. [28] National Nosocomial Infections Surveillance (NNIS) report. Data summary from October 1986 to April 1996, issued May 1996. Am J Infect Control 1996;24:380–8. [29] Tablan OC, Anderson RM, Arden NH, Breiman RF, Butler JC, Melvin ZS. Guideline for prevention of nosocomial pneumonia. Infect Control Hosp Epidemiol 1994;15:587–627. [30] Peck MD, Weber J, McManus AM, Sheridan R, Heimbach D. Surveillance of burn wound infections: a proposal for definitions. J Burn Care Rehab 1998;19:386–9. [31] The Swedish study group, Hanberger H, Nilsson LE. High frequency of antibiotic resistance among gram-negative isolates in intensive care units at 10 Swedish hospitals. Clin Microbiol Infect 1997;3:208–15. [32] Gould IM. A review of the role of antibiotic policies in the control of antibiotic resistance. J Antimicrob Chemother 1999;43:459–65. [33] Bang RL, Gang RK, Sanyal SC, Mokaddas EM, Lari ARA. Beta-haemolytic Streptococcus infection in burns. Burns 1999;25:242–6. [34] Ransjö U. Isolation care of infection prone burn patients. Scand J Infect Dis 1978;(Suppl. 11):1–46. [35] Cook N. Methicillin-resistant Staphylococcus aureus versus the burn patient. Burns 1998;24:91–8. [36] Garner JS. Guideline for isolation precautions in hospitals. Infect Control Hosp Epidemiol 1996;17:53–80. [37] Chechotisakd P, Phelps CL, Hartstein AI. Assessment of bacterial cross-transmission as a cause of infections in patients in intensive care units. Clin Infect Dis 1994;18:929–37. [38] Kibbler CC, Quick A, O’Neill AM. The effect of increased bed numbers on MRSA transmission in acute medical wards. J Hosp Infect 1998;39:213–9. [39] Lee JJ, Marvin JA, Heimbach DM, Grube BJ, Engrav LH. Infection control in a burn center. J Burn Care Rehab 1990;11:575–80.
A prospective study of infections in burn patients Pia Appelgren a , Viveca Björnhagen b,∗ , Katarina Bragderyd b , Carl Evert Jonsson b , Ulrika Ransjö c b
a Department of Infectious Diseases, Karolinska Hospital, SE-171 76 Stockholm, Sweden Burns Unit, Department of Surgical Sciences, Section of Reconstructive Plastic Surgery, Karolinska Hospital, SE-171 76 Stockholm, Sweden c Department of Clinical Microbiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden
Accepted 17 April 2001
Abstract In a 3-year prospective study, all infections presenting in the burns unit of a university hospital were registered in a specially designed database. Two-hundred and thirty adult patients were included. Eighty-three patients had in all 176 infections, giving an infection rate of 48 per 1000 patient days including both nosocomial and community-acquired infections. Thirty-five blood-stream infections (BSI) occurred in 22 patients; most common micro-organisms were coagulase-negative staphylococci and methicillin-sensitive Staphylococcus aureus. The device-specific BSI rate was 6 per 1000 central venous catheter days, which is low compared to other burn units. The pneumonia rate was 41 per 1000 ventilator days. Seventy-two patients had 107 burn wound infections. Antibiotics were given to only 50% of the burn patients, including 96% of the patients with infection and 26% of those without infection. Most frequently used antimicrobials were cloxacillin, penicillin and gentamicin. The antibiotic resistance rates were low, and multi-resistant bacteria or fungi were rare. The database can be used to evaluate the effects of changes in burn treatment, staffing and design of burn units, and antimicrobial resistance development in relation to antibiotic usage. © 2002 Elsevier Science Ltd and ISBI. All rights reserved. Keywords: Burn; Infection; Prospective; Database; Antibiotic
1. Introduction Measures to prevent and treat infections are essential for the survival of patients with extensive burns. Many studies indicate that infection is correlated to mortality [1]. In patients with less extensive burns, infections may increase morbidity and hospital stay. Infection is one indicator of outcome in the field of quality assurance in burn management [2]. To assess the quality of care and to identify risk factors for infection an other complications, a prospective monitoring system is necessary. The structure of burn care: personnel resources, isolation room standards and recording system must be known. The process of patient care must be monitored, and all procedures recorded. The outcome should be defined, monitored, and correlated to injury severity and to procedures undertaken. The diagnosis of infection in burn patients is based on clinical and laboratory parameters. The collection of information for diagnosis and treatment by paper files may well work in the clinical routine, but the retrieval of such a vast ∗ Corresponding author. Tel.: +46-8-5177-2345; fax: +46-8-5177-3404. E-mail address: [email protected] (V. Björnhagen).
amount of data for analysis is at best erratic. A systematic filing of data by means of a computer system is necessary for scientific analysis. In this prospective study we describe a specially designed computer system for the analysis of data, and report the results from the first 3 years of using the system for routine registration of infection in a consecutive series of burn patients.
2. Material and methods 2.1. Patients Burn patients consecutively admitted to the burn unit of Karolinska Hospital during 1993–1995 were included in this prospective study. The patients were followed to discharge or death. During the same period 67 patients not included in the study were treated in the unit due to other diseases. For the estimation of burn area, the Lund & Bowder chart was used [3]. The total body surface area burned (TBSAB) was calculated by adding percentages of dermal and subdermal burns. To assess the injury severity for each patient, the Abbreviated Burn Severity Index (ABBSI) was used [4].
0305-4179/02/$22.00 © 2002 Elsevier Science Ltd and ISBI. All rights reserved. PII: S 0 3 0 5 - 4 1 7 9 ( 0 1 ) 0 0 0 7 0 - 5
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This index is a scoring system based on sex, age group, presence of inhalation injury and full thickness burn, and total body surface burn area in per cent.
Statistical methods used were Fisher’s exact test, Chi-square analysis with Yates’ correction and logistic regression analysis (statistica 1995, for Windows, StatSoft, Inc., Tulsa, OK).
2.2. Burn treatment 2.4. Laboratory investigations The Karolinska Hospital Burn Unit with an average of 75 burn admissions annually, consisted of six one-patient rooms with ante-rooms but no separate ventilation. At direct patient contact a protective gown and disposable gloves were used [5]. Hands were washed with conventional soap when necessary, and disinfected with 70% ethanol/glycerol before and after every patient contact. Fluid replacement was given according to a modified Parkland formula [6]. Plasma was given from the second day. Intravenous supplement with amino acids and lipids was given from the third day. Enteral feeding was started as soon as gastrointestinal function allowed. Pain relief [7] and ventilatory support was given when needed. Sucralfate was given as stress ulcer prophylaxis. Central venous catheters were placed in the subclavian or jugular vein at the discretion of the anaesthesiologist. The catheters were removed on clinical grounds, i.e. no further indication, mechanical failure or suspected catheter infection. Catheters were not changed routinely. Exposure to dry, warm air, regular wound cleansing and hydrotherapy was the routine for treatment of burned areas [8]. Dressings with nitrofurazone [9] were used until mid 1995, but since then no other topical chemotherapy has been used. Early excision and skin grafting was performed within the first 5 days in full thickness burns when the patients condition permitted [10]. Gentle removal of the burn eschar started 7–10 days after injury and was repeated every second or third day, allowing granulation tissue to be formed. Grafted areas were usually left exposed. 2.3. Data registration and statistical analysis Since 1993, we have used a computerised recording system for all patients, built in the relational data base system OMNIS 7 (Software Ltd., Brackwell, Berkshire, UK) and linked to a statistical programme (jmp, statistical software for the Macintosh 1994, SAS Institute Inc, Cary, NC). The system consisted of nine main files, all of which were linked to the patient file, namely: infections, background pain and temperature, antibiotics, operations, dialysis, other treatments, laboratory, complications, diagnosis. Besides personal data, relevant data about the injury were registered: sex, vital status, date of accident, date of admission, reason for admission, underlying diagnoses, site of injury, depth and width of burn, type of injury, smoke inhalation and ABBSI. The procedures were recorded, such as operations, intubation, mechanical ventilation and vascular accesses, as well as outcome in terms of date of discharge and length of stay, time to infection, and other complications. For readmissions only the ward days were registered.
Cultures were taken on admission from throat, urine, and burned areas, and then routinely twice a week from nasopharynx, urine (if indwelling catheter), tracheal aspirate (ventilated patients), and burn wounds one swab from every 5% of burned surface [11]. All catheter tips were cultured when removed [12]. On suspicion of blood stream infection (BSI), two to three sets of blood cultures were drawn by syringe from a peripheral vein and one culture from any suspected focus of infection. On suspicion of pneumonia culture specimens from protected brush or bronchoalveolar lavage via fiberoptic bronchoscopy were taken as often as was practically possible. Microbial cultures and serology were processed according to current methods [13]. Bronchial specimens were also examined for viruses in the herpes group. Fungal surveillance was performed in patients at risk of contracting disseminated candida infection, that is patients exposed to three or more antibiotics, patients with prolonged central line and bladder catheterisation together with parenteral nutrition. Surveillance fungal cultures from urine, stool, oropharynx, throat, gastric aspirate, intravascular sites were in such patients taken weekly. Haematological and biochemical tests were performed once daily in mechanically ventilated patients, every third day in others. 2.5. Infection and antimicrobial therapy Infections in all patients, admitted and treated for burn injury, have been registered prospectively, according to previously defined criteria. Prophylactic antimicrobial therapy was not given. Patients colonised with candida in three or more body orifices received antifungal prophylactic treatment with oral fluconazol. Antimicrobial therapy was instituted with the help of an infectious disease consultant from the Department of Infectious Diseases (mostly author PA) who visited the unit regularly. All infections were registered, starting at the day of admittance. Only burn wound infections already present on admission were excluded. Data on infections were recorded daily on a paper form, and fed into the computer by the same nurse (author KB). Infections were grouped in four major classes: blood stream infection, pneumonia, burn wound infection, and urinary tract infection. The criteria for infections, except those for wound infections, were mainly based on those given by the Centre for Disease Control, Atlanta, USA [14]. These criteria are shown in Appendix A. If there was any doubt about the diagnosis, a final decision was reached by consensus between the infectious disease consultant (author PA) and the burn surgeon directly in
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charge of the patient (author VB). In patients with infection caused by a known micro-organism, the appearance of another microbe was required in order to classify subsequent symptoms as a new infection. Whenever we found positive blood cultures a BSI was registered even if the patient at the same time had pneumonia and/or wound infection, which were also registered.
3. Results Two-hundred and thirty patients with burn injuries, consecutively admitted to the Burn Unit of Karolinska Hospital during 1993–1995, were included in the study. Most patients admitted were 16 years or older. Eighty-six female and 144 male patients were included in the study. Median age for the 230 patients was 44 years (range 5–90), 49 (range 16–90) in women and 40 (range 5–88) in men. Median TBSAB was for women 5% (range 1–60%, mean 9%) and for men 4% (range 1–82%, mean 8%). Median ABBSI was for women 6 (range 3–12, mean 6,1) and for men 4 (range 2–14, mean 4.4), all patients 5 (2–14). 193 patients had up to 20% TBSAB, 28 21–40%, 3 41–60% and 6 >60%. 140 of the patients had flame injuries or fire in clothes; 53 were scald injuries, 17 contact injuries and 6 electrical injuries. Twelve patients had smoke inhalation injury. One-hundred and sixty four patients stayed >72 h in the unit. The median length of stay was 10 days (range 1–92 days). One-hundred and fifty eight patients were admitted on the day of injury and 43 had been treated in another hospital before admission. Twenty patients were infected on admission. Of these, 18 had wound infections. Ten came from home and eight from other hospitals. Thirteen patients (eight women and five men) died during their stay in the burns unit: seven in 1993, none in 1994 and six in 1995. Median age for those patients was 75 years
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(range 29–90). TBSAB was median 30% (range 2–82%) and burn score median 9 (range 7–14). Seven patients had signs of severe infections at the time of death. The main contributing factors to death in patients without infection were pulmonary and cardiac failure. 3.1. Comparison between infected and uninfected patients Eighty-three patients had in total 176 infections, whereas 147 patients were not infected. Comparison between infected and not infected patients are given in Table 1. One-hundred and seventy six infections in 230 burn patients is equivalent to an infection ratio of 76.5 infections per 100 patients, or an incidence density of 48 infections per 1000 patient days [15]. The TBSAB for the infected patients was median 10% (1–82%). Fifty-one of the 83 patients (61%) with infection and 36 of 147 (24%) patients without infection were subjected to surgery and skin grafting (P<0.001). Twenty-four infected and 11 non-infected (P=0.007) patients were intubated, for median 11 (range 1–45) and 3 (1–11) days, respectively (P=0.004). Patients with infection were older and had larger burns. Infected patients were submitted to more procedures such as ventilator therapy, central venous catheters and arterial catheters. Patients with infections stayed longer in the unit. 3.2. Bloodstream infection (BSI) and intravascular accesses Twenty-two of 67 blood-cultured patients (33%) had 35 verified BSI episodes. Their median age was 53 (range 23–90) years. Their median TBSAB was 25% (4–82%) and burn score 8 (3–14). All BSI patients but one had full thickness burns. The median time to first BSI was 5 days (range 1–50). Their median length of stay was 52 days (range 3–92).
Table 1 Comparison between infected and uninfected patients
Patients (n) Women Men Age (years, median, range) TBSAB% (median, range) total Women Men ABBSI (median, range) Mortality Intubation Ventilator days median No. of central venous catheters/in no. of patients Central venous catheter days median (range) No. of arterial catheters/in no. of pat Arterial catheter days median (range) Length of stay median (range)
Infected
Uninfected
83 38 45 50 (11–90) 10 (1–82) 10 (1–38) 9 (1–82) 6 (3–14) 8 24 11 66/33 9 (1–23) 62/31 5 (1–36) 30 (1–92)
147 48 99 38 (5–89) 5 (1–92) 5 (1–60) 4 (1–92) 4 (2–14) 5 11 3 4/4 6.5 (2–9) 7/6 4 (1–5) 3 (1–53)
P 0.048 <0.001 <0.001 <0.001 0.09 0.007 0.004 <0.001 <0.001 <0.001
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Table 2 Micro-organisms that caused wound and bloodstream infection Micro-organisms
Wound
Bloodstream
Coagulase-negative staphylococci Staphylococcus aureus Streptococci group A, B, G Streptococcus pneumoniae Enterococcus faecalis Lactobacillus Bacillus Clostridium species Propionebacterium acnes Pseudomonas aeruginosa Acinetobacter Sphingotrophomonas maltophilia Escherichia coli Enterobacter Citrobacter Klebsiella Morganella morganii Candida
17 61 26 1 0 0 2 1 0 27 3 2 0 10 0 8 0 1
10 8 3 0 2 1 0 0 1 4 0 0 1 1 2 4 2 2
The micro-organisms causing BSI are listed in Table 2. Coagulase-negative staphylococci (CoNS) were the most common micro-organisms causing BSI (n = 9), and next in frequency were methicillin sensitive Staphylococcus aureus (MSSA) (n = 5), Klebsiella (n = 5), Enterococcus (n = 2), Pseudomonas aeruginosa (n = 2), Lactobacillus (n = 2) and Streptococcus species (n = 2). Among the nine patients with CoNS BSI, seven had more than one positive blood culture. In 26/35 blood stream infections the same micro-organism was identified in burn wounds. Six patients had more than one micro-organism in one BSI episode: the four patients who died had group A streptococci and S. aureus, group B streptococci and S. aureus, P. aeruginosa and enterococci or klebsiella and citrobacter bacteremia, whereas the two survivors had CoNS and S. aureus or CoNS and propionebacteria. Six patients had more than one episode of BSI. One patient belonged to both groups. The mortality rate for patients with verified and strongly suspected BSI (27%, 6/22) was nine times greater than for the non septic patients (3%, 7/208) (OR 10.8, CI 2.9–42, P < 0.0001). The mortality in polymicrobial bacteremia was 4/6 and in monomicrobial bacteremia 0/14 (P = 0.003). Seventy central venous catheters were inserted in 37 patients, and 69 arterial catheters were inserted in 37 patients. Two patients had central venous but no arterial catheter and two patients had arterial but no central venous catheter. Five patients had a catheter-associated blood stream infection and four patients had a suspected catheter-related blood stream infection. The device-specific bloodstream infection rate [16,17] was 6 catheter-associated blood stream infections per 1000 central venous catheter days and 7 catheter-associated blood stream infections per 1000 arterial catheter days. Most frequently found micro-organism
in catheter-associated blood stream infection was S. aureus (n = 6). 3.3. Pneumonia and smoke inhalation Fourteen patients developed 17 pneumonia episodes. Besides positive radiology, the diagnosis of pneumonia was verified by bronchoscopy and culture from protected brush in 12 episodes, culture from tracheal aspirates in two and BSI in two episodes. Median age was 52 years (range 29–87). Median TBSAB was 18% (2–45%) and median burn score 8 (range 4–10). All patients except two had full thickness burns. The median time to first pneumonia was 3 days (range 2–51). The median length of stay was 40.5 days (6–92). The device-specific rate of pneumonia [16,17] was 41 pneumonias per 1000 ventilator days. Thirteen pneumonias were caused by bacteria, one by herpes simplex, one by influenza A, one by influenza B and one causative agent was never found. The most common micro-organisms causing pneumonia were pneumococci (n = 6) and MSSA (n = 3). Four of 14 patients died with pneumonia (TBSAB 2, 13, 30 and 45%, burn score 8, 7, 10 and 8, respectively). Twelve of 230 patients had been exposed to smoke inhalation, and 11 of these were intubated. Median TBSAB was 17% (1–82%) and median burn score 7 (range 4–14). The risk of pneumonia was higher in patients with smoke inhalation (7/12, TBSAB median 16%, range 2–35) than in other burn patients (7/218, TBSAB median 30%, range 2–45) (P<0.001). Two of the patients died (TBSAB 30% and 82%). There was no significant difference in mortality between patients with or without smoke inhalation (2/12 against 11/218, P = 0.9). 3.4. Burn wound infection Seventy-two patients had 107 registered burn wound infections. Their median age was 50 years (range 10–85). TBSAB was median 10% (0.5–45%) and burn score median 6 (range 3–10). All except ten patients had full thickness burns. The median time to first wound infection was 5 days (range 2–33). Their median length of stay was 30 days (1–92). Fourty-five patients had one, 21 patients two, four patients three and two patients had four wound infections. The micro-organisms causing burn wound infection are listed in Table 2. The most frequent organism causing wound infection was MSSA (n = 61), and next in frequency were P. aeruginosa (27), -haemolytic streptococcus spp (n = 26), coagulase-negative staphylococci (n = 17), Enterococcus (n = 13) and Enterobacter (n = 10). 3.5. Urinary tract infections Seventeen patients, six men and 11 women, had 17 urinary tract infections. Their median age was 65 years (range 21–90). TBSAB was median 12% (1–35%) and burn score median 7 (range 6–9). In 14 of these 17 patients a urinary
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tract catheter had been used. All patients had full thickness burns. Median time to first urinary tract infection was 22 days (range 1–49). Their median length of stay was 50 days (range 1–92). The most common micro-organism causing urinary tract infection was E. coli (n = 9), and second in frequency was P. aeruginosa (n = 3). 3.6. Antibiotic usage and antimicrobial resistance About 1300 cultures were taken per year, with 54–61% positive. All S. aureus isolates were sensitive to isoxazolylpenicillins. Coagulase-negative staphylococci were resistant to isoxazolylpenicillins in 57% and to gentamicin in 53% of isolates tested. Enterococci were sensitivity tested in 45 patients, of which six carried gentamicin-resistant strains. Stenotrophomonas maltophilia was found in seven patients (no blood cultures), two of which were gentamicin resistant. P. aeruginosa in 126 patients (no blood cultures), none were resistant to gentamicin or cephtazidim. K. pneumoniae in 19 patients (three blood) and K. oxytoca in 29 patients (two blood), none resistant to ceftazidime. Enterobacter aerogenes 7 (no blood) and Enterobacter cloacae 45 (no blood), one resistant to cephtazidim. Two patients had a candida BSI and one patient had a wound infection caused by candida. Seven patients were colonised with candida in three or more body orifices and underwent antifungal prophylactic treatment with oral fluconazol. In all, ten patients were treated in 11 periods with antifungal therapy, and median length of treatment was 16 days (range 3–34 days), TBSAB in these ten patients was median 34% (range 15–45%), median length of stay 55 days (range 10–92 days). One-hundred and fifteen of the 230 patients (50%) received antibiotics during their stay in the burns unit. Three-hundred and seventy-two courses of antibiotics were given for proven infection, with a median duration of 5 days (range 0–45). Seventy-seven out of 83 patients (94%) with infection were treated with antibiotics. Most commonly used antibiotics were cloxacillin, penicillin and gentamicin. All antibiotic courses are shown in Fig. 1.
Fig. 1. Number of courses of antibiotics given to patients.
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Thirteen of 176 infections were not treated with antibiotics. These were four urinary tract infections and nine burn wound infections. Thirty-eight out of 147 patients (26%) without infection were given antibiotics. Median TBSAB was 4% (range 1–32%), median length of stay was 13 days (range 1–53 days), none of these patients died. Antimicrobials were given for median 6 days (range 2–34 days). Most frequently used antimicrobial was isoxazolypenicillin (n = 31), penicillin (n = 14), clindamycin (n = 5) and cefuroxim (n = 3). 4. Discussion In Europe, this is the first prospective study of long-term incidence of infection in a burns unit. The number of patients is large compared to many other studies. Our patients were adults, with very few exceptions. The mean patient age was at least 10 years higher than in other prospective studies [18,19]. Median burn size in our patients was comparatively small. Median age is given as this is more adequate than means in non-normally distributed populations. In other studies burn sizes are usually given as means, and mean burn sizes are often 25–45% [18], i.e. three to five times higher than in our study. The mortality rate in our study of burn patients is consistent with those reported from other studies when these differences in patient materials are taken into account [18,20–22]. The patients who died without signs of infection were very old and suffered from chronic heart or lung disease. These patients did not survive long enough to contract a nosocomial infection. Large burns, late primary excisions, old age and polymicrobial bacteremias are well recognised risk factors for mortality in burn patients [22–24]. The non-survivors in our study were older and had larger burns as well as a higher incidence of inhalation injury (23%, 3/13) than the survivors (4%, 9/217). Polymicrobial BSI has been described in burn patients from USA [25] as associated with a high mortality. In agreement, we found that four out of six patients that died from BSI had polymicrobial blood stream infection. Candida infections were not a great problem in our burn unit. Two patients died with Candida infections; one with a mixed blood culture of bacteria and Candida, and the other with a clinical suspicion of disseminated Candida infection and where no post mortem investigation was performed. We believe our strict antibiotic policy, avoiding systemic prophylaxis and topical antibiotic agents which promotes proliferation of yeast and fungi in burn wounds, is one of the reasons [26,27]. In all patients, we registered all infections not present on admission [19]. Infected patients were older, had larger burns, higher burn score, longer stay in hospital, more operations, and a larger number of central venous catheters and arterial catheters, compared to uninfected patients.
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Prospective studies of infection in burn patients are few, and comparisons between units are problematical. In a 6-month study Wurtz et al. [18] registered only signs and symptoms of infection starting 72 h or more after admission to the burns unit. In that study, tracheal intubation and central venous catheterisation were seen as risk factors for infection, but the severity of burn injury was not considered. Taylor 1992 [19] is a 1-year study using the CDC criteria, and starting to register from the time of admission. In Taylor 1992 [19] the average burn size was not given. They used topical antimicrobial therapy and antimicrobial prophylaxis but no hydrotherapy. Their main infecting microorganisms were staphylococci. Other risk factors for infection were not analysed. Wurtz et al. [18] had 90 nosocomial infections per 100 discharges and deaths, whereas we had 77 infections per 100 patients and Taylor [19] 78. The patients in these studies were not equivalent, however. Our patients were older, had smaller burns as expressed by TBSA and a shorter average length of stay. Old age has been found to lead to a higher incidence of infections. BSI figures in our study contains both primary septicemia and positive blood cultures originating from localized infections such as pneumonia. Wurz [18] excluded early septicemias and Taylor [19] counted only first primary septicemias, which accounts for their lower figures. Our device-specific BSI rates were low compared to other reports [28]. S. aureus was our main BSI organism, indicating that the patients were infected with strains from their wounds [24]. The diagnosis of pneumonia is notoriously difficult [29]. Our incidence of pneumonia is much lower than in other studies [18,19]. Our injuries were smaller and the inhalation injuries fewer. Nearly all our pneumonias were diagnosed by positive protected brush culture, which is not often used in other studies. The majority of our infections were wound infections. Wound infection rates varies greatly between studies [18,19]. These differences seem to be related to differences in criteria, but might also describe differences regarding the use of topical antimicrobials and frequent swab cultures contra burn biopsy specimens. There is a great need for better definitions of burn wound infection [30]. Antimicrobial therapy can cause severe problems with resistance mainly against cephalosporins and other betalactams as well as quinolones in intensive care units [31]. A strict antibiotic policy is of importance in the control of antibiotic resistance [32]. In particular, broad-spectrum betalactam antibiotics have been shown to cause gram-negative problems in areas of the hospital with a high number of courses of empirical treatment. Antibiotic prophylaxis has been shown to be of little use [33], and has not been practised in our unit for several years. Our strict criteria for infection have helped us to keep the number of patients empirically treated with antibiotics low. We have shown that it is possible to reserve antibiotics for
proven infection and to limit the use of broad-spectrum drugs without increasing mortality and other complication rates. We believe that this is the reason for the favourable situation concerning antimicrobial resistance rates in the unit, both against betalactams and aminoglycosides. Infection rates in burns units have been reported to be high, compared to other intensive care units [28]. The burn patient is infection-prone and very contagious when infected [34]. Isolation care of the burn patient consists of barrier nursing in single rooms, and also of control of airborne infection [34]. Transmission of MRSA in burn units is common [35]. We have managed to prevent transmission of MRSA and other multiresistant micro-organisms in the unit through successful barrier nursing, despite repeated introduction of these bacteria from other centra. That isolation care in general is important in the prevention of nosocomial transmission of infection has long been known, and detailed guidelines are available [36]. Cross-transmission of multi-resistant micro-organisms is common in intensive care units [37]. If transmission occurs, this is an indicator of poor quality of nursing care—nursing overload and patient crowding are the most important factors [38]. Simple barrier nursing using gloves and gown at patient contact is more effective than elaborate isolation care with gowning, sterile gloves, cap etc on every patient visit [39]. 4.1. Conclusion Careful surveillance of infection, good isolation techniques and procedure routines, and a restrictive antimicrobial policy can keep antimicrobial resistance rates and infection rates low in infection-prone burn patients.
Acknowledgements The authors are indebted to Anneli Holmsten, BSc, and Ove Tullberg, MD, for the design and development of the computerised medical record system.
Appendix A. Criteria for nosocomial infection A.1. Blood stream infection 1. Verified blood stream infection One or several positive blood cultures and at least one sign from the list below 2. Suspected blood stream infection No positive blood culture but sign (f) and at least another two signs and antimicrobial therapy instituted 3. Catheter-associated blood stream infection
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Positive catheter tip culture and blood culture obtained by separate venipuncture with the same micro-organism and at least one sign 4. Suspected catheter-associated blood stream infection No positive blood culture but positive catheter tip culture >1000 colony forming units and at least two signs
4. Positive swab culture from burn wound and at least two signs from the list below. 5. Pus and/or foul smelling discharge from wound, abscess, drain or fistula beneath fascia.
A.1.1. Clinical and laboratory signs of BSI
(a) temperature >38.5 ◦ C or <36 ◦ C during at least 12 h or ongoing antipyretic therapy (b) leucocyte count <4 or >12×109 /l in blood (c) C-reactive protein >50 mg/l
<36 ◦ C
(a) temperature >38.5 or during at least 12 h or ongoing antipyretic therapy (b) pulse rate >100/min (c) mean arterial pressure <75 mmHg (d) respiratory rate >28/min or FiO2 >0.21 (e) septic emboli (f) disturbance of mental orientation or level of consciousness (g) hypotension <90 mmHg or inotropic drugs (h) C-reactive protein >100 mg/l (i) platelet count <100×109 /l (j) leucocyte count <4 or >12×109 /l A.2. Pneumonia Positive chest radiography (new or progressive infiltrates where circulatory reasons or ARDS can be excluded) and one of the following criteria: 1. positive quantitative culture with protected brush (threshold 103 cfu/ml) and at least one sign from the list below 2. broncho-alveolar lavage (threshold 104 cfu/ml) and at least one sign 3. purulent sputum or tracheal secretion and at least two signs 4. positive blood culture and at least one sign 5. positive virus isolation/antigen test via bronchoscopy and/or serological or cytological signs of virus infection
A.3.1. Clinical and laboratory signs of burn wound infection
A.4. Urinary tract infection 1. In patients with indwelling catheter: 1.1. two urinary cultures>100 000 cfu/ml with the same micro-organism and at least two signs from the list below 2. in patients without indwelling catheter: 2.1. one urinary culture >100 000 cfu/ml and at least one sign 2.2. two urinary cultures >10 000 cfu/ml with the same micro-organism and at least two signs A.4.1. Clinical and laboratory signs of urinary tract infection (a) temperature >38.5 ◦ C or <36 ◦ C during at least 12 h or ongoing antipyretic therapy (b) suprapubic tenderness (c) frequent micturition (d) dysuria (e) C-reactive protein >50 mg/l (f) leukocyte count <4<12×109 /l in blood
References
A.2.1. Clinical and laboratory signs of pneumonia (a) temperature >38.5 ◦ C or <36 ◦ C during at least 12 h or ongoing antipyretic therapy (b) leucocyte count <4 or >12×109 /l in blood (c) C-reactive protein >100 mg/l A.3. Burn wound infection 1. Pus and/or foul smelling discharge from skin, wound, blister, abscess, drain, fistula or vascular insertion site above fascia. 2. Change in burn wound appearance or character, such as dark discoloration of the eschar, increased bleeding tendency, signs of inflammation in or around the wound or vascular insertion site and positive swab culture 3. Skin graft detached more than 2 days after grafting and positive swab culture.
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