59 Risk Factors for Nosocomial Bloodstream Infections Due to Acinetobacter baumannii: A Case-Control Study of Adult Burn Patients Hilmar Wisplinghoff, Walter Perbix, and Harald Seifert From the Institute of Medical Microbiology and Hygiene, University of Cologne, and the Department of Plastic Surgery, Städtisches Krankenhaus Köln-Merheim, Cologne, Germany Risk factors for Acinetobacter baumannii bloodstream infection (BSI) were studied in patients with severe thermal injury in a burn intensive care unit where A. baumannii was endemic. Of 367 patients hospitalized for severe thermal injury during the study period, 29 patients with nosocomial A. baumannii BSI were identified (attack rate, 7.9%). Cases were compared with 58 matched controls without A. baumannii BSI. The overall mortality rate was 31% among cases and 14% among controls; only two deaths (7%) were considered directly related to A. baumannii BSI. Molecular typing of A. baumannii blood isolates by means of randomly amplified polymorphic DNA analysis and pulsed-field gel electrophoresis revealed the presence of three different strain types. Multivariate analysis showed that female gender (P Å .027), total body surface area burn of ú50% (P Å .016), prior nosocomial colonization with A. baumannii at a distant site (P Å .0002), and use of hydrotherapy (P Å .037) were independently associated with the acquisition of A. baumannii BSI in burn patients. These data underscore the need for effective infection control measures for this emerging nosocomial problem. During the past 20 years, Acinetobacter baumannii has emerged as a significant nosocomial pathogen mainly affecting patients with impaired host defenses in the intensive care unit (ICU) setting [1]. Clinical illnesses associated with A. baumannii include pneumonia, meningitis, endocarditis, peritonitis, skin and soft-tissue infections, urinary tract infections, and bloodstream infections (BSIs) [2]. The clinical course of A. baumannii BSI may range from benign transient bacteremia to fulminant septic shock, with a crude mortality rate as high as 52% [3 – 5]. Outbreaks of infections have been linked to contaminated respiratory therapy equipment [6], intravascular access devices [3], bedding materials [7, 8], and transmission via hands of hospital personnel [9]. Multidrug resistance is common among these organisms and may complicate the treatment of serious infections [10, 11]. As with other nosocomial pathogens, various risk factors have been found to be associated with A. baumannii colonization and infection, such as extended hospital stay, severity of illness markers, organ failure, mechanical ventilation, presence of intravascular access devices, prior antibiotic therapy, and male gender [12 – 16]. Nosocomial infection remains the leading cause of morbidity and death in patients with burns [17]. These patients constitute Received 5 May 1998; revised 6 August 1998. This work was presented in part at the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy held on 28 September – 1 October 1997 in Toronto (abstract J-202). Grant support: This work was supported by the Medical Center of the University of Cologne (Köln Fortune no. V99 / 1996). Reprints or correspondence: Dr. Harald Seifert, Institute of Medical Microbiology and Hygiene, University of Cologne, Goldenfelsstrasse 19 – 21, 50935 Cologne, Germany ([email protected]). Clinical Infectious Diseases 1999;28:59–66 q 1999 by the Infectious Diseases Society of America. All rights reserved. 1058–4838/99/2801–0010$03.00 / 9c5e$$ja02 12-27-98 17:58:46 a homogeneous patient population who usually do not have other serious underlying diseases. However, they present with a unique combination of factors that are of potential significance for the development of nosocomial infection, such as large burn wound areas, mechanical ventilation, multiple surgical procedures, parenteral nutrition, and decreased fluid, electrolyte, and serum protein levels. Previous studies that have tried to identify risk factors for the acquisition of nosocomial A. baumannii infections did not include a significant number of burn patients [12 – 16]. The goal of this study was to analyze risk factors specific for A. baumannii bacteremia in burn patients. In addition, we present the largest series of BSI due to A. baumannii in burn patients reported to date. Molecular typing methods were used to analyze strain relatedness among A. baumannii isolated from blood and other clinical specimens. Materials and Methods Background Krankenhaus Köln-Merheim is an 800-bed university-affiliated tertiary care teaching hospital in Cologne, Germany. It has four separate ICUs, including one of the major burn centers in Germany with 10 beds in the burn intensive care unit (BICU) and 10 beds in a separate plastic surgery ward for convalescing patients that is adjacent to the BICU. Annually, about 120 – 150 thermally injured adults and children from all parts of Germany are admitted. All patients in the BICU are cared for in single cubicles. All microbiological testing for the hospital was performed at the Institute for Medical Microbiology and Hygiene, University of Cologne. cida UC: CID 60 Wisplinghoff, Perbix, and Seifert Study Design To identify risk factors associated with the acquisition of A. baumannii BSI, a retrospective case-control study was conducted. A case was defined as any patient admitted to the BICU during the study period (1 January 1990 through 31 December 1992) for whom one or more blood cultures were positive for A. baumannii and who met the Centers for Disease Control and Prevention’s definition for nosocomial BSI [18]. Second episodes were excluded. Controls were randomly selected from burn patients without A. baumannii bacteremia and were required to have been hospitalized in the same unit and during the same period as the cases. A control was included only if his or her BICU stay was at least as long as that of the corresponding case before the onset of A. baumannii BSI. Controls were matched to cases on a 2:1 ratio for age ({10 years) and length of stay before A. baumannii bacteremia. Data Collection and Definitions of Clinical Parameters Data recorded at the time of admission included age, sex, severity of underlying burn injury as determined by the percent of total body surface area (TBSA) burn [19], and the abbreviated burn severity index (ABSI) [20]. The ABSI is a prognostic score system that correlates the probability of survival with the presence of adverse prognostic factors such as age (1 point for every 10 years), percent of TBSA burn (1 point for every 10%), female gender (1 point), inhalation injury (1 point), and fullthickness burn (1 point). The probability of survival with a score of ú12 points is õ10%. The cause of the burn injury (exposure to flames, electricity, acid, hot surfaces, or explosion), accompanying traumata (fractures, severe tissue damage, and head injury), and the presence of other significant comorbidities were also recorded. In addition, the following data were extracted from the laboratory and medical records for the patients: length of BICU stay before A. baumannii bacteremia; number of days in the BICU before the first culture was positive for A. baumannii; site of infection or colonization with A. baumannii; presence of prior bloodstream infections, burn wound infections, and/or urinary tract or respiratory tract infections due to agents other than A. baumannii; duration of mechanical ventilation; presence of any of the five organ system failures defined below; presence of peripheral, central venous, or arterial intravascular catheters, urinary catheters, and nasogastric tubes; number and type of prior surgical procedures, in particular surgical wound excision and grafting; use of hydrotherapy; use of prior antimicrobial therapy; and outcome. Controls were followed up until the date of bacteremia in the corresponding case. Colonization and infection were defined according to previously published criteria for the study of nosocomial infections [18]. Sepsis, severe sepsis, and septic shock were defined according to criteria reported by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Con- / 9c5e$$ja02 12-27-98 17:58:46 CID 1999;28 (January) ference Committee [21]. The presence of organ system failure was assessed by using the criteria described by Fagon et al. [22] with the following minor modifications: respiratory failure, FiO2 of ú0.4 for ú3 days during mechanical ventilation; cardiovascular failure, any need for epinephrine or norepinephrine or a need for dopamine (ú5 mg/[kgrmin]) to maintain a systolic blood pressure of ú90 mm Hg; renal failure, decreased urine output (õ500 mL/d), acute increase in serum creatinine level of ú2.0 mg/dL, or requirement of acute dialysis or ultrafiltration; hematopoetic system failure, platelet count of õ100 1 109/L; and liver failure, serum bilirubin level of ú5 mg/dL. Microbiology For surveillance, tracheal aspirate and burn wound specimens for cultures were obtained from burn patients at the time of admission and twice weekly thereafter. Quantitative cultures of burn wound biopsy specimens were not performed for the diagnosis of burn wound infection. A. baumannii isolates were identified by using the simplified identification scheme of Bouvet and Grimont [23]: growth at 377C, 417C, and 447C; production of acid from glucose; gelatin hydrolysis; and use of 14 different carbon sources. All A. baumannii isolates recovered from blood as well as from other body site specimens were prospectively collected during the study period and stored in glycerol broth at 0707C until further use. MICs of selected antibiotics were determined with a broth microdilution method (MicroScan; Baxter Laboratories, West Sacramento, CA) in accordance with guidelines established by the National Committee for Clinical Laboratory Standards [24]. Isolates of A. baumannii were further characterized by means of molecular typing methods such as randomly amplified polymorphic DNA PCR analysis with use of two different primers (ERIC-2 and M13) and Ready-To-Go RAPD Analysis Beads (Pharmacia Biotech, Freiburg, Germany) [25] and analysis of genomic DNA by pulsed-field gel electrophoresis with use of the restriction enzyme ApaI as described previously [26]. Statistical Analyses Results were expressed as the mean {SD or as a proportion of the total number of patients. Univariate analysis was conducted by the x2 test for categorical variables and the MannWhitney U test for continuous variables. Factors were considered significant at a P value of £.05. All P values are twotailed. Risk factors independently associated with A. baumannii BSI were identified by stepwise logistic regression analysis of variables selected by univariate analysis, with a limit for entering and removing variables at 0.05. Only variables observed in at least 10% of the patients were included. All statistical analyses were done by using SPSS software (SPSS, Chicago). cida UC: CID CID 1999;28 (January) A. baumannii Bloodstream Infections in Burn Patients 61 Table 1. Characteristics of burn patients with (cases) and without (controls) Acinetobacter baumannii bloodstream infection at the time of admission to the BICU. Characteristic No. (%) of females Mean age { SD in y (range) Mean ABSI { SD (range) Mean percentage of TBSA burn { SD (range) No. (%) of patients with inhalation injury Mean length of stay in BICU { SD in d (range) No. (%) of patients who died Cases (n Å 29) Controls (n Å 58) Total* (n Å 367) 17 (59) 36 { 15 (9 – 75) 8.1 { 2.5 (4 – 13) 16 (28) 36 { 14 (6 – 74) 6.2 { 2.2 (2 – 12) 108 (29) 39 { 19 (1 – 96) 6.3 { 2.5 (1 – 16) 42 { 21 (14 – 95) 26 { 18 (2 – 80) 25 { 18 (2 – 99) 15 (52) 19 (33) 102 (28) 50 { 27 (5 – 106) 9 (31) 30 { 23 (6 – 86) 8 (14) 26 { 24 (3 – 156) 70 (19) NOTE. ABSI Å abbreviated burn severity index; BICU Å burn intensive care unit; TBSA Å total body surface area. * Total no. of burn patients treated for §48 hours. Results Study Population and Patient Characteristics Between 1 January 1990 and 31 December 1992, 389 patients with severe thermal injury were admitted to the BICU; 22 of these patients were treated for õ48 hours and were excluded from the study. Of the remaining 367 patients, 35 had A. baumannii BSI (attack rate, 9.5 cases per 100 admissions). Six cases were excluded from further considerations because their medical records were not available (four patients) or because appropriate controls could not be identified (two patients). The study cohort comprised the remaining 29 patients. Patient characteristics at the time of admission are shown in table 1. Seventeen cases (59%) and 16 controls (28%) were female. The mean age {SD for the cases was 36 { 15 years (range, 9 – 75 years), and the mean total length of stay in the BICU { SD for the cases was 50 { 27 days (range, 5 – 106 days). The mean percent of TBSA burn { SD was 42 { 21 (range, 14 – 95) for the cases and 26 { 18 (range, 2 – 80) for the controls; the mean ABSI { SD was 8.1 { 2.5 for the cases and 6.2 { 2.2 for the controls. Fifteen cases (52%) and 19 controls (33%) had inhalation injury. Exposure to open fire led to thermal injury in 54% of patients, 21% of burns were secondary to an explosion, 6% were caused by electricity, and 19% were due to other causes such as contact with hot surfaces, liquids, or gases. There was no significant difference between cases and controls in terms of the type of burn injury. The origin of A. baumannii bacteremia in 18 cases could not be determined, mainly because A. baumannii was isolated from multiple sites. Nine cases were considered catheterrelated, and in two cases, bacteremia was considered secondary to a burn wound infection. A. baumannii bacteremia secondary to a respiratory tract infection was probably underreported because of difficulties in performing chest roentgenography as / 9c5e$$ja02 12-27-98 17:58:46 well as chest physical examinations on these cases. Only two cases had A. baumannii bacteremia without prior colonization at a distant site. Clinical sepsis at the time of bacteremia was evident in all cases. Seven cases (24%) met the criteria for severe sepsis, and three cases (10%) presented with septic shock. Bacteremia was polymicrobial in 14 cases; Pseudomonas aeruginosa, enterococci, and coagulase-negative staphylococci were isolated most frequently as copathogens. The overall in-hospital mortality rate among all patients admitted for severe burns during the study period was 19%. Nine cases and eight controls died during their hospital stay; therefore, the crude mortality rate among cases was more than twice that among controls (31% vs. 14%, respectively). In only two cases, however, was death considered related to A. baumannii bacteremia. Microbiological Data During the study period, A. baumannii was highly endemic in the BICU, with maximum rates of colonization as high as 48 cases per 100 admissions [27]. The most common microorganisms isolated from burn patients during the study period were, in decreasing order of frequency, P. aeruginosa (21.5%), A. baumannii (19.5%), and Staphylococcus aureus (11.9%); 11.2% of blood culture isolates were A. baumannii. All A. baumannii isolates were multidrug-resistant with three different resistance patterns: strain A was susceptible to amikacin and imipenem only; strain B, amoxicillin/clavulanate, piperacillin, and imipenem; and strain C, tobramycin and imipenem. Forty-nine patients (27 cases [93%] and 22 controls [38%]) were colonized with A. baumannii; A. baumannii was not isolated from any of these patients at the time of admission. The mean duration of hospitalization { SD from the time of admission to the first culture positive for A. baumannii was 10 { 10 cida UC: CID 62 Wisplinghoff, Perbix, and Seifert Figure 1. Fingerprint patterns for blood culture isolates of Acinetobacter baumannii recovered from burn patients following PCR amplification with the primer ERIC-2. Three different A. baumannii strain types were found: A (lanes 2 – 7), B (lanes 8 and 9), and C (lanes 10 – 18). Lanes 1 and 19, 100-bp ladder. days (range, 1 – 41 days) for both groups. For cases, the mean time { SD between colonization and the onset of bacteremia with A. baumannii was 13 { 10 days (range, 1 – 78 days). The primary site of colonization was most often the respiratory tract (57% of cases) followed by contaminated burn wounds (37%). Randomly amplified polymorphic DNA PCR typing of blood culture isolates revealed that three different A. baumannii strain types infected 13, 12, and 4 cases, respectively (figure 1). These strains corresponded to the strains isolated from a distant site in a given patient as well as to the A. baumannii strains found to be endemic in the BICU. Typing results obtained by PCR fingerprinting were confirmed by pulsed-field gel electrophoresis (data not shown). Case-Control Study Clinical characteristics of cases and controls and risk factors for A. baumannii BSI according to univariate analysis are shown in table 2. Cases had more severe burn injuries than did controls as determined by a higher mean ABSI (8.1 vs. 6.2, respectively; OR, 5.8), and more cases had a TBSA burn of ú50% than did controls (34% vs. 9%, respectively; OR, 4.8). The severity of illness was greater in cases than in controls as illustrated also by a higher frequency of organ failure (69% vs. 43%, respectively; OR, 2.9) and a greater mean total number of organs affected (1.6 vs. 0.8, respectively; OR, 3.5). Cases received support with mechanical ventilation more frequently (97% vs. 64%, respectively; OR, 18.4) and for longer periods than did controls. The mean duration of mechanical ventilation was 22 days for cases and 15 days for controls. Cases were more likely than controls to have received hydrotherapy (86% vs. 55%, respectively; OR, 5.1) at least once during their hospital stay as part of their burn wound care. The mean number of courses of hydrotherapy was five for cases and three for controls. / 9c5e$$ja02 12-27-98 17:58:46 CID 1999;28 (January) Prior antimicrobial therapy was administered more often for cases than for controls. Cases were significantly more likely than controls to have received therapy with broad-spectrum penicillins, cephalosporins, and aminoglycosides. Twentyseven cases and 22 controls were colonized with A. baumannii prior to bacteremia (93% vs. 38%, respectively; OR, 22.1). Prior BSIs due to organisms other than A. baumannii were more frequent in cases than in controls (41% vs. 12%, respectively; OR, 5.1). All cases and 50 controls (86%) had at least one intravascular catheter in place (OR, 4.5). Cases had a mean { SD of 2.2 { 0.4 intravascular access devices per patient, whereas controls had a mean { SD of 1.5 { 0.9. Intravascular catheters were in place for a mean duration of 23 days for both cases and controls. Urinary catheters (93% vs. 74%, respectively; OR, 4.7) and nasogastric tubes (97% vs. 67%, respectively; OR, 13.6) were also more frequent in cases than in controls. Multivariate logistic regression analysis identified four independent risk factors associated with the acquisition of A. baumannii BSI in burn patients: female gender (P Å .027), prior nosocomial colonization with A. baumannii (P Å .0002), TBSA burn of ú50% (P Å .016), and use of hydrotherapy (P Å .037) (table 3). Discussion Nosocomial infections in thermally injured patients remain a common complication, contributing substantially to burnassociated morbidity and mortality [17, 28, 29]. P. aeruginosa is considered the major cause of life-threatening infections in these patients; the overall mortality rate among patients with P. aeruginosa bacteremia has been reported as high as 77% [30, 31]. In recent years, A. baumannii, another opportunistic gram-negative nosocomial pathogen, has also emerged as an important organism in major burn units around the world [7, 32 – 37]. Multidrug resistance in these organisms, including resistance to imipenem, is a cause of concern [5, 11, 36, 37]. A. baumannii was highly endemic in our hospital during the entire study period. The overall incidence of colonization and infection with A. baumannii (48 cases per 100 admissions) was higher than in most other previous investigations performed in various types of ICUs for which reported attack rates ranged from 3% to 14% [6, 12, 13, 15]. This difference may be explained by the fact that large burn wounds contaminated with A. baumannii provide an excellent reservoir for patient-to-patient spread of this organism. Only two previous studies reported comparable colonization rates of 61% and 51%, respectively [7, 32]. Both studies were from other burn centers, and attack rates were recorded during hospital outbreaks of limited duration. The present study included 29 cases of A. baumannii BSI in burn patients, which to our knowledge is the largest series of cases in this patient population that has been reported to date. During the study period, A. baumannii was the second cida UC: CID CID 1999;28 (January) A. baumannii Bloodstream Infections in Burn Patients 63 Table 2. Results of univariate analysis of potential risk factors for acquisition of Acinetobacter baumannii bacteremia in burn patients. Finding Female gender TBSA burn of ú50% Mean ABSI { SD Mechanical ventilation Organ failure Respiratory Cardiovascular Hematologic Renal Mean total number of organs affected { SD Prior colonization with A. baumannii Prior surgical procedures Use of hydrotherapy Prior BSI not caused by A. baumannii Prior RTI not caused by A. baumannii Prior use of antibiotics Broad-spectrum penicillins Cephalosporins Aminoglycosides Central venous catheter Arterial catheter Urinary catheter Nasogastric tube Cases (n Å 29) Controls (n Å 58) P value 17 (59) 10 (34) 8.1 { 2.5 28 (97) 20 (69) 11 (38) 16 (55) 13 (45) 5 (17) 1.6 { 1.2 27 (93) 27 (93) 25 (86) 12 (41) 12 (41) 16 (28) 5 (9) 6.2 { 2.2 37 (64) 25 (43) 12 (21) 17 (29) 11 (19) 5 (9) 0.8 { 1.1 22 (38) 49 (84) 32 (55) 7 (12) 15 (26) .0049 .0073 .0002 .0004 .0229 .0856 .0191 .0110 .7805 .0110 õ.0001 .2541 .0041 .0018 .1403 3.7 4.8 5.8 18.4 2.9 .0002 .0002 .0005 .0358 .0003 .0175 .0022 11.8 11.8 5.4 4.5 14.7 4.7 13.6 27 27 21 29 29 27 28 (93) (93) (72) (100) (100) (93) (97) 31 31 17 50 38 43 39 (53) (53) (29) (86) (66) (74) (67) OR (95% CI) 3.0 3.5 3.2 22.1 5.1 5.1 (1.5 – 9.5) (1.4 – 16.0) (2.2 – 15.5) (2.3 – 145) (1.1 – 7.5) NS (1.2 – 7.5) (1.3 – 9.3) NS (1.1 { 11.4) (4.8 – 102) NS (1.6 – 16.5) (1.7 – 15.2) NS (2.6 – 54.1) (2.6 – 54.1) (2.0 – 14.4) (1.7 – 23.8) (1.9 – 116) (1.0 – 22.2) (1.7 – 108) NOTE. ABSI Å abbreviated burn severity index; NS Å not significant; RTI Å respiratory tract infection; TBSA Å total body surface area. Unless otherwise indicated, all values represent no. (%) of patients. most common pathogen isolated; 11.2% of blood cultures were positive for this organism. The incidence of bacteremia due to A. baumannii was 7.9 cases per 100 admissions. Lyytikäinen and co-workers [37] isolated A. baumannii from blood specimens from eight patients with thermal injury, but these investigators did not provide data on infection rates. Sherertz and Sullivan [7] found acinetobacter BSI in seven (6.8%) of 103 patients admitted to the hospital during a 21-month epidemic period. A. baumannii BSI was rare in other studies of burn patients [32, 36]. In our study, the mortality rate was 31% among burn patients with A. baumannii BSI (cases), 14% among burn patients without A. baumannii BSI (controls), and 19% among the total burn population; however, these findings may rather reflect more severe burn injuries in cases than the intrinsic virulence of A. baumannii, since death directly related to A. baumannii bacteremia was observed only in two (7%) of 29 cases. Sherertz and Sullivan [7] also observed a lower mortality rate among patients with acinetobacter bacteremia (14%) than among patients with BSI due to other organisms (44%). These investigators even speculated that Acinetobacter might be functioning in a protective role by preventing colonization and infection with more virulent organisms. These findings contrast the attributable mortality rate associated with A. baumannii infection that ranged from 19% to 34% in other recent series [4, 5, 13]. In our experience, A. baumannii bacteremia Table 3. Results of multivariate logistic regression analysis of factors associated with the acquisition of Acinetobacter baumannii bacteremia in burn patients. Factor Coefficient SE of coefficient P value OR (95% CI) 1.6351 1.8136 3.2668 1.7135 0.7390 0.9290 0.8794 0.8215 .027 .016 .0002 .037 5.13 (1.20 – 21.83) 6.13 (1.21 – 37.80) 26.23 (4.68 – 147) 5.5 (1.11 – 27.76) Female gender TBSA burn of ú50% Prior colonization with A. baumannii Use of hydrotherapy NOTE. TBSA Å total body surface area. / 9c5e$$ja02 12-27-98 17:58:46 cida UC: CID 64 Wisplinghoff, Perbix, and Seifert in burn patients often results from noninvasive burn wound infection and sometimes may be transient after burn wound manipulation [28], thus running a more benign course with a lower mortality rate. A. baumannii respiratory tract infection, which is associated with a less favorable prognosis [4, 38], is less frequently observed in this patient population [7]. Unfortunately, the source of A. baumannii bacteremia was not identified in most of our patients, since invasive diagnostic techniques such as quantitative cultures of protected specimen brush or bronchoalveolar lavage samples and quantitative burn wound biopsy cultures that were proposed by other investigators [38, 39] were not employed. Investigations of hospital outbreaks have suggested that exposure to colonized patients and contaminated medical equipment is associated with A. baumannii colonization and infection [6, 9, 14, 37]. Sherertz and Sullivan [7] identified contaminated mattresses in a burn unit as the source of an outbreak of acinetobacter infection that could be controlled only after each patient’s mattress was discarded after the patient was discharged from the unit. PCR fingerprinting as well as DNA macrorestriction analysis showed that three different A. baumannii strain types, which corresponded to the strains known to be endemic in the BICU, caused bacteremia in our patients. These strains were all multidrug-resistant. Increased resistance among A. baumannii was generally observed in more recent studies [4, 11, 36, 37]. The concurrent transmission of two epidemic A. baumannii strains was also observed in previous reports [14, 37]. The retrospective design of our study, however, did not allow us to identify any point source of infection or to prove patient-to-patient transmission. Various studies have analyzed potential risk factors predisposing to the nosocomial acquisition of A. baumannii. Risk factors identified previously included male sex [14], underlying malignancy [16], APACHE II score [13, 16], prior length of stay in the unit [7, 13 – 15, 40], mechanical ventilation [12, 14 – 16, 40], prior use of antibiotics [12 – 14, 16] (in particular, third-generation cephalosporins [12, 14, 15] and aminoglycosides [12]), enteral hyperalimentation [14, 15], presence of a nasogastric tube [14], exposure to invasive procedures such as prior surgery [15], tracheostomy [14, 15, 40], placement of intravascular catheters [3, 14 – 16] and/or urinary catheters [14 – 16], prior infection, and organ system failure [13]. Most of these potential risk factors were identified by univariate analysis and may simply reflect the severity of the underlying disease and the current management of severe diseases in the modern ICU setting that leads to the frequent impairment of natural host defenses and provides multiple opportunities for the invasion of bacterial pathogens. Severity of illness [13], male sex [14], duration of ICU stay [13 – 15], mechanical ventilation [16], prior infection [13], and use of third-generation cephalosporins [14, 15] were also confirmed by multivariate regression analysis as independent risk factors for acquisition of A. baumannii. Previous investigators have not differentiated between colonization and infection with A. baumannii in their analysis of / 9c5e$$ja02 12-27-98 17:58:46 CID 1999;28 (January) risk factors, however. Most researchers analyzed the acquisition of A. baumannii in the setting of a nosocomial outbreak and only rarely included a sufficient number of patients with A. baumannii BSI [9, 12, 13, 15, 16]. In addition, previously reported data may be difficult to compare since they were obtained for a mixed population of patients with multiple underlying diseases who were cared for in various types of ICUs. In the present study, risk factors for A. baumannii BSI were analyzed in a population of burn patients (who are rather homogeneous with regard to their underlying illnesses, invasive procedures, and type of care). Several of the factors found to be significant by univariate analysis in previous studies were also found to be significant for our patients, including mechanical ventilation, prior use of antimicrobials, prior infection due to organisms other than A. baumannii, presence of organ system failure, and use of intravascular catheters, urinary catheters, and nasogastric tubes. The severity of the underlying burn injury is expressed by both the ABSI and the percent of TBSA burn rather than by the APACHE II score. Both markers are specific for thermally injured patients, and the percent of TBSA burn was identified as a significant risk factor by logistic regression analysis. However, most of the other factors that mainly reflect the severity of the underlying burn injury were not found to be independently associated with A. baumannii BSI in our patient population. Hydrotherapy administered to patients with extensive fullthickness burns continues to be an integral part of wound care in many burn centers in the United States and elsewhere [41]. However, hydrotherapy (which usually includes immersion of the patient in tap water during administration of intravenous narcotic analgesics) may facilitate the dissemination of nosocomial pathogens to other wounds in the same patient and may serve as a reservoir for patient cross-contamination [41]. The risk of infection associated with hydrotherapy was recently assessed in an outbreak of wound infections with P. aeruginosa in burn patients [31]. In contrast to the findings of Sherertz and Sullivan [7], hydrotherapy was found to be independently associated with the development of A. baumannii BSI in our study. The mechanism by which hydrotherapy may favor A. baumannii BSI has not been established. It seems possible that meticulous cleaning and disinfection of hydrotherapy equipment alone may be sufficient to eliminate this risk factor. Of note, female gender was also found to be an independent risk factor for nosocomial A. baumannii bacteremia in burn patients in our study. There is currently no explanation for this finding, which is in contrast to data reported by Mulin and colleagues [14] who found that male sex was an independent risk factor in their study. In our series, on the other hand, 14 (82%) of 17 female patients with A. baumannii BSI survived, while only six (50%) of 12 male patients survived. This finding is even more surprising since female gender is usually considered an adverse prognostic factor for survival in patients with severe burn trauma [20]. Prior colonization with A. baumannii was the most significant independent risk factor for A. baumannii BSI in our study. cida UC: CID CID 1999;28 (January) A. baumannii Bloodstream Infections in Burn Patients None of our patients were colonized at the time of admission. The mean interval between colonization with A. baumannii at a distant site and the onset of bacteremia was 13 days. This finding is not surprising since colonization is a prerequisite for infection, but it underscores the need for effective infection control measures. In conclusion, this study demonstrates that burn patients with large burn wound areas are at high risk for the development of nosocomial BSI due to A. baumannii in a unit where this organism is endemic. Mortality rates among these patients are high. Epidemiological typing revealed that three different A. baumannii strain types were responsible for BSI. 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