Risk Factors for Late-Onset Nosocomial Pneumonia Caused by Stenotrophomonas maltophilia in Critically Ill Trauma Patients

Clinical Infectious Diseases, Aug 2002

Patients with nosocomial pneumonia caused by Stenotrophomonas maltophilia often receive inadequate empiric antibiotic therapy, potentially increasing mortality. Knowledge of the risk factors associated with S. maltophilia pneumonia may better guide the selection of empiric antibiotic therapy. Potential risk factors for S. maltophilia pneumonia were retrospectively analyzed for critically ill trauma patients with late-onset gram-negative pneumonia. The effects of S. maltophilia infection and inadequate empiric antibiotic therapy on patient outcomes were also assessed. By multivariate analysis, S. maltophilia pneumonia was found to be associated with cefepime exposure and tracheostomy in patients with a single pneumonia episode and with higher Injury Severity Score and pulmonary contusion in patients with multiple pneumonia episodes. S. maltophilia pneumonia was associated with increased patient morbidity; only inadequate empiric antibiotic therapy was associated with a higher mortality rate. In critically ill trauma patients with late-onset ventilator-associated pneumonia and these risk factors, empiric antibiotic therapy should include agents active against S. maltophilia.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://cid.oxfordjournals.org/content/35/3/228.full.pdf

Risk Factors for Late-Onset Nosocomial Pneumonia Caused by Stenotrophomonas maltophilia in Critically Ill Trauma Patients

CID Risk Factors for Late-Onset Nosocomial Pneumonia Caused by Stenotrophomonas maltophilia in Critically Ill Trauma Patients Scott D. Hanes () 1 3 4 Kutay Demirkan 1 4 5 6 Elizabeth Tolley 1 2 4 Bradley A. Boucher 1 3 4 Martin A. Croce 0 1 4 G. Christopher Wood 1 3 4 Timothy C. Fabian 0 1 4 0 Surgery, University of Tennessee Health Science Center 1 Received 12 October 2001; revised 22 February 2002; electronically published 2 July 2002 2 Biostatistics and Epidemiology 3 Clinical Pharmacy 4 Departments of 5 Present affiliation: Hacettepe University, Faculty of Pharmacy , Ankara , Turkey. S. Dunlap St., Rm. 210, Memphis, TN 38163 6 Department of Pharmacy Services, Baptist Memorial Hospital , Memphis Patients with nosocomial pneumonia caused by Stenotrophomonas maltophilia often receive inadequate empiric antibiotic therapy, potentially increasing mortality. Knowledge of the risk factors associated with S. maltophilia pneumonia may better guide the selection of empiric antibiotic therapy. Potential risk factors for S. maltophilia pneumonia were retrospectively analyzed for critically ill trauma patients with late-onset gram-negative pneumonia. The effects of S. maltophilia infection and inadequate empiric antibiotic therapy on patient outcomes were also assessed. By multivariate analysis, S. maltophilia pneumonia was found to be associated with cefepime exposure and tracheostomy in patients with a single pneumonia episode and with higher Injury Severity Score and pulmonary contusion in patients with multiple pneumonia episodes. S. maltophilia pneumonia was associated with increased patient morbidity; only inadequate empiric antibiotic therapy was associated with a higher mortality rate. In critically ill trauma patients with late-onset ventilator-associated pneumonia and these risk factors, empiric antibiotic therapy should include agents active against S. maltophilia. - Stenotrophomonas maltophilia is becoming a frequently seen pathogen in intensive care units (ICUs), particularly among respiratory tract isolates [ 1–5 ]. In addition to methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter species, S. maltophilia has been identified as a high-risk pathogen; S. maltophilia infection is associated with increased length of ICU stay, duration of mechanical ventilator support, and mortality among patients with ventilator-associated pneumonia (VAP) [ 6, 7 ]. These poor outcomes have been attributed at least partially to the provision of inadequate empiric antibiotic therapy [ 6, 8, 9 ]. Unfortunately, empiric antibiotic therapy often does not include agents active against S. maltophilia, as a result of this pathogen’s intrinsic resistance to most antibiotics that are commonly used in the intensive care setting [ 1, 10 ]. Knowledge of the risk factors for the development of S. maltophilia pneumonia would be useful in determining which patients should empirically receive antibiotics active against S. maltophilia. Although risk factors have been identified for medical ICU patients [ 11 ] and for patients with cystic fibrosis [ 12 ], limited information is available with regard to the development of S. maltophilia pneumonia in trauma patients. Duration of mechanical ventilator support, the need for tracheostomy or air transport to the hospital, and the number of antibiotics received have been identified as being risk factors for S. maltophilia in trauma patients [ 13 ]. However, in that study, both S. maltophilia infection and S. maltophilia colonization were included, the diagnosis of pneumonia was based solely on clinical judgment, and all pneumonia cases (early and late onset) were included, which had the potential to skew risk-factor analyses. Most studies have analyzed all S. maltophilia infections [ 11, 13 ]; however, risk factors may differ depending on the site of infection. To further elucidate this issue, we retrospectively analyzed potential risk factors associated with the development of lateonset S. maltophilia VAP (SM-VAP) against those associated with the development of late-onset VAP caused by other gramnegative bacteria (GN-VAP). In addition, we also analyzed the effects of S. maltophilia pneumonia and inadequate empiric antibiotic therapy on patient outcomes. METHODS We reviewed the records of patients admitted to the trauma ICU at the Presley Memorial Trauma Center, Memphis, Tennessee, from 1 January 1997 to 31 December 1999 who received a diagnosis of pneumonia during the ICU stay. The study was approved by the University of Tennessee Institutional Review Board; informed consent was not required. Patients were included in the study if they had documented late-onset GNVAP that occurred at least 7 days after hospital admission [ 14, 15 ] but was diagnosed within 5 days of transfer out of the ICU, if they were 18 years of age, and if they had needed mechanical ventilator support. Patients were excluded if they stayed in another hospital 12 days before admission to the ICU or if they had been transferred from the ICU to another hospital’s ICU within 2 weeks of admission to the ICU at the Presley Memorial Trauma Center. Pneumonia was defined by a result of a quantitative bacterial bronchoalveolar lavage (BAL) culture of 105 cfu/mL, the appearance of a new or changing infiltrate on chest radiograph, and at least 2 of the following clinical signs of pneumonia: abnormal temperature ( 38 C or !35.5 C), abnormal WBC count ( 10,000 cells/mm3 or 4000 cells/mm3 or the presence of 10% immature bands), or macroscopically purulent sputum [16]. BAL was performed via fiberoptic bronchoscopy. Briefly, the bronchoscope was advanced into the lung segment in which radiographic changes were seen or, for patients who had diffuse bilateral infiltrates, into the left lower lobe. With the bronchoscope wedged into the appropriate lung segment, 100 mL of sterile nonbacteriostatic saline was instilled into the lung in five 20-mL aliquots. The effluent was pooled and sent to the microbiology laboratory for quantitative culture. The antimicrobial susceptibility of isolates was tested by the hospital microbiology laboratory, and the results were interpreted by National Committee for Clinical Laboratory Standards guidelines [ 17 ]. The following demographic information was retrieved from each patient’s medical record for assessment of potential risk factors for S. maltophilia pneumonia: age; sex; mechanism of injury; type of injury; presence of predisposing chronic diseases (i.e., diabetes mellitus, cancer, or chronic lung disease); alcohol abuse or current use of cigarettes, as identified in the social history; Glasgow Coma Scale score [ 18 ]; Injury Severity Score (ISS) [ 19 ]; and chest Abbreviated Injury Scale (AIS) score [ 20 ]. The following variables were documented and assessed as risk factors associated with exposure before the development of pneumonia: duration of mechanical ventilator support; length of ICU stay; length of hospital stay; presence of tracheostomy; number and types of surgeries; previous antibiotic use; number of bronchoscopic procedures; use of respiratory therapy (aerosolized medications); type of stress-ulcer prophylactic agent administered, if any; use of glucocorticoids; whether enteral or parenteral nutrition was received; presence of a nasogastric or nasotracheal tube; presence of a chest tube; and presence of central venous catheters. Finally, the following variables were documented at the time of each pneumonia episode and assessed as risk factors: Acute Physiology and Chronic Health Evaluation (APACHE) II score [ 21 ] and multiple organ dysfunction score [ 22 ] (using worst values within previous 24 h), witnessed or suspected aspiration, WBC count, temperature, and sputum characteristics. Data from a single case of pneumonia for each patient were included in the study analysis. For patients who experienced multiple episodes of late-onset pneumonia, only the most recent ICU-associated pneumonia episode was included in the analysis. Once S. maltophilia pneumonia developed, only that pneumonia episode was included in the analysis. We postulated that the nature of the risk factors may change over time. Therefore, we analyzed risk factors for S. maltophilia for patients who developed a single late-onset VAP episode and for patients who experienced multiple late-onset VAP episodes. To assess the effect of S. maltophilia pneumonia on patient outcomes, the following information was retrieved from the medical record: total length of ICU and hospital stay, total duration of mechanical ventilator support, need for tracheostomy, and survival status at hospital discharge. In addition, patient outcomes were also assessed according to receipt of adequate or inadequate empiric antibiotic therapy. Empiric antibiotic therapy was considered to be adequate when all isolates found in numbers 105 cfu/mL on culture of a BAL sample were reported by the hospital microbiology laboratory to be susceptible to the antibiotics included in the empiric regimen. Inadequate empiric antibiotic therapy was defined by the presence of any bacterial isolate in numbers exceeding 105 cfu/ mL on culture of a BAL sample that was reported by the hospital microbiology laboratory to be intermediately resistant or resistant to the antibiotics included in the empiric regimen. The variables identified as being potential risk factors for the development of S. maltophilia pneumonia were assessed by univariate analysis. Continuous data were compared by the Mann-Whitney U test or Student’s t test, and categorical data were compared by x2 test or Fisher’s exact test, as appropriate. NOTE. Data are percentage of patients, unless otherwise indicated. AIS, Abbreviated Injury Scale; GCS, Glasgow Coma Scale; GN-VAP, ventilator-associated pneumonia caused by gram-negative pathogens other than Stenotrophomonas maltophilia; HEENT, head, ears, eyes, neck, and throat; IQR, interquartile range; ISS, Injury Severity Score; SM-VAP, ventilatorassociated pneumonia caused by S. maltophilia. a Predisposing medical conditions include cancer, diabetes mellitus, and chronic lung disease. Variables for which P .25 were then included in a forward, stepwise multiple logistic regression analysis to determine the independent variable and identify variables associated with the development of S. maltophilia pneumonia. Survival analysis by Kaplan-Meier estimation was used to compare patient outcomes; death and hospital discharge were used as censored variables, as appropriate. Continuous data are reported as mean SD or median (interquartile range [IQR]), as appropriate, for parametrically and nonparametrically distributed data. P .05 was considered to be statistically significant. RESULTS A total of 513 patient charts that listed a diagnosis of pneumonia were screened for enrollment. Of these patients, 163 met the study criteria and were included in the analysis. The remaining patients were excluded for the following reasons: visit of !7 days in the ICU (n p 113), patient had only early-onset nosocomial pneumonia (n p 105), no episodes of pneumonia fulfilled the study definition (n p 81), patient had only grampositive late-onset pneumonia (n p 20), patient was not directly admitted to the ICU (n p 15), medical record was unavailable (n p 8), late-onset pneumonia developed 15 days after ICU transfer (n p 5), and patient was transferred to another hospital ICU (n p 3). The demographic characteristics of the patients with SMVAP were similar to those of the patients with GN-VAP (table 1), with a trend toward more frequent chest injury in the SMVAP group (80.8% vs. 59.9%; P p .07) and more frequent spinal cord injury in the GN-VAP group (19.7% vs. 3.8%; P p .09). The overall prevalence of SM-VAP was 16% (26 of 163 patients). SM-VAP occurred in 14% of patients (18 of 130 patients) who experienced a single episode of late-onset nosocomial pneumonia and in 24% of patients (8 of 33 patients) who experienced multiple episodes. In the group of patients with multiple episodes of pneumonia, most experienced 2 episodes of late-onset nosocomial pneumonia (87.5% for SMVAP and 64% for GN-VAP), and the remainder experienced 3 episodes. In addition, all episodes of SM-VAP were the last diagnosed pneumonia episode experienced by the patient before the end of the study period. Overall, pneumonia was polymicrobial in 46% (75 of 163) of the episodes; the frequency was significantly higher among episodes of SM-VAP than episodes of GN-VAP (92.3% vs. 37.2%; P ! .001). There were no differences in the distribution of bacterial species between the groups, except for a higher prevalence of Alcaligenes xylosoxidans among SM-VAP patients (23.1% for SM-VAP vs. 2.2% for GN-VAP; P ! .001) (table 2). Acinetobacter baumanii and P. aeruginosa were the most frequently identified gram-negative bacteria isolated and were equally distributed between cases of polymicrobial and cases of monomicrobial pneumonia (for A. baumanii, 49.3% vs. 35.2%, respectively; P p .10 and for P. aeruginosa, 64.0% vs. 61.4%; P p .85) and between cases of polymicrobial SM-VAP and cases of polymicrobial GN-VAP (for A. baumanii, 50.9% vs. 45.8%, respectively; P p .86 and for P. aeruginosa, 64.7% vs. 62.5%; P p .94). Antibiotic use is listed in table 3. Except for a difference in use of cefepime and carbapenems in the group of patients who experienced only a single episode of pneumonia, there were no statistically significant differences noted in antibiotic use between the SM-VAP and GN-VAP groups. For patients who experienced a single episode of late-onset pneumonia, univariate analysis identified the number of BAL procedures, days in the ICU and receiving mechanical ventilator support prior to the development of pneumonia, presence of tracheostomy, exposure to cefepime, exposure to carbapenem antibiotics, and APACHE II score as risk factors significantly associated with the development of S. maltophilia pneumonia (table 4). Variables that were included in the multivariate analysis but for which the comparison between patients with SMVAP and patients with GN-VAP did not reach statistical significance were age (mean SD, 49.1 18.0 vs. 40.8 17.8 years; P p .069) and chest AIS score (median [IQR], 3 [ 3–4 ] vs. 3 [ 0–4 ]; P p .194). Multivariate analysis identified cefepime exposure and the presence of a tracheostomy as the most significant risk factors for development of SM-VAP (table 5). For patients who experienced multiple episodes of late-onset pneumonia, an increased ISS and the presence of a brain injury were associated with SM-VAP on univariate analysis (table 4). The following variables (for which P .25) were also entered into multivariate analysis: for SM-VAP and GN-VAP, respectively, age (mean SD, 36.8 19.6 vs. 49.9 21.3 years), Glasgow Coma Scale score (mean SD, 8.8 3.7 vs. 11.4 3.9), male sex (50% vs. 80%), thoracic injury (87.5% vs. 52%), pulmonary contusion (75% vs. 36%), thorocostomy (75% vs. 44%), previous stay in the ICU (mean SD, 22.6 5.8 vs. 28.7 11.1 days), and exposure to ampicillin-sulbactam (100% vs. 64%). Multivariate analysis identified higher ISS and the presence of pulmonary contusion as significant risk factors for the development of SM-VAP in patients with multiple pneumonia episodes (table 5). The overall mortality rate was 18.4% (30 of 163 patients); no significant difference was seen in mortality between the SMVAP group and the GN-VAP group (23.1% vs. 17.5%; P p .69). The Kaplan-Meier estimation curves for the SM-VAP and GN-VAP groups are shown in figure 1A and 1B. There was no difference in mortality between the SM-VAP and GN-VAP groups (P p .784). However, SM-VAP patients were more likely to continue to need mechanical ventilator support (P p .025; figure 1A) and to remain in the ICU (P p .047; figure 1B), with a trend toward increased length of hospital stay (P p .064). The proportion of patients receiving inadequate empiric antibiotic therapy in the SM-VAP group was significantly higher than that in the GN-VAP group (93.2% vs. 43.8%; P ! .001; figure 1C). Inadequate empiric antibiotic therapy was associated with increased mortality (P p .020) but not with a difference in the duration of mechanical ventilator support (P p .525), ICU stay (P p .487), or hospital stay (P p .419). The ISSs were similar for patients receiving inadequate empiric antibiotic therapy and those receiving adequate therapy (median [IQR], 29.0 [24.0–34.5] vs. 29.0 [24.0–38.75]; P p .343). In this retrospective analysis of critically ill trauma patients, we identified cefepime exposure and the presence of a tracheostomy as the most significant factors associated with S. maltophilia pneumonia among patients who experienced a single episode of late-onset VAP. Among patients who experienced multiple episodes of late-onset pneumonia, higher ISS and the presence of a pulmonary contusion were most significantly associated with S. maltophilia pneumonia. The presence of central venous catheters [ 11 ], previous antibiotic therapy [ 11, 12, 23–25 ], severity of illness [ 24, 25 ], and receipt of imipenem therapy [ 11, 26 ] have been identified as risk factors for S. maltophilia infection in various patient populations. Unfortunately, only 2 of those studies identified risk factors by multivariate analysis [ 11, 12 ]. These risk factors may not apply to the critically ill trauma patient, because patient characteristics, comorbidities, and treatment may differ significantly from those of nontrauma ICU patients. In addition, because nosocomial S. maltophilia infections typically are late-occurring, previous studies may have skewed the analysis of risk factors by including patients who were at low risk for S. maltophilia infection (i.e., patients with early-onset nosocomial pneumonia). Nonetheless, these results are consistent with risk factors for trauma patients with S. maltophilia colonization or infection [13]. Villarino et al. [ 13 ] found that duration of mechanical ventilator support, presence of a tracheostomy, number of antimicrobial agents used, and use of air transport to the hospital were independent risk factors for S. maltophilia infection. Our study significantly adds to these results, because we excluded colonized patients, analyzed risk factors for pneumonia only, and used a P more objective definition of pneumonia. In contrast to the findings of Villarino et al. [ 13 ], the duration of mechanical ventilator support was not significantly associated with SM-VAP on multivariate analysis. This is most likely because we compared risk factors for SM-VAP against those for GN-VAP, which resulted in a more homogeneous group of patients. Previous antibiotic exposure, particularly to broad-spectrum antibiotics, has consistently correlated with S. maltophilia infections in trauma, medical ICU, and other patient populations [ 11, 12, 23, 24 ]. In particular, imipenem therapy has been associated with the emergence of S. maltophilia infections [ 11, 26 ]. Although we found that cefepime therapy posed a significant risk for S. maltophilia pneumonia on multivariate analysis, the identification of carbapenem use as a significant risk factor on univariate analysis supports the idea that exposure to broad-spectrum antibiotics may be more important than exposure to any single antibiotic agent. The association of cefepime with S. maltophilia pneumonia likely reflects the heavy use of this antibiotic as part of a standard empiric antibiotic regimen for treatment of late-onset nosocomial pneumonia within the Presley Memorial Trauma Center ICU. Previous studies have shown that imipenem and ceftazidime were associated with similar rates of S. maltophilia acquisition among hospitalized patients [ 27 ]. Interestingly, the development of SM-VAP in patients with a single pneumonia episode was more strongly influenced by therapeutic interventions, whereas in multiple-episode pneumonia patients, SM-VAP was more strongly associated with severity of illness. In patients with a single episode of pneumonia, antibiotic exposure, number of BAL procedures, and presence of tracheostomy were associated with SM-VAP. It could be argued that the number of required BAL procedures and the need for tracheostomy may merely indicate greater severity of lung injury. However, there were no significant differences in indicators of chest injury such as chest AIS score, prevalence of thoracic injury, or requirement for thoracostomy. The finding that increased severity of injury was a significant risk factor for S. maltophilia infections is in agreement with findings that increased severity of illness is a risk factor in other ICU populations [ 4, 25 ]. The lack of association between therapeutic interventions and SM-VAP seen in the group of patients with multiple episodes of pneumonia likely is a result of the longer duration of ICU stay in that group, which increases the chance that patients in the SM-VAP and GN-VAP groups will have equal exposure to therapeutic interventions. Pulmonary contusion is known to be a risk factor for the development of nosocomial pneumonia [ 28 ]; however, the present study is, to our knowledge, the first to identify it as a risk factor for S. maltophilia pneumonia. Other potential risk factors analyzed in the present study were not associated with increased risk of developing S. maltophilia pneumonia. In particular, the clinical presentation (temperature, WBC count, presence of purulent aspirates, ratio of partial pressure of arterial oxygen to fraction of inspired oxygen) of S. maltophilia pneumonia was not different from that of pneumonia caused by other gram-negative bacteria, which indicates that the severity of illness is similar. Unfortunately, analyses of other factors, such as previous receipt of aerosolized medications, systemic glucocorticoid administration, medical history, and previous alcohol abuse and tobacco use, were limited by low statistical power and, thus, cannot be definitively excluded as risk factors. S. maltophilia infection has been associated with increased mortality among patients with respiratory isolates [ 29 ] and bacteremia [ 30 ]. In our study, SM-VAP was not associated with higher mortality than GN-VAP. However, SM-VAP patients did have longer durations of mechanical ventilator support and ICU stay, with a trend toward a longer hospital stay than among GN-VAP patients. The ability to detect a difference, if any, in mortality among SM-VAP patients and GN-VAP patients may have been affected by the relatively high proportion of GNVAP patients receiving inadequate empiric antibiotic therapy. Our results are consistent with previous reports that high mortality is associated with inadequate empiric antibiotic therapy in patients with pneumonia, and we extend this to the critically ill trauma patient [ 6, 8, 9 ]. Currently, trimethoprim-sulfamethoxazole is the antibiotic of choice for treatment of S. maltophilia infections, because 190% of S. maltophilia isolates are susceptible to this combination [ 31, 32 ]. Because trimethoprim-sulfamethoxazole is bacteriostatic and lacks significant activity against other gramnegative bacteria, such as P. aeruginosa, it is not commonly used as empiric antibiotic therapy for nosocomial pneumonia. Ticarcillin-clavulanate and ceftazidime are potential alternatives, but, because only ∼50% of S. maltophilia isolates are susceptible to these drugs, their ability to provide adequate empiric coverage is limited [ 31, 32 ]. In vitro data suggest that the newer fluoroquinolones and doxycycline may be useful; however, clinical experience with these agents is sparse [ 33, 34 ]. Given the relative lack of agents that have significant activity against S. maltophilia, it is not surprising that the majority of SM-VAP patients in our study did not receive adequate empiric antibiotic therapy. An appropriate conclusion may be that patients do not die as a result of S. maltophilia pneumonia but, rather, as a result of the lack of adequate empiric antibiotic therapy associated with S. maltophilia pneumonia. Given the deleterious outcomes, it seems reasonable to include trimethoprim-sulfamethoxazole as empiric antibiotic therapy in treatment of patients with the risk factors we have identified. In addition to the previously discussed limitations, the effect of the retrospective nature of the data collection on our results must be considered. The results of this study should only be applied to the critically ill trauma patient, because the mechanism of injury, younger age, and infrequency of comorbid conditions in this group renders such patients distinctly different from other ICU populations. In addition, in ICUs with a low prevalence of S. maltophilia pneumonia, the risk of severe allergic reactions and the risk associated with large intravenous volume administration may outweigh the benefits associated with trimethoprim-sulfamethoxazole therapy. Although we identified a significant association between exposure to cefepime and carbapenem antibiotics and S. maltophilia pneumonia, proper evaluation of other antibiotics or antibiotic classes was limited by low statistical power. Therefore, we cannot definitively exclude the possibility that exposure to other antibiotics is a risk factor for S. maltophilia pneumonia. Further risk-factor analysis for S. maltophilia pneumonia in patients with multiple episodes of pneumonia may be warranted, because the present study included relatively few patients and, thus, could have missed other important risk factors or produced spurious findings. A study of at least 10 patients per variable would be required to validate our results. Finally, in the univariate analysis, a type 1 error may have occurred as a result of the multiple comparisons required to analyze all potential risk factors. In conclusion, risk factors for the emergence of S. maltophilia pneumonia were identified in critically ill trauma patients with late-onset nosocomial pneumonia. Stenotrophomonas pneumonia was associated with increased morbidity but not increased mortality, whereas inadequate empiric antibiotic therapy was associated with increased mortality but had no effect on morbidity. As a result of the high intrinsic resistance of S. maltophilia to most antibiotics, patients with S. maltophilia pneumonia commonly receive inadequate empiric antibiotic therapy. Consequently, empiric antibiotic therapy for patients with suspected late-onset VAP and patients with the risk factors we have identified should include agents (preferably trimethoprim-sulfamethoxazole) with activity against S. maltophilia. Acknowledgments We thank Kristal Coval, Katie Suda, and Britt Ritter (PharmD) for their assistance in data collection. 1. Gales AC , Jones RN , Forward KR , Lin˜ares J , Sader HS , Verhoef J . Emerging importance of multidrug-resistant Acinetobacter species and Stenotrophomonas maltophilia as pathogens in seriously ill patients: geographic patterns, epidemiological features, and trends in the SENTRY antimicrobial surveillance program ( 1997 - 1999 ). Clin Infect Dis 2001 ; 32 ( Suppl 2 ): S104 - 13 . 2. Khardori N , Elting L , Wong E , Schable B , Bodey GP . Nosocomial infections due to Xanthomonas maltophilia (Pseudomonas maltophilia) in patients with cancer . Rev Infect Dis 1990 ; 12 : 997 - 1003 . 3. Cornwell EE III, Willey P , Belzberg H , Berne TV , Morales IR , Demetriades D. Characteristics of Xanthomonas infections in critically ill surgical patients . Am Surg 1996 ; 62 : 478 - 80 . 4. Maningo E , Watanakunakorn C . Xanthomonas maltophilia and Pseudomonas cepacia in lower respiratory tracts of patients in critical care units . J Infect 1995 ; 31 : 89 - 92 . 5. Alfieri N , Ramotar K , Armstrong P , et al. Two consecutive outbreaks of Stenotrophomonas maltophilia (Xanthomonas maltophilia) in an intensive care unit defined by restriction fragment-length polymorphism typing . Infect Control Hosp Epidemiol 1999 ; 20 : 553 - 6 . 6. Luna CM , Vujacich P , Neiderman MS , et al. Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia . Chest 1997 ; 111 : 676 - 85 . 7. Kollef MH , Silver P , Murphy DM , Trovillion E. The effect of late-onset ventilator-associated pneumonia in determining patient mortality . Chest 1995 ; 108 : 1655 - 62 . 8. Dupont H , Mentec H , Sollet JP , Bleichner G . Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator-associated pneumonia . Intensive Care Med 2001 ; 27 : 355 - 62 . 9. Kollef MH , Ward S. The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilatorassociated pneumonia . Chest 1998 ; 113 : 412 - 20 . 10. Valdezate S , Vindel A , Loza E , Baquero F , Canto´ n R. Antimicrobial susceptibilities of unique Stenotrophomonas maltophilia clinical strains . Antimicrob Agents Chemother 2001 ; 45 : 1581 - 4 . 11. Elting LS , Khardori N , Bodey FP , Fainstein V . Nosocomial infection caused by Xanthomonas maltophilia: a case-control study of predisposing factors . Infect Control Hosp Epidemiol 1990 ; 11 : 134 - 8 . 12. Talmaciu I , Varlotta L , Mortensen J , Schidlow DV . Risk factors for emergence of Stenotrophomonas maltophilia in cystic fibrosis . Pediatr Pulmonol 2000 ; 30 : 10 - 5 . 13. Villarino ME , Stevens LE , Schable B , et al. Risk factors for epidemic Xanthomonas maltophilia infection/colonization in intensive care unit patients . Infect Control Hosp Epidemiol 1992 ; 13 : 201 - 6 . 14. Croce MA , Fabian TC , Waddle-Smith L , et al. Utility of Gram's stain and efficacy of quantitative cultures for posttraumatic pneumonia . Ann Surg 1998 ; 227 : 743 - 55 . 15. Costa SF , Newbaer M , Santos CR , Basso M , Soares I , Levin AS . Nosocomial pneumonia: importance of recognition of aetiological agents to define an appropriate initial empirical coverage . Int J Antimicrob Agents 2001 ; 17 : 147 - 50 . 16. Croce MA , Fabian TC , Schurr MJ , et al. Using bronchoalveolar lavage to distinguish nosocomial pneumonia from systemic inflammatory response syndrome: a prospective analysis . J Trauma 1995 ; 39 : 1134 - 9 . 17. National Committee for Clinical Laboratory Standards (NCCLS). Performance standards for antimicrobial disk susceptibility tests: approved standard . 6th ed. NCCLS document M2-A6 . Wayne, PA: NCCLS, 1997 . 18. Teasdale GM , Jennett B . Assessment of coma and impaired consciousness . Lancet 1974 ; 2 : 81 - 4 . 19. Baker SP , O'Neill B , Haddon W , Long WB . The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care . J Trauma 1974 ; 14 : 187 - 96 . 20. Committee on Medical Aspects of Automotive Safety. Rating the severity of tissue damage. I. The abbreviated scale . JAMA 1971 ; 215 : 277 - 80 . 21. Knaus WA , Draper EA , Wagner DP , Zimmerman JE . APACHE II: a severity of disease classification system . Crit Care Med 1985 ; 13 : 818 - 29 . 22. Marshall JC , Cook DJ , Christou NV , Bernard GR , Sprung CL , Sibbald WJ . Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome . Crit Care Med 1995 ; 23 : 1638 - 52 . 23. VanCouwenberghe CJ , Farver TB , Cohen SH . Risk factors associated with isolation of Stenotrophomonas (Xanthomonas) maltophilia in clinical specimens . Infect Control Hosp Epidemiol 1997 ; 18 : 316 - 21 . 24. Rosenberger DS , Bach A . Nosocomial infection and colonization by S. maltophilia: analysis of risk factors and etiology by DNA-fingerprint [abstract 604] . Intensive Care Med 2000 ; 26 ( Suppl 3 ): S367 . 25. Gopalakrishnan R , Hawley HB , Czachor JS , Markert RJ , Bernstein JM . Stenotrophomonas maltophilia infection and colonization in the intensive care units of two community hospitals: a study of 143 patients . Heart Lung 1999 ; 28 : 134 - 41 . 26. Sanyal SC , Mokaddas EM . The increase in carbapenem use and emergence of Stenotrophomonas maltophilia as an important nosocomial pathogen . J Chemother 1999 ; 11 : 28 - 33 . 27. Carmeli Y , Samore MH . Comparison of treatment with imipenem vs. ceftazidime as a predisposing factor for nosocomial acquisition of Stenotrophomonas maltophilia: a historical cohort study . Clin Infect Dis 1997 ; 24 : 1131 - 4 . 28. Croce MA , Fabian TC , Waddle-Smith L , Maxwell RA . Identification of early predictors for post-traumatic pneumonia . Am Surg 2001 ; 67 : 105 - 10 . 29. Morrison AJ Jr, Hoffmann KK , Wenzel RP. Associated mortality and clinical characteristics of nosocomial Pseudomonas maltophilia in a university hospital . J Clin Microbiol 1986 ; 24 : 52 - 5 . 30. Senol E , Desjardin JA , Stark P , Barefoot L , Snydman DR . Attributable mortality of Stenotrophomonas maltophilia bacteremia [abstract 1719] . In: Programs and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (Toronto). Washington, DC: American Society for Microbiology, 2000 : 426 . 31. Cohn ML , Waites KB . Antimicrobial activities of gatifloxacin against nosocomial isolates of Stenotrophomonas maltophilia measured by MIC and time-kill studies . Antimicrob Agents Chemother 2001 ; 45 : 2126 - 8 . 32. Betriu C , Sa´nchez A , Palau ML , Go´ mez M, Picazo JJ . Antibiotic resistance surveillance of Stenotrophomonas maltophilia, 1993 - 1999 . J Antimicrob Chemother 2001 ; 48 : 152 - 4 . 33. Biedenbach DJ , Croco MAT , Barrett TJ , Jones RN . Comparative in vitro activity of gatifloxacin against Stenotrophomonas maltophilia and Burkholderia species isolates including evaluation of disk diffusion and E test methods . Eur J Clin Microbiol Infect Dis 1999 ; 18 : 428 - 31 . 34. Tripodi MF , Andreana A , Sarnataro G , Ragone E , Adinolfi LE , Utili R . Comparative activities of isepamicin, amikacin, cefepime, and ciprofloxacin alone or in combination with other antibiotics against Stenotrophomonas maltophilia . Eur J Clin Microbiol Infect Dis 2001 ; 20 : 73 - 5 .


This is a preview of a remote PDF: http://cid.oxfordjournals.org/content/35/3/228.full.pdf

Scott D. Hanes, Kutay Demirkan, Elizabeth Tolley, Bradley A. Boucher, Martin A. Croce, G. Christopher Wood, Timothy C. Fabian. Risk Factors for Late-Onset Nosocomial Pneumonia Caused by Stenotrophomonas maltophilia in Critically Ill Trauma Patients, Clinical Infectious Diseases, 2002, 228-235, DOI: 10.1086/341022