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Original Research: CRITICAL CARE MEDICINE |

Predictors of 30-Day Mortality and Hospital Costs in Patients With Ventilator-Associated Pneumonia Attributed to Potentially Antibiotic-Resistant Gram-Negative Bacteria* FREE TO VIEW

Katherine E. Kollef; Garrett E. Schramm, PharmD; Angela R. Wills, PharmD; Richard M. Reichley, RPh; Scott T. Micek, PharmD; Marin H. Kollef, MD, FCCP
Author and Funding Information

*From the Division of Pulmonary and Critical Care Medicine (Ms. Kollef and Dr. Kollef), Washington University School of Medicine; Center for Quality and Effectiveness (Mr. Reichley), BJC Healthcare; and Department of Pharmacy (Drs. Schramm, Wills, and Micek), Barnes-Jewish Hospital, St. Louis, MO.

Correspondence to: Marin H. Kollef, MD, FCCP, Campus Box 8052, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110; e-mail: mkollef@im.wustl.edu



Chest. 2008;134(2):281-287. doi:10.1378/chest.08-1116
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Published online

Objective: To identify predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia (VAP) attributed to potentially antibiotic-resistant Gram-negative bacteria (PARGNB) [Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia].

Design: A retrospective, single-center, observational cohort study.

Setting: Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital.

Patients: Adult patients requiring hospitalization with microbiologically confirmed VAP attributed to PARGNB.

Interventions: Retrospective data collection from automated hospital, microbiology, and pharmacy databases.

Measurements and main results: Seventy-six patients with VAP attributed to PARGNB were identified over a 5-year period. Nineteen patients (25.0%) died during hospitalization. Patients receiving their first dose of appropriate antibiotic therapy within 24 h of BAL sampling had a statistically lower 30-day mortality rate compared to patients receiving the first dose of appropriate therapy >24 h after BAL (17.2% vs 50.0%; p = 0.005). VAP due to Acinetobacter species was most often initially treated with an inappropriate antibiotic regimen, followed by S maltophilia and P aeruginosa (66.7% vs 33.3% vs 17.2%; p = 0.017). Overall, total hospitalization costs were statistically similar in patients initially treated with an inappropriate antibiotic regimen compared to an appropriate regimen ($68,597 ± $55,466 vs $86,644 ± $64,433; p = 0.390).

Conclusions: These data suggest that inappropriate initial antibiotic therapy of microbiologically confirmed VAP attributed to PARGNB is associated with greater 30-day mortality. High rates of VAP attributed to antibiotic-resistant bacteria (eg, Acinetobacter species) may require changes in the local empiric antibiotic treatment of VAP in order to optimize the prescription of appropriate initial therapy.

Figures in this Article

Gram-negative bacteria continue to be an issue of concern in health-care–associated infections, especially ventilator-associated pneumonia (VAP).13 Of particular interest are infections caused by potentially antibiotic-resistant Gram-negative bacteria (PARGNB). Several studies46 have demonstrated an association between VAP attributed to PARGNB and greater mortality. Additionally, PARGNB are more likely to be treated with an inappropriate initial antibiotic regimen, which at least partly explains the higher mortality rate associated with these infections.78

Given the increasing occurrence of nosocomial infections attributed to PARGNB, we performed a clinical study with two main goals. The first goal of this study was to identify predictors of 30-day mortality in patients with VAP attributed to PARGNB. The second goal of the study was to determine the health-care costs associated with these infections and whether they varied based on the appropriateness of initial antibiotic treatment.

Study Location and Patients

This study was conducted at a university-affiliated, urban teaching hospital: Barnes-Jewish Hospital (1,200 beds). During a 5-year period (January 2002 to June 2006), all hospitalized patients with VAP attributed to PARGNB, microbiologically confirmed by BAL cultures, were eligible for this investigation. Patients with polymicrobial infection demonstrated by BAL cultures, patients requiring antimicrobial treatment for Staphylococcus aureus, and patients treated with antibiotics for <72 h were excluded from evaluation. This study was approved by the Washington University School of Medicine Human Studies Committee, and informed consent was waived.

Study Design and Data Collection

A retrospective cohort study design was employed with a main outcome measure of 30-day mortality. Secondary outcomes evaluated included duration of intensive care and hospitalization, hospital costs, occurrence of septic shock, appropriateness of initial antibiotic treatment, and escalation or deescalation of the initial antibiotic regimen. A computerized list of patients with VAP attributed to PARGNB was generated by the Medical Informatics Department through retrospective query of the Microbiology Laboratory database at Barnes-Jewish Hospital (performed by R.M.R.), which allowed identification of potential study patients. Patients could not be entered into the study more than once. At Barnes-Jewish Hospital, patients with suspected VAP are initially treated with combination IV antimicrobial therapy that includes Gram-negative coverage (cefepime, 1 g q8h, or piperacillin/tazobactam, 4.5 g q6h, or meropenem, 1 g q8h plus gentamicin, 5 mg/kg q24h) and Gram-positive coverage (vancomycin, 15 mg/kg body weight q12h, or linezolid, 600 mg q12h). Patients receiving antibiotic therapy can have their antibiotic dose and interval of dosing adjusted based on their underlying renal function and hepatic function.

Definitions

All definitions were selected prospectively as part of the original study design. PARGNB were defined as infection due to either Pseudomonas aeruginosa, Acinetobacter species, or Stenotrophomonas maltophilia. These three pathogens are the most common PARGNB associated with VAP at Barnes-Jewish Hospital.2,910 APACHE (acute physiology and chronic health evaluation) scores were calculated based on clinical data available on the day the BAL was performed confirming the diagnosis of VAP attributed to PARGNB.11 A modified APACHE II score was employed because an assessment of the Glasgow coma score was not included. Thirty-day mortality was assessed from the time the diagnostic BAL was performed. For patients discharged prior to the 30-day cutoff for mortality evaluation, a computerized medical records search was undertaken to determine if hospital readmission and death had occurred. All 11 hospitals in the Barnes-Jewish-Christian Healthcare system have a common computerized medical records system allowing tracking of patients at all system hospitals.

A clinical diagnosis of VAP was based on criteria modified from those established by the American College of Chest Physicians.12These criteria require the occurrence of new and persistent radiographic infiltrates in conjunction with two of the following: fever, leukocytosis, and purulent tracheal aspirate or sputum. The clinical pulmonary infection score (CPIS) was also assessed in each patient.13 In addition to the clinical criteria for VAP, BAL cultures with appropriate quantitative thresholds were obtained bronchoscopically to support the diagnosis of VAP. Quantitative thresholds ≥104 cfu/mL were considered positive for the diagnosis of VAP attributed to PARGNB. Septic shock was defined as VAP requiring the administration of vasopressors to maintain the mean arterial pressure >65 mm Hg.

Antibiotic regimens were ranked according to activity spectrum against Gram-negative bacteria (Table 1 ).10,14 For combination regimens, rank was assigned according to the most potent drug. Escalation of therapy was defined as the switch to or addition of a drug classes with a broader spectrum (using definitions in Table 1). Deescalation was a switch to or discontinuation of a drug class resulting in a less broad spectrum of coverage. Total costs were calculated by reviewing hospital billing records. Prior to pooling charges from all hospital departments into a final value, charges were converted to costs via department specific cost-to-charge ratios. Department cost centers included hospital wards, ICUs, pharmacy, laboratory, radiology, respiratory therapy, emergency department, and operating rooms.

Microbiological Data

The microbiology laboratory performed antimicrobial susceptibility of clinical isolates by the Kirby-Bauer disk diffusion method according to guidelines and break points established by the Clinical Laboratory and Standards Institute, using 150-mm round plates of Mueller-Hinton agar (BBL; Becton-Dickinson; Cockeysville, MD). A technologist experienced in reading zones of inhibition with a ruler against a black background measured the zone diameters manually.

Statistical Analysis

All comparisons were unpaired, and all tests of significance were two tailed. Continuous variables were compared using the Student t test for normally distributed variables and the Mann-Whitney U test for nonnormally distributed variables. The χ2 or Fisher exact test were to compare categorical variables. The primary data analysis compared 30-day nonsurvivors with survivors. We performed multiple logistic-regression analysis using statistical software (SPSS version 11.0 for Windows; SPSS; Chicago, IL). Multivariate analysis was performed using models that were judged a priori to be clinically sound.15 This was prospectively determined to be necessary to avoid producing spuriously significant results with multiple comparisons. All potential risk factors significant at the 0.15 level in univariate analyses were entered into the model. Linear regression analysis was employed using the same software to identify potential risk factors associated with greater hospital costs. The relationship between total hospital costs and total hospital length of stay was analyzed using Spearman ρ correlation coefficient. For all analyses, a two-tailed p value <0.05 was considered statistically significant.

Patient Characteristics

A total of 87 patients with microbiologically confirmed VAP attributed to PARGNB were evaluated at Barnes-Jewish Hospital during the study period. Eleven patients were excluded due to polymicrobial infection, including 9 patients with S aureus infection, leaving 76 patients in the study cohort. Mean age of the population was 56.6 ± 16.9 years (range, 18 to 83 years); there were 50 male (65.8%) and 26 female (34.2%) patients. Patient baseline characteristics are provided in Table 2 . Mean APACHE II score was 17.5 ± 6.2 (range, 5 to 29), and mean CPIS was 6.0 ± 1.5 (range, 4 to 10).

Characteristics of the PARGNB

P aeruginosa was the most common PARGNB isolated from BAL cultures in 64 patients (84.2%), followed by Acinetobacter species in 6 patients (7.9%) and S maltophilia in 6 patients (7.9%). Acinetobacter species was most frequently treated with an initial inappropriate antibiotic regimen followed by S maltophilia and P aeruginosa (66.7% vs 33.3% vs 17.2%; p = 0.017). Antimicrobial administration during the same hospitalization but prior to VAP occurred statistically more often in patients with Acinetobacter species and S maltophilia compared to P aeruginosa (100% vs 100% vs 62.5%; p = 0.037). Among the 17 patients treated with an inappropriate initial antibiotic regimen, 12 patients (70.5%) received antibiotic treatment during the same hospitalization but prior to the onset of VAP (Table 3 ). The 17 episodes of VAP attributed to PARGNB treated with an inappropriate initial antibiotic regimen had pathogens with overall susceptibilities to specific antibiotic classes of 23.5% for ciprofloxacin, 35.3% for piperacillin-tazobactam, 47.1% for cefepime, and 64.7% for meropenem. The addition of gentamicin increased susceptibility for each drug class to 64.7%, 64.7%, 70.6%, and 76.5%, respectively.

Predictors of 30-Day Mortality

Nineteen patients (25.0%) died within 30 days of the development of VAP attributed to PARGNB. The remaining 57 patients (75.0%) were all confirmed to have survived beyond the 30-day cutoff from the performance of the diagnostic BAL. Thirty-day nonsurvivors had statistically greater APACHE II scores and CPIS scores compared to patients surviving >30 days (Table 2). Thirty-day nonsurvivors also had a statistically greater likelihood of having underlying coronary artery disease, administration of vasopressors for shock, and an ICU admitting diagnosis of pneumonia or sepsis compared to 30-day survivors. Thirty-day nonsurvivors were statistically more likely to receive a first dose of appropriate antibiotic therapy >24 h after the performance of BAL compared to survivors, and had a statistically greater overall delay in the administration of appropriate initial therapy following BAL (Fig 1 , Table 4 ). Patients receiving initial antibiotic treatment that was subsequently deescalated had a greater 30-day survival compared to patients having no change or escalation of the initial regimen (Table 4).

Logistic regression analysis identified increasing APACHE II scores, vasopressor administration, and inappropriate initial antibiotic therapy as independent predictors of 30-day mortality (Table 5 ). A second logistic regression model was performed to identify predictors of inappropriate initial antibiotic therapy. The only variable independently associated with the administration of inappropriate initial antibiotic therapy was VAP attributed to either Acinetobacter species or S maltophilia (adjusted odds ratio, 2.97; 95% confidence interval [CI], 1.94 to 4.57; p = 0.011; Hosmer-Lemeshow goodness-of-fit test, p = 0.796).

Secondary Outcomes and Hospital Costs

The total number of antibiotic days administered for VAP were similar for patients treated with appropriate and inappropriate initial antibiotic regimens (11.2 ± 4.9 days vs 11.8 ± 3.6 days; p = 0.664). ICU length of stay and hospital length of stay following the diagnosis of VAP were also similar for both patient groups (Table 6 ). Patients treated with an appropriate initial antibiotic regimen had statistically similar total hospital costs compared to patients receiving an inappropriate initial antibiotic regimen ($86,644 ± $64,433 vs $68,597 ± $55,466, respectively; p = 0.390). Total hospital costs and hospital length of stay were linearly related (Fig 2 ).

A linear regression model controlling for APACHE II score, mortality, administration of inappropriate initial antibiotic therapy, gender, and race found that increasing hospital length of stay (adjusted cost per hospital day, $2,357; 95% CI, $2,042 to $2,672; p < 0.001) and increasing age (adjusted cost per year >18 years, $612; 95% CI, $192 to $1,030; p = 0.005) were independently associated with greater hospital costs. A similar analysis using hospital length of stay as the dependent outcome variable identified hospital mortality (−14.7 days; 95% CI, −3.2 to −26.2 days; p = 0.013) as the only independent predictor associated with hospital length of stay. Overall hospital length of stay was statistically lower for nonsurvivors compared to hospital survivors (Table 6).

We found that inappropriate initial antibiotic therapy is common among patients with VAP attributed to PARGNB and is associated with increased risk of 30-day mortality. We also observed that Acinetobacter species and S maltophilia were more likely to be treated with inappropriate initial antibiotic regimens compared to P aeruginosa. Our data also confirmed the earlier observation that delayed administration of appropriate initial antibiotic therapy and escalation of the initial antibiotic regimen are associated with greater mortality.10,16 Total hospital costs were lower for patients receiving inappropriate initial antibiotic treatment. However, the main identified determinant of total hospital costs was hospital length of stay. Patients treated with inappropriate initial antibiotics had shorter hospital lengths of stay due to excess mortality and thus lower total hospital costs. These data suggest that appropriate initial antimicrobial therapy of VAP attributed to PARGNB may improve patient outcomes but may not reduce health-care costs due to greater patient survival and utilization of hospital resources.

A number of reports1718 have demonstrated that nosocomial infections, including VAP, are increasingly being caused by PARGNB. However, it is important to note that regional differences have been reported for the prevalence of nosocomial infections attributed to specific Gram-negative bacteria. At Barnes-Jewish Hospital, to the present date, Pseudomonas aeruginosa is the predominant Gram-negative species associated with VAP and other nosocomial infections. In other hospitals in the United States and Europe, different Gram-negative bacterial pathogens including Acinetobacter species and β-lactamase–producing bacteria may predominate.22 The changing patterns of nosocomial infections attributed to Gram-negative bacteria with greater antimicrobial resistance have resulted in the introduction of novel approaches aimed at optimizing the delivery of appropriate initial therapy. In general, these novel strategies are aimed at earlier recognition of infection due to PARGNB in order to achieve appropriate initial therapy.

Several investigators have employed respiratory surveillance cultures in order to determine the likely pathogens associated with subsequent episodes of VAP. Depuydt et al23found that thrice-weekly tracheal aspirate and urinary cultures along with once-weekly anal swabs predicted the presence of infection due to multidrug-resistant pathogens in 88% of VAP cases. In 86% of the bloodstream infections associated with pneumonia, early (ie, within 48 h) antibiotic therapy was found to be appropriate. Similarly, Michel and coworkers24 demonstrated that endotracheal aspirate surveillance cultures performed twice weekly in intubated patients made it possible to prescribe appropriate initial antibiotic therapy in 95% of patients with subsequent VAP. This was also true for patients with VAP attributed to multidrug-resistant Gram-negative bacteria and methicillin-resistant S aureus. An alternative approach that has been evaluated is the rapid assessment of antimicrobial susceptibility from respiratory cultures of VAP patients. Bouza and coworkers25 and Kollef26 used a rapid assessment of respiratory cultures with an E-test to determine antibiotic susceptibility. Direct inoculation of the respiratory specimens onto the E-test allowed antibiotic susceptibility to be determined within 1.4 days, compared to 4.2 days using standard methods.25 Patients managed with the rapid E-test method had fewer days of fever, fewer days of antibiotic administration until resolution of VAP, lower antimicrobial costs, and less Clostridium difficile-associated diarrhea compared to patients managed with the standard method.

Several important limitations of our investigation should be noted. First, we performed this study at a single hospital, and these results may not be applicable to other centers. For example, several reports1920,22 suggest that some hospitals have specific antibiotic-resistant Gram-negative bacteria accounting for their nosocomial infections, including Acinetobacter species, extended-spectrum β-lactamase–containing bacteria, and carbapenemase-producing bacteria. Second, we limited our analysis to the PARGNB most commonly associated with VAP in our institution. Therefore, these findings may not apply to VAP attributed to other antibiotic-resistant bacteria. However, our results are consistent with the findings made in more general patient populations as well as with other multidrug-resistant bacteria including methicillin-resistant S aureus.,910,27 Third, the assessment of hospital costs in our study was strongly influenced by hospital mortality and may not reflect the actual costs of treating patients with VAP attributed to PARGNB. Finally, we limited our analysis to patients with microbiologically confirmed VAP. Therefore, we do not know if these findings are applicable to patients with clinically diagnosed VAP attributed to PARGNB.

In summary, we found that inappropriate initial antibiotic administration was associated with greater 30-day mortality and no overall impact on total hospital costs in patients with VAP attributed to PARGNB. Given the increasing prevalence of PARGNB, it is likely that larger numbers of patients with VAP will be at risk for the administration of inappropriate initial antibiotic therapy with its associated greater morbidity and mortality. Clinicians caring for patients at risk of nosocomial infections, including VAP, should be aware of the local prevalence of infections due to PARGNB and should develop local strategies aimed at optimizing the delivery of appropriate initial therapy for these high-risk infections. Additionally, future research aimed at more rapid and cost-effective identification of bacterial pathogens and their susceptibilities should be pursued.

Abbreviations: APACHE = acute physiology and chronic health evaluation; CI = confidence interval; CPIS = clinical pulmonary infection score; PARGNB = potentially antibiotic-resistant Gram-negative bacteria; VAP = ventilator-associated pneumonia

The authors have no conflicts of interest to report regarding this article.

Table Graphic Jump Location
Table 1. Antimicrobial Therapy Ranking According to Activity Spectrum Against Gram-Negative Bacteria
* 

Highest rank is 5, and lowest rank is 1.

Table Graphic Jump Location
Table 2. Baseline Patient Characteristics*
* 

Data are presented as mean ± SD or No. (%). AEOLD = acute exacerbation of obstructive lung disease.

 

Septic shock was defined as the requirement for vasopressors to maintain the mean arterial pressure at ≥65 mm Hg.

Table Graphic Jump Location
Table 3. Pathogens Treated With an Initially Inappropriate Antibiotic Regimen
* 

Antibiotics with Gram-negative bacterial activity administered earlier during the same hospitalization.

Figure Jump LinkFigure 1. Kaplan-Meier plot showing the proportion of patients alive over time according to whether or not appropriate initial antibiotic therapy was administered. The curves are statistically different by the log-rank test (p < 0.001).Grahic Jump Location
Table Graphic Jump Location
Table 4. Pneumonia-Related Characteristics*
* 

Data are presented as mean ± SD or No. (%).

 

Onset of time interval determined from performance of BAL.

Table Graphic Jump Location
Table 5. Multivariate Analysis of Independent Risk Factors for 30-Day Mortality*
* 

Other covariates not presented had a p value >0.05, including presence of bacteremia, specific bacterial pathogen, underlying coronary artery disease, antibiotic escalation, and admission to the ICU with pneumonia. The Hosmer-Lemeshow goodness-of-fit test for the model is p = 0.643.

Table Graphic Jump Location
Table 6. Lengths of Stay Stratified by 30-Day Mortality and Appropriateness of Initial Antibiotic Therapy*
* 

Data are expressed as mean ± SD.

Figure Jump LinkFigure 2. Scatterplot of total hospital costs vs total hospital days. The relationship between the two variables was statistically significant: Spearman ρ correlation coefficient = 0.916 (p < 0.001).Grahic Jump Location
. American Thoracic Society (ATS), Infectious Diseases Society of America (IDSA). (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.Am J Respir Crit Care Med171,388-416. [PubMed] [CrossRef]
 
Ibrahim, EH, Ward, S, Sherman, G, et al Experience with a clinical guideline for the treatment of ventilator-associated pneumonia.Crit Care Med2001;29,1109-1115. [PubMed]
 
Kollef, MH, Shorr, A, Tabak, YP, et al Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia.Chest2005;128,3854-3862. [PubMed]
 
Fagon, JY, Chastre, J, Hance, AJ, et al Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay.Am J Med1993;94,281-288. [PubMed]
 
Diaz, E, Munoz, E, Agbaht, K, et al Management of ventilator-associated pneumonia caused by multiresistant bacteria.Curr Opin Crit Care2007;13,45-50. [PubMed]
 
Garnacho-Montero, J, Ortiz-Leyba, C, Fernandez-Hinojosa, E, et al Acinetobacter baumanniiventilator-associated pneumonia: epidemiological and clinical findings.Intensive Care Med2005;31,649-655. [PubMed]
 
Kollef, MH Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients.Clin Infect Dis2000;31,S131-S138. [PubMed]
 
Mueller, EW, Hanes, SD, Croce, MA, et al Effect from multiple episodes of inadequate empiric antibiotic therapy for ventilator-associated pneumonia on morbidity and mortality among critically ill trauma patients.J Trauma2005;58,94-101. [PubMed]
 
Kollef, MH, Ward, S The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia.Chest1998;113,412-420. [PubMed]
 
Kollef, MH, Morrow, LE, Niederman, MS, et al Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia.Chest2006;29,1210-1218
 
Knaus, WA, Draper, EA, Wagner, DP, et al APACHE II: a severity of disease classification system.Crit Care Med1985;13,818-829. [PubMed]
 
Pingleton, SK, Fagon, JY, Leeper, KV, Jr Patient selection for clinical investigation of ventilator-associated pneumonia: criteria for evaluating diagnostic techniques.Chest1992;102,553S-556S. [PubMed]
 
Pugin, J, Auckenthaler, R, Mili, N, et al Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid.Am Rev Respir Dis1991;143,1121-1129. [PubMed]
 
Micek, ST, Heuring, TJ, Hollands, JM, et al Optimizing antibiotic treatment for ventilator-associated pneumonia.Pharmacotherapy2006;26,204-213. [PubMed]
 
Concato, JA, Feinstein, F, Holford, TR The risk of determining risk with multivariate models.Ann Intern Med1993;118,201-210. [PubMed]
 
Iregui, M, Ward, S, Sherman, G, et al Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia.Chest2002;122,262-268. [PubMed]
 
Diaz, E, Munoz, E, Agbaht, K, et al Management of ventilator-associated pneumonia caused by multiresistant bacteria.Curr Opin Crit Care2007;13,45-50. [PubMed]
 
Fritsche, TR, Sader, HS, Toleman, MA, et al Emerging metallo-β-lactamase-mediated resistances: a summary report from the worldwide SENTRY antimicrobial surveillance program.Clin Infect Dis2005;41,S276-S278. [PubMed]
 
Antoniadou, A, Kontopidou, F, Poulakou, G, et al Colistin-resistant isolates ofKlebsiella pneumoniaeemerging in intensive care unit patients: first report of a multiclonal cluster.J Antimicrob Chemother2007;59,786-790. [PubMed]
 
Zarrilli, R, Casillo, R, Di Popolo, A, et al Molecular epidemiology of a clonal outbreak of multidrug-resistantAcinetobacter baumanniiin a university hospital in Italy.Clin Microbiol Infect2007;13,481-489. [PubMed]
 
Neuhauser, MM, Weinstein, RA, Rydman, R, et al Antibiotic resistance among Gram-negative bacilli in US intensive care units: implications for fluoroquinolone use.JAMA2003;289,885-888. [PubMed]
 
Manikal, VM, Landman, D, Saurina, G, et al Endemic carbapenem-resistantAcinetobacterspecies in Brooklyn, New York: citywide prevalence, interinstitutional spread, and relation to antibiotic usage.Clin Infect Dis2000;31,101-106. [PubMed]
 
Depuydt, PO, Blot, SI, Benoit, DD, et al Antimicrobial resistance in nosocomial bloodstream infection associated with pneumonia and the value of systematic surveillance cultures in an adult intensive care unit.Crit Care Med2006;34,653-659. [PubMed]
 
Michel, F, Franceschini, B, Berger, P, et al Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia: a role for routine endotracheal aspirate cultures.Chest2005;127,589-597. [PubMed]
 
Bouza, E, Torres, MV, Radice, C, et al Direct E-test (AB Biodisk) of respiratory samples improves antimicrobial use in ventilator-associated pneumonia.Clin Infect Dis2007;44,382-387. [PubMed]
 
Kollef, MH Moving towards real-time antimicrobial management of ventilator-associated pneumonia.Clin Infect Dis2007;44,388-390. [PubMed]
 
Schramm, GE, Johnson, JA, Doherty, JA, et al Methicillin-resistantStaphylococcus aureussterile-site infection: the importance of appropriate initial antimicrobial treatment.Crit Care Med2006;34,2069-2074. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Kaplan-Meier plot showing the proportion of patients alive over time according to whether or not appropriate initial antibiotic therapy was administered. The curves are statistically different by the log-rank test (p < 0.001).Grahic Jump Location
Figure Jump LinkFigure 2. Scatterplot of total hospital costs vs total hospital days. The relationship between the two variables was statistically significant: Spearman ρ correlation coefficient = 0.916 (p < 0.001).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Antimicrobial Therapy Ranking According to Activity Spectrum Against Gram-Negative Bacteria
* 

Highest rank is 5, and lowest rank is 1.

Table Graphic Jump Location
Table 2. Baseline Patient Characteristics*
* 

Data are presented as mean ± SD or No. (%). AEOLD = acute exacerbation of obstructive lung disease.

 

Septic shock was defined as the requirement for vasopressors to maintain the mean arterial pressure at ≥65 mm Hg.

Table Graphic Jump Location
Table 3. Pathogens Treated With an Initially Inappropriate Antibiotic Regimen
* 

Antibiotics with Gram-negative bacterial activity administered earlier during the same hospitalization.

Table Graphic Jump Location
Table 4. Pneumonia-Related Characteristics*
* 

Data are presented as mean ± SD or No. (%).

 

Onset of time interval determined from performance of BAL.

Table Graphic Jump Location
Table 5. Multivariate Analysis of Independent Risk Factors for 30-Day Mortality*
* 

Other covariates not presented had a p value >0.05, including presence of bacteremia, specific bacterial pathogen, underlying coronary artery disease, antibiotic escalation, and admission to the ICU with pneumonia. The Hosmer-Lemeshow goodness-of-fit test for the model is p = 0.643.

Table Graphic Jump Location
Table 6. Lengths of Stay Stratified by 30-Day Mortality and Appropriateness of Initial Antibiotic Therapy*
* 

Data are expressed as mean ± SD.

References

. American Thoracic Society (ATS), Infectious Diseases Society of America (IDSA). (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.Am J Respir Crit Care Med171,388-416. [PubMed] [CrossRef]
 
Ibrahim, EH, Ward, S, Sherman, G, et al Experience with a clinical guideline for the treatment of ventilator-associated pneumonia.Crit Care Med2001;29,1109-1115. [PubMed]
 
Kollef, MH, Shorr, A, Tabak, YP, et al Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia.Chest2005;128,3854-3862. [PubMed]
 
Fagon, JY, Chastre, J, Hance, AJ, et al Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay.Am J Med1993;94,281-288. [PubMed]
 
Diaz, E, Munoz, E, Agbaht, K, et al Management of ventilator-associated pneumonia caused by multiresistant bacteria.Curr Opin Crit Care2007;13,45-50. [PubMed]
 
Garnacho-Montero, J, Ortiz-Leyba, C, Fernandez-Hinojosa, E, et al Acinetobacter baumanniiventilator-associated pneumonia: epidemiological and clinical findings.Intensive Care Med2005;31,649-655. [PubMed]
 
Kollef, MH Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients.Clin Infect Dis2000;31,S131-S138. [PubMed]
 
Mueller, EW, Hanes, SD, Croce, MA, et al Effect from multiple episodes of inadequate empiric antibiotic therapy for ventilator-associated pneumonia on morbidity and mortality among critically ill trauma patients.J Trauma2005;58,94-101. [PubMed]
 
Kollef, MH, Ward, S The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia.Chest1998;113,412-420. [PubMed]
 
Kollef, MH, Morrow, LE, Niederman, MS, et al Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia.Chest2006;29,1210-1218
 
Knaus, WA, Draper, EA, Wagner, DP, et al APACHE II: a severity of disease classification system.Crit Care Med1985;13,818-829. [PubMed]
 
Pingleton, SK, Fagon, JY, Leeper, KV, Jr Patient selection for clinical investigation of ventilator-associated pneumonia: criteria for evaluating diagnostic techniques.Chest1992;102,553S-556S. [PubMed]
 
Pugin, J, Auckenthaler, R, Mili, N, et al Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid.Am Rev Respir Dis1991;143,1121-1129. [PubMed]
 
Micek, ST, Heuring, TJ, Hollands, JM, et al Optimizing antibiotic treatment for ventilator-associated pneumonia.Pharmacotherapy2006;26,204-213. [PubMed]
 
Concato, JA, Feinstein, F, Holford, TR The risk of determining risk with multivariate models.Ann Intern Med1993;118,201-210. [PubMed]
 
Iregui, M, Ward, S, Sherman, G, et al Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia.Chest2002;122,262-268. [PubMed]
 
Diaz, E, Munoz, E, Agbaht, K, et al Management of ventilator-associated pneumonia caused by multiresistant bacteria.Curr Opin Crit Care2007;13,45-50. [PubMed]
 
Fritsche, TR, Sader, HS, Toleman, MA, et al Emerging metallo-β-lactamase-mediated resistances: a summary report from the worldwide SENTRY antimicrobial surveillance program.Clin Infect Dis2005;41,S276-S278. [PubMed]
 
Antoniadou, A, Kontopidou, F, Poulakou, G, et al Colistin-resistant isolates ofKlebsiella pneumoniaeemerging in intensive care unit patients: first report of a multiclonal cluster.J Antimicrob Chemother2007;59,786-790. [PubMed]
 
Zarrilli, R, Casillo, R, Di Popolo, A, et al Molecular epidemiology of a clonal outbreak of multidrug-resistantAcinetobacter baumanniiin a university hospital in Italy.Clin Microbiol Infect2007;13,481-489. [PubMed]
 
Neuhauser, MM, Weinstein, RA, Rydman, R, et al Antibiotic resistance among Gram-negative bacilli in US intensive care units: implications for fluoroquinolone use.JAMA2003;289,885-888. [PubMed]
 
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