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Original Research: CRITICAL CARE MEDICINE |

Clinical Characteristics and Treatment Patterns Among Patients With Ventilator-Associated Pneumonia* FREE TO VIEW

Marin H. Kollef, MD, FCCP; Lee E. Morrow, MD, FCCP; Michael S. Niederman, MD, FCCP; Kenneth V. Leeper, MD, FCCP; Antonio Anzueto, MD; Lisa Benz-Scott, BS; Frank J. Rodino, MS
Author and Funding Information

*From the Washington University School of Medicine (Dr. Kollef), St. Louis, MO; the Department of Pulmonary and Critical Care Medicine (Dr. Morrow), Creighton University, Omaha, NE; the Department of Internal Medicine (Dr. Niederman), Winthrop University Hospital, Mineola, NY; the Department of Pulmonary and Critical Care Medicine (Dr. Leeper), Emory University, Atlanta, GA; the Department of Pulmonary and Critical Care Medicine (Dr. Anzueto), University of Texas Health Sciences Center, Houston, TX; and Rodino Healthcare (Drs. Bullard and Rodino), Millburn, NJ.

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



Chest. 2006;129(5):1210-1218. doi:10.1378/chest.129.5.1210
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Study objectives: To evaluate clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia (VAP), including the implementation of and outcomes associated with deescalation therapy.

Design: Prospective, observational, cohort study.

Setting: Twenty ICUs throughout the United States.

Patients: A total of 398 ICU patients meeting predefined criteria for suspected VAP.

Interventions: Prospective, handheld, computer-based data collection regarding routine VAP management according to local institutional practices, including clinical and microbiological characteristics, treatment patterns, and outcomes.

Measurements and results: The most frequent ICU admission diagnoses in patients with VAP were postoperative care (15.6%), neurologic conditions (13.3%), sepsis (13.1%), and cardiac complications (10.8%). The mean (± SD) duration of mechanical ventilation prior to VAP diagnosis was 7.3 ± 6.9 days. Major pathogens were identified in 197 patients (49.5%) through either tracheal aspirate or BAL fluid and included primarily methicillin-resistant Staphylococcus aureus (14.8%), Pseudomonas aeruginosa (14.3%), and other Staphylococcus species (8.8%). More than 100 different antibiotic regimens were prescribed as initial VAP treatment, the majority of which included cefepime (30.4%) or a ureidopenicillin/monobactam combination (27.9%). The mean duration of therapy was 11.8 ± 5.9 days. In the majority of cases (61.6%), therapy was neither escalated nor deescalated. Escalation of therapy occurred in 15.3% of cases, and deescalation occurred in 22.1%. The overall mortality rate was 25.1%, with a mean time to death of 16.2 days (range, 0 to 49 days). The mortality rate was significantly lower among patients in whom therapy was deescalated (17.0%), compared with those experiencing therapy escalation (42.6%) and those in whom therapy was neither escalated nor deescalated (23.7%; χ2 = 13.25; p = 0.001).

Conclusions: Treatment patterns for VAP vary widely from institution to institution, and the overall mortality rate remains unacceptably high. The deescalation of therapy in VAP patients appears to be associated with a reduction in mortality, which is an association that warrants further clinical study.

Figures in this Article

Pneumonia is the second most common nosocomial infection reported among ICU patients and is the number one cause of death from nosocomial infection in the United States.13 The estimated prevalence of ventilator-associated pneumonia (VAP) within the ICU setting ranges from 5 to 67%, with reported fatality rates ranging from 24 to 50%.2,47 Despite improvements in diagnosis, treatment, and prevention of VAP, it remains a significant cause of hospital mortality. VAP is also associated with significant morbidity, including longer hospital and ICU stays and longer periods of mechanical ventilation, all of which impact medical resources and finances.6,8 A number of economic analyses have concluded that a single VAP episode prolongs the duration of hospital stay by 6 to 30 days or even longer, and incurs additional medical expenses ranging from $5,000 to $40,000 per patient.6,910

The initial choice of antimicrobial regimen appears to be of critical importance in determining the eventual clinical outcomes in patients with VAP, particularly hospital mortality. Early, aggressive, empiric therapy with broad-spectrum agents targeted at likely pathogens has been associated with a reduction in VAP mortality rates.1114 Luna et al13 prospectively studied 132 VAP patients. Fifty patients with positive BAL findings received empiric treatment prior to undergoing bronchoscopy. The mortality rate was significantly lower among patients whose initial therapy was considered to be adequate (n = 16), based on BAL results, compared to that among patients whose empiric regimen was considered to be inadequate (n = 34) [38% vs 91%, respectively; p < 0.001]. Alvarez-Lerma,12 in an analysis of 430 patients with VAP, reported a significantly higher mortality rate among patients given inappropriate, empiric antimicrobial coverage vs those given an appropriate empiric regimen (24.7% vs 16.2%, respectively; p = 0.039). Rello et al11 also reported a significantly higher VAP-attributable mortality rate among patients with initially inadequate antimicrobial coverage compared with those treated with adequate empiric regimens (37.0% vs 15.4%, respectively; p < 0.05). Finally, Kollef and Ward,14 in a study examining the utility of mini-BAL in patients with VAP, observed differences in mortality rates among patients whose therapy stayed the same after mini-BAL results were available (33.3%) compared with patients who either started therapy anew after undergoing mini-BAL or experienced regimen changes based on mini-BAL findings (60.8%; p < 0.001).

The concept of deescalation therapy is emerging as an effective strategy for the management of VAP and other serious infections.7,15This concept entails the early implementation of broad-spectrum empiric coverage followed by a regimen tailored according to susceptibility findings. This strategy, while ensuring a high likelihood of adequate initial coverage, at the same time avoids the long-term use of unnecessary antibiotics, thereby minimizing resistance concerns.16 The most recent VAP treatment guidelines put forth by the American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA)5 include recommendations for early, appropriate, broad-spectrum coverage and subsequent deescalation of antibiotic regimens when possible, based on culture findings.

The Assessment of Local Antimicrobial Resistance Measures study was designed as a large, observational analysis of clinical characteristics and treatment patterns among patients with VAP across the United States. The objective of this study was to evaluate clinical characteristics and treatment patterns among patients with VAP, including the implementation of and outcomes associated with deescalation therapy.

The Assessment of Local Antimicrobial Resistance Measures study was a prospective, observational, cohort study of outcomes variables for VAP. Investigators affiliated with 20 ICUs across the United States identified and enrolled eligible patients with VAP. The study was approved by the individual institutional review boards associated with the participating sites. As most of the eligible patients were sedated for mechanical ventilation and because of the purely observational nature of the study, informed consent was waived. However, the study required access to and use of protected information. To this end, all patient information was deidentified in accordance with the Health Insurance Portability and Accountability Act final privacy rule §164.514,17 and study staff was not to retain any information linkable to specific patients.

Patient Eligibility

Patients were eligible for inclusion in the study if they met the following criteria: hospitalized > 48 h; intubated and receiving mechanical ventilation; and > 18 years of age. The diagnosis of VAP was based on American College of Chest Physicians criteria18 and was prospectively defined as the occurrence of new and persistent radiographic infiltrates following intubation. In addition, at least following criteria must have been present: (1) temperature > 38.3°C; (2) leukocytosis > 10,000 cells/mm3; and/or (3) purulent tracheobronchial secretions. When available, bronchoscopic and nonbronchoscopic BAL cultures with appropriate quantitative thresholds were used to support the diagnosis of VAP.,1819 All eligible patients must have had a respiratory tract culture (tracheal aspirate or other) prior to beginning antibiotic treatment. Patients were excluded from the study if they had received a lung transplant or had been studied during a previous ICU admission. Only first-episode cases of VAP were eligible.

Data Collection

Data collected included patient demographics, hospital and ICU admission dates, ICU admitting diagnosis, chest radiograph findings, tracheal aspirate cultures, antimicrobial therapy prior to and during ICU stay, days of mechanical ventilation received prior to and after therapy initiation, and severity-of-illness indexes, including the Acute Physiology and Chronic Health Evaluation (APACHE) II score20and the clinical pulmonary infection score (CPIS).21 Data were recorded up to the time of ICU discharge or death. Information sources included medical records, bedside flow sheets, computerized bedside nursing stations, computerized radiographic reports, and reports of microbiological studies including sputum Gram stains and cultures of sputum, tracheal aspirate, blood, and pleural and BAL fluids.

Definitions

Culture and sensitivity (C&S) testing of tracheal aspirates was performed by the laboratories of each participating institution. Organisms were classified as either sensitive or not sensitive to specific antibiotics typically used for the treatment of VAP. Organisms reported as being “susceptible” were considered to be sensitive. Both “intermediate” and “resistant” C&S reports were considered to be not sensitive. Therapy was defined as “inappropriate” if an NS result was reported for the antibiotic currently being prescribed in a particular patient. “Time to appropriate therapy,” measured in 4-h intervals, was the time from when the diagnosis of VAP was established to when the first correct/appropriate antibiotic regimen was administered.

Escalation/Deescalation of Therapy

Antibiotic regimens were ranked according to the activity spectrum against Gram-negative bacteria (5, highest; 1, lowest). For combination regimens, rank was assigned according to the most potent drug. (Table 1 ). Therapy escalation was defined as the switch to or addition of a drug class or classes with a broader spectrum (using definitions in Table 1) or additional coverage. Deescalation was defined as a switch to or discontinuation of a drug class resulting in a less broad spectrum of coverage.

Statistical Analysis

Data were entered into a preprogrammed palm personal digital assistant and were forwarded electronically to a secure, central database for compilation and analysis. The palm personal digital assistants were preprogrammed (Theradoc; Salt Lake City, UT). Data were analyzed using a statistical software package (SPSS; SPSS; Chicago, IL). Univariate analyses were carried out using the χ2 test and Fisher exact test for categoric data. Continuous variables were compared using the Student t test for normally distributed variables and the Wilcoxon rank-sum test for nonnormally distributed variables. Comparisons were unpaired, and all tests of significance were two-tailed.

A total of 398 eligible patients were identified among the 20 sites between May 2003 and December 2004. Two sites were responsible for 43% of all enrollments (111 and 62 patients, respectively). Nine sites enrolled between 19 and 30 patients, and the remaining nine sites enrolled ≤ 6 patients each.

Clinical Characteristics

Table 2 provides a summary of baseline demographics and clinical characteristics. The most frequent ICU admission diagnoses included general postoperative care (15.6%), neurologic conditions (13.3%), sepsis (13.1%), and cardiac complications (10.8%). The mean (± SD) CPIS score at baseline was 8.44 ± 2.34, and the mean APACHE II score was 22.8 ± 8.3. The mean duration of mechanical ventilation prior to VAP diagnosis was 7.3 days (range, 0 to 44 days).

Cultures were performed using tracheal aspirate samples in 58.3% of cases and BAL fluid samples in 33.7%; both procedures were performed in 1.8% of cases. Only 6.3% of patients had neither tracheal aspiration nor BAL performed. Major pathogens were identified in 197 patients, representing 49.5% of the total population and 52.8% of the population for which cultures were performed. The organisms most frequently identified included methicillin-resistant Staphylococcus aureus (MRSA) (14.8%) and Pseudomonas aeruginosa (14.3%), and other Staphylococcus species (8.8%) [Table 3] .

One hundred sixty-two patients were receiving antibiotics prior to or during VAP treatment for non-VAP indications in the following categories: quinolone (14.6%); ureidopenicillin/monobactam (11.1%); cefepime (9.3%); and carbapenem (5.8%). The percentage of cases with positive culture results for a major pathogen was not different between the group receiving antibiotics prior to VAP diagnosis (192 positive results of 286 patients with prior antibiotic use; 67.1%) compared with antibiotic-naïve subjects (57 positive results of 84 antibiotic-naïve patients; 67.9%; p = 0.90).

VAP Treatment Patterns

There were > 100 different antibiotic regimens/combinations prescribed as initial therapy for VAP. For initial treatment, most patients received therapy with one (27.9%), two (46.2%), or three (22.6%) different antibiotics. Among the 11 study sites that enrolled at least 10 patients each, there was a wide range in initial therapies. The percentage of patients per institution who were initially prescribed carbapenem ranged from 0 to 25%. For other spectrum categories, the ranges in initial usage per institution were as follows: cefepime (0 to 73%); ureidopenicillin/monobactam (0 to 70%); quinolone (2 to 38%); and other/none (0 to 65%). Seven percent of patients finished therapy receiving a greater number of antibiotics than when they started therapy for VAP, while 22.6% of patients finished therapy receiving a fewer number of antibiotics than initially prescribed. The change in the mean number of drugs prescribed from initial therapy (1.95) to final therapy (1.75) was −0.20.

Figure 1 illustrates the breakdown of initial therapies according to the spectrum of Gram-negative coverage. The majority of patients were prescribed regimens with a spectrum equivalent to cefepime (30.4%) or a ureidopenicillin/monobactam combination (27.9%). In addition, 51.7% of patients were prescribed vancomycin as part of their initial therapy. The mean baseline APACHE II scores correlated increasingly with the spectrum of antibiotic coverage chosen for initial therapy, ranging from 19.78 ± 8.08 among patients in the lowest therapy spectrum category to 26.40 ± 8.67 among patients in the highest therapy spectrum category (p = 0.0001; Spearman correlation coefficient, 0.27).

The mean duration of therapy for VAP was 11.8 ± 5.9 days (range, 0 to 51 days). The mean duration of therapy was not significantly different among patients receiving cefepime-based, vancomycin-based, or pip/tazo-based regimens (p = 0.721). The majority of patients (n = 289; 72.6%) finished VAP treatment using either the exact same regimen (n = 227) or a regimen within the same spectrum category (n = 62) as their initial therapy. Among the 168 patients who experienced a regimen change, the final therapy spectrum by category was as follows: cefepime (23.8%); carbapenem (20.8%); ureidopenicillin/monobactam (12.5%); quinolone (11.3%); and other (31.5% [included vancomycin]).

In 27.6% of cases, initial therapy for VAP was instituted within 4 h of the presumed diagnosis (Fig 2 ). Another 40.2% of patients received initial therapy within 4 to 12 h. For 10.8% of patients, initial therapy was instituted > 24 h after the presumed diagnosis of VAP. As illustrated in Figure 2, the time to appropriate therapy lagged slightly behind.

With respect to the escalation/deescalation of therapy, most patients (61.6%) experienced no escalation or a deescalation in therapy from the initial to the final regimen. Overall, escalation of therapy occurred in 15.3% of patients, and deescalation in 22.1%. Figure 3 provides a breakdown of specific escalation/deescalation patterns as reflected by changes in the number of drugs, the spectrum of activity, or both. Deescalation was more common among patients who originally were prescribed three antibiotics (32 of 90 patients; 35.6%) or four antibiotics (2 of 6 patients; 33.3%), compared with those who were initially prescribed two antibiotics (44 of 183 patients; 24.0%) or one antibiotic (10 of 108 patients; 9.3%).

Deescalation occurred more frequently among patients in whom a major pathogen was isolated (26.8%), compared with patients who did not have a major pathogen identified (6.5%). The rates of therapy escalation in these patient subgroups were 15.6% and 6.5%, respectively. The majority of patients with no pathogen isolated experienced no change in escalation/deescalation status (87.1%), compared with slightly more than half of patients (57.6%) with a major pathogen isolated. Among patients who initially received adequate therapy (ie, within the first 12 h), deescalation was observed in 27.1% of cases, compared with a deescalation rate of 16.6% among patients whose initial therapy was not adequate (χ2 = 6.15; p = 0.013). According to the culture technique used, deescalation occurred in 27.7% of patients in whom cultures were performed with BAL fluid (χ2 = 3.59; p = 0.06) and in 20.5% of patients in whom cultures were performed with tracheal aspirates (χ2 = 0.84; p = 0.36), compared with 8.3% of patients in whom cultures were not performed with either.

The two most commonly isolated pathogens were MRSA and P aeruginosa. Among the 59 patients in whom MRSA was isolated as the major pathogen, the initial therapy included vancomycin-based regimens in 40 patients (67.8%). Thirty of the 59 patients continued to received the same therapy following the isolation of MRSA. Among the 29 patients in whom therapy was changed, 17 patients were switched to vancomycin monotherapy or combination regimens, 7 patients were switched to a cefepime/linezolid combination therapy, 3 patients were switched to linezolid therapy alone or another combination regimen, 1 patient was switched to cefepime monotherapy, and 1 final patient was categorized as receiving “other” therapy. Therapy was deescalated in 17 of 59 MRSA cases (29%) and escalated in only 3 cases (5%).

There were a total of 57 patients in whom P aeruginosa was isolated as the major pathogen. The initial therapy in these patients, by spectrum, included carbapenem (15.8%), cefepime (33.3%), ureidopenicillin/monobactam (36.8%), quinolone (3.5%), or other (10.5%). Twenty-six of these 57 patients (45.6%) completed treatment for VAP with their initial therapy. Among 29 patients in whom therapy was changed following the isolation of P aeruginosa (data were missing on 2 patients), therapy was switched to reflect the following spectrum categories: carbapenem (n = 11); cefepime (n = 8); ureidopenicillin/monobactam (n = 6); quinolone (n = 2); or other (n = 2). Among patients with P aeruginosa isolates, deescalation and escalation of therapy were reported with nearly equal frequency (13 cases deescalated; 14 cases escalated).

Outcomes

One hundred of the 398 patients died during this study period, reflecting a mortality rate of 25.1%. The mean time to death was 16.2 days (range, 0 to 49 days). Among the surviving 298 patients during a 30-day follow-up period, 89 (22.4%) were discharged to a non-ICU floor, 71 (17.8%) were discharged to an extended care facility, 56 (14.1%) were discharged to home, and 82 (20.6%) had not been discharged from the ICU.

According to the initial therapy, mortality rates were fairly similar among patients in the categories therapy with carbapenem (31.1%), cefepime (30.6%), ureidopenicillin/monobactam (25.2%), and quinolone (26.7%) [Fig 1]. Mortality was significantly lower among patients in the initial treatment category of other/none, which included vancomycin therapy (19.1%). According to escalation/deescalation patterns, the mortality rate was lowest among patients in whom therapy had been deescalated (17.0%), compared with the categories of “no change” (23.7%) or “escalation” (42.6%; χ2 = 13.25; p = 0.001) [Fig 4] . Table 4 provides a breakdown of initial therapy categories according to spectrum and subsequent patterns of escalation/deescalation within each.

When mortality was stratified according to the specific pathogens isolated (Table 3), the highest death rates were among those with Acinetobacter (50.0%), MRSA (32.2%), and P aeruginosa (28.6%). Among patients whose tracheal aspirates were cultured, 21.0% died (χ2 = 5.51; p = 0.019), and 32.6% of those whose BAL fluid was cultured died (χ2 = 6.42; p = 0.011). A mortality rate of 36.0% was observed among patients in whom neither tracheal aspiration nor BAL was performed.

When mortality was stratified by time to adequate therapy, the mortality rate was highest among patients in whom the time to adequate therapy was > 24 h (30.9%) [Fig 5] . This compares with a mortality rate of 22.7% for all patients combined for whom adequate therapy was initiated in ≤ 24 h, a difference that is quantitatively lower but not statistically significantly different. Among patients who began receiving adequate therapy within the first 12 h, the mortality rate was 23.1%, a rate just slightly lower than that for patients who received any initial therapy during the same time frame (25.2%).

The mean CPIS score at 72 h for the entire population was 6.69 ± 2.98 (range, 0 to 14), an overall mean decrease of 1.75 from baseline. The mean change in CPIS score at 72 h was significantly less among patients who subsequently died (−0.10) compared with those who survived (−2.35; p < 0.05). The mean duration of mechanical ventilation after the initiation of VAP therapy was 12.9 ± 11.4 days (range, 0 to 67 days) and was not significantly different among patients treated with the three most common antibiotic-based regimens (ie, vancomycin, cefepime, and pip/tazo) [p = 0.147]. Among patients who survived, the mean duration of mechanical ventilation prior to the diagnosis of VAP was 7.7 days, compared with 6.3 days for patients who died (p = 0.09). Patients who survived received mechanical ventilation for a mean duration of 14.1 days after therapy was initiated, which is significantly longer than that in patients who died (mean duration, 9.1 days; p < 0.0001).

In this prospective observational study, we found that VAP remains a significant cause of mortality in the ICU setting, and that treatment patterns for this disease vary widely across institutions. The distribution of identified pathogens was similar to that observed in other VAP studies, including high frequencies of MRSA and P aeruginosa.

There were > 100 different antibiotic regimens prescribed as initial therapy among the patients that were studied. The majority of patients experienced no degree of therapy escalation or deescalation. The mean APACHE II score at baseline was 22.8, which is a score that is associated with a predicted death rate of approximately 40%.20 The actual mortality rate in the study population was 25.1%. The mortality rate was significantly lower among patients in whom therapy was deescalated, compared with those who experienced therapy escalation or “no change.”

Several clinical studies evaluating the prevalence and clinical impact of VAP have been published, although many have involved single-center populations and/or non-US sites.2,2225 Rello et al6 have published the largest US study to date of VAP epidemiology and outcomes, encompassing a cohort of 842 VAP patients identified through a national medical database. In this analysis of 842 VAP cases, the mortality rate was 30.5%, which was not significantly lower than that reported among 2,243 matched control subjects without VAP (30.4%). With regard to other clinical and economic outcomes, patients with VAP demonstrated a significantly longer duration of mechanical ventilation (14.3 vs 4.7 days, respectively; p < 0.001), and longer ICU and hospital stays (additional 6.1 and 11.5 days, respectively; both p < 0.001).

Few VAP studies to date have provided detailed analyses of antibiotic usage patterns, although some investigators have addressed issues regarding the adequacy of early antibiotic therapy, as discussed earlier.1114 A delay in the initiation of appropriate therapy has clearly been shown to have measurable consequences on VAP-attributable mortality. Iregui et al26 noted significantly higher hospital and VAP-attributable mortality rates among VAP patients in whom appropriate therapy was delayed for ≥ 24 h, compared with those in whom such therapy was initiated earlier (p < 0.01 and p = 0.001, respectively). Our findings are consistent with those previously reported, including an overall trend, although not statistically significant, for higher mortality among patients in whom appropriate therapy was initiated > 24 h after diagnosis.

The concept of therapy deescalation is increasingly being advocated as an appropriate strategy for managing VAP. The deescalation strategy provides clinical balance between one extreme of using broad-spectrum, empiric antimicrobial agents as the sole treatment strategy and the other extreme of delaying the initiation of targeted therapy pending bacteriologic results. The latter approach has clearly been associated with adverse outcomes,1114 and the former has potential implications for fostering organism resistance. In our study, the association between therapy deescalation and lower VAP mortality rate was an important finding.

The newest, evidence-based treatment guidelines for VAP put forth by the ATS-IDSA5 emphasize the need for early and appropriate antibiotic therapy followed by deescalation whenever possible, based on culture results and patient response. The guidelines also stress the importance of maintaining local, frequently updated antibiograms within individual hospitals and ICUs to ensure the appropriateness of antibiotic coverage. Initially inappropriate therapy is associated with worse outcomes, even if therapy is subsequently changed to reflect bacteriologic findings. This assumption is supported by our finding that comparative mortality was highest among patients in whom therapy was escalated compared to those who experienced deescalation or no change in therapy.

A key factor in empiric therapy selection is a consideration of patient risk for multiple-drug-resistant organisms, including those with a recent history of hospitalization or residence in another health-care facility (eg, nursing home), and patients whose current hospital stay has exceeded 5 days. The ATS-IDSA guidelines5 include suggestions for specific agents that are likely to provide appropriate coverage for initial therapy for VAP in patients with suspected risk factors for multiple-drug-resistant disease. In our cohort, in whom the mean duration of mechanical ventilation prior to diagnosis was 7.3 days, the majority of patients were initially placed on seemingly appropriate antibiotic regimens having a Gram-negative spectrum of activity equivalent to that of cefepime (30.4%) or piperacillin-tazobactam (27.9%). However, in almost one fifth of our patients, initial therapy fell within a Gram-negative spectrum category of “other or none.” Of further concern is the finding that there were > 100 different antibiotic regimens or combination regimens prescribed as initial coverage for the 398 patients studied.

The treatment of VAP has traditionally consisted of antibiotic administration for 14 to 21 days.5 Based on clinical evidence, the new ATS-IDSA guidelines5 advocate that attempts should be made to shorten the duration of treatment to as few as 7 days in appropriate circumstances, and that prolonged treatment can lead to colonization with resistant organisms. Attitudes toward shorter VAP treatment durations may be gaining acceptance in clinical practice, as reflected by a mean treatment duration in our study of 11.8 days.

Our data should be interpreted in light of certain limitations. Despite the involvement of 20 separate ICUs across the United States, the majority of patients were enrolled at only two sites, and the results may be biased somewhat toward the practices at those particular institutions. In addition, the lack of a standardized approach to the diagnosis of VAP may have impacted patient inclusion and outcomes. Regardless, our results appear to be generally consistent with findings reported elsewhere and represent one of the larger VAP patient populations that have been studied to date.

In conclusion, VAP continues to pose a therapeutic challenge in the ICU setting. Our observations confirm that treatment patterns for VAP vary widely from institution to institution, and that the overall mortality rate remains unacceptably high. The practice of deescalation therapy appears to be associated with a reduction in patient mortality due to this disease. Additional study is warranted to investigate the reasons for this finding and to further define the potential impact of deescalation strategies in improving VAP outcomes.

Abbreviations: APACHE = acute physiology and chronic health evaluation; ATS = American Thoracic Society; CPIS = clinical pulmonary infection score; C&S = culture and sensitivity; IDSA = Infectious Disease Society of America; MRSA = methicillin-resistant Staphylococcus aureus; VAP = ventilator-associated pneumonia

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

Highest, 5; lowest, 1.

Table Graphic Jump Location
Table 2. Baseline Patient Demographics and Clinical Characteristics
Table Graphic Jump Location
Table 3. Major Pathogens Isolated Among 398 Patients With Ventilator-Associated Pneumonia Using Tracheal Aspirate and/or BAL Fluid Cultures and Corresponding Mortality Rates*
* 

Values are given as No. (%). TRACH = tracheal aspirate.

 

Percentages reflect patients in organism category only.

 

Bronchoscopic and nonbronchoscopic.

Figure Jump LinkFigure 1. Initial antimicrobial therapy for VAP based on drug category (n = 398) and corresponding mortality rates within each category.Grahic Jump Location
Figure Jump LinkFigure 2. Time frames within which initial therapy for VAP was instituted and time frames within which patients were considered to be receiving “adequate therapy” based on C&S results.Grahic Jump Location
Figure Jump LinkFigure 3. Escalation/deescalation patterns observed among VAP patients according to changes in the number of antimicrobial drugs and/or spectrum of antibiotic coverage experienced during treatment. (n = 394; data missing on 4 subjects).Grahic Jump Location
Figure Jump LinkFigure 4. Mortality rates among patients with VAP according to whether therapy was escalated or deescalated. (χ2 = 13.25; p = 0.001) (n = 394; data missing on 4 subjects).Grahic Jump Location
Table Graphic Jump Location
Table 4. Patterns of Escalation and Deescalation Among Patients Treated for VAP, Stratified According to the Initial Therapy Spectrum Category*
* 

Values are given as No. (%). Data are missing on four patients.

Figure Jump LinkFigure 5. Mortality rates among patients with VAP according to time to adequate therapy (n = 396; data missing on 2 subjects).Grahic Jump Location
Richards, MJ, Edwards, JR, Culver, DH, et al (1999) Nosocomial infections in medical intensive care units in the United States: National Nosocomial Infections Surveillance System.Crit Care Med27,887-892. [CrossRef] [PubMed]
 
Kollef, MH Ventilator-associated pneumonia: a multivariate analysis.JAMA1993;270,1965-1970. [CrossRef] [PubMed]
 
Bowton, DL Nosocomial pneumonia in the ICU: year 2000 and beyond.Chest1999;340,627-634
 
Chastre, J, Fagon, J-Y Ventilator-associated pneumonia.Am J Respir Crit Care Med2002;165,867-903. [PubMed]
 
American Thoracic Society.. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.Am J Respir Crit Care Med2005;171,388-416. [CrossRef] [PubMed]
 
Rello, J, Ollendorf, DA, Oster, G, et al Epidemiology and outcomes of ventilator-associated pneumonia in a large US database.Chest2002;122,2115-2121. [CrossRef] [PubMed]
 
Rello, J, Vidaur, L, Sandiumenge, A, et al De-escalation therapy in ventilator-associated pneumonia.Crit Care Med2004;32,2183-2190. [PubMed]
 
McEachern, R, Campbell, GD Hospital-acquired pneumonia: epidemiology, etiology and treatment.Infect Dis Clin North Am1998;12,761-779. [CrossRef] [PubMed]
 
Centers for Disease Control and Prevention.. Public Health Focus: Surveillance, prevention, and control of nosocomial infections.MMWR Morb Moral Wkly Rep1992;41,783-787
 
Jarvis, WR Selected aspects of the socioeconomic impact of nosocomial infections: morbidity, mortality, cost, and prevention.Infect Control Hosp Epidemiol1996;17,552-557. [CrossRef] [PubMed]
 
Rello, J, Gallego, M, Mariscal, D, et al The value of routine microbial investigation in ventilator-associated pneumonia.Am J Respir Care Med1997;156,196-200
 
Alvarez-Lerma, F Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit: ICU-Acquired Pneumonia Study Group.Intensive Care Med1996;22,387-394. [CrossRef] [PubMed]
 
Luna, CM, Vujacich, P, Niederman, MS, et al Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia.Chest1997;111,676-685. [CrossRef] [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. [CrossRef] [PubMed]
 
Hoffken, G, Niederman, MS The importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU.Chest2002;122,2183-2196. [CrossRef] [PubMed]
 
Kollef, MH Appropriate empiric antimicrobial therapy of nosocomial pneumonia: the role of the carbapenems.Respir Care2004;49,1530-1541. [PubMed]
 
Department of Health and Human Services. Health Insurance Portability and Accountability Act Final Privacy Rule 164.514, other requirements relating to uses and disclosures of protected health information. Available at: http://aspe.hhs.gov/admnsimp/final/PvcTxt01.htm. Accessed April 26, 2005.
 
Baselski, VS, El-Tory, M, Coalson, JJ, et al The standardization of criteria for processing and interpreting laboratory specimens in patients with suspected ventilator-associated pneumonia.Chest1992;102(suppl),571S-579S
 
Kollef, MH, Bock, KR, Richards, RD, et al The safety and diagnostic accuracy of minibronchoalveolar lavage in patients with suspected ventilator-associated pneumonia.Ann Intern Med1995;122,743-748. [PubMed]
 
Knaus, WA, Draper, EA, Wagner, DP, et al APACHE II: a severity of disease classification system.Crit Care Med1985;13,818-829. [CrossRef] [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]
 
Vincent, JL, Bihari, DJ, Suter, PM, et al The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) Study; EPIC International Advisory Committee.JAMA1995;274,639-644. [CrossRef] [PubMed]
 
Heyland, DK, Cook, DJ, Griffith, L, et al The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient.Am J Respir Crit Care Med1999;159,1249-1256. [PubMed]
 
Pawar, M, Mehta, Y, Khurana, P, et al Ventilator-associated pneumonia: incidence, risk factors, outcome, and microbiology.J Cardiothorac Vasc Anesth2003;17,22-28. [CrossRef] [PubMed]
 
Fagon, J-Y, 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. [CrossRef] [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. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Initial antimicrobial therapy for VAP based on drug category (n = 398) and corresponding mortality rates within each category.Grahic Jump Location
Figure Jump LinkFigure 2. Time frames within which initial therapy for VAP was instituted and time frames within which patients were considered to be receiving “adequate therapy” based on C&S results.Grahic Jump Location
Figure Jump LinkFigure 3. Escalation/deescalation patterns observed among VAP patients according to changes in the number of antimicrobial drugs and/or spectrum of antibiotic coverage experienced during treatment. (n = 394; data missing on 4 subjects).Grahic Jump Location
Figure Jump LinkFigure 4. Mortality rates among patients with VAP according to whether therapy was escalated or deescalated. (χ2 = 13.25; p = 0.001) (n = 394; data missing on 4 subjects).Grahic Jump Location
Figure Jump LinkFigure 5. Mortality rates among patients with VAP according to time to adequate therapy (n = 396; data missing on 2 subjects).Grahic Jump Location

Tables

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

Highest, 5; lowest, 1.

Table Graphic Jump Location
Table 2. Baseline Patient Demographics and Clinical Characteristics
Table Graphic Jump Location
Table 3. Major Pathogens Isolated Among 398 Patients With Ventilator-Associated Pneumonia Using Tracheal Aspirate and/or BAL Fluid Cultures and Corresponding Mortality Rates*
* 

Values are given as No. (%). TRACH = tracheal aspirate.

 

Percentages reflect patients in organism category only.

 

Bronchoscopic and nonbronchoscopic.

Table Graphic Jump Location
Table 4. Patterns of Escalation and Deescalation Among Patients Treated for VAP, Stratified According to the Initial Therapy Spectrum Category*
* 

Values are given as No. (%). Data are missing on four patients.

References

Richards, MJ, Edwards, JR, Culver, DH, et al (1999) Nosocomial infections in medical intensive care units in the United States: National Nosocomial Infections Surveillance System.Crit Care Med27,887-892. [CrossRef] [PubMed]
 
Kollef, MH Ventilator-associated pneumonia: a multivariate analysis.JAMA1993;270,1965-1970. [CrossRef] [PubMed]
 
Bowton, DL Nosocomial pneumonia in the ICU: year 2000 and beyond.Chest1999;340,627-634
 
Chastre, J, Fagon, J-Y Ventilator-associated pneumonia.Am J Respir Crit Care Med2002;165,867-903. [PubMed]
 
American Thoracic Society.. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.Am J Respir Crit Care Med2005;171,388-416. [CrossRef] [PubMed]
 
Rello, J, Ollendorf, DA, Oster, G, et al Epidemiology and outcomes of ventilator-associated pneumonia in a large US database.Chest2002;122,2115-2121. [CrossRef] [PubMed]
 
Rello, J, Vidaur, L, Sandiumenge, A, et al De-escalation therapy in ventilator-associated pneumonia.Crit Care Med2004;32,2183-2190. [PubMed]
 
McEachern, R, Campbell, GD Hospital-acquired pneumonia: epidemiology, etiology and treatment.Infect Dis Clin North Am1998;12,761-779. [CrossRef] [PubMed]
 
Centers for Disease Control and Prevention.. Public Health Focus: Surveillance, prevention, and control of nosocomial infections.MMWR Morb Moral Wkly Rep1992;41,783-787
 
Jarvis, WR Selected aspects of the socioeconomic impact of nosocomial infections: morbidity, mortality, cost, and prevention.Infect Control Hosp Epidemiol1996;17,552-557. [CrossRef] [PubMed]
 
Rello, J, Gallego, M, Mariscal, D, et al The value of routine microbial investigation in ventilator-associated pneumonia.Am J Respir Care Med1997;156,196-200
 
Alvarez-Lerma, F Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit: ICU-Acquired Pneumonia Study Group.Intensive Care Med1996;22,387-394. [CrossRef] [PubMed]
 
Luna, CM, Vujacich, P, Niederman, MS, et al Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia.Chest1997;111,676-685. [CrossRef] [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. [CrossRef] [PubMed]
 
Hoffken, G, Niederman, MS The importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU.Chest2002;122,2183-2196. [CrossRef] [PubMed]
 
Kollef, MH Appropriate empiric antimicrobial therapy of nosocomial pneumonia: the role of the carbapenems.Respir Care2004;49,1530-1541. [PubMed]
 
Department of Health and Human Services. Health Insurance Portability and Accountability Act Final Privacy Rule 164.514, other requirements relating to uses and disclosures of protected health information. Available at: http://aspe.hhs.gov/admnsimp/final/PvcTxt01.htm. Accessed April 26, 2005.
 
Baselski, VS, El-Tory, M, Coalson, JJ, et al The standardization of criteria for processing and interpreting laboratory specimens in patients with suspected ventilator-associated pneumonia.Chest1992;102(suppl),571S-579S
 
Kollef, MH, Bock, KR, Richards, RD, et al The safety and diagnostic accuracy of minibronchoalveolar lavage in patients with suspected ventilator-associated pneumonia.Ann Intern Med1995;122,743-748. [PubMed]
 
Knaus, WA, Draper, EA, Wagner, DP, et al APACHE II: a severity of disease classification system.Crit Care Med1985;13,818-829. [CrossRef] [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]
 
Vincent, JL, Bihari, DJ, Suter, PM, et al The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) Study; EPIC International Advisory Committee.JAMA1995;274,639-644. [CrossRef] [PubMed]
 
Heyland, DK, Cook, DJ, Griffith, L, et al The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient.Am J Respir Crit Care Med1999;159,1249-1256. [PubMed]
 
Pawar, M, Mehta, Y, Khurana, P, et al Ventilator-associated pneumonia: incidence, risk factors, outcome, and microbiology.J Cardiothorac Vasc Anesth2003;17,22-28. [CrossRef] [PubMed]
 
Fagon, J-Y, 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. [CrossRef] [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. [CrossRef] [PubMed]
 
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