Jan p. 2

RESEARCH REPORTS Critical Care

Multicenter Treatment and Outcome Evaluation of Aspiration Syndromes in Critically Ill Patients Sandra L Kane-Gill, Keith M Olsen, Jill A Rebuck, Rhonda S Rea, D Wesston Boatwright, Maureen A Smythe, Terrence R Walker, Stephanie L Lager, and Tudy Hodgman, for the Aspiration Evaluation Group of the Clinical Pharmacy and Pharmacology Section

ritically ill patients have numerous BACKGROUND: Aspiration syndromes (pneumonia and pneumonitis) have sigrisk factors for the development of a nificantly different processes. An evaluation of treatment and outcomes for these pulmonary aspiration syndrome, includdifferent syndromes has not been reported previously. ing impaired consciousness, endotracheal OBJECTIVE: To characterize and assess antimicrobial prescribing patterns for or nasogastric intubation, inappropriate aspiration syndromes in intensive care unit (ICU) patients and describe outcomes of those patients. positioning, neurologic disorders, anesMETHODS: A retrospective, observational evaluation was conducted using a thesia, gastrointestinal dysmotility, drug convenience sample of patients at 27 hospitals in North America; these patients overdose, and alcoholism.1-4 One type of were admitted to an adult ICU with a diagnosis of suspected/confirmed aspiration this syndrome, aspiration pneumonia, or had a suspected/confirmed aspiration while in the ICU. Hospital demographic, occurs when an infectious agent is aspidiagnosis, treatment, and clinical outcome data were collected. rated, mediating a parenchymal inflamRESULTS: Over a 12 month period, 187 patients were observed. Aspiration matory reaction that is characterized by syndromes included suspected aspiration (31%; n = 58), aspiration pneumonitis an infiltrate shown on chest radiogra(12%; n = 23), aspiration pneumonia (55%; n = 103), and diagnosis not available (1.6%; n = 3). Antimicrobial management for the aspiration syndromes was as phy.5 Critically ill patients with multilofollows: suspected aspiration: 59% single agent, 38% multiple agents, and 3% no bar aspiration pneumonia have a mortaltherapy; aspiration pneumonitis: 48% single agent, 39% multiple agents, and ity rate of 90% compared with 40% for 13% no therapy; aspiration pneumonia: 48% single agent, 52% multiple agents, those with single-lobe involvement.6 and 0% no therapy. Antimicrobial therapy was prescribed in patients with Pulmonary aspiration does not always suspected (97%) and confirmed (100%) aspiration. Antibiotic therapy duration involve an infectious complication; pawas significantly longer for aspiration pneumonia (9.1 ± 7.5 days) than for aspiration pneumonitis (5.2 ± 3.6 days; p = 0.013). Length of ICU stay was similar tients without symptoms 2 hours after across patient groups. their apparent clinical aspiration are un7 CONCLUSIONS: Antimicrobial agents are frequently prescribed to treat aspiration likely to develop respiratory sequelae. syndromes despite the lack of demonstrated efficacy for aspiration pneumonitis. Aspiration pneumonitis is a noninfecOutcomes between aspiration syndromes were similar with the exception of tious acute inflammatory process caused duration of antibiotic treatment. by aspiration of gastric material and KEY WORDS: aspiration syndromes, intensive care unit, critically ill, pneumonia, characterized by an infiltrate shown on pneumonitis. chest radiograph.7 Differentiating aspiraAnn Pharmacother 2007;41:549-55. tion pneumonitis from aspiration pneuPublished Online, 27 Mar 2007, www.theannals.com, DOI 10.1345/aph.1H675 monia is challenging.8,9 A survey of intensivists suggested that empiric antimiOptimizing outcomes in patients with aspiration syncrobial therapy is often initiated for noninfectious 10 dromes involving an infectious process requires the approaspiration pneumonitis. This practice can increase both priate selection of antimicrobial agents. Recent data sugtreatment costs and the potential for antimicrobial resisgest that prescribing patterns in clinical practice are incontance.11,12 sistent with current recommendations for antimicrobial therapy.8,10 A comprehensive evaluation of antimicrobial Author information provided at the end of the text. therapy for the management of aspiration syndromes may

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The Annals of Pharmacotherapy

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2007 April, Volume 41

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be useful for improving outcomes, but none has been published. The primary objectives of this evaluation were to characterize national antimicrobial prescribing patterns for aspiration pneumonia and pneumonitis in adult intensive care unit (ICU) patients and compare these findings with intensivist perceptions and published recommendations. A secondary objective was to describe the outcomes of critically ill patients diagnosed with an aspiration syndrome. Methods

PATIENTS

This was a retrospective, observational, multicenter quality-improvement evaluation. The convenience sample of patients included adults with pulmonary aspiration in ICUs. Participating investigators (Appendix I) at each site were selected from the Clinical Pharmacy and Pharmacology Section of the Society of Critical Care Medicine. Quality-improvement committee or institutional review board approval was obtained at all participating sites in accordance with institutional procedures. A maximum of 20 ICU patients per site were enrolled. The majority of sites identified appropriate patients during routine clinical rounds; however, 2 sites used ICD -9 codes (507.0). Data collection included hospital demographics; patient demographics; information needed to calculate the severity of illness score (APACHE II) on admission and day of aspiration syndrome; information regarding diagnosis of the aspiration syndrome, including pneumonia versus pneumonitis and community versus hospital acquired; treatment modalities; and clinical outcomes. Definitions were provided a priori for open unit,13 closed unit,13 transitional unit,13 and length of antibiotic therapy.14 A treatment day was defined as a 24 hour period. The ICU discharge day was considered a full day if the minimum stay was 8 hours. Each investigator entered data into a case report form available on a secure Web site; patient identifiers were not recorded. Aggregate findings from data collected in this evaluation were compared with previously published intensivists’ opinions about the management of aspiration syndromes and recently published management recommendations.8,10 The University of Pittsburgh was the coordinating center for data management. Data were entered into the Statistical Package for the Social Sciences, version 13.0 (SPSS, Chicago, IL) and descriptive analysis was performed. Analysis of group data was performed using χ2 test of proportions and Fisher’s exact test for the nominal data and Mann–Whitney U test or Student’s t-test for interval data when appropriate. A p value less than 0.05 was regarded as significant. Results HOSPITALS

Twenty-seven North American sites in 16 US states and 1 Canadian province participated in this project. Hospitals 550

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were located in East North Central (40.7%), Mid-Atlantic (18.5%), South Atlantic (14.8%), Pacific (11.1%), West North Central (3.7%), New England (3.7%), and Mountain (3.7%) regions of the US and in Ontario, Canada (3.7%).15 The institutions included 14 university teaching, 10 community teaching, 2 community nonteaching, and 1 Veterans Affairs hospital. Clinical pathways for aspiration syndromes existed at only one site.

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One hundred eighty-seven patients (69% male) were observed over a 12 month period. The majority of patients were located in hospitals from the East North Central (33.7%), Mid-Atlantic (22.5%), West North Central (10.7%), and New England (9.6%) areas of the US. The patients’ mean ± SD age was 61 ± 18 years. The mean and median APACHE II scores at ICU admission were 18 ± 7.3 and 18, respectively, with a range of 2– 49. Pulmonary, medical, and surgical patients accounted for 25%, 21%, and 18% of the sample, respectively. Forty-nine percent of patients were in an open ICU, 30% in a closed ICU, and 21% in a transitional care unit. DIAGNOSIS

The initial diagnoses were aspiration pneumonia (55%; n = 103), suspected aspiration (31%; n = 58), aspiration pneumonitis (12%; n = 23), and no diagnosis available (1.6%; n = 3). Diagnosis was made based on one or more of the following: chest radiography (62%; n = 116), witnessed event (33%; n = 61), and clinical suspicion (43%; n = 81). A diagnosis of suspected aspiration progressed to confirmed aspiration in 53% (31/58) of patients within 48–72 hours after the initial diagnosis. Of the different aspiration syndromes, 46% (n = 87) occurred in the community, 45% (n = 84) occurred in the hospital, and 9% (n = 16) occurred in the nursing home. TREATMENT

Gram stains for potential pathogenic organisms were performed in 51% (n = 95) of patients. Mixed gram-positive and -negative organisms were identified in 20% (n = 38), gram-positive in 19% (n = 35), and gram-negative in 12% (n = 22) of the patients. These isolates were obtained from sputum in non-intubated (11.6%; n = 11), endotracheal (74.7%; n = 71), bronchial alveolar lavage (10.5%; n = 10), and no response (3.2%; n = 3) patients. Forty-eight per cent (n = 89) of patients had pathogenic organisms identified from cultures. Of this subset, gram-negative (42%; n = 37), gram-positive (34%; n = 30), and mixed gram-positive and gram-negative (25%; n = 22) organisms were identified (Table 1). In 18% (n = 16) of cases, resis-


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Aspiration Syndromes in Critically Ill Patients

tant organisms such as Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae influenced the treatment decision. The primary organism identified in community-acquired pneumonia was Haemophilus influenzae, Streptococcus pneumoniae, and S. aureus and, in nosocomial pneumonia, S. aureus and P. aeruginosa were the most commonly identified organisms (Table 1). None of the patients in our evaluation had anaerobic organisms isolated from cultures. Table 2 lists treatment options for the various aspiration syndromes. There were no differences in the number of antimicrobials prescribed between the aspiration groups. Corticosteroids were not initiated in any patients for treatment of aspiration syndromes. The most commonly prescribed antibiotic for monotherapy of aspiration pneumonitis was ampicillin/sulbactam. The primary choice for multiple antimicrobial regimens of aspiration pneumonitis was a fluoroquinolone (gatifloxacin or levofloxacin). Piperacillin/

tazobactam was frequently prescribed as monotherapy for aspiration pneumonia, and clindamycin was the primary selection in multiple antimicrobial regimens. The most commonly prescribed antibiotics for suspected aspiration pneumonia were piperacillin/tazobactam in monotherapy and vancomycin in multiple antibiotic regimens. Antibiotics used to treat the aspiration syndromes are listed in Table 3. CLINICAL OUTCOMES

A summary of the clinical outcomes of patients diagnosed with an aspiration syndrome is listed in Table 4. The ICU antibiotic duration was significantly longer for aspiration pneumonia compared with aspiration pneumonitis (p = 0.013). Significantly more patients diagnosed with aspiration pneumonitis survived their ICU stay compared with those with aspiration pneumonia (p = 0.045). Hospital survival, however, was not significantly different. CHARACTERIZATION AND ASSESSMENT OF ANTIMICROBIAL PRESCRIBING

Table 1. Pathogenic Organisms Frequency Isolated by Location of Sample Organism

Staphylococcus aureus Pseudomonas aeruginosa Klebsiella pneumoniae Escherichia coli Streptococcus pneumoniae Haemophilus influenzae Staphylococcus epidermidis Streptococcus spp.b Moraxella spp.b Gram-negative bacillib Enterobacter cloacae Candida albicans Candida glabrata Stenotrophomonas maltophilia Acinetobacter baumannii Klebsiella oxytoca Klebsiella spp.b Enterobacter aerogenes Acinetobacter spp.b Morganella spp.b Enterococcus faceium Citrobacter spp.b Proteus mirabilis Enterobacter spp.b Stenotrophomonas spp.b Gram-positive coccib Considered to have pathogenic organisms in culture, but details not provided

Community

Hospital

Nursing Home

5 0 3 3 5 5 4 2 0 0 0 0 1 0 0 0 1 1 0 0 0 0 0 0 0 1 7

8 8 3 4 1 0 3 1 1 1 2 2 0 1 1 1 0 0 1 1 1 1 1 1 1 0 10

3 2 2 0 0 1 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

Totala 16 10 8 7 6 6 7 3 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 17

Antimicrobial therapy was prescribed in 97% (n = 56) of patients with suspected aspiration and 100% (n = 103) of those with confirmed pneumonia. Multiple antibiotics were prescribed in 38% (n = 22) and 52% (n = 54) of patients with suspected aspiration and aspiration pneumonia, respectively. For communityacquired aspiration pneumonia, the most commonly prescribed antibiotic was piperacillin/ tazobactam, which differs from recommendations that specify levofloxacin or ceftriaxone.8 Antibiotics that provide anaerobic coverage were prescribed in 79% (n = 148) of patients. Antibiotic therapy was withheld in only 3 patients with aspiration pneumonitis. Twenty patients with aspiration pneumonitis received antimicrobial therapy within 48 hours of diagnosis, 19 of whom were treated within 12 hours. Antibiotic therapy was prescribed to a higher percentage of patients with suspected and confirmed aspiration in this evaluation than suggested by an intensivist survey.10 The survey suggested that approximately 52% of physicians would prescribe antimicrobial therapy for suspected aspiration and 75% for a confirmed aspiration. Discussion

a

89 Patients had cultures that identified pathogenic organisms; however, more than 1 organism was isolated for some patients (eg, mixed gram-positive and gramnegative). b Additional clarification of species was not provided.

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This evaluation offers a previously unreported, unique multicenter assessment of treatment approaches to patient-specific aspiration


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syndromes. Disparity in published definitions of aspiration syndromes and lack of uniform diagnostic criteria promote confusion in identifying the most appropriate treatment approach. It is difficult to quantitate the continuum of aspiration syndromes accurately, since gross aspiration may not be witnessed and thus remains unconfirmed.2,16 Diagnosis of aspiration pneumonia includes a witnessed aspiration or risk factors for aspiration and an altered level of consciousness.17,18 Most critically ill patients have altered consciousness as the result of either multiple underlying disease states or the use of sedative and paralytic medications, further complicating an accurate diagnosis.19 In our current evaluation, aspiration-related pneumonia and noninfectious aspiration syndromes were managed using a similar approach. The treatment of aspiration pneumonitis differs from published recommendations and physician opinion according to our findings. Antimicrobial agents were found to be initiated earlier and more frequently in aspiration pneumonitis cases than previously reported.10 Other studies have shown that the inappropriate use of antimicrobial agents can result in undesirable effects, including increasing the risk of acquiring resistant pathogens; likelihood of secondary infections, such as vancomycin-resistant enterococci and Clostridium difficile–associated disease; and use of unnecessary drug- and nursing administration–related costs.20,21 Our findings highlight a high utilization of antimicrobial agents for both suspected and confirmed aspiration. Antimicrobial therapy was withheld in only 3% of patients

Table 2. Treatment of Suspected Aspiration and Aspiration Syndromes

Antibiotic Therapy Single

Multiple

None

Prior to diagnosis

Antibiotics changed postdiagnosis

Suspected Aspiration (n = 58) n (%)

Aspiration Pneumonitis (n = 23) n (%)

Aspiration Pneumonia (n = 103) n (%)

34 (59)

11 (48)

49 (48)

22 (38)

9 (39)

54 (52)

2 (3)

3 (13)

17 (29)

5 (22)

31 (30)

9 (16)

4 (17)

24 (23)

0

with suspected aspiration. Of those receiving antibiotics for suspected aspiration, 47% did not develop a documented infection. Although national consensus guidelines for the management of aspiration syndromes are lacking, findings in our evaluation were compared with previously published recommendations for managing aspiration8 and a published survey of prescribing perceptions.10 This comparison revealed important findings: patients were exposed to antimicrobial agents for an extended time and received broad-spectrum antibiotics unnecessarily. Antimicrobial therapy in aspiration pneumonia should be chosen with consideration of the site of aspiration (ie, community vs hospital). The recommended antimicrobial therapy for pneumonia acquired in these settings can be selected to target likely organisms as a result of the aspiration.22,23 In practice, clinicians often manage aspiration pneumonia as a separate disease entity from that of community- or hospital-acquired pneumonia. For example, in our evaluation, clindamycin was the most frequently prescribed antimicrobial agent in a dual regimen. This practice may require reevaluation since recent studies and our evaluation have not identified anaerobic organisms as pathogens in patients with aspiration pneumonia.24,25 Furthermore, clindamycin and fluoroquinolone use is linked to Clostridium difficile acquisition.26,27 While it is recognized that anaerobic organisms are notoriously difficult to culture from standard sputum samples, a combination of a β-lactam antibiotic with a β-lactamase inhibitor (ampicillin/sulbactam if community-acquired; piperacillin/tazobactam for hospital-acquired aspiration) generally provides adequate anaerobic coverage for suspected/ confirmed aspiration pneumonia. We recommend that institutions initiate educational activities to promote awareness of the differences between aspiration pneumonia and aspiration pneumonitis. The development of guidelines for initiating treatment and selecting appropriate antimicrobial therapy in aspiration p Value syndromes may reduce the frequency and du0.982a ration of inappropriate antibiotic use.11,12 b

0.178 0.378c 0.249a 0.077b 0.920c 0.005a,d 0.128b,d 0.136c,d 0.379a 0.933b 0.438c 0.741a,d 0.525b 1.000c,d

a

Pneumonia versus pneumonitis. Pneumonia versus suspected aspiration. c Pneumonitis versus suspected aspiration. d Fisher’s Exact test. b

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LIMITATIONS AND FUTURE DIRECTIONS

This was a retrospective evaluation; there are inherent limitations associated with this type of analysis, including being dependent on the existing information for diagnosis. Lack of isolated anaerobic organisms in this analysis may not be a true indication of the absence of these bacteria in the patients. In addition to the difficulty in culturing anaerobes, the type of sampling procedure may preclude the likelihood of culturing these organisms. This evaluation contained a convenience sample and www.theannals.com

Aspiration Syndromes in Critically Ill Patients

does not reflect true incidence rates. Also, the selection bias associated with the convenience sample and the different mechanisms for patient identification at participating institutions may have influenced the results. This evaluation did not find differences in clinical outcomes except antibiotic length of stay; however, it was not powered to detect differences between pneumonia groups for treatment nor the outcomes. Confounding variables influencing length of stay or mortality were not considered. Appropriate initial antibiotic selection was not evaluated for this project; however, this would be a suitable outcome to consider for future aspiration investigations, as it has been shown to increase mortality in patients with ventilator-associated pneumonia.28-30 Secondary infections were not reviewed in our evaluation; they would be an interesting outcome for future studies. Additional well designed studies evaluating outcomes of aspiration syndromes in critically ill patients are needed.

Conclusions This evaluation provides a greater understanding of national physician prescribing patterns for aspiration syndromes. Physicians commonly prescribe and continue antimicrobial therapy for suspected aspiration in the absence of a documented infection. Antimicrobial prescribing is often unnecessarily broad, which raises a concern for the development of bacterial resistance. Well defined controlled studies of aspiration syndromes in the ICU are necessary to generate the data required for evidenced-based treatment guidelines. Sandra L Kane-Gill PharmD MSc, Assistant Professor, Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Center for Pharmacoinformatics and Outcomes Research, Pittsburgh, PA Keith M Olsen PharmD FCCP FCCM, Professor of Pharmacy, University of Nebraska Medical Center, Omaha, NE Jill A Rebuck PharmD BCPS, Clinical Assistant Professor of Surgery, Trauma/Critical Care, Department of Pharmacotherapy, Fletcher Allen Health Care, Burlington, VT

Table 3. Antibiotics Used in Treatment of Suspected Aspiration and Aspiration Syndromesa Suspected Aspiration (n = 58) Antibiotic Amikacin Amoxicillin/clavulanate Ampicillin Ampicillin/sulbactam Azithromycin Aztreonam Cefazolin Cefepime Cefotaxime Ceftazidime Ceftriaxone Cefuroxime Ciprofloxacin Clindamycin Doxycycline Ertapenem Gatifloxacin Gentamicin Imipenem Levofloxacin Linezolid Meropenem Metronidazole Moxifloxacin Piperacillin/tazobactam Ticarcillin Tobramycin Trimethoprim/ sulfamethoxazole Vancomycin TOTAL

Single, n (%)

Aspiration Pneumonitis (n = 23)

Multiple, n (%)

Single, n (%)

0 (0) 2 (3.6) 0 (0) 8 (14.3) 0 (0) 0 (0) 0 (0) 0 (0) 4 (7.1) 0 (0) 4 (7.1) 0 (0) 1 (1.8) 2 (3.6) 0 (0) 0 (0) 0 (0) 0 (0) 2 (3.6) 10 (17.9) 0 (0) 2 (3.6) 0 (0) 1 (1.8) 16 (28.6) 0 (0) 2 (3.6) 0 (0)

0 (0) 0 (0) 1 (1.8) 0 (0) 2 (3.6) 1 (1.7) 0 (0) 2 (3.6) 1 (1.8) 0 (0) 4 (7.3) 0 (0) 1 (1.8) 6 (10.9) 0 (0) 0 (0) 0 (0) 2 (3.6) 2 (3.6) 7 (12.7) 1 (1.8) 1 (1.8) 2 (3.6) 1 (1.8) 7 (12.7) 1 (1.8) 2 (3.6) 1 (1.8)

0 (0) 0 (0) 0 (0) 3 (23.1) 2 (15.4) 0 (0) 0 (0) 0 (0) 1 (7.7) 1 (7.7) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 1 (7.7) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2 (15.4) 0 (0) 0 (0) 2 (15.4) 0 (0) 1 (7.7) 0 (0)

2 (3.6) 56

10 (18.2) 55

0 (0) 13

Aspiration Pneumonia (n = 103)

Multiple, n (%)

Single, n (%)

Multiple, n (%)

0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2 (9.5) 1 (4.8) 0 (0) 3 (14.3) 3 (14.3) 0 (0) 0 (0) 1 (4.8) 1 (4.8) 0 (0) 6 (28.6) 0 (0) 0 (0) 1 (4.8) 0 (0) 2 (9.5) 0 (0) 0 (0) 0 (0)

1 (1.3) 0 (0) 0 (0) 12 (15.8) 0 (0) 0 (0) 2 (2.6) 1 (1.3) 0 (0) 0 (0) 8 (10.5) 0 (0) 3 (3.9) 11 (14.5) 0 (0) 0 (0) 2 (2.6) 1 (1.3) 3 (3.9) 1 (1.3) 1 (1.3) 4 (5.3) 2 (2.6) 0 (0) 18 (23.7) 1 (1.3) 0 (0) 1 (1.3)

1 (0.8) 1 (0.8) 0 (0) 3 (2.3) 3 (2.3) 1 (0.8) 0 (0) 4 (3.1) 3 (2.3) 2 (1.6) 6 (4.7) 2 (1.6) 8 (6.2) 24 (18.6) 2 (1.6) 0 (0) 1 (0.8) 1 (0.8) 1 (0.8) 23 (17.8) 1 (0.8) 2 (1.6) 9 (7.0) 0 (0) 21 (16.3) 0 (0) 2 (1.6) 0 (0)

1 (4.8) 21

4 (5.3) 76

8 (6.2) 129

a

Total number of antibiotics exceeds number of patients with the diagnosis of aspiration syndrome, because antibiotic regimens were changed throughout therapy, based on culture results and intravenous to oral formulation switch.

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Rhonda S Rea PharmD, Assistant Professor, Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh; Critical Care Specialist, University of Pittsburgh Medical Center, Pittsburgh D Wesston Boatwright PharmD, Medical Affairs, Roche Laboratories, Inc., Jacksonville, FL Maureen A Smythe PharmD FCCP BCPS, Professor, Department of Pharmacy Practice, Wayne State University, Detroit, MI Terrence R Walker PharmD, Associate Director, Clinical Affairs, Ortho Biotech, Bridgewater, NJ Stephanie L Lager PharmD, Critical Care Specialist, Department of Pharmacy, Heartland Regional Medical Center, St. Joseph, MO Tudy Hodgman PharmD BCPS, Critical Care Specialist, Department of Pharmacy, Northwest Community Hospital, Arlington Heights, IL Reprints: Dr. Kane-Gill, University of Pittsburgh Center for Pharmacoinformatics and Outcomes Research, 918 Salk Hall, 3501 Terrace St., Pittsburgh, PA 15261, fax 412/624-1850, KaneSL@ upmc.edu This study was funded, in part, by Roche Pharmaceuticals, Nutley, NJ. Dr. Rea is a member of the Speaker’s Bureau for Pfizer, Inc.

References 1. Metheny NA. Risk factors for aspiration. JPEN J Parenter Enteral Nutr 2002;26(suppl 6):S26-31. 2. Miller CD, Rebuck JA, Ahern JW, Rogers FB. Daily evaluation of macroaspiration in the critically ill trauma patient. Curr Surg 2005; 62:504-8. 3. DeLegge MH. Aspiration pneumonia: incidence, mortality, and at-risk populations. JPEN J Parenter Enteral Nutr 2002;26(suppl 6):S19-24. 4. Elpern EH, Scott MG, Petro L, Ries MH. Pulmonary aspiration in mechanically ventilated patients with tracheostomies. Chest 1994;105:563-6. 5. McClave SA, DeMeo MT, DeLegge MH, et al. North American Summit on Aspiration in the Critically Ill Patient: consensus statement. JPEN J Parenter Enteral Nutr 2002;26(suppl 6):S80-5. 6. Cameron JL, Mitchell WH, Zuidema GD. Aspiration pneumonia. Clinical outcome following documented aspiration. Arch Surg 1973;106:49-52. 7. Warner MA, Warner ME, Weber JG. Clinical significance of pulmonary aspiration during the perioperative period. Anesthesiology 1993;78:56-62. 8. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med 2001;344:665-7. 9. Marik PE. Aspiration pneumonia: mixing apples with oranges and tangerines (letter). Crit Care Med 2004;32:1236. 10. Rebuck JA, Rasmussen JR, Olsen KM. Clinical aspiration–related practice patterns in the intensive care unit: a physician survey. Crit Care Med 2001;29:2239-44. 11. Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003;290:2588-98. 12. Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 2000;162:505-11. 13. Brilli RJ, Spevetz A, Branson RD, et al. Critical care delivery in the intensive care unit: defining clinical roles and the best practice model. Crit Care Med 2001;29:2007-19. 14. Paladino JA, Fell RE. Pharmacoeconomic analysis of cefmenoxime dual individualization in the treatment of nosocomial pneumonia. Ann Pharmacother 1994;28:384-9. 15. US Consensus Regions and Divisions. Available at Energy Information Administration. www.eia.doe.gov/emeu/reps/maps/us_census.html (accessed 2007 Feb 7). 16. Shifrin RY, Choplin RH. Aspiration in patients in critical care units. Radiol Clin North Am 1996;34:83-96. 17. Bartlett JG, Gorbach SL, Finegold SM. The bacteriology of aspiration pneumonia. Am J Med 1974;56:202-7.

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Appendix I. Participating Centers in the Clinical Pharmacy and Pharmacology Aspiration Evaluation Group Christiana Care Health Services, DE Tep Kang Clarian Medical Center, IN Maria Seta Community Medical Center, CA Mary Pung Detroit Receiving Hospital, MI Jeff Barletta Carilion Roanoke Memorial Hospital, VA Michael Bentley Erie County Medical Center, NY Curtis Haas Fletcher Allen Health Care, VT Jill Rebuck Gunderson Lutheran Medical Center, WI Peter Herout Hamot Medical Center, PA Brad Cooper Hahnemann Medical Center, PA Eric Wittbrodt Heartland Regional Medical Center, MO Stephanie Lager Kingsbrook Jewish Medical Center, NY Henry Cohen Los Angeles County + University of Southern California Medical Center, CA Maria Rudis McKay-Dee Hospital Center, UT Arthur Harwood Moses Cone Health System, NC Nita Johnston New York Presbyterian Hospital, NY Christine Lesch North Chicago VA Medical Center, IL Carrie Quigley Northwest Community Hospital, IL Tudy Hodgman Ohio State Medical Center, OH Anthony Gerlach Mary Beth Shirk SW Washington Medical Center, WA Long Nguyen Tampa General Hospital, FL Earnest Alexander The Ottawa Hospital, ON Salmaan Kanji Avinder Singh Riverside Methodist Hospital, OH Angie Swerlein University Hospitals, OH Steve Pass University of Pittsburgh Medical Center, PA Rhonda Rea Ted Rice Amy Seybert William Beaumont Hospital, MI Allycia Marie Wishard Memorial Hospital, IN Christopher Scott


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Aspiration Syndromes in Critically Ill Patients 19. Hubmayr RD, Burchardi H, Elliot M, et al. Statement of the 4th International Consensus Conference in Critical Care on ICU-Acquired Pneumonia—Chicago, Illinois, May 2002. Intensive Care Med 2002;28:1521-36. 20. Donskey CJ, Chowdhry TK, Hecker MT, et al. Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients. N Engl J Med 2000;343:1925-32. 21. Quale J, Landman D, Saurina G, Atwood E, DiTore V, Patel K. Manipulation of a hospital antimicrobial formulary to control an outbreak of vancomycin-resistant enterococci. Clin Infect Dis 1996;23:1020-5. 22. Mandell LA, Bartlett JG, Dowell SF, et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003;37:1405-33. 23. American Thoracic Society. Guidelines for the management of adults with hospital acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;131:388- 416. 24. Mier L, Dreyfuss D, Darchy B, et al. Is penicillin G an adequate initial treatment for aspiration pneumonia? A prospective evaluation using a protected specimen brush and quantitative cultures. Intensive Care Med 1993;19:279-84.

25. Marik PE, Careau P. The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. Chest 1999;115:178-83. 26. Muto CA, Pokrywka M, Shutt K, et al. A large outbreak of Clostridium difficile–associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol 2005;26:273-80. 27. Gerding DN. Clindamycin, cephalosporins, fluoroquinolones, and Clostridium difficile–associated diarrhea: this is an antimicrobial resistance problem. Clin Infect Dis 2004;38:646-8. 28. Kollef MH. Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients. Clin Infect Dis 2000;31(suppl 4):S131-8. 29. Dupont H, Mentec H, Sollet JP, et al. Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator-associated pneumonia. Intensive Care Med 2001;27:355-62. 30. Brun-Buisson C. Guidelines for treatment of hospital-acquired pneumonia. Semin Respir Crit Care Med 2002;23:457-69.

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