1. Evaluation of susceptibility patterns of Pseudomonas aeruginosa in respiratory vs. non-respiratory infections and implications for empiric treatment
Stephanie Weisberg, PharmD
PGY-1 Pharmacy Resident
St. Joseph’s/Candler Health System
Co-Investigators: Natalie Labrador, PharmD Candidate 2017;
Geneen Gibson, PharmD, MS, BCPS (AQ-ID)

2. Disclosure Statement
Disclosure statement: these individuals have the following to disclose concerning possible personal or financial relationships with commercial entities (or their competitors) that may be referenced in this presentation
Stephanie Weisberg, PharmD: nothing to disclose
Natalie Labrador, PharmD Candidate: nothing to disclose
Geneen Gibson, PharmD, MS, BCPS (AQ-ID) : nothing to disclose

3. Background Pseudomonas aeruginosa
Non-lactose fermenting Gram negative bacillus
Potential for multi-drug resistance
Suspected pathogen in many healthcare-associated infections
Pier (2015) Mandell

4. ATS and IDSA (2005) Am J Respir Crit Care Med
Background
Combination Therapy
Concept initially came from empiric treatment of pneumonia in patients at high risk for multidrug-resistant organisms (MDROs)
At St. Joseph’s/Candler Health System
Extrapolated and applied to other infections
Sometimes used for definitive treatment, after susceptibilities are known
Including combination of inhaled and systemic antibiotics
ATS and IDSA (2005) Am J Respir Crit Care Med

5. Background Current IDSA Guideline Recommendations:
Specific criteria to evaluate pneumonia patients and make decision for mono- vs. combination empiric therapy
Goal of combination therapy is to empirically treat 95% of patients with agent active against pathogen
No recommendations for combination therapy outside of pneumonia and septic shock
Kalil (2016) Clin Infect Dis
Rhodes (2016) Intensive Care Med
Stevens (2014) Clin Infect Dis
Hooton (2010) Clin Infect Dis

6. Background Current IDSA Guideline Recommendations:
Do not use combination therapy for definitive treatment unless patient remains in septic shock or at high risk of death
Use of inhaled antibiotics in combination with systemic antibiotics only recommended for pneumonia caused by Gram-negative bacillus susceptible to only aminoglycosides or polymixins
Kalil (2016) Clin Infect Dis
Rhodes (2016) Intensive Care Med

7. Study Objectives Primary Objective Secondary Objectives
Susceptibility patterns of P. aeruginosa from respiratory sources compared to non-respiratory sources
Secondary Objectives
Impact of prescribed empiric treatment on
Total antibiotic days of therapy
Use of combination definitive treatment
Use of inhaled antibiotics
Adverse drug events
Total antibiotic cost

8. Study Center St. Joseph’s/Candler Health System
Community health system with 714 inpatient beds divided between two anchor hospitals

9. Methods Study design Population
Retrospective, observational investigation
Population
Adult inpatients treated at St. Joseph’s/Candler Health System from August 1, 2015 to July 31, 2016 that were initiated on empiric antibiotics for the treatment of P. aeruginosa from respiratory, blood, wound, urinary or other source

10. Methods Inclusion Criteria: Exclusion Criteria:
Adults  18 years of age
Treated inpatient at St. Joseph’s/Candler from August 1, 2015 to July 31, 2016
Positive culture for P. aeruginosa from respiratory, blood, wound, urinary, or other source
Treated with empiric antibiotics for at least 24 hours
Exclusion Criteria:
Positive culture for another gram-negative organism during admission that resulted prior to or at the same time as P. aeruginosa
Urine culture growing < 100,000 CFU
Included at prior visit
Lack of susceptibility data

11. Methods Primary Outcomes
Percentage of isolates susceptible to at least one agent in the first-prescribed empiric regimen
Percentage of isolates susceptible to first-prescribed empiric anti-pseudomonal β-lactam
Percentage of isolates susceptible to individual non-β-lactam agent in first-prescribed empiric regimen

12. Methods Secondary Outcomes
Total antibiotic days of therapy (Gram-negative active agents only)
Combination therapy for definitive treatment
Use of inhaled antibiotics
Adverse drug events
Assay documented C. difficile infection after receiving empiric therapy
Total antibiotic cost (Gram-negative active agents only)

13. Methods Treatment Groups Categorized based on source of infection
Respiratory
Non-Respiratory
Wound, urine, blood, other
Primary and secondary outcomes were compared between groups

14. Methods
Data analysis
Chi-square or Fisher’s exact tests were used for categorical variables
Student’s t-test was used for continuous variables
p<0.05 was considered statistically significant

15. Patient Selection 526 patients screened
391 patients met inclusion criteria
*Exclusions:
177 second Gram negative organism
70 urine culture < 100,000 CFU
10 included previously
18 missing susceptibility data
275 patients were excluded*
526 patients screened
- 135 patients (35 not PSAR, 43 not inpatient, 57 no empiric tx)
391 patients met initial inclusion
- 275 patients (177 growing another gram neg, 70 urine < 100,000, 10 previous included, 18 missing susceptibility data)
116 patients analyzed (42 resp, 74 non-resp)
42 patients in respiratory group
74 patients in non-respiratory group

16. Demographics Respiratory n = 42 Non-Respiratory n = 74 p-value 0.0004
Age (years ± SD)
66.0 ± 14.4
67.5 ± 14.6
0.5941
Gender, n(%)
Male
21 (50.0)
48 (64.9)
0.1177
Female
26 (35.1)
SBP (mm Hg ± SD)
125 ± 20
133 ± 26
0.0874
DBP (mm Hg ± SD)
72 ± 16
73 ± 14
0.7263
# of SIRS Criteria (AVG ± SD)
1.57 ± 1.11
1.16 ± 1.07
0.0528
# of MDRO Risk Factors (AVG ± SD)
1.76 ± 1.49
0.93 ± 0.94
0.0004
IV ABX w/in 90 days, n(%)
19 (45.2)
46 (62.2)
0.0775
ICU Admission, n(%)
8 (10.8)
<
Mechanical Ventilation, n(%)
20 (47.6)
3 (4.1)
High Invasive Device Score*, n(%)
16 (38.1)
12 (16.2)
0.0083
Combination Empiric Therapy, n(%)
15 (20.3)
0.0382
*Presence of both a Foley catheter and a central line

17. Primary Outcomes
p = 0.041
p =
p =

18. Secondary Outcomes Respiratory n = 42 Non-Respiratory n = 74 p-value
Total Antibiotic Days (Days ± SD)
14.95 ± 12.85
9.27 ± 7.16
0.0027
Combination Definitive Treatment, n(%)
Including inhaled antibiotics
21 (50.0)
9 (12.2)
<
Systemic antibiotics only
10 (23.8)
0.1064
Inhaled antibiotics, n(%)
14 (33.3) -
Adverse Drug Events, n(%)
2 (4.76)
6 (8.11)
0.4957
Diarrhea 1 4
Other 2
Hospital-acquired C. difficile, n(%)
0 (0)
1 (1.35)
0.4515
Cost ($ ± SD)
11003 ± 10542
1982 ± 2008
3308 ± 6628
0.1122

19. Combination Empiric Therapy

20. Discussion
The percentage of isolates susceptible to the initial empiric regimen was significantly higher in the non- respiratory group
The susceptibility rates were higher for initial β-lactam than for initial non-β-lactam in both groups
This statistically significant difference held up for patients with non-respiratory infections initiated on a combination empiric regimen
Patients with respiratory P. aeruginosa were more likely to be treated with definitive combination therapy, most of which included inhaled antibiotics

21. Limitations
The small, retrospective cohort nature limits the external validity of the results
Due to exclusion criteria, many of the sickest patients were excluded from this study
The inclusion of nebulized antibiotics introduces some bias as these are not utilized for non-respiratory sources of infection

22. Conclusions
Patients presenting with non-respiratory sources of infection likely do not need to be started on combination empiric treatment against P. aeruginosa
Antibiotic regimens should be deescalated appropriately once susceptibilities return

23. Acknowledgements Geneen Gibson, PharmD, MS, BCPS (AQ-ID)
Bruce Jones, PharmD, BCPS
Rachel Musgrove, PharmD
Natalie Labrador, PharmD Candidate

24. Objective and Self-Assessment
Presentation Objective: Identify specific patient populations or disease states that require combination therapy for empiric treatment of P. aeruginosa.
Self-Assessment: Which patient or disease state factors would prompt the use of combination empiric treatment of P. aeruginosa?
Respiratory source of infection AND
Septic shock OR
History or high risk of MDROs

25. References
Pier, G. B., & Ramphal, R. (2015). Pseudomonas aeruginosa. In Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Philadelphia, PA: Elsevier.
American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA). Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare- associated Pneumonia. Am J Respir Crit Care Med. 2005;171:
Kalil, A. C., Metersky, M. L., Klompas, M., Muscedere, J., Sweeney, D. A., Palmer, L. B., Brozek, J. L. (2016, July 14). Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. Clinical Infectious Diseases, 63(5). doi: /cid/ciw353
Rhodes, A., Evans, L., Dellinger, R. P., Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, Intensive Care Med Intensive Care Medicine.
Bliziotis, I. A., Petrosillo, N., Michalopoulos, A., Samonis, G., & Falagas, M. E. (2011, October 26). Impact of Definitive Therapy with Beta-Lactam Monotherapy or Combination with an Aminoglycoside or a Quinolone for Pseudomonas aeruginosa Bacteremia. PLoS ONE, 6(10). doi: /journal.pone

26. References
Aloush, V., Navon-Venezia, S., Seigman-Igra, Y., Cabili, S., & Carmeli, Y. (2005, October 23). Multidrug-Resistant Pseudomonas aeruginosa: Risk Factors and Clinical Impact. Antimicrobial Agents and Chemotherapy, 50(1), doi: /aac
Stevens, D. L., Bisno, A. L., Chambers, H. F., Dellinger, E. P., Goldstein, E. J., Gorbach, S. L., Wade, J. C. (2014, June 18). Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 59(2). doi: /cid/ciu296
Hooton, T. M., Bradley, S. F., Cardenas, D. D., Colgan, R., Geerlings, S. E., Rice, J. C., Nicolle, L. E. (2010, March 01). Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clinical Infectious Diseases, 50(5), doi: /650482
Dellinger, R. P., Levy, M. M., Rhodes, A., Annane, D., Gerlach, H., Opal, S. M., Moreno, R. (2013, January 30). Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, Intensive Care Med Intensive Care Medicine, 39(2), doi: /s

27. Evaluation of susceptibility patterns of Pseudomonas aeruginosa in respiratory vs. non-respiratory infections and implications for empiric treatment
Stephanie Weisberg, PharmD
PGY-1 Pharmacy Resident
St. Joseph’s/Candler Health System
Co-Investigators: Natalie Labrador, PharmD Candidate 2017;
Geneen Gibson, PharmD, MS, BCPS (AQ-ID)