Empiric Double Coverage for Healthcare-Associated Pneumonia (HCAP) – Is it Still Necessary?

Background: Patients with healthcare-associated pneumonia (HCAP) are at risk for multidrug resistant gram-negative organisms, including Pseudomonas aeruginosa. Current empirical therapy recommendations include 2 agents with activity against Pseudomonas. However, the need for double coverage has been questioned. We characterized recent trends in resistance of gram-negative organisms in culture-positive HCAP using a large US inpatient database.

Methods: This retrospective cohort study assessed adult patients admitted with HCAP from 2010- 2015 to 170 US hospitals that participate in the Premier data base, providing administrative and microbacteriological data. HCAP was defined as ≥1 of the following: prior hospitalization within 90 days, hemodialysis, admission from skilled nursing facility, or immune suppression. Patients with identical gram negative organisms in blood and urine were excluded. Resistance to each class of antipseudomonal therapy was assed at the patient level.

Results: We identified 48,440 patients with HCAP, 17,452 (36.0%) patients were admitted to ICU. Mean age was 69±15 (range 18-89) and 23,896 (49.3%) were male, and 9,354 (19.7%) had a positive blood (21.5%) or respiratory (8.1%) culture. Of these, 50.5% were gram-negatives, most commonly P. aeruginosa, E. coli and K. pneumoniae; 50.8% were sensitive to all antipseudomonal drugs; 27.2% were resistant to 1 antipseudomonal class and 21.9% were resistant to 2 or more; 40.7% were resistant to quinolones, 21.0% to antipseudomonal cephalosporins, 21.0% to aminoglycosides, 22.3% to antipseudomonal penicillin (piperacillin/tazobactam) and 12.8% to carbapenems. Unadjusted mortality was similar for patients with organisms resistant to any antipseudomonal drug compared to those sensitive to all drugs (17.1% vs 17.6%, p=0.65). Resistance to any antipseudomonal drug fell from 55.6 in 2010 to 45.6 in 2015 (p for trend 0.004).

Conclusion: In a large contemporary US inpatient database, more than half of all gram negative HCAP pathogens were resistant to at least one class of antipseudomonal antibiotics, most often to quinolones. Resistance declined over five years, but our findings still support the recommendation for empiric double coverage of Pseudomonas in HCAP.