ALARM was a prospective, observational, cohort study designed to capture and analyze management and outcome variable patterns for ventilator-associated pneumonia (VAP).
Investigators from 20 institutions within the United States identified 398 (60.8% male; mean age, 58.3 yrs) ICU patients with a diagnosis of VAP. Clinical, diagnostic, and treatment data were gathered on each patient for the duration of ICU stay. Escalation/de-escalation of therapy was defined as switching to or adding a drug class(es) with a broader/narrower spectrum, respectively, or additional/less coverage as defined by the following spectrum categories: carbapenem> cefepime> ureidopenicillin/monobactam> quinolone> other/none.
The mean duration of mechanical ventilation prior to VAP diagnosis was 7.3 + 6.9 days (range, 0-44 days). Tracheal aspirate cultures (58.3% of patients), bronchoalveolar lavage fluid cultures (33.7%), or both (1.8%) were used to identify major pathogens, which included methicillin-resistant Staphylococcus aureus (14.8%), Pseudomonas aeruginosa (14.3%), other Staphylococcus species (8.8%), Klebsiella pneumoniae (3.3%), Enterobacter (3.3%), E coli (3.0%), and Acinetobacter (2.0%). The most common initial treatment regimens consisted of (alone or with other agents): cefepime (30.4%), piperacillin/ tazobactam (27.9%), and vancomycin (17.8%). Mean duration of therapy was 11.8 days. Patterns of antibiotic therapy changes for VAP are shown in Table 1. Escalation of therapy occurred in 14.8% of patients and de-escalation in 22.4%. Overall mortality was 25.1%. Comparative mortality was lower among patients whose therapies were de-escalated (16.9%) compared to both patients undergoing escalation (42.4%) and those for whom therapy was neither escalated nor de-escalated (31.6%). Mean change in CPIS score at 72 hours was significantly less among patients who died (-0.10) compared with survivors (-2.35) (p<.05).
This multicenter study confirms that VAP in the ICU setting is associated with unacceptably high mortality rates.
Choices regarding initial antibiotic regimens and subsequent escalation/de-escalation of therapy have significant implications for patient outcomes.
Patterns of Antibiotic Prescription Changes for Therapy of VAP from Initial to FinalIncreasedNo ChangeDecreasedNumber of antibiotics7.0%70.1%*22.7%Spectrum of antibiotics12.1%72.6%*14.3%*
57.0% of patients started and finished therapy on the same regimen.
Marin Kollef, Grant monies (from industry related sources), The ALARM Study has been funded by a grant from Elan Pharmaceuticals.