Early adequate source control was associated with fewer deaths within 30 days among hospitalized patients with Pseudomonas aeruginosa bloodstream infection in a multicenter Italian cohort. The 30-day death rate was 7% among patients who received early adequate source control, compared with 24% among those for whom source control was necessary but who did not receive it early.
The retrospective study, published online in Open Forum Infectious Diseases, included 639 adults with P. aeruginosa bloodstream infection treated at 14 public hospitals across eight regions of Italy from January 2021 through December 2022. Patients were required to have at least one peripheral blood culture positive for P. aeruginosa. Exclusion criteria included polymicrobial bloodstream infection and recurrent P. aeruginosa bloodstream infection, with only the first episode per patient considered in the analysis. The primary endpoint was 30-day all-cause mortality following the first positive blood culture for P. aeruginosa.
The source of P. aeruginosa bloodstream infection was classified by the investigators at each participating center during data collection, before the statistical analysis, according to predefined study criteria and based on the clinical, microbiological, and imaging information available in the medical records.
Source-control procedures included removal of infected intravascular hardware, resolution of urinary tract obstruction, drainage or debridement of infected collections, drainage for septic arthritis or osteomyelitis, and cardiac surgery for endocarditis when indicated. Early adequate source control was defined as intervention within 72 hours of P. aeruginosa bloodstream infection onset.
Of the 639 bloodstream infection episodes, 32% had an unknown source, 23% were central venous catheter-related, 20% were associated with hospital-acquired or ventilator-associated pneumonia, 11% originated from urinary tract infections and 7% from intra-abdominal infections. Source control was deemed necessary for 217 patients, or 34% of the cohort, and was performed adequately within 72 hours in 107 of those patients, or 49%.
Overall, 153 patients, or 24%, died within 30 days. The 30-day death rate was 7% among patients who received early adequate source control, compared with 24% among patients for whom source control was necessary but was not performed early and 28% among those for whom source control was considered unnecessary.
Association persists after adjustment
In the primary multivariable analysis, early adequate source control was associated with a lower hazard of death within 30 days compared with no early adequate source control among patients for whom source control was deemed necessary (adjusted hazard ratio, 0.26). Appropriate antibiotic therapy also was associated with a lower hazard of death within 30 days (adjusted hazard ratio, 0.27). In contrast, corticosteroid therapy (adjusted hazard ratio, 1.99) and septic shock at bloodstream infection onset (adjusted hazard ratio, 3.85) were associated with higher hazards of death. Older age also was independently associated with a higher hazard of death, whereas previous P. aeruginosa colonization was associated with a lower hazard.
Because the timing of source control could introduce immortal time bias, investigators conducted additional analyses treating source control as time-dependent and restricting another analysis to the 562 patients who remained alive on day 4. In the day-4 landmark analysis, early adequate source control remained associated with a lower hazard of death within 30 days (adjusted hazard ratio, 0.35), as did appropriate antibiotic therapy (adjusted hazard ratio, 0.41). Septic shock was associated with a higher hazard of death (adjusted hazard ratio, 2.44). Models accounting for differences among study centers and evaluating source control irrespective of whether it initially was considered necessary produced results consistent with the primary analysis.
Patients requiring source control
Investigators separately analyzed the 217 patients for whom source control was deemed necessary. Of these, 107 received early adequate source control and 110 did not. The groups generally had similar baseline characteristics, although intermittent dialysis was more common among patients who did not receive early adequate source control. The 30-day death rate was 7% with early adequate source control versus 24% without it.
Within this subgroup, multivariable analysis found that early adequate source control was associated with a lower hazard of death within 30 days (adjusted hazard ratio, 0.22), whereas septic shock was associated with a higher hazard of death (adjusted hazard ratio, 6.16). Additional sensitivity models produced similar findings.
A propensity score-matched analysis included 70 pairs of patients with and without early adequate source control. After adjustment for the remaining imbalance in hematological malignancy, early adequate source control was associated with a lower hazard of death within 30 days (adjusted hazard ratio, 0.15).
In an exploratory analysis limited to patients requiring source control who survived at least 4 days, the 30-day death rate remained low among those who received early adequate source control, at 0% and 6% according to antibiotic appropriateness; the difference was not statistically significant. Among patients without early adequate source control, the 30-day death rate was 17% with appropriate antibiotic therapy and 22% without it, also a nonsignificant difference.
Study limitations
The authors noted that confounding factors may have influenced the observed association between early interventions and improved survival, including decisions to limit or withdraw care and the availability and willingness of surgeons or interventional radiologists to perform adequate source-control procedures.
Infection source and the need for source control also were determined by investigators at individual centers, raising the possibility that some infections classified as having an unknown source had an unidentified focus.
The propensity score analysis could not fully account for time-dependent bias, and the day-4 landmark analysis excluded early deaths, potentially affecting estimates of the effects of early interventions among the most severely ill patients. The study also recorded only the first source-control intervention and did not evaluate subsequent procedures, duration of appropriate antibiotic therapy or the potential effect of source control on the development of antimicrobial resistance.
The authors concluded that the “findings underscore the critical importance of early identification and appropriate implementation of source control in patients with P. aeruginosa BSI,” noting that further research is needed to refine source control strategies and assess their impact on antimicrobial resistance and treatment duration.
The study was supported by independent medical grants from Pfizer Inc., Shionogi & Co., Ltd. and Tillotts Pharma AG; the authors stated that the funders had no role in study design, data collection or analysis, the decision to publish or manuscript preparation. Antonio Vena reported research grants and/or personal fees from Gilead, Menarini, MSD, Pfizer, Astellas and Shionogi. Matteo Bassetti reported research grants and/or personal fees from BioMérieux, Cidara, Gilead, Menarini, MSD, Pfizer and Shionogi. Daniele Roberto Giacobbe reported investigator-initiated grants from Pfizer, Shionogi, BioMérieux and Gilead Italia and personal fees from Pfizer, Menarini and Tillotts Pharma. All other authors reported no potential conflicts of interest.