Effect of appropriate empirical antimicrobial therapy on mortality of patients with Gram-negative bloodstream infections: a retrospective cohort study

Abstract

Background Little evidence exists regarding the prevalence of pathogens in bloodstream infections (BSIs), the mortality risk, and the benefit of combination therapy over monotherapy. This study aims to describe patterns of empiric antimicrobial therapy, and the epidemiology of Gram-negative pathogens, and to investigate the effect of appropriate therapy and appropriate combination therapy on the mortality of patients with BSIs. Methods This was a retrospective cohort study including all patients with BSIs of Gram-negative pathogens from January 2017 to December 2022 in a Chinese general hospital. The in-hospital mortality was compared between appropriate and inappropriate therapy, and between monotherapy and combination therapy for patients receiving appropriate therapy. We used Cox regression analysis to identify factors independently associated with in-hospital mortality. Results We included 205 patients in the study, of whom 147 (71.71%) patients received appropriate therapy compared with 58 (28.29%) who received inappropriate therapy. The most common Gram-negative pathogen was Escherichia coli (37.56%). 131 (63.90%) patients received monotherapy and 74 (36.10%) patients received combination therapy. The in-hospital mortality was significantly lower in patients administered appropriate therapy than inappropriate therapy (16.33% vs. 48.28%, p = 0.004); adjusted hazard ratio [HR] 0.55 [95% CI 0.35–0.84], p = 0.006). In-hospital mortality was also not different in combination therapy and monotherapy in the multivariate Cox regression analyses (adjusted HR 0.42 [95% CI 0.15–1.17], p = 0.096). However, combination therapy was associated with lower mortality than monotherapy in patients with sepsis or septic shock (adjusted HR 0.94 [95% CI 0.86–1.02], p = 0.047). Conclusions Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to Gram-negative pathogens. Combination therapy was associated with improved survival in patients with sepsis or septic shock. Clinicians need to choose optical empirical antimicrobials to improve survival outcomes in patients with BSIs.

Epidemiology and clinical relevance of persistent bacteraemia in patients with Gram-negative bloodstream infection: a retrospective cohort study

“… 9 Being on inappropriate or inadequate empiric therapy is also independently associated with worse clinical outcomes including mortality. 29 , 30 We thus cannot confirm whether persistent bacteraemia, in itself, is independently associated with increased mortality, or if this association is confounded by the fact that patients with persistent bacteraemia may be more likely to have had inadequate therapy due to multi-drug resistance. Residual confounding may also be present in studying the association between individual organisms and risk of persistence, since there may be common underlying factors (e.g.…”

Tigecycline–Rifampicin Restrains Resistance Development in Carbapenem-Resistant Klebsiella pneumoniae

“…29 Moreover, it is a common practice among infectious disease physicians to employ drug combinations for severe infections when the specific pathogen causing the infection and its susceptibility profile have not been identified yet. 30 The synergy between multiple antibacterial agents is a typical rationale for utilizing a combination antibacterial treatment. As a result, there is an obvious need to study novel pharmacological combinations.…”

“…In light of increasing bacterial resistance worldwide, the selection of effective drugs and combination therapy is becoming increasingly crucial in medical practice, and numerous effective combination therapy strategies have been described. , For instance, certain drugs are expressly marketed and endorsed as combination therapies, such as trimethoprim–sulfamethoxazole, β-lactam−β-lactamase inhibitors, and quinupristin–dalfopristin. − Additionally, approved combinations are utilized as standard treatments for tuberculosis (TB) therapy . Moreover, it is a common practice among infectious disease physicians to employ drug combinations for severe infections when the specific pathogen causing the infection and its susceptibility profile have not been identified yet . The synergy between multiple antibacterial agents is a typical rationale for utilizing a combination antibacterial treatment.…”