DOI: 10.1097/CCM.0000000000001368

,  

,  

PMID: 26672942

Issn Print: 0090-3493

Publication Date: 2016/01/01


Print

The authors reply

Marin H. Kollef; Jason P. Burnham

    loading  Checking for direct PDF access through Ovid

Excerpt

We thank Roux et al (1) for their letter regarding our recent retrospective study on 510 patients with Enterobacteriaceae bacteremia (2). In our study, all 510 patients with Enterobacteriaceae bacteremia received appropriate antibiotic therapy within 12 hours of when blood cultures were drawn. Furthermore, for both survivors and nonsurvivors, the mean time to appropriate antibiotic therapy after blood cultures were drawn was less than 4 hours. For this selected group of patients, we found that the multidrug resistance (MDR) status of the infecting organism was not a determinant of mortality. Sepsis severity, severity of illness, underlying comorbidities, and race were found to be independent predictors of 30-day all-cause mortality for this cohort. The importance of these results is that with increasing resistance to currently available antibiotics, more and more patients are treated with initial inappropriate regimens, thereby increasing their risk for mortality and other adverse events. By eliminating or minimizing the influence of MDR status with appropriate antibiotic therapy, we can not only improve the outcome of individual patients but also allow more uniform patient conditions when designing trials of sepsis.
Roux et al (3) suggest that loss of endogenous resistance can lead to increased antibiotic sensitivity and decreased virulence of bacteria in animal models. We agree with Roux et al that many host factors, pathogen characteristics, and processes of medical care could influence the outcomes of patients with sepsis. We also agree that many genes impacting fitness and virulence of both MDR and non-MDR bacteria can influence bacterial fitness and virulence.
The influence of virulence factors and antimicrobial resistance on patient outcomes is a complex one. This is illustrated in a recent study by Peña et al (4) focusing on Pseudomonas aeruginosa bloodstream infections with or without expression of the type III secretion system as a major virulence determinant. In that study on 590 patients, the small exoU genotype for type III secretion system was associated with early hospital mortality, whereas infection with an MDR strain was found to be an independent predictor for late mortality. This suggests that there is a complex interaction between virulence and antibiotic resistance that may impact patient outcomes. Early mortality and morbidity could be more affected by the presence of virulence factors such as the expression of certain toxins and surface proteins, whereas late mortality could be a consequence of inappropriate antibiotic treatment as a result of MDR status. It is very likely that both of these factors influence outcomes and are interrelated, in part, because of the many bacterial genes impacting both fitness and virulence of MDR and non-MDR strains.
At the present time, we have no approved treatments directed toward virulence factors in bacteria, to include vaccines and monoclonal antibodies, or no routine identification of virulence factors for each patient with an infection is currently feasible. Clinicians need to continue to optimize antibiotic treatment of serious bacterial infections to include MDR strains. The availability of rapid diagnostics, including both molecular and advanced microscopy methods, should allow for more rapid administration of appropriate antibiotic therapy. These technologies should also help to minimize the unnecessary use of broad-spectrum antibiotics, given our limited ability to clinically exclude the presence of resistant pathogens in many clinical settings.
    loading  Loading Related Articles