Antibiotic Choice Does Matter:Antimicrobial Therapy and Outcome in Bacteremia
August 15, 2000 5 minutes read
Antibiotic Choice Does Matter:Antimicrobial Therapy and Outcome in Bacteremia
abstract & commentary
Synopsis: In a prospective study of 492 ICU patients with bacteremia, inadequate antimicrobial therapy was independently associated with hospital mortality.
Source: Ibrahim EH, et al. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000;118:146-155.
In a prospective study performed in the medical and sur-gical intensive care units (ICUs) of a university-affiliated hospital, Ibrahim and colleagues identified 492 patients with bloodstream infection. Of these, 147 were judged to have received inadequate antimicrobial therapy. The crude hospital mortality rate of patients receiving inadequate therapy was 62%, compared with a mortality rate of 28% for those receiving appropriate therapy (P < 0.001). On multiple logistic regression analysis, hospital mortality was associated with inadequate therapy (odds ratio [OR] 6.7, 95%; confidence interval [CI] 5.1-9.2), number of acquired organ system derangements (OR 2.3, 95%; CI 2.1-2.6), increasing Apache II score (OR 1.04, 95%; CI 1.02-1.06), and increasing age (OR 1.03, 95%; CI, 1.02-1.04). The most frequently identified pathogens, and the associated rate of inappropriate treatment, were: coagulase-negative Staphylococcus spp. (96 cases, 22%), methicillin-resistant S. aureus (46 cases, 33%), Candida spp. (41 cases, 95%), Pseudomonas aeruginosa (22 cases, 10%), and vancomycin-resistant enterococci (17 cases, 100%). On multiple logistic regression analysis, the administration of inappropriate therapy was independently associated with Candida infection, prior administration of antibiotics, decreasing serum albumin concentrations, and increasing duration of central catheter insertion.
Ibrahim et al conclude that critical care unit patients who receive inadequate therapy for bacteremia are significantly more likely to die than those who are appropriately treated, and patients who are likely to be inappropriately treated have certain risk factors that can be used to identify them. Ibrahim et al recommend early administration of broad-spectrum antimicrobials to high-risk patients suspected of bloodstream infections as a potential means of decreasing mortality. This should be followed by rapid tailoring of antimicrobial therapy once culture and susceptibility results are available.
Comment by Robert Muder, md
Many readers would feel that it is intuitively obvious that appropriate antibiotic therapy for bloodstream infections will result in improved survival. However, the published literature is far from unanimous in this conclusion. Although a number of studies have found an association between appropriate therapy and survival,1-3 others have not, or have found an association only on subset analysis.4,5 One possible reason for this is that the definition of appropriate therapy can in itself be the subject of some confusion. For example, Ibrahim et al define "inadequate therapy" as "microbiologic documentation of infection. . . that was not effectively treated at the time the causative microorganism and its antibiotic susceptibility were known." This definition is somewhat imprecise, lacking explicit criteria as to choice of agents, time of initiation, and duration. The choice of in-hospital mortality as the primary end point may not have been the most appropriate; some researchers6,7 have argued that survival for a specified time interval after onset of bacteremia (e.g., 14 days) should be used to remove the possibility of unintentional bias in attributing the cause of death to bacteremia.
It is, however, difficult to argue with their conclusion that initial antimicrobial therapy in critically ill patients suspected of bloodstream infections should include agents active against the most likely organisms, based on local susceptibility patterns and the patients’ risk of infection with a resistant organism. But will this eminently reasonable approach improve the outcome of bacteremia? Unfortunately, one cannot conclude this from the evidence presented. Most patients receiving inadequate therapy in this study were infected with antibiotic-resistant organisms, including Candida. Like such patients in many prior studies, they had more organ system derangements, more prior antibiotics, and more exposure to invasive devices. Caution is warranted in making the leap from statistical association to cause and effect.
However, it should be noted that several large prospective studies of bacteremia due to single organism classes such as Bacteroides8 and Enterococcus9 found independent associations between poor outcome and inadequate therapy. These studies are notable for using explicit criteria for adequate therapy, standardized susceptibility testing of blood isolates, and time-delimited criteria for mortality.
A practical issue applying the results of the current study remains. One is left with the problem of designing the most appropriate initial regimen. In the ICU studies by Ibrahim et al, such a regimen might include quinupristin/dalfopristin, an anti-pseudomonal beta-lactam, an aminoglycoside, and amphotericin B to provide optimal therapy against resistant staphylococci, enterococci, Pseudomonas, and Candida. The optimal initial antimicrobial regimen would, of course, vary among facilities and within the same facility over time. One additional issue involves the potential effect of routine use of broad spectrum therapy on the incidence of antimicrobial resistance in the ICU. Over the long term, this may prove to be counterproductive in improving outcomes. Ibrahim et al are correct in recommending revision of the treatment regimen to more targeted therapy once the culture and susceptibility results are known.
Finally, as a hospital epidemiologist, I am disappointed that Ibrahim et al did not mention reduction in the incidence of infection by resistant organisms as a potential strategy for reducing the mortality associated with bloodstream infections. Although there is some conflict among published studies, a number of large, multicenter studies show a strong, independent association between bloodstream infection by multiresistant organisms and mortality.7,9 Whether reduction in the incidence of bacteremia by multi-resistant organisms through infection control measures and judicious antimicrobial usage will result in a reduction in mortality is not clear. It is, however, definitely worth investigating.
References
1. Lebovici L, et al. The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 1998;244:379-386.
2. Bryan CS, et al. Analysis of 1186 episodes of gram-negative bacteremia in non-university hospitals: The effects of antimicrobial therapy. Rev Infect Dis 1983; 5:629-638.
3. Hoge CW, et al. Enterococcal bacteremia: To treat or not to treat, a reappraisal. Rev Infect Dis 1991;13: 600-605.
4. Gray J, et al. Enterococcal bacteraemia: A prospective study of 125 episodes. J Hosp Infect 1994;27:179-186.
5. Vidal F, et al. Epidemiology and outcome of Pseudomonas aeruginosa bacteremia, with special emphasis on the influence on antibiotic treatment. Analysis of 189 episodes. Arch Intern Med 1996; 156:2121-2126.
6. Hilf M, et al. Antibiotic therapy for Pseudomonas bacteremia: Outcome correlations in a prospective study of 200 patients. Am J Med 1989;87:540-546.
7. Chow JW, et al. Enterobacter bacteremia: Clinical features and emergence of antibiotic resistance during therapy. Ann Intern Med 1991;115:585-590.
8. Nguyen MH, et al. Antimicrobial resistance and clinical outcome of Bacteroides bacteremia: Findings of a multicenter prospective observational trial. Clin Infect Dis 2000;20:870-876.
9. Vergis EN, et al. Vancomycin resistance predicts mortality in enterococcal bacteremia; A prospective, multicenter study of 375 patients. Abstract J6. Program and Abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto: 1997.
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