最新研究进展.docx

1、最新研究进展减少ICU中抗生素抵抗病原体发生率的策略Strategies to Reduce the Incidence of Antibiotic-Resistant Pathogens in the ICUHenry Masur, MD IntroductionAt the 32nd Critical Care Congress, strategies to reduce the frequency of antibiotic-resistant pathogens received considerable attention. Marin H. Kollef, MD,1 of Wash

2、ington University School of Medicine in Manchester, Missouri, stressed that in every intensive care unit (ICU), the incidence of resistance should be closely monitored, just as ICUs monitor the frequency of self-extubations and deep vein thrombosis. Collecting and reviewing data that indicate what t

3、he pathogens are in a unit, and what their antimicrobial susceptibility is, must be the foundation for an ICUs program to reduce the incidence of infectious complications, and to minimize antibiotic resistance.Antibiotic Rotation in the ICUAntibiotic Rotation in the ICURestricting antibiotics is one

4、 approach to minimizing the incidence of antibiotic resistance, but decreasing the duration of antibiotic courses deserves emphasis as well. Cycling and rotation of antibiotics represent attempts to minimize resistance against one particular drug. This strategy can restore susceptibility of organism

5、s to that one particular drug. Rahal and colleagues2 published a before-and-after study in 1998 looking at the incidence of cephalosporin-resistant extended-spectrum beta-lactamase-producing Klebsiella during a period of time when cephalosporins were widely used. They showed that restricting the use

6、 of cephalosporins in favor of carbapenems reduced the incidence of cephalosporin-resistant Klebsiella dramatically. However, the incidence of imipenem-resistant Pseudomonas increased substantially. Rahals approach really exchanged one type of resistance for another type of resistance. This strategy

7、 exchanges one homogeneous strategy of antibiotic use for another homogeneous strategy, rather than using a heterogeneous strategy that might not lead to so much resistance against one class of drugs. Scheduled changes of drug use might be one approach to produce such heterogeneity; changes in drug

8、use could also be made in response to changes in susceptibility patterns. Dr. Kollef3,4 has done such a study, and found a decrease in incidence of bacteremias and nosocomial pneumonias over the first 6 months after an antibiotic policy change. However, he did not have data demonstrating that this a

9、dvantage persisted for more than 6 months. Landman and colleagues5 did a similar study between 1993 and 1996 that restricted the use of cephalosporins, vancomycin, and clindamycin in favor of ampicillin-sulbactam and piperacillin-tazobactam. The incidence of certain pathogens such as methicillin-res

10、istant Staphylococcus aureus (MRSA) declined, but the incidence of Acinetobacter resistant to cephalosporins increased. Thus, the restriction strategies do not always have long-term efficacy in terms of reducing total antibiotic resistance.A preferable approach might be to monitor antibiotic resista

11、nce patterns in real time and to change antibiotic use based on these data. Didier Gruson and colleagues6 have shown that this strategy can improve patient outcomes, probably by allowing clinicians to use empiric regimens that were more likely to be active against the offending pathogen (ie, allowin

12、g quicker institution of active therapy). A study reviewing 5 years of experience with this approach will be published shortly.Dr. Kollef summarized by emphasizing that cycling or rotating antibiotics can be beneficial, but only if such cycling is part of a strategy of monitoring antibiotic resistan

13、ce and responding wisely to changing patterns of causative organisms and antibiotic susceptibility. Dr. Kollef was asked during the question-and-answer period whether these cycling strategies,focusing primarily on Gram-negative bacilli, could also be useful for Gram-positive organisms. Dr. Kollef re

14、plied that in the past, there were limited options for treating Gram-positive cocci, so that cycling was not really feasible. However, with the emergence of linezolid, quinupristin-dalfopristin, and perhaps daptomycin, such strategies are reasonable considerations.Antibiotic Use in SepsisAntibiotic

15、Use in SepsisJonathan Cohen, MD,7 then spoke about antibiotic choice in sepsis. It might seem appropriate to have a critical pathway that mandated the same antibiotic selection for every patient who was septic. This monolithic approach would be consistent, but would not likely maximize outcome. The

16、appropriate choice of antibiotic for an individual patient may increase efficacy by increasing the likelihood that an active drug is chosen. Knowledge of prior antibiotics, or prior colonizing or infecting organisms, would influence drug selection. The appropriate choice of antibiotic might also dec

17、rease toxicity by avoiding drugs that might exacerbate underlying organ dysfunction. In a study published in 1980, Kreger and coworkers8 demonstrated that the choice of antibiotic therapy that is active against the causative organism improves patient outcome compared with patients who received drugs

18、 that were not active against the offending pathogen, as clinicians might intuitively suspect. More recent studies have confirmed Kregers results.Dr. Cohen described the utility of a test that has not been used for many years in understanding outcome. Laboratory tests can measure the ability of anti

19、biotic-containing serum to kill the patients pathogen. The bacteridical titer has been defined as the concentration of serum that kills 95% of an inoculum. These titers assess both the effect of host factors and the effect of the antibiotic. Patients with higher peak titers have better outcomes than

20、 patients who have lower peak titers. However, this assay is not terribly practical because of wide variability in laboratory techniques and resulting nonreproducibility of results. More recently, automated blood culture systems measure the hours until growth of bacteria is recognized. This time is

21、an approximation of bactericidal activity. (This is also a surrogate marker for the quantity of circulating bacteria, which is a reciprocal concept.) The shorter the time to culture positivity, the worse the patients prognosis. Increasing the amount of antibiotic in each specimen (ie, higher serum a

22、ntibiotic levels) also leads to longer time to culture positivity.Focusing Drug Antibiotic Delivery on Infected TissueFocusing Drug Antibiotic Delivery on Infected TissueH. Shaw Warren, MD,9 of Massachusetts General Hospital East in Charlestown, Massachusetts, described some fascinating work designe

23、d to focus drug delivery to the infected tissues. Dr. Warren used amikacin, an aminoglycoside that (unlike gentamicin) had a convenient side chain for bonding, as a ligand with the chemotactic factor f-met-leu-fe (formyl-methionine-leucine-phenylalanine). This allowed amikacin to be delivered with n

24、eutrophils to the areas where the pathogenic bacteria elicited an inflammatory response. Analogues of this factor can aggregate with neutrophils without activating the neutrophils. There are a variety of technical problems that must be solved with this approach, but the principle is intriguing and p

25、reliminary results in animal models are promising.Limiting Antibiotic Use in the ICULimiting Antibiotic Use in the ICUJohn Marshall, MD,10 of Toronto General Hospital in Toronto, Ontario, Canada, then focused on limiting the use of antibiotics in the ICU. He likened the strategies of antibiotic cycl

26、ing and other strategies that take advantage of antibiotic heterogeneity to rearranging the deck chairs on the Titanic. The problem is not which class of agent is used, it is that there is too much use of all antimicrobial agents. Normal microbial flora resist the propagation of pathogenic organisms

27、; when we give antibiotics and alter that normal flora, we disrupt homeostasis. There are considerable data from both animal and human studies to support this concept. e summarized several studies that supported relatively short-course therapy for ventilator-associated pneumonia. He detailed one stu

28、dy that demonstrated that short-course antibiotic therapy (3 days) in patients with new infiltrates and at low risk for pneumonia (CPIS score less than 6) decreased the rates of colonization or superinfection with resistant organisms in an ICU.11 A second study12 demonstrated that patients had a hig

29、her mortality when antibiotics were administered for clinical indications compared with patients who had antibiotics administered by strict and specific criteria obtained after invasive diagnostic testing with quantitative cultures from bronchoscopy. His take-home message was to believe objective di

30、agnostic results and not to start antibiotics unless one has specific data to indicate there is an infection with a pathogenic organism.Once-Daily Dosing of AminoglycosidesOnce-Daily Dosing of AminoglycosidesEdward Timm, PharmD,13 of Albany Medical Center, Schenectady, New York, reviewed the data su

31、pporting once-daily dosing of aminoglycosides in ICU patients. He outlined the rationale for such a once-daily dose strategy by emphasizing 3 points: 1. This strategy takes advantage of concentration-dependent killing of microorganisms and allows for maximal antibiotic efficacy; 2. This strategy min

32、imizes nephrotoxicity and ototoxicity and has an added advantage of decreasing medication errors by using a consistent dose that is not based on the interpretation of aminoglycoside levels; and3. Dollar costs are decreased when the costs of mixing and hanging drugs more than once a day and the laboratory charges incurred when getting levels are considered.Dr. Timm suggested that once-daily aminoglycoside therapy is appropriate for many patient populations. However, he indicated that not all patients are candidates for this dosing regimen. Specifically, there a