Strategies in the Selection of Antibiotic Therapy in the ICU

1. Strategies in the Selection of Antibiotic Therapy in the ICU Mazen Kherallah, MD, FCCP King Faisal Specialist Hospital & Research Center

2. Scope of the Problem

3. Infection Distribution in Adult ICU�sMajor Types of Infection (NNIS data, 1992-1997)

4. Nosocomial Infection

5. NNIS

6. Pathogens Most Frequently associated with Nosocomial Pneumonia in the ICU

7. Inadequate Initial Antibiotic Therapy

8. Initial Inadequate Therapy

9. Mortality Associated with Initial Inadequate Therapy

10. Resistant Pathogens, Inadequate Treatment and Mortality (BSI)

11. Inadequate Antimicrobial Therapy 2000 consecutive MICU/SICU patients 655 (25.8%) with infections 169 (8.5%) with inadequate therapy

12. Infection Classification

13. Cohort of Infected Patients and Inadequate Therapy

14. Most Common Pathogens Inadequate therapy (n=169) P. aeruginosa: 53 MRSA: 45 VRE: 13 Adequate therapy (n=486) Escherchia coli: 76 MSSA: 88

15. Clinical Outcomes

16. Hospital Mortality of Infected Patients

17. Reduce Inappropriate Initial Antimicrobial Therapy Guidelines Broad spectrum and combination antibiotics ID consultation Automated antibiotic consultant More selective and sensitive diagnostic methods

18. Clinical Guidelines for the Treatment of Ventilator Associated Pneumonia Prospective study: 50 patients were evaluated in the before group and 52 in the after group Administration of vancomycin/imipenem/ciprofloxacin within 12 hours of clinical diagnosis Antibiotic modification after24-48 hrs Seven-day course of therapy (>7 days if symptoms and signs are persisted)

19. Clinical Guidelines for the Treatment of Ventilator Associated Pneumonia

20. Automated Antibiotic Consultant

21. Broad-Spectrum and Combination Antibiotics

22. ID Consultation

23. Emergent Bacterial Resistance

24. Impact of Antibiotic Restriction on ResistanceNeurosurgical Intensive Care Unit in London This was an outbreak in a neurosurgical intensive care unit in London, and they had really a big problem. In 1968 about 20% of their patients were infected with a multidrug resistant Klebsiella aerogenes. Again, remember this is 30 years ago. There was no effective therapy for this organism. Worse yet, their nosocomial infection rate was about 50%. And they tried a lot of interventions during 1968 and 1969, and then in July of 1969 they did something that even today I find incredible. The medical staff at this institution determined that they were going to stop all antibiotics in this ICU for every reason. So if a patient had meningitis, no antibiotics. Nosocomial pneumonia, no antibiotics. Postoperative wound infection, blood stream infection -- they were prepared not to give any patient an antibiotic in their ICU for any reason. Well they were lucky because there were no patients who had meningitis, but they stopped all their antibiotics in July of 1969 and looked what happened. Their nosocomial infection rate dropped from about 45% down to about 20%, and they completely eradicated this resistant KlebsiellaThis was an outbreak in a neurosurgical intensive care unit in London, and they had really a big problem. In 1968 about 20% of their patients were infected with a multidrug resistant Klebsiella aerogenes. Again, remember this is 30 years ago. There was no effective therapy for this organism. Worse yet, their nosocomial infection rate was about 50%. And they tried a lot of interventions during 1968 and 1969, and then in July of 1969 they did something that even today I find incredible. The medical staff at this institution determined that they were going to stop all antibiotics in this ICU for every reason. So if a patient had meningitis, no antibiotics. Nosocomial pneumonia, no antibiotics. Postoperative wound infection, blood stream infection -- they were prepared not to give any patient an antibiotic in their ICU for any reason. Well they were lucky because there were no patients who had meningitis, but they stopped all their antibiotics in July of 1969 and looked what happened. Their nosocomial infection rate dropped from about 45% down to about 20%, and they completely eradicated this resistant Klebsiella

25. Decrease in Hospital-acquired ICU Infection Rates, NNIS, 1990-1999

26. Possible Explanation for Decrease in Infection Rate Efforts to prevent infections: new research findings, prevention guidelines Shift of health care from hospital-based care True decrease secondary to adhesion to infection control policies

27. Rates of Resistance Among Nosocomial Infections Reported in Intensive Care Patients, Comparison of 1999 (January-July) with Historical Data If we look at the rates of resistance of nosocomial pathogens in our intensive care unit patients in our National Nosocomial Infection Surveillance System and look at 1993 to 1997 which is shown here in gray versus January to November 1998, we see that the number of infections caused by vancomycin-resistant Enterococci have increased tremendously. Methicillin-resistant Staph aureus has also increased to the point where over 50% of the infections in our intensive care unit patients in our hospitals are resistant to methicillin. Third-generation cephalosporin, E.coli-resistant, Klebsiella-resistant has not changed too much. Imipenem-resistant Pseudomonas aeruginosa and Acinetobacters is starting to increase, as is quinolone-resistant Pseudomonas aeruginosa. So we are seeing increasing resistance and pathogen in our hospitals.If we look at the rates of resistance of nosocomial pathogens in our intensive care unit patients in our National Nosocomial Infection Surveillance System and look at 1993 to 1997 which is shown here in gray versus January to November 1998, we see that the number of infections caused by vancomycin-resistant Enterococci have increased tremendously. Methicillin-resistant Staph aureus has also increased to the point where over 50% of the infections in our intensive care unit patients in our hospitals are resistant to methicillin. Third-generation cephalosporin, E.coli-resistant, Klebsiella-resistant has not changed too much. Imipenem-resistant Pseudomonas aeruginosa and Acinetobacters is starting to increase, as is quinolone-resistant Pseudomonas aeruginosa. So we are seeing increasing resistance and pathogen in our hospitals.

28. Emerging Pathogens Methicillin-resistant Staphylococcus aureus (MRSA) Methicillin-resistant Staphylococcus epidermitis (MRSE) Vancomycin-resistant enterococci (VRE) Vancomycin-intermediate Staphylococcus aureus (VISA) Extended-spectrum beta-lactamase (ESBL)-producing gram-negative organisms Multidrug-resistant Acinetobacter spp. We have a large number of pathogens that we're concerned about, but we're going to focus primarily on those in the healthcare setting -- including methicillin-resistant Staph aureus, vancomycin-resistant Enterococci, vancomycin intermediate-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing gram-negative organisms, and multidrug-resistant Acinetobacter species. We have a large number of pathogens that we're concerned about, but we're going to focus primarily on those in the healthcare setting -- including methicillin-resistant Staph aureus, vancomycin-resistant Enterococci, vancomycin intermediate-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing gram-negative organisms, and multidrug-resistant Acinetobacter species.

29. Antibacterial Resistance in Nosocomial InfectionsGram-Negative Pathogens

30. Antibacterial Resistance in Nosocomial InfectionsGram-Positive Pathogens

31. Methicillin Resistant Staphylococci by setting Now it's important to look at the different setting in which patients acquire these infections. It's primarily a problem with coagulase negative Staphylococci in intensive care units, but also it's a problem with Staph aureus both in the ICU and non-ICU. You've heard the role of the outpatient setting for MRSA, and to a certain extent it's a semantics issue whether a patient truly has an outpatient infection or not; and I think the most appropriate way to talk about it is, is it healthcare-associated or not? If a patient is coming back and forth to a dialysis unit three times a week and develops an MRSA infection, is that community-acquired or not? Clearly it's healthcare-associated. Now it's important to look at the different setting in which patients acquire these infections. It's primarily a problem with coagulase negative Staphylococci in intensive care units, but also it's a problem with Staph aureus both in the ICU and non-ICU. You've heard the role of the outpatient setting for MRSA, and to a certain extent it's a semantics issue whether a patient truly has an outpatient infection or not; and I think the most appropriate way to talk about it is, is it healthcare-associated or not? If a patient is coming back and forth to a dialysis unit three times a week and develops an MRSA infection, is that community-acquired or not? Clearly it's healthcare-associated.

32. Vancomycin-resistant Staphylococcus aureus June 2202- First case of VRSA isolated from a swab obtained from a catheter exit site The isolate was resistant to: Oxacillin (MIC >16 �g/ml) Vancomycin (MIC >128 �g/ml) The isolate contained: The oxacillin-resistant gene mecA The vanA vancomycin resistant gene from enterococci

33. Epidemiology of VRE Present in all 50 states in the United States Number of isolated continues to grow Recognized in Europe, Japan, Central and South America Resistance to alternate antibiotic therapy continues to be a problem Now let's move on to VRE. Certainly present in all 50 states in the United States, and it's now starting to emerge internationally with reports in Europe, Japan, and Central and South America. The number of isolates continues to grow, and the resistance to alternate therapeutic agents continues to be a problem. And even with the recent release and approval in the United States of two additional agents, there are great concerns that resistance to those agents may emerge rapidly. Now let's move on to VRE. Certainly present in all 50 states in the United States, and it's now starting to emerge internationally with reports in Europe, Japan, and Central and South America. The number of isolates continues to grow, and the resistance to alternate therapeutic agents continues to be a problem. And even with the recent release and approval in the United States of two additional agents, there are great concerns that resistance to those agents may emerge rapidly.

34. Risk Factors for VRE Prior broad spectrum antibiotics (especially cephalosporins and vancomycin) Prolonged hospitalization Immunocompromised host Neutropenia Admission to an intensive care unit Renal failure requiring dialysis

35. Antibiotics and Colonization with VRE Now this is another study that looked at antimicrobial exposure and the risk of developing VRE. Again, this study showed that second- and/or third-generation cephalosporins were an important risk factor. Antianaerobic drugs like metronidazole and neither the fluoroquinolones or penicillin served as a risk factor. Prior exposure to vancomycin was a risk factor. Now this is another study that looked at antimicrobial exposure and the risk of developing VRE. Again, this study showed that second- and/or third-generation cephalosporins were an important risk factor. Antianaerobic drugs like metronidazole and neither the fluoroquinolones or penicillin served as a risk factor. Prior exposure to vancomycin was a risk factor.

36. Use of Vancomycin in US and Rate of VRE

37. Independent Predictors of Vancomycin-Resistant Enterococci in Adult Intensive Care Units If we look at ICU patients and look at independent predictors of vancomycin use, one of the major factors is how much VRE do you have in the rest of your institution so that patients can get colonized and then go into the ICU? Use of third-generation cephalosporins, use of vancomycin, and then the type of ICU with medical ICU being a stronger risk factor than surgical ICU. If we look at ICU patients and look at independent predictors of vancomycin use, one of the major factors is how much VRE do you have in the rest of your institution so that patients can get colonized and then go into the ICU? Use of third-generation cephalosporins, use of vancomycin, and then the type of ICU with medical ICU being a stronger risk factor than surgical ICU.

38. Enterococcal Resistance by Species There's some differences with regards to resistance based on the species, and it really emphasizes the importance of identifying enterococcal down to the species level because most of the resistance is among Enterococcus faecium. In fact, you could almost screen for faecium by looking at ampicillin resistance; 80% of all Enterococcus faecium are ampicillin-resistant. About half of Enterococcus faecium are vancomycin-resistant in contrast to Enterococcus faecalis, where it's about 3% for both vancomycin resistance and ampicillin resistance. There's some differences with regards to resistance based on the species, and it really emphasizes the importance of identifying enterococcal down to the species level because most of the resistance is among Enterococcus faecium. In fact, you could almost screen for faecium by looking at ampicillin resistance; 80% of all Enterococcus faecium are ampicillin-resistant. About half of Enterococcus faecium are vancomycin-resistant in contrast to Enterococcus faecalis, where it's about 3% for both vancomycin resistance and ampicillin resistance.

39. Outcome of Enterococcus faecium Bacteremia And finally, how does infection with this organism impact patient outcome? And this is data that we published in the Archives a couple of years ago looking at mortality in patients with vancomycin-susceptible Enterococci versus a vancomycin-resistant Enterococci. One of the things that you need to be cognizant of when you look at the literature is not only the crude mortality rate but the attributable mortality because so many of these patients are critically ill, have underlying diseases. The question is are they dying with this infection or from this infection? And at least in our institution the mortality directly related to VRE bacteremia was statistically higher than patients who had acceptable enterococcal bacteremia. Equally as important, we had about a $30,000 difference in total healthcare costs resulting from patients who had VRE bacteremia.And finally, how does infection with this organism impact patient outcome? And this is data that we published in the Archives a couple of years ago looking at mortality in patients with vancomycin-susceptible Enterococci versus a vancomycin-resistant Enterococci. One of the things that you need to be cognizant of when you look at the literature is not only the crude mortality rate but the attributable mortality because so many of these patients are critically ill, have underlying diseases. The question is are they dying with this infection or from this infection? And at least in our institution the mortality directly related to VRE bacteremia was statistically higher than patients who had acceptable enterococcal bacteremia. Equally as important, we had about a $30,000 difference in total healthcare costs resulting from patients who had VRE bacteremia.

40. Extended Spectrum ?-lactamasesESBLs ESBL inactivates oxyamino beta-lactams and fourth-generation cephalosporins (to some extent) and aztreonam Large plasmids encoding multiple antibiotic resistance determinants including aminoglycoside modifying enzymes Strains producing ESBL are typically sensitive to cephamycins and carbapenems Common ESBL-producers: K. pneumoniae, and less common other Enterobactericae Now let's move on to gram-negative organisms and the extended-spectrum beta-lactamases. First described in Germany in 1983 and then in the United States in the late 80s, these ESBL-producers are usually resistant to extended spectrum or third-generation cephalosporins and aztreonam. These organisms are usually susceptible to cefoxitin. Common producers are Klebsiella and less common are Enterobacteriaceae, but the plasmid can be transferred in some of these strains from Klebsiella to E.coli and other Enterobacteriaceae. Now let's move on to gram-negative organisms and the extended-spectrum beta-lactamases. First described in Germany in 1983 and then in the United States in the late 80s, these ESBL-producers are usually resistant to extended spectrum or third-generation cephalosporins and aztreonam. These organisms are usually susceptible to cefoxitin. Common producers are Klebsiella and less common are Enterobacteriaceae, but the plasmid can be transferred in some of these strains from Klebsiella to E.coli and other Enterobacteriaceae.

41. As you can see in the slide, all of the multiresistant Klebsiella pneumoniae isolates exhibit this same antibiotic-resistant profile, were resistant to ampicillin, to piperacillin, all oxyamino betalactams, gentamicin, and quinolones. They were only susceptible to pip/tazo and quite susceptible to carbapenems. As you can see in the slide, all of the multiresistant Klebsiella pneumoniae isolates exhibit this same antibiotic-resistant profile, were resistant to ampicillin, to piperacillin, all oxyamino betalactams, gentamicin, and quinolones. They were only susceptible to pip/tazo and quite susceptible to carbapenems.

42. K. pneumoniae Resistant to Extended-Spectrum ?-lactam (ESBL) at NNISEvidence of Inter-hospital Transmission We look at data from NNIS again. We're looking at Klebsiella resistance to extended-spectrum beta-lactamases. If you look at Hospital A, gradually increased. Shortly thereafter Hospital B, which was within 20 miles. Several hospitals actually had an increase as well, whereas hospitals that were more than 20 miles away did not have an increase, showing that you can have interfacility transmission of these strains and gradually incubate this problem in the vicinity that you're in. We look at data from NNIS again. We're looking at Klebsiella resistance to extended-spectrum beta-lactamases. If you look at Hospital A, gradually increased. Shortly thereafter Hospital B, which was within 20 miles. Several hospitals actually had an increase as well, whereas hospitals that were more than 20 miles away did not have an increase, showing that you can have interfacility transmission of these strains and gradually incubate this problem in the vicinity that you're in.

43. Emergence of Carbapenem-resistant Acinetobacter spp. Frequent use of aminoglycosides, fluroquinolones, ureidopenicillins and third generation cephalosporins Reported from South America, Europe, Far East, Middle East, and United States Numerous outbreaks (some strains susceptible only to polymyxin B) High mortality rates Endemic in some hospitals But what happens when you do that? Well then you lead to the emergence of carbapenem resistance, which we're seeing now in several areas of the world. Frequent use of aminoglycosides, fluoroquinolones, ureidopenicillins and third-generation cephalosporins can lead to the emergence of these strains. They were first reported in South America, but they've now been reported from Europe, the Far East, the Middle East, and the United States. There have been numerous outbreaks, and the greatest concern is that some of these strains are virtually resistant to all antimicrobials that are commonly used and susceptible only to polymyxin B. They're associated with high mortality rates, and they've become endemic in some hospitals. But what happens when you do that? Well then you lead to the emergence of carbapenem resistance, which we're seeing now in several areas of the world. Frequent use of aminoglycosides, fluoroquinolones, ureidopenicillins and third-generation cephalosporins can lead to the emergence of these strains. They were first reported in South America, but they've now been reported from Europe, the Far East, the Middle East, and the United States. There have been numerous outbreaks, and the greatest concern is that some of these strains are virtually resistant to all antimicrobials that are commonly used and susceptible only to polymyxin B. They're associated with high mortality rates, and they've become endemic in some hospitals.

44. Endemic Carbapenem-Resistant Acinetobacter spp. In Brooklyn, New York 15 hospitals November 1997, all aerobic bacteria collected Acinetobacter spp. (233) accounted for 10% of the gram negative bacilli Carbapenem resistance ranged from 0-100% 10% of isolated were susceptible only to polymyxin Risk factors Use of third generation cephalosporins plus aztreonam Environment and healthcare worker hands contamination documented PFGE documented inter- and intra-hospital spread One example of that is a paper that's in CID this month from Manikal from Brooklyn, New York, where they're seeing endemic carbapenem-resistant Acinetobacters. They did a study in 15 hospitals in Brooklyn, collected all aerobic bacteria in November of '97; and they found that Acinetobacter species accounted for 10% of the gram-negative bacilli. If you look at most reports from microbiology laboratories, seldom do these strains of Acinetobacter account for more than about 2 to 5% of strains -- certainly not 10%. The carbapenem's resistance ranged from 0 to 100% depending upon what hospital they were at. Ten percent of the isolates were susceptible only to polymyxin. Risk factors included use of third-generation cephalosporins plus aztreonam. Both environment contamination and healthcare worker hand contamination were documented, and they did pulsed-field gel electrophoresis on the strains that they obtained; and they were able to document both inter- and intra-hospital transmission.One example of that is a paper that's in CID this month from Manikal from Brooklyn, New York, where they're seeing endemic carbapenem-resistant Acinetobacters. They did a study in 15 hospitals in Brooklyn, collected all aerobic bacteria in November of '97; and they found that Acinetobacter species accounted for 10% of the gram-negative bacilli. If you look at most reports from microbiology laboratories, seldom do these strains of Acinetobacter account for more than about 2 to 5% of strains -- certainly not 10%. The carbapenem's resistance ranged from 0 to 100% depending upon what hospital they were at. Ten percent of the isolates were susceptible only to polymyxin. Risk factors included use of third-generation cephalosporins plus aztreonam. Both environment contamination and healthcare worker hand contamination were documented, and they did pulsed-field gel electrophoresis on the strains that they obtained; and they were able to document both inter- and intra-hospital transmission.

45. Antimicrobial Susceptibility of 233 Acinetobacter spp., 15 Hospital, Brooklyn, New York When we looked at the antimicrobial susceptibility of these Acinetobacter strains, you can see here widespread resistance with less than 20% being susceptible with trimethoprim sulfa, gentamicin, ciprofloxacin, ceftazidime, ceftriaxone. And when you look at over 50% susceptibility, you only have doxycycline, polymyxin, and aminoglycoside. And 20% of strains were only susceptible to polymyxin B. So a major, major problem in terms of what do you treat these patients with. When we looked at the antimicrobial susceptibility of these Acinetobacter strains, you can see here widespread resistance with less than 20% being susceptible with trimethoprim sulfa, gentamicin, ciprofloxacin, ceftazidime, ceftriaxone. And when you look at over 50% susceptibility, you only have doxycycline, polymyxin, and aminoglycoside. And 20% of strains were only susceptible to polymyxin B. So a major, major problem in terms of what do you treat these patients with.

46. Efforts to Decrease the Rate of Emergent Antimicrobial Resistance CDC guidelines and barrier precautions Antibiotic restriction Selective bowel decontamination Rotation antibiotics Short course antibiotic course But if outbreaks can be limited throughout control programs, there is still a lack of agreement about the efficacy of control measures. All the interventions mentioned in this slide had some degree of efficacy in large reported outbreaks. First, such as barrier precautions including cohorting of infected or colonized patients. Second, measures based in antibiotic policy, particularly third-generation cephalosporin restriction; and third, measures such as selective bowel contamination. But if outbreaks can be limited throughout control programs, there is still a lack of agreement about the efficacy of control measures. All the interventions mentioned in this slide had some degree of efficacy in large reported outbreaks. First, such as barrier precautions including cohorting of infected or colonized patients. Second, measures based in antibiotic policy, particularly third-generation cephalosporin restriction; and third, measures such as selective bowel contamination.

47. Impact of CDC Guidelines on Endemic VRE When we've looked at three different studies where we have gone in and reinforced the CDC recommendations, we have seen that they do have an impact. In a New York Hospital on an oncology ward where VRE was endemic and 30% of patients were colonized at any one time and the number of bloodstream infections in this hospital was the highest of virtually any in the United States, we first found that barrier precaution before the intervention was implemented was only 28%. So you can't expect that it's going to work. With the implementation of reinforcement of policies, they increased to 92%. There was not a major effort to control vancomycin use. Vancomycin use probably results in the emergence of strains, but then the increase in transmission is more of an infection control problem. By merely improving infection control, colonization was decreased by 50%, and infections were decreased by 35%; and both of these were statistically significant. A similar intervention in a Maryland hospital where initial precaution compliance was about 64% -- a more major influence on antimicrobial use with a decrease in IV vancomycin use by 59%. It decreased colonization, but it did not decrease it statistically significantly. And part of the problem was this intervention was over the entire hospital, and it's much more difficult to police an intervention over the entire hospital. The third intervention was in an Indianapolis, Indiana, hospital where VRE precaution compliance increased from 22 to 88% when we moved all VRE patients to one ward rather than scattered throughout the hospital. They were able to decrease colonization by 80% and virtually eliminate infections. When we've looked at three different studies where we have gone in and reinforced the CDC recommendations, we have seen that they do have an impact. In a New York Hospital on an oncology ward where VRE was endemic and 30% of patients were colonized at any one time and the number of bloodstream infections in this hospital was the highest of virtually any in the United States, we first found that barrier precaution before the intervention was implemented was only 28%. So you can't expect that it's going to work. With the implementation of reinforcement of policies, they increased to 92%. There was not a major effort to control vancomycin use. Vancomycin use probably results in the emergence of strains, but then the increase in transmission is more of an infection control problem. By merely improving infection control, colonization was decreased by 50%, and infections were decreased by 35%; and both of these were statistically significant. A similar intervention in a Maryland hospital where initial precaution compliance was about 64% -- a more major influence on antimicrobial use with a decrease in IV vancomycin use by 59%. It decreased colonization, but it did not decrease it statistically significantly. And part of the problem was this intervention was over the entire hospital, and it's much more difficult to police an intervention over the entire hospital. The third intervention was in an Indianapolis, Indiana, hospital where VRE precaution compliance increased from 22 to 88% when we moved all VRE patients to one ward rather than scattered throughout the hospital. They were able to decrease colonization by 80% and virtually eliminate infections.

48. Impact of Formulary Change on VREEmpiric therapy for febrile neutropenia This is based on a presentation looking at empiric therapy for the febrile neutropenic. And at this hospital they had primarily used piperacillin as their empiric therapy for patients with fever and neutropenia. They switched from piperacillin to cefepime in 1999, and you can see there was appropriate differences between the use of the agents and that one intervention alone with nothing else being done resulted in an increase in their VRE colonization rate from 1.5 per thousand patient days up to 5.5 per thousand patient days. But equally as important, not only were patients becoming more and more colonized with this organism, they've got a three-fold increase of bloodstream infections related to VRE. This is based on a presentation looking at empiric therapy for the febrile neutropenic. And at this hospital they had primarily used piperacillin as their empiric therapy for patients with fever and neutropenia. They switched from piperacillin to cefepime in 1999, and you can see there was appropriate differences between the use of the agents and that one intervention alone with nothing else being done resulted in an increase in their VRE colonization rate from 1.5 per thousand patient days up to 5.5 per thousand patient days. But equally as important, not only were patients becoming more and more colonized with this organism, they've got a three-fold increase of bloodstream infections related to VRE.

49. Prevention of GRETherapy for Febrile Neutropenia Purpose: reduce glycopeptide resistant enterococci (GRE) Situation: 50% colonization rate in oncology units Methods: Phase 1: no intervention (ceftazidime) Phase 2a and 2b: replace ceftazidime with piperacillin/tazobactam Phase 3: return to ceftazidime This is results from a study that came from the U.K. looking at glycopeptide-peptide resistant Enterococci in an oncology unit. The situation in this oncology unit was that about half of all the patients were colonized with glycopeptide-resistant Enterococci. And they participated in a three-phase study. In Phase 1 there was really no intervention, and ceftazidime was used for the initial therapy of febrile neutropenia. During Phase 2 which was divided into 2 4-month blocks, ceftazidime was replaced with piperacillin/tazobactam; and then during Phase 3 piperacillin/tazobactam was changed back to ceftazidime. This is results from a study that came from the U.K. looking at glycopeptide-peptide resistant Enterococci in an oncology unit. The situation in this oncology unit was that about half of all the patients were colonized with glycopeptide-resistant Enterococci. And they participated in a three-phase study. In Phase 1 there was really no intervention, and ceftazidime was used for the initial therapy of febrile neutropenia. During Phase 2 which was divided into 2 4-month blocks, ceftazidime was replaced with piperacillin/tazobactam; and then during Phase 3 piperacillin/tazobactam was changed back to ceftazidime.

50. Results And these are the results. During Phase 1 the colonization rate was 57%. There were five patients that were infected. During Phase 2A, 29%. During the last 4 months, down to 8%. And then when they switched back from piperacillin/tazobactam to ceftazidime, their colonization rate bump back up to 36%. Again, probably equally or perhaps more important than the colonization rate was during the use of piperacillin/tazobactam. There were no infections in contrast to five infections and three infections respectively during Phases 1 and Phase 3. And these are the results. During Phase 1 the colonization rate was 57%. There were five patients that were infected. During Phase 2A, 29%. During the last 4 months, down to 8%. And then when they switched back from piperacillin/tazobactam to ceftazidime, their colonization rate bump back up to 36%. Again, probably equally or perhaps more important than the colonization rate was during the use of piperacillin/tazobactam. There were no infections in contrast to five infections and three infections respectively during Phases 1 and Phase 3.

51. Antimicrobial Utilization and Resistance Interdisciplinary team in Indianapolis to control resistant organisms Interventions: Reduce third generation cephalosporin use Reduce imipenem use Encourage use of ampicillin/sulbactam and piperacillin/tazobactam Enhance compliance with infection control Education regarding antimicrobial resistance How did that impact outcome? Was it better, worse, or the same? Well, the reality is it was the same. There was no adverse patient outcome, and some people have even argued that the outcome was better because you reduce your nosocomial infection rate in half and you eliminated a resistant organism. So this is really an important illustration of how controlling antibiotics can address problems of resistance. This is a paper from the group in Indianapolis that looked at a multidisciplinary approach to controlling resistance, and what they decided was that they needed to target a couple antibiotics. They needed to reduce their use of third-generation cephalosporins, they needed to reduce the use of imipenem, and then they said that we have to have some alternative. So they encouraged the use of ampicillin/sulbactam for community-acquired infection and then piperacillin/tazobactam primarily for moderate to serious infection or for healthcare-associated infections. You've already heard that controlling antibiotics alone is probably not adequate and it does require an approach that includes both infection control and antibiotic control. And then they educated their staff regarding the problems of emerging antibiotic resistanc How did that impact outcome? Was it better, worse, or the same? Well, the reality is it was the same. There was no adverse patient outcome, and some people have even argued that the outcome was better because you reduce your nosocomial infection rate in half and you eliminated a resistant organism. So this is really an important illustration of how controlling antibiotics can address problems of resistance. This is a paper from the group in Indianapolis that looked at a multidisciplinary approach to controlling resistance, and what they decided was that they needed to target a couple antibiotics. They needed to reduce their use of third-generation cephalosporins, they needed to reduce the use of imipenem, and then they said that we have to have some alternative. So they encouraged the use of ampicillin/sulbactam for community-acquired infection and then piperacillin/tazobactam primarily for moderate to serious infection or for healthcare-associated infections. You've already heard that controlling antibiotics alone is probably not adequate and it does require an approach that includes both infection control and antibiotic control. And then they educated their staff regarding the problems of emerging antibiotic resistanc

52. Antimicrobial Utilization and Resistance And these are the results from their intervention that occurred over a 3-year period. They reduced vancomycin-resistant Enterococci from 16% down to 6%, some issues of gram-negatives, and they reduced their MRSA rate from 34% down to 23%.HAnd these are the results from their intervention that occurred over a 3-year period. They reduced vancomycin-resistant Enterococci from 16% down to 6%, some issues of gram-negatives, and they reduced their MRSA rate from 34% down to 23%.H

53. Impact of Formulary Changes on MRSA and Ceftazidime Resistant K. Pneumoniae Reduce usage of cephalosporins, imipenem, clindamycin and vancomycin Increased use of ?-lactam/?-lactamase inhibitors And this is Landman's study that suggested that prior antimicrobial therapy may be a risk factor for MRSA. And what they showed was that reducing the use of cephalosporins, imipenem, clindamycin, and vancomycin could result in a reduction in MRSA as well as ceftazidime-resistant Klebsiella. And this is Landman's study that suggested that prior antimicrobial therapy may be a risk factor for MRSA. And what they showed was that reducing the use of cephalosporins, imipenem, clindamycin, and vancomycin could result in a reduction in MRSA as well as ceftazidime-resistant Klebsiella.

54. Ceftazidime Resistant K. pneumoniaeCleveland VA Medical Center

55. Impact of a Rotating Empiric Antibiotic Schedule on Infectious Mortality in an Intensive Care Unit

56. Impact of a Rotating Empiric Antibiotic Schedule on Infectious Mortality in an Intensive Care Unit

57. Short Course Antibiotic TherapyHospital Acquired Pneumonia

58. Short Course Antibiotic TherapyHospital Acquired Pneumonia

59. In Conclusion:

60. Reduce Inappropriate Initial Antimicrobial Therapy Guidelines and goal directed protocols Broad spectrum and combination antibiotics ID consultation Automated antibiotic consultant! More selective and sensitive diagnostic methods

61. Efforts to Decrease the Rate of Emergent Antimicrobial Resistance CDC guidelines and barrier precautions Antibiotic restriction and appropriate utilization: Decrease cephalosporin use Increase extended-spectrum penicillin/beta-lactamase inhibitor use Limit carbapenem and vancomycin use to desired therapy Selective bowel decontamination Rotation antibiotics Short course antibiotic course: HAP But if outbreaks can be limited throughout control programs, there is still a lack of agreement about the efficacy of control measures. All the interventions mentioned in this slide had some degree of efficacy in large reported outbreaks. First, such as barrier precautions including cohorting of infected or colonized patients. Second, measures based in antibiotic policy, particularly third-generation cephalosporin restriction; and third, measures such as selective bowel contamination. But if outbreaks can be limited throughout control programs, there is still a lack of agreement about the efficacy of control measures. All the interventions mentioned in this slide had some degree of efficacy in large reported outbreaks. First, such as barrier precautions including cohorting of infected or colonized patients. Second, measures based in antibiotic policy, particularly third-generation cephalosporin restriction; and third, measures such as selective bowel contamination.

62. ConclusionJudicious Use of Antimicrobial Decrease cephalosporin use Increase extended-spectrum penicillin/beta-lactamase inhibitor use Limit carbapenem and vancomycin use to desired therapy

63. Handwashing compared to Alcohol Hand