Multidrug-Resistant Organisms

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  • 1. Enzymatic degradation: Hydrolysis of the chemical structures of beta-lactam ring, aminoglycosides 2. Binding site mutation: Most common resistance mechanism for Gram-negative bacilli for fluoroquinolones 3. Decreased permiability: Loss of outer membrane protein, e.g. pseudomonas loss of OprD in outer membrane Pumps: 3 component protein system located on cytoplasmic membrane and outer membrane porin. 5. Gene transduction- transfer of gene from one organism to another.
  • Mechanism of Resistance- Resistance to methicillin confers resistance to all penicillinase-resistant penicillins and cephalosporins The resistance requires the presence of mecA gene that encode penicillin-binding protein 2a (PBP 2a) MecA genes originate from a different species of staphylococci. PBP= penicillin binding proteins- aka transpeptidase PBP 2a is involved in assembly of the bacteria cell wall. Penicillin have poor ability to inactivate this protein hence the cell wall continues to build without disruption.
  • What are the symptoms? The symptoms of a VRE infection depend on where the infection is. If VRE is causing a wound infection, that area of your skin may be red or tender. If you have a urinary tract infection , you may have back pain, a burning sensation when you urinate, or a need to urinate more often than usual. Some people with VRE infections have diarrhea, feel weak and sick, or have fever and chills.
  • Enterococcus faecium- treated with synercid (quinupristin and dalfopristin)
  • Definition: Standard precautions:
  • ESBLs are capable of efficiently hydrolyzing penicillins, narrow spectrum cephalosporins, many extended-spectrum cephalosporins, the oxyimino group containing cephalosporins (cefotaxime, ceftazidime), and monobactams (aztreonam). Beta-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) generally inhibit ESBL producing strains.
  • How can I prevent VRE? As more antibiotic-resistant bacteria develop and more cases of VRE are documented, hospitals and other healthcare facilities are taking extra care to practice infection control, which includes frequent hand-washing and isolation of patients infected with VRE. Even though most healthy people are not at risk for becoming infected or colonized with VRE, you can take steps to prevent getting VRE. Practice good hygiene. Keep your hands clean by washing them thoroughly with soap and warm water or using an alcohol-based hand sanitizer. Hand-washing is the best way to avoid infection of any kind. Keep cuts and scrapes clean and covered with a bandage and avoid contact with other people’s wounds or bandages. Do not share personal items such as towels or razors. Keep your environment clean by wiping frequently touched surfaces (such as countertops, doorknobs, and light switches) with a disinfectant, especially if someone in the house has VRE. Be smart about using antibiotics. Know that antibiotics can help treat bacterial infections but they cannot cure viral infections. Always ask your doctor if antibiotics are the best treatment, and avoid pressuring your doctor into prescribing antibiotics when he or she thinks they won't help you get better. Always take all your antibiotic medicine as prescribed by your doctor. If you use only part of the medicine, it may not cure your infection. Also, it can cause antibiotic-resistant bacteria to develop. Do not save any antibiotics, and do not use antibiotics that were prescribed for someone else or for a different problem. If you are in the hospital, remind doctors and nurses to wash their hands before they touch you.
  • Clostridium difficile assocated Disease (CDAD) is now called clostridium difficile Toxic megacolon is characterized by extreme inflammation and distention of the colon. Symptoms are: pain, distention of the abdomen, fever, tarchycardia and dehydration. This is a medical emergency. 3. Pseudomembranous colitis: The Clostridium difficile bacteria is normally present in the intestine. However, it may overgrow when antibiotics are taken. The bacteria release a powerful toxin that causes the symptoms. The lining of the colon becomes inflamed and bleeds, and takes on a characteristic appearance called pseudomembranes.
  • Estimates: 13% of patient with 2 weeks of hospital stay develop C.Diff 50% of patients with more than 4 weeks develop C.Diff
  • Multidrug-Resistant Organisms

    1. 1. Multidrug-Resistance Organisms & Clostridium difficile Presented by: Peter Ndaraya Mercer College of Pharmacy WellStar Hospital- Paulding June 2009
    2. 2. Objectives <ul><li>Describe MDROs </li></ul><ul><li>Review development of MDRO resistance </li></ul><ul><li>Describe Clostridium difficile </li></ul><ul><li>Present a case of a patient with Clostridium Difficile Associated Diarrhea (CDAD) </li></ul>
    3. 3. MDRO: Definition <ul><li>Multidrug-Resistant Organisms (MDROs) are defined as microorganisms that are resistant to one or more classes of antimicrobial agents. </li></ul><ul><li>Three most common MDROs are: </li></ul><ul><ul><li>1. Methicillin-Resistant Staph aureus (MRSA) </li></ul></ul><ul><ul><li>2. Vancomycin Resistant Enterococci : (VRE) </li></ul></ul><ul><ul><li>3. Extended Spectrum Beta-Lactamase producing Enterobacteria. (ESBLs) </li></ul></ul>CDC: Management of Multidrug-Resistant Organisms in Healthcare Settings, Healthcare Infection Control Advisory Committee, Jane D. Siegel et. al. pg 7-12
    4. 4. Epidemiology of MDROs <ul><li>Trends </li></ul><ul><ul><li>Prevalence varies temporarily, by regions, and by health care facilities. </li></ul></ul><ul><ul><li>Type and level of care influence prevalence </li></ul></ul><ul><ul><li>Prevalence in United States hospitals has increased steadily </li></ul></ul>CDC: Management of Multidrug-Resistant Organisms in Healthcare Settings, Healthcare Infection Control Advisory Committee, Jane D. Siegel et. al. pg 7-12
    5. 5. Epidemiology cont’d <ul><li>Percentages of isolates of the organisms that developed resistance in the United States </li></ul>CDC: Management of Multidrug-Resistant Organisms in Healthcare Settings, Healthcare Infection Control Advisory Committee, Jane D. Siegel et. al. pg 7-12 Organism Year MRSA VRE 1990 20-25% 1-15% 1999 > 50% 25% 2003 > 59.5% 28.5%
    6. 6. Implication of MDROs <ul><li>Increase hospital stay </li></ul><ul><ul><li>Average 3-5 additional days </li></ul></ul><ul><li>Increase hospital costs </li></ul><ul><li>Increase morbidity and mortality </li></ul>CDC: Management of Multidrug-Resistant Organisms in Healthcare Settings, Healthcare Infection Control Advisory Committee, Jane D. Siegel et. al. pg 7-12
    7. 7. Causes of Resistance in MDROs <ul><li>Enzymatic degradation </li></ul><ul><li>Mutation at binding site </li></ul><ul><li>Down regulation of outer membrane proteins </li></ul><ul><li>Efflux pumps </li></ul><ul><li>Transduction of genes </li></ul>
    8. 8. Bacteria Outer Membrane <ul><li>Uppermost layer contains lipopolysaccharide (LPS) for Gram (-ve) </li></ul><ul><ul><li>Lipid portion is an endotoxin- stimulates immune response, fever… </li></ul></ul><ul><li>Special channels (porins) allow passage of small molecules and drugs </li></ul>
    9. 9. Mechanisms of Resistance: Efflux <ul><li>Active, energy dependent pumps cause efflux of drugs </li></ul>Bacterial Cytosol PG layer Outer membrane drug Efflux pump
    10. 10. Mechanisms of Resistance: Efflux <ul><li>Active, energy dependent pumps can also cause efflux of drugs </li></ul>
    11. 12. 1.Methicillin-Resistant Staph aureus (MRSA) <ul><li>These are organisms that are not sensitive to common penicillin based drugs such as methicillin, amoxicillin, penicillin, oxacillin 1 </li></ul><ul><li>Normal flora- lives on human skin, noses, vaginal tract </li></ul><ul><li>May cause infections if enters the body </li></ul><ul><li>Contagious- through person to person contact </li></ul><ul><li>Treatment - Vancomycin </li></ul>
    12. 13. 2. Vancomycin Resistant Enterococci (VRE) <ul><li>Enterococci resistant to Vancomycin </li></ul><ul><li>Present in human body such as urinary tract and GI tract. </li></ul><ul><li>Contagious </li></ul><ul><li>Hospital patients can get it from contact via health care providers. </li></ul><ul><li>Normal flora that may cause disease especially in vulnerable populations: </li></ul><ul><ul><li>Eg elderly, children and immunocompromised patients. </li></ul></ul>
    13. 14. VRE cont’d <ul><li>VRE include: </li></ul><ul><ul><li>Enterococcus faecalis </li></ul></ul><ul><ul><li>Enterococcus faecium </li></ul></ul><ul><ul><ul><li>Treated with Synercid (quinupristin and dalfopristin) </li></ul></ul></ul><ul><li>VRE can live on surfaces for up to 7 days!!! </li></ul><ul><ul><li>Haemophilus influenzae lives about 2 days </li></ul></ul>Drugs.com: http://www.drugs.com/cg/vancomycin-resistant-enterococcus.html Accessed June1st 2009
    14. 15. Transmission of VRE Center for Disease Control and Prevention: http://www.cdc.gov/ncidod/eid/vol3no3/mcdonald.htm , Accessed June 17 th 2009
    15. 16. VRE prevention <ul><li>Standard precautions </li></ul><ul><ul><li>Hand hygiene </li></ul></ul><ul><ul><li>Personal Protective Equipment (PPE) </li></ul></ul><ul><ul><li>Needlestick and sharps injury prevention. </li></ul></ul><ul><ul><li>Cleaning & disinfection </li></ul></ul><ul><ul><li>Respiratory hygiene (Cough Etiquette) </li></ul></ul><ul><ul><li>Waste disposal </li></ul></ul><ul><ul><li>Safe injection practices </li></ul></ul>Center for Disease Control and Prevention: http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf Accessed June 17 th 2009   Wisconsin Department of Health Services: http://dhs.wisconsin.gov/communicable/InfectionControl/StdPrecautions.htm , Accessed July 17 th 2009.
    16. 17. 3. Extended Spectrum Beta-Lactamase producing Enterobacteria. (ESBL) <ul><li>ESBLs are plasmid-mediated beta lactamases described in gram negative bacilli 2 </li></ul><ul><ul><li>Eg. Klebsiella, Acinebacter </li></ul></ul><ul><li>MOA – hydrolysis of beta- lactam ring in </li></ul><ul><ul><li>Penicillins </li></ul></ul><ul><ul><li>Narrow spectrum cephalosporins </li></ul></ul><ul><li>Beta-lactamase inhibitors inhibit ESBL producing strains </li></ul><ul><ul><li>Clavulanic acid </li></ul></ul><ul><ul><li>Sulbactam </li></ul></ul><ul><ul><li>Tazobactam . </li></ul></ul>
    17. 18. Enzymatic degradation of ESBLs: Mechanisms of  -lactamase N O N O OH S CH 3 CH 3 O R H  -lactamase CH 2 OH  -lactamase CH 2 OH N O N O OH S CH 3 CH 3 O R H  -lactamase CH 2 O H H 2 O N O N O OH S CH 3 CH 3 O R H H OH  -lactamase CH 2 OH + Hydrolysis of Oxyimino group Penicillin drug Inactivated drug
    18. 19. Other Drug Resistant Diseases <ul><li>Extensively-Drug Resistant Tuberculosis (XDR-TB) </li></ul><ul><ul><li>This is a TB causing organism that is resistant to almost all drugs that are used to treat TB. </li></ul></ul><ul><ul><ul><li>Isoniazid </li></ul></ul></ul><ul><ul><ul><li>Rifampin </li></ul></ul></ul><ul><ul><ul><li>Fluoroquinolones </li></ul></ul></ul><ul><ul><ul><li>At least one of: Amikacin, kanamycin, capreomycin </li></ul></ul></ul><ul><ul><li>The main cuasitive organism is M ycobacterium tuberculosis 3 </li></ul></ul><ul><ul><li>Contagious through droplets but slower than viral infection such as flu </li></ul></ul>
    19. 20. MDROs prevention <ul><li>Observe the universal standard precautions </li></ul><ul><li>Practice 200% percent safety rule </li></ul><ul><li>Good hygiene practice </li></ul><ul><ul><li>Frequent hand wash </li></ul></ul><ul><ul><li>Cover cuts and scrapes </li></ul></ul><ul><ul><li>Do not share personal items eg razors </li></ul></ul><ul><li>Do not pressure doctors for antibiotics </li></ul><ul><li>Finish all antibiotic medications </li></ul><ul><li>Health care providers to wash hands before touching patients </li></ul><ul><li>Isolation for serious cases </li></ul>
    20. 21. Clostridium difficile <ul><li>Clostridium difficile ( C. diff ) is a gram positive bacteria of the clostridium genus. </li></ul><ul><li>Contagious- especially in hospitals through contact </li></ul><ul><li>Responsible for Clostridium difficile Infection (CDI) </li></ul><ul><ul><li>Infections include: </li></ul></ul><ul><ul><ul><li>Uncomplicated diarrhea (CDAD) </li></ul></ul></ul><ul><ul><ul><li>Toxic megacolon </li></ul></ul></ul><ul><ul><ul><li>Pseudomembranous colitis </li></ul></ul></ul><ul><li>These diseases can lead to fulminant sepsis and death </li></ul>
    21. 22. Clostridium difficile Clostridium difficile: http://www.kaiscience.com/ph_163-Clostridium_difficile_Copyright_Dennis_Kunkel_Microscopy Accessed June 1st 2009 C. Diff is a gram positive rod of clostridium species
    22. 23. Toxic megacolon All Refer health: http://health.allrefer.com/health/toxic-megacolon-pictures-images.htm Accessed June 15 th 2009l
    23. 24. Pseudomembranous colitis http://www.tommyroshek.com/log/uploaded_images/pseudomembranes-748375.JPG Accessed, June 15 th 2009
    24. 25. Pathogenesis of Clostridium difficile infection American Family Physician: http://www.aafp.org/afp/20050301/921.html , Accessed June 14, 2009 13% with 2 weeks hospitalization 50% after 4 weeks hospitalization
    25. 26. C. diff treatment <ul><li>1 st line Metronidazole </li></ul><ul><ul><li>Dose </li></ul></ul><ul><ul><ul><li>Adults: 500 mg po TID for 10-14 days </li></ul></ul></ul><ul><ul><ul><li>Children: 15-35 mg/kg/ day po TID </li></ul></ul></ul><ul><li>2 nd line Vancomycin </li></ul><ul><ul><li>Dose </li></ul></ul><ul><ul><ul><li>Oral: 125-250mg po QID </li></ul></ul></ul><ul><ul><ul><ul><li>Oral dosing is more effective than IV </li></ul></ul></ul></ul><ul><ul><ul><li>Rectal enema: 500mg once daily </li></ul></ul></ul>http://www.ohsu.edu/medicine/residency/handouts/pharmpearls/Gastrointestinal/GuidelinesForTreatmentOfCdiffi.pdf , Accessed June 17 th 2009
    26. 27. Patient Case http://www.clipartguide.com/_pages/0060-0808-1313-1328.html , Accessed June 17 th 2009 Ouch!!!
    27. 28. Patient Case <ul><li>CC -EE is a 68-year-old caucasian male who presented in the hospital with a chief complain of diarrhea and abdominal pain. </li></ul><ul><li>HPI - Came back to hospital 30 days since last discharge after C.diff colitis treatment. Has diarrhea x10 per day, watery stool, foul smell, abdominal pain on & off. </li></ul><ul><li>PMH - CAD, CABG, Diabetes mellitus, C. difficile colitis </li></ul><ul><li>Allergies - sulfa, penicillin </li></ul><ul><li>Vital Signs : </li></ul><ul><ul><li>Admission: BP=119/77, HR=66, R=20, T=97, pulse oximetry 98% on room air </li></ul></ul><ul><ul><li>Current: BP=120/63, HR=60 irregular, R=20, O2 sat= 99% on room air </li></ul></ul><ul><li>Labs : WBC 6.8, Hb 14.0, hematorict 41, platelets 98, Sodium 136, Potassium 4.3, Amylase 59, lipase 33, </li></ul>
    28. 29. Patient Case cont’d <ul><li>Home Medications: </li></ul><ul><ul><li>Spironolactone 25mg 2 tablets p.o. daily </li></ul></ul><ul><ul><li>Coreg 3.125mg p.o. b.i.d. </li></ul></ul><ul><ul><li>Lasix 40mg p.o. daily </li></ul></ul><ul><ul><li>Novolin N 35 to 50 units SC b.i.d. p.r.n. </li></ul></ul><ul><ul><li>Lactinex </li></ul></ul><ul><ul><li>Glipizide </li></ul></ul><ul><ul><li>The patient says he is not taking asprin as it causes nosebleeds </li></ul></ul>
    29. 30. Patient case cont’d <ul><li>Hospital Medications: </li></ul><ul><ul><li>Insulin regular 1U-10U SC ACHS </li></ul></ul><ul><ul><li>Fondaparinux 2.5mg SC Q24H </li></ul></ul><ul><ul><li>Pantoprazole 40mg po ACB </li></ul></ul><ul><ul><li>Vancomycin 500mg/10ml po QID x 2 days </li></ul></ul><ul><ul><li>Metronidazole 500 mg IV Q6H X 3 days </li></ul></ul><ul><ul><li>Lactobacillus 1 cap po TID </li></ul></ul><ul><ul><li>Colesevelam 1,250mg po BIDWM </li></ul></ul><ul><ul><li>Spironolactone 50mg po Daily </li></ul></ul><ul><ul><li>Carvedilol 3.125mg po BID </li></ul></ul><ul><ul><li>Furosemide 40mg po Daily </li></ul></ul><ul><ul><li>Glipizide 5mg po ACB </li></ul></ul><ul><ul><li>Lidocaine 2% (lidocaine jet) prn </li></ul></ul>
    30. 31. Assessment and Plan <ul><li>1. Colitis, probably clostridium difficile . </li></ul><ul><ul><li>Patient was recently discharged with C.diff colitis. He had same symptoms: diarrhea and abdominal pain. </li></ul></ul><ul><ul><li>He was started on Flagyl 500mg IV q8 hours and Vancomycin 500mg po q.i.d. </li></ul></ul><ul><li>2. History of Coronary Artery Disease. </li></ul><ul><ul><li>Patient is stable and will continue coreg </li></ul></ul><ul><ul><li>Not on any blood thinners </li></ul></ul><ul><li>3. Diabetes Mellitus, type 1. He is currently on sliding scale insulin. Currently on liquid diet. His sugars will be monitiored closely. </li></ul><ul><li>4. Congestive heart failure. The patient is stable and will continue on Lasix, Adactone and coreg. </li></ul><ul><li>5. Thrombocytopenia. This is probably secondary to liver dysfunction. He is stable. </li></ul><ul><li>6. Skin ulcers. Wound care was consulted . </li></ul>
    31. 32. Clinical course <ul><li>The labs were positive for C. diff </li></ul><ul><li>Had recurrent diarrhea. </li></ul><ul><li>Was on metronidazole IV and vancomycin IV one time but redeveloped diarrhea after one week. </li></ul><ul><li>Responded well to vancomycin </li></ul>
    32. 33. Discharge <ul><li>Discharged after four days with; </li></ul><ul><ul><li>Vancomycin 250mg p.o. qid x 3 weeks </li></ul></ul><ul><ul><li>Probiotics </li></ul></ul><ul><ul><li>Continue all other home medications prior to admission </li></ul></ul><ul><li>Condition: At the time of discharge, the patient was afibrile, tolerating oral intake, no abdominal pain, still had diarrhea but formed stool </li></ul><ul><li>Recent labs: WBC 4.4, Hb 14, hematocrit 40 </li></ul>
    33. 34. Patient case comment <ul><li>The patient had failed initial treatment with metronidazole. </li></ul><ul><li>Patient was started on both metronidazole IV and oral vancomycin. This was appropriate because the regimen provided double coverage and enhanced killing of C. diff . </li></ul><ul><li>The patient was discharged with vancomycin 250mg q.i.d. for 3 weeks. This was appropriate because the guidelines indicate for vancomycin when failure with metronidazole occurs after 5 days of treatment. 4 </li></ul><ul><li>According to the literature, there is evidence that probiotics can treat recurrent C.diff 5 . Therefore, inclusion of probiotics was appropriate. </li></ul><ul><li>Vancomycin may kill some of the normal flora and hence potential for C. diff overgrowth. Probiotics would re-establish normal flora and keep C.diff under control. </li></ul>
    34. 35. Home at last!
    35. 36. Reference <ul><li>WebMD: http://www.webmd.com/skin-problems-and-treatments/understanding-mrsa-methicillin-resistant-staphylococcus-aureus Accessed June 15 th , 2009. </li></ul><ul><li>John Hopkins: http://www.hopkinsmedicine.org/heic/ID/esbl/ Accessed June 15 th 2009 </li></ul><ul><li>Healia: http://www.healia.com/healthguide/guides/tuberculosis/what-causes-tuberculosis Accessed June 15 th 2009 </li></ul><ul><li>http://www.ohsu.edu/medicine/residency/handouts/pharmpearls/Gastrointestinal/GuidelinesForTreatmentOfCdiffi.pdf , Accessed June 17 th 2009 </li></ul><ul><li>Meta-Analysis of Probiotics for the Prevention of Antibiotic Associated Diarrhea and the Treatment of Clostridium difficile Disease; Lynne V. McFarland, American Journal of Gastroenterology. ISSN 0002-9270 pg 812-822 </li></ul>

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