Transactions of the Korean Nuclear Society Autumn Meeting PyeongChang, Korea, October 25-26, 2007 Long Term Asset Management (LTAM) Strategy for Feedwater Heater at Kori 3 & 4 Nuclear Power Plants Se Youl Won and Young Sheop Park Nuclear Engineering & Technology Institute, Korea Hydro & Nuclear Power Co. Ltd., 25-1 Yuseong-Gu, Daejeon, KOREA, 305-343, [email protected]
12sat handouts.inddJanuary 20-22, 2012
Des Moines Marrio , 700 Grand Avenue, Des Moines, IA
Session 3: New Evidence-Based
Clinical Prac ce Guidelines
C: Treatment of MRSA Infec ons in
Adults and Children
4:15pm - 5:15pm
ACPE UAN 107-000-12-025-L01-P
Ac vity Type: Applica on-Based
Program Objec ves for Pharmacists: Upon compleƟ on of this CPE acƟ vity parƟ cipants should be able to:
1. Summarize an microbials used in the treatment of MRSA infec ons
2. Apply knowledge of clinical prac ce guidelines to recommend therapy for MRSA infec ons
3. Use guidelines to provide dosing and monitoring sugges ons for vancomycin
4. Iden fy clinical situa ons where alterna ve therapies may be appropriate
5. Recognize important considera ons for pediatric pa ents
Speaker: Erika J. Ernst, PharmD, is an Associate Professor of Pharmacy at the University of Iowa and clinical
pharmacy specialist in infec ous diseases at UIHC where she also serves on the pharmacy and therapeu cs and
an bio c advisory commi ees. She received her PharmD from the University of Southern California where she
also completed a pharmacy prac ce residency. She went on to complete an infec ous diseases fellowship at
the University of California, San Francisco prior to joining the faculty at the University of Iowa. Her prac ce and
research interests are in an microbial u liza on and resistance. In addi on to having several publica on in the
infec ous diseases literature, she is also the President-elect of the Society of Infec ous Diseases Pharmacists.
Speaker Disclosure: Erika Ernst does not report any actual or poten al confl icts of interest in rela on to this CPE
ac vity. Oﬀ -label use of medica ons will be discussed during this presenta on.
Faculty Disclosure Treatment of MRSA Infections in Erika Ernst reports she has no actual or potential conflicts of interest associated with this presentation. Adults and Children Erika Ernst has indicated that off-label use of medication will be discussed during this presentation.
Erika J. Ernst, Pharm.D.
Associate Professor University of Iowa College of Pharmacy Learning Objectives Pre-Assessment Questions Upon completion of this activity pharmacists will be able to: Select the desirable serum level for vancomycin.
Summarize antimicrobials used in the treatment of MRSA infections Apply knowledge of clinical practice guidelines to recommend therapy for MRSA infections Use guidelines to provide dosing and monitoring suggestions for vancomycin d. None of the above, measuring serum levels is not necessary Identify clinical situations where alternative therapies may be appropriate Which of the following have activity against MRSA? Recognize important considerations for pediatric patients a. Clindamycin (Cleocin)b. TMP/SMX (Bactrim)c. Doxycycline (Vibramycin)d. Vancomycin (Vancocin)e. All of the above First guideline on treatment of MRSA from IDSA.
Clinical Practice Guidelines by the Infectious Diseases Primary objective to provide recommendations on Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults management of clinical syndromes caused by MRSA.
Address vancomycin dosing and monitoring, susceptibility Catherine Liu,1 Arnold Bayer,3,5 Sara E. Cosgrove,6 Robert S. Daum,7 Scott K. Fridkin,8 Rachel J. Gorwitz,9Sheldon L. Kaplan,10 Adolf W. Karchmer,11 Donald P. Levine,12 Barbara E. Murray,14 Michael J. Rybak,12,13 David testing and use of alternate therapies A. Talan,4,5 and Henry F. Chambers1,2 Clinical Infectious Diseases 2011; 52(3):e18-e55 Do not address Surveillance testing or infection-prevention strategies Antimicrobial Therapy Skin and Soft tissue Adjunctive therapies for infections (SSTIs) Recurrent SSTIs Vancomycin dosing and Bacteremia and Infective Rifampin – in combo Susceptibility Testing Gentamicin – in combo Persistent Bacteremia & Bone and Joint Infections "treatment failures" CNS Infections 44 year old male with 3 days of enlarging painful area on For abscesses Incision and Drainage is the most important right forearm. There is an apparent fluctuant collection. The man is afebrile with normal blood pressure and pulse. Antibiotics indicated for abscesses with What is the most important factor in the management of this Severe disease (associated with cellulitis or rapidly progressive) Signs of systemic illness a. Incision and drainage of the fluid collection.
Immune suppressed b. Oral antimicrobial therapy .
Extremes of age c. I & D plus oral therapy to cover MRSA.
Difficult to drain (face, hand) Failure of prior I&D Microbiology of Purulent SSTIs Oral therapy for purulent cellulitis Adult Dose
<45 kg 2 mg/kg/dose (TMP component) PO every 12 h; >45 kg adult dose B-hemolytic strep 10-13 mg/kg/dose PO every 6-8 h 10 mg/kg/dose PO every 8 h NTE 600 mg/dose Oral therapy for NON-purulent cellulitis Adult Dose
25-50 mg/kg divided every 6-12 h 15 mg/kg IV Q8-12h 10 mg/kg/dose PO/IV every 8 h <40 kg: 3.125 to 6.25 mg/kg >40 kg: 125 to 250 mg every 6 h Study ongoing clincaltrials.gov 10-13 mg/kg/dose every 6-8 h 600 mg IV/PO Q12 h Under study: <75 kg: 8 mg/kg >75 kg: 600 mg 10 mg/kg/dose every 8 h NTE 600 mg/dose 10-13 mg/kg/dose PO/IV every 6-8 h NTE 40 mg/kg/day Management of Recurrent SSTIs A patient asks for advice for her child who is having Personal hygiene / Wound Care recurrent MRSA skin infections. She asks if there is anything Cover draining wounds she can do to help with these recurrent infections. What is Hand hygiene after touching infected skin an appropriate response for this patient? Avoid reusing / sharing personal items Environmental hygiene a. Recommend she see an Infectious Disease Specialist Clean high touch surfaces b. Suggest she request oral antibiotics for decolonization Decolonization c. Suggest she cover draining wounds and emphasize hand Mupirocin BID for 5-10 days Mupirocin BID for 5-10 days plus topical skin antiseptic d. Recommend her dogs and cats be tested for MRSA to (chlorhexidine) x 5-14 days determine if they are a source of infection Dilute bleach baths (1 tsp per gallon; ¼ cup per ¼ tub) for 15 min twice weekly for 3 months Oral antibiotics NOT recommended for decolonization MRSA bacteremia and Endocarditis Adult Dose
15 mg/kg IV Q 8-12 15 mg/kg IV Q 8-12 h 10 mg/kg/dose PO/IV every 8 h 10-13 mg/kg/dose PO/IV every 6-8 h NTE 40 mg/kg/day Linezolid not recommended for bacteremia or endocarditis due to increased Daptomycin not used for pneumonia – inactivated by pulmonary surfactant- mortality when organism is not known.
but may be use in patients with hematogenous septic pulmonary emboli as a complication of bacteremia/endocarditis.
Tigecycline not recommended for hospital acquired pneumonia or ventilator associated pneumonia due to increased mortality.
Vancomycin Treatment Failure Vancomycin Treatment Failure Persistent MRSA bacteremia Persistent MRSA bacteremia Definition of treatment failure Search for focus of infection with surgery or drainage Median time to clearance of bacteremia Daptomycin (if susceptible) in combination with another MSSA with B-lactam – 3-4 days MRSA with Vanco – 7-9 days Overall clinical response Vancomycin serum concentrations TMP/SMX IV 5 mg/kg Q12 h Susceptibility testing results (vanco MIC) Foci of infection Prior treatment with vanco and elevated vanco MICs are associated with elevated Dapto MICs Vancomycin Treatment FailurePersistent MRSA bacteremia MRSA Bone and Joint Infections If reduced susceptibility to vanco and dapto Adult Dose
15 mg/kg IV Q 8-12 h 10 mg/kg/dose PO/IV every 8 h NTE 600 mg/dose 10-13 mg/kg/dose PO/IV every 6-8 h NTE 40 mg/kg/day TMP/SMX plus rifampin 3.5-4 mg/kg/dose PO/IV every 8-12 h600 mg PO QD (300-450 mg PO BID) MRSA CNS infections Adjunctive therapies Adult Dose
Protein synthesis inhibitors (eg. Clindamycin or linezolid) 15 mg/kg IV Q 8-12 h and IVIG are not routinely recommended as adjunctive 10 mg/kg/dose PO/IV every 8 h NTE 600 mg/dose Some limited in vitro and animal model data exist but has some conflicting results Vancomycin Dosing and Monitoring Vancomycin Target Vancomycin 15 mg/kg (total body weight) max 2 gm.
Trough of 15 estimates an AUC of 400.
AUC of > 400 has been associated with improved clinical Q 8 hours suggested for Age < 40 and Scr < 1.4 Q12 hours suggested for age 40-65 and Scr < 1.4 Higher troughs (> 20) have been associated with increased Q24 hours suggested for age >65 or Scr >1.4 (regardless of age) Loading dose (25-30 mg) may be considered for seriously ill or Elevated vancomycin MICs (> 2 mcg/ml) have been obese patients (max 3-4 gm). associated with increased likelihood of vancomycin failure Measure trough at steady state (prior to 4th or 5th dose-when dosing interval selected as above) if patient will remain on vancomycin.
A 72 year old 61 kg female with a Scr of 1.3 is started on She was not at steady state when the level was taken after the vancomycin 1 gm Q 12 h for cellulitis that did not respond 3rd dose, she continued to accumulate drug leading to renal to oral antibiotics. After the 3rd dose a vancomycin level is insufficiency. Her level was taken too early and she was obtained an the level is 14 mcg/ml. She is sent home that discharged prematurely evening to continue receiving vancomycin by home care.
A more appropriate starting dose and monitoring plan would She will have a Scr 2x/week and vanco level in 1 week.
have been 15 mg/kg (915 mg) rounded up to 1 gram given He Scr rises to 1.6. She is feeling poorly and is now every 24 hours. Draw the serum level after the 3rd dose.
Perhaps could have been discharged but the level in the home She is readmitted and her Scr is 1.7 and her vancomycin level environment would have occurred the next day.
taken 12 hours after a dose is 37 mcg/ml Clindamycin (Cleocin) Ceftaroline (Teflaro) FDA approved for S. aureus infections FDA approved for SSTI and CAP Bacteriostatic – not recommended for endovascular Cephalosporin with MRSA activity (high affinity for penicillin binding protein (PBP) 2a Excellent tissue penetration Safety profile similar to ceftriaxone Limited CSF penetration D-zone test for detection of inducible clindamycin resistance in Erythromycin-resistant, Clindamycin susceptible isolates Diarrhea occurs in up to 20% of patients Oral suspension not well tolerated (may need to add Daptomycin (Cubicin) Linezolid (Zyvox) FDA approved for adults with S. aureus bacteremia, right FDA approved for SSTI and nosocomial pneumonia caused by sided endocarditis and cSSTI.
MRSA in adults and children Bacteriostatic Not used for MRSA pneumonia (inactivated by surfactant) 100% oral bioavailability; only use IV if patient unable to take Highly protein bound; renally excreted Elevation of CPK is most common adverse effect (monitor Hematologic toxicity, thrombocytopenia, anemia, Eosinophilic pneumonia has been reported Peripheral and optic neuropathy and lactic acidosis Weak non-selective MAOI inhibitor – has been associated with serotonin syndrome in pts taking SSRI Telavancin (Vibativ) FDA approved for cSSTI in adults and children > 16 yrs FDA approved for cSSTI in adults Inhibits protein synthesis but the combo is bactericidal Arthralgias, myalgias, nausea and infusion-related reactions.
Nephrotoxicity is more common than vancomycin Monitor Scr, drug level monitoring not available Taste disturbances, nausea, headache, foamy urine Adverse fetal outcomes in animal studies, potential for abnormal fetal development TMP/SMX (Bactrim) Vancomycin (Vancocin) Not FDA approved for staphylococcal infections, however FDA approved for the treatment of MRSA infections 95-100% of CA-MRSA strains are susceptible in vitro Slowly bactericidal Hyperkalemia – especially in elderly patients on renin- Possible emergence of resistant strains angiotension inhibitors or with chronic renal insufficiency.
Tissue penetration is variable (limited penetration into bone, Not recommended in third trimester of pregnancy or in lung epithelial lining fluid and CSF).
infants under 2 months due to possibility of kernicterus.
Renal toxicity at higher doses Monitor Scr, and drug levels Doxycycline (Vibramycin)/Minocycline (Minocin) Tigecycline (Tygacil) FDA approved for SSTI due to S. aureus but not specific for FDA approved for cSSTI and intraabdominal infections Glycylcycline, derivative of minocycline In vitro activity against MRSA Bacteriostatic Bacteriostatic High tissue concentrations; low serum concentrations Some isolates R to doxycycline may be S to minocycline FDA warning for serious infections to consider alternative Not recommended in pregnancy or children < 8 yrs agents due to increased all cause mortality in clinical trials of tigycycline Nausea and vomiting are common adverse effects Not recommended in pregnancy or children Rifampin (Rifadin) Gentamicin (Garamycin) Bactericidal activity agains S. aureus, achieves high levels and Bactericidal penetrated biofilm Used in combination, not used as primary therapy Do not use alone, resistance develops rapidly Nephrotoxicity and ototoxicity Do not use until blood cultures are negative Role not clearly defined Drug interactions Post-Assessment Questions A 6 year old child has cellulitis associated with a recent A 26 year old male is admitted for a knee injury sustained abrasion. The area is red, swollen, warm to the touch, but playing sports. Following reconstruction he develops an there is no apparent fluid collection or pus. She is allergic to MRSA wound infection. He is otherwise healthy. His Serum ampicillin (rash). Select the most appropriate treatment.
creatinine is 0.8 and he weighs 100 kg. He will receive vancomycin 15 mg/kg. You suggest the vancomycin be given b. Every 12 hours d. By continuous infusion A 65 year old male is admitted for MRSA bacteremia. His A 45 year old female is seen for purulent cellulitis that was vancomycin MIC is 2 (S); Daptomycin MIC is 0.5 (S) and drained but hasn't healed. She takes sertraline (zoloft) for Linezolid MIC is 0.5 (S). He takes atorvastatin (Lipitor) and depression. Select the most appropriate therapy.
lisinopril (Zestril). Select the most appropriate therapy.
d. Any of the above Continuing Pharmacy Education A 38 year old HIV positive male is admitted with signs and Go to www.GoToCEI.org click on My Portfolio
symptoms of pneumonia. Sputum grows MRSA. Blood Scroll down to Take Exam – Enter Access Code: (case
cultures are negative. Which of the following should NOT be used to treat this infection.
New vidence-Based Clinical Practice Guidelines:
Treatment of MRSA Infections in Adults and Children
What went wrong? (Assessment)
A 72 year old 61 kg female with a Scr Patient problems:
of 1.3 is started on vancomycin 1 gm Q 12 h for cellulitis that did not Cellulitis
respond to oral antibiotics. After the 3rd dose a vancomycin level is obtained an the level is 14 mcg/ml. Acute Renal Failure
She is sent home that evening to continue receiving vancomycin by She will have a Scr 2x/week and vanco level in 1 week. He Scr rises to 1.6. She is feeling System problems:
poorly and is now confused. She is readmitted and her Scr is 1.7 Her vancomycin level was assessed
and her vancomycin level taken 12 before reaching steady state and she
hours after a dose is 37 mcg/ml was discharged home too early/with
Hold vancomycin. Monitor Scr. Plan to restart vancomycin with prolonged interval.
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