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1、Choosing Antibiotics:Before and After the Culture ResultsGopi Patel,MDAugust 20,2010ProphylaxisEmpiricTargetedPicking AntibioticsWhat has the patient grown before?What is the patient growing now?What is the patient at risk for growing?What are the patients signs and symptoms?Antibiotic selectionRisk
2、 factors for drug resistanceRecent antimicrobial exposuresUnderlying comorbiditiesAllergiesRecent interventionsAvailable and previous culture dataHistory of MRSA,VRE,PseudomonasESBL-producing GNRThe flora and fauna of the hospitalAnd perhaps even the unit How sick is the patient?Can always“go big”an
3、d narrow as you get more informationJust to refresh your memoryCase 148 M IVDA admitted with fevers and chillsFresh track marks on Left armFebrile to 39 BP 70/55 HR 112 93%RAIII/VI systolic murmur at LLSBB/L cracklesChest X-ray-Congestion B/LEmpiric antibiotics?As expectedAt 14 hours both sets of bl
4、ood cultures are growing Gram-positive cocci in clustersPrevious history of MRSATTE cant rule out vegetation on mitral valveTEE refusedPatient grows MRSAVancomycin continuedVancomycinDiscovered in 1956Mechanism of actionInhibits bacterial cell wall synthesisBinds firmly to D-Ala-D-Ala of the peptido
5、glycan,preventing elongation and cross-linkingMechanism of resistanceAltered peptidoglycan binding siteD-Ala-D-Ala is replaced by D-Ala-D-lactateThickened cell wallLinear IgA Bullous DermatosisDosingMonitoringTroughs are most accurate and practical Obtain trough just prior to the next dose at steady
6、-state(usually after 4th dose)Levels should be maintained 10 mg/LMinimum troughs of 15-20 mg/L are recommended for severe or complicated infections(endocarditis,osteomyelitis,meningitis,and pneumonia)1 Am J Resp Crit Care Med.2005;171:338.2 Clin Infect Dis.2004;39:1267-84.3 Circulation.2005;111:e394
7、-e433.DaptomycinFDA approved in 2003Depolarizes the cell membrane and is rapidly bactericidal against Gram-positivesApproved for the treatment of complicated skin and skin structure infectionsS.aureus(including MRSA),GAS,Streptococcus agalactiae,and vanco-susceptible Enterococcus faecalisNot approve
8、d for E.faecium(CLSI breakpoint 4)Non-inferior to vanco and anti-staph penicillins in S.aureus bacteremia and right-sided endocarditis1Jury is out for left-sided endocarditisNOT indicated for treatment of pneumonia1 NEJM.2006;355(7):652-65 DosingUse actual body weightFor serious,life-threatening inf
9、ections dosing regimens of 8 to 12 mg/kg have been used1Requires 24-hour Antibiotic ApprovalIndicationCrCl(mL/min)DoseSSTI 30 30(HD)4 mg/kg every 24 hrs4 mg/kg every 48 hrsBacteremia 30100,000 CFU/mL GRAM NEGATIVE BACILLIIsolate 01 Klebsiella pneumoniae,an ESBL producerCONTACT PRECAUTIONSANTIBIOTICS
10、 Mic SYSTEMIC URINE Aztreonam 16 R Ceftriaxone 16 R*Cefepime 16 R*Cefuroxime 16 R*Tetracycline 4 S Ertapenem 2 S Gentamicin 4S Imipenem 4 S Levofloxacin 2 S Trimethoprim/Sulf16 R Ceftriaxone 16 R*Cefepime 16 R*Cefuroxime 16 R*Tetracycline 4 S Ertapenem 2 S Gentamicin 4S Imipenem 2 R Trimethoprim/Sul
11、f16/8 R Aztreonam 16 R Ceftriaxone 32 R Ceftazidime 16 R Ciprofloxacin 2R Cefepime 16 R Amikacin 32 R Ertapenem 4 R Gentamicin 8 R Levofloxacin 4 R Meropenem 8 R Piperacillin/tazo 64 R Trimethoprim/Sulf2/38 R Tetracycline 4 R Tobramycin 8 R Call an ID fellowSusceptibilities at MSH 2009CarbapenemGent
12、AmikTobraE.coli99%K.pneumoniae64%(E)76%70%55%P.aeruginosa86%(M)76%93%93%A.baumannii21%(I)29%45%40%E.cloacae76%(E)73%97%70%Other susceptibilitiesTigecyclinePolymyxinK.pneumoniae75%84%A.baumannii13%97%E.cloacae58%92%A.baumannii-38%susceptible to sulbactam component of amp-sulbactamCase 455 F DM,HTN,PV
13、D,ESRD on HDAdmitted with hyperglycemia/HONKTransferred out of MICU to 9W after stabilized on HD#3On HD#5 febrile to 38.7 and lethargicCXR orderedBlood cultures sentU/A and Urine cultures orderedCXRLateralEmpiric AntibioticsHospital-Acquired Pneumonia 48 hours after admissionVentilator-Associated Pn
14、eumoniaHealthcare-Associated PneumoniaHealthcare-associated PneumoniaMost recent guidelines emphasize obtaining lower respiratory tract culturesEarly,appropriate broad-spectrum antibiotics at the adequate dosesMicrobiology varies from one hospital to another and one unit to anotherNarrowing coverage
15、Shorter durationsThe role for anaerobic coverage and“aspiration pneumonia”Pip-tazo vs.CefepimePip-TazoProsAmpicillin-susceptible EnterococcusAnaerobesConsPotent inducer of beta-lactamase production“Higher salt load”CefepimeProsMore stable against many beta-lactamases including some ESBLsBetter GNR d
16、rug here at MSH?(personal opinion)CheaperConsNo activity against Enterococcus or Anaerobes“Aspiration”and the AnaerobeDo you need to add metronidazole or clindamycin?Rarely necessaryLevofloxacin and ceftriaxone have some anaerobic activityMost pneumonia arises from aspiration of bacteria colonizing
17、the oropharynx/nasopharynxAwful dentition(different from lack of dentition)Abscess formationUsually a more indolent presentationChemical pneumonitisAspiration of gastric contents vs.aspiration of bowel contentsWhere do anaerobes live?Use antibiotics with thoughtHelpful HintsWhat has the patient grow
18、n before?Previous antibiotic exposuresIf the patient is in contact isolation from admission chances are they grew something in the pastSCC is probably the best system to look at culturesWhat is the patient at risk for growing now?Previous antibiotic exposures Recent interventionsWhat is the patient
19、growing now?Narrow coverageLimiting antibiotic exposuresCall for adviceAntibiotic Approval 9407General ID 0649Transplant ID 8679Pop Quiz47 yo F s/p allo SCT 8/08 complicated by GVHD of the skin and gut,CMV viremia,and presumed aspergillus with worsening shortness of breath and B/L nodular infiltrate
20、sIntubated on 11C and comes to MICU on Linezolid,Imipenem,Tigecycline,Gentamicin,Azithromycin,Ambisome,and GanciclovirPop QuizSputum gram stain with 1-9 PMNs Blood cultures with GNR in aerobic bottle at 5 hoursWhat do you add?A.BactrimB.Inhaled colistinC.LevofloxacinD.Palliative care consultStenotrophomonas maltophiliaInherently resistant to CarbapenemsDrug of choice is TMP-SMXTMP-SMXLevoCeftazS.maltophilia98%88%47%