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 resistance Recent antimicrobial exposuresUnderlying comorbidities AllergiesRecent interventionsAvailable and previous culture data History of MRSA,VRE,Pseudomonas ESBL-producing GNRThe flora and fauna of the hospital And perhaps even the unit How sick is the patient?Can always“go b
3、ig”and narrow as you get more informationJust to refresh your memoryCephalosporins*1stCefazolinCephalexin Gram-positive cocci(e.g.,MSSA,GBS)E.coli,K.pneumoniae,P.mirabilis2ndCefuroximeCefoxitinCefotetan Cefuroxime-H.influenzae Cephamycins-Bacteroides spp3rdCefotaximeCeftriaxoneCeftazidime Some anaer
4、obic coverage Ceftazidime-Pseudomonas Crosses the BBB Potent inducers of-lactamases4thCefepime Pseudomonas Crosses the BBB Stable against many-lactamases*Do NOT cover Enterococcus,Listeria,Legionella,or MRSACase 1 48 M IVDA admitted with fevers and chills Fresh track marks on Left arm Febrile to 39
5、BP 70/55 HR 112 93%RA III/VI systolic murmur at LLSB B/L crackles Chest X-ray-Congestion B/L Empiric antibiotics?As expected At 14 hours both sets of blood cultures are growing Gram-positive cocci in clusters Previous history of MRSA TTE cant rule out vegetation on mitral valve TEE refused Patient g
6、rows MRSA Vancomycin continuedVancomycin Discovered in 1956 Mechanism of action Inhibits bacterial cell wall synthesis Binds firmly to D-Ala-D-Ala of the peptidoglycan,preventing elongation and cross-linking Mechanism of resistance Altered peptidoglycan binding site D-Ala-D-Ala is replaced by D-Ala-
7、D-lactate Thickened cell wallToxicity Nephrotoxicity Most often in the setting of other nephrotoxic agents and unstable renal function Hypersensitivity reactions1 Red man syndrome Anaphylaxis Rare reactions Ototoxicity Neutropenia and/or thrombocytopenia2 Linear IgA bullous dermatosis1 Crit Care.200
8、3;7(2)119-202 NEJM.2007;356(9)904-910Linear IgA Bullous DermatosisDosingDosingCrCl(mL/min)Dosing Regimen 7015 mg/kg every 8-12 hours40-6915 mg/kg every 12-24 hours 10 mg/L Minimum troughs of 15-20 mg/L are recommended for severe or complicated infections(endocarditis,osteomyelitis,meningitis,and pne
9、umonia)1 Am J Resp Crit Care Med.2005;171:338.2 Clin Infect Dis.2004;39:1267-84.3 Circulation.2005;111:e394-e433.What if a person cant“tolerate”Vanco?-Anaphylaxis-Patient“refuses”drug-Cant get the right levels-Ease of dosingDaptomycin FDA approved in 2003 Depolarizes the cell membrane and is rapidly
10、 bactericidal against Gram-positives Approved for the treatment of complicated skin and skin structure infections S.aureus(including MRSA),GAS,Streptococcus agalactiae,and vanco-susceptible Enterococcus faecalis Not approved for E.faecium(CLSI breakpoint 4)Non-inferior to vanco and anti-staph penici
11、llins in S.aureus bacteremia and right-sided endocarditis1 Jury is out for left-sided endocarditis NOT indicated for treatment of pneumonia1 NEJM.2006;355(7):652-65 Dosing Use actual body weight For serious,life-threatening infections dosing regimens of 8 to 12 mg/kg have been used1 Requires 24-hour
12、 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 Mic SYSTEMIC URINE Aztreonam 16 R Ceftriaxone 16 R*Cefepime 16 R*Cefuro
13、xime 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/Sulf16/8 R Aztreonam 16 R Ceftriaxone 32 R Ceftazidime 16 R Ciprofloxacin 2
14、R 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 fellow a.Use only when organisms are resistant to narrower spectrum agents.Aminoglycosides Cephalosporins-Lactams Miscel
15、laneous Gentamicin Tobramycin Amikacina Cefazolin Cefuroxime Cefoxitin Ceftriaxone Ceftazidimea Cefepimea Ampicillin Ampicillin-sulbactama Piperacillin-tazobactam a Aztreonam Ertapenema Meropenema Imipenema Levofloxacin Ciprofloxacin Nitrofurantoin*Tetracycline SMZ-TMP Gram-negative species Escheric
16、hia coli(n=1680)83 79 98 71 65 88 84 84 86 36 42 92 84 99 99 99 57 57 94 61 63 Klebsiella pneumoniae(n=1045)76 55 70 49 49 57 53 53 54 0 47 57 52 64 65 66 56 54 31 67 53 Klebsiella oxytoca(n=93)94 91 97 53 83 91 90 95 93 0 70 86 91 97 97 98 94 87 79 87 86 Pseudomonas aeruginosa(n=610)76 93 93 86 86
17、84 69 86 80 68 69 Acinetobacter baumannii#(n=361)29 40 45 12 23 20 38*15 23 21 18 16 22 28 Proteus mirabilis(n=332)84 84 96 82 92 95 92 92 93 71 89 97 86 99 99 99 75 71 80 Erterobacter cloacae(n=230)73 70 97 0 24 0 52 54 67 0 19 61 54 74 76 76 70 67 22 71 62 Morganella morganii(n=118)80 89 98 0 9 81
18、 92 88 98 0 8 94 88 99 99 99 74 70 40 65 Serratia marcescens(n=103)98 87 96 0 0 14 85 75 92 0 0 75 80 96 98 97 97 92 21 92 Stenotrophomonas maltophilia(N=94)47 88 98 Enterobacter aerogenes(n=80)89 81 91 0 46 0 70 68 85 0 30 80 78 89 93 93 88 85 70 76 Citrobacter freundii(n=79)91 91 100 0 48 9 76 79
19、92 10 47 87 71 100 100 100 88 87 81 78 85 Susceptibilities at MSH 2009CarbapenemGentAmikTobraE.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.
20、baumannii-38%susceptible to sulbactam component of amp-sulbactamCase 4 55 F DM,HTN,PVD,ESRD on HD Admitted with hyperglycemia/HONK Transferred out of MICU to 9W after stabilized on HD#3 On HD#5 febrile to 38.7 and lethargic CXR ordered Blood cultures sent U/A and Urine cultures orderedCXRLateralEmpi
21、ric Antibiotics Hospital-Acquired Pneumonia 48 hours after admission Ventilator-Associated Pneumonia Healthcare-Associated PneumoniaHealthcare-associated Pneumonia Most recent guidelines emphasize obtaining lower respiratory tract cultures Early,appropriate broad-spectrum antibiotics at the adequate
22、 doses Microbiology varies from one hospital to another and one unit to another Narrowing coverage Shorter durations The role for anaerobic coverage and“aspiration pneumonia”Pip-tazo vs.CefepimePip-TazoProsAmpicillin-susceptible EnterococcusAnaerobesConsPotent inducer of beta-lactamase production“Hi
23、gher salt load”CefepimeProsMore stable against many beta-lactamases including some ESBLsBetter GNR drug here at MSH?(personal opinion)CheaperConsNo activity against Enterococcus or Anaerobes“Aspiration”and the Anaerobe Do you need to add metronidazole or clindamycin?Rarely necessary Levofloxacin and
24、 ceftriaxone have some anaerobic activity Most pneumonia arises from aspiration of bacteria colonizing the oropharynx/nasopharynx Awful dentition(different from lack of dentition)Abscess formation Usually a more indolent presentation Chemical pneumonitis Aspiration of gastric contents vs.aspiration
25、of bowel contents Where do anaerobes live?Use antibiotics with thoughtHelpful Hints What has the patient grown before?Previous antibiotic exposures If the patient is in contact isolation from admission chances are they grew something in the past SCC is probably the best system to look at cultures Wh
26、at is the patient at risk for growing now?Previous antibiotic exposures Recent interventions What is the patient growing now?Narrow coverage Limiting antibiotic exposuresCall for adviceAntibiotic Approval 9407General ID 0649Transplant ID 8679Pop Quiz 47 yo F s/p allo SCT 8/08 complicated by GVHD of
27、the skin and gut,CMV viremia,and presumed aspergillus with worsening shortness of breath and B/L nodular infiltrates Intubated on 11C and comes to MICU on Linezolid,Imipenem,Tigecycline,Gentamicin,Azithromycin,Ambisome,and GanciclovirPop Quiz Sputum gram stain with 1-9 PMNs Blood cultures with GNR in aerobic bottle at 5 hours What do you add?A.Bactrim B.Inhaled colistin C.Levofloxacin D.Palliative care consultStenotrophomonas maltophilia Inherently resistant to Carbapenems Drug of choice is TMP-SMXTMP-SMXLevoCeftazS.maltophilia98%88%47%
