1、Clinically Relevant Microbiology and PharmacologyEdward L.Goodman,MDJuly 21,2003lAntibiotic use(appropriate or not)leads to microbial resistancelResistance results in increased morbidity,mortality,and cost of healthcare lAppropriate antimicrobial stewardship will prevent or slow the emergence of res
2、istance among organisms(Clinical Infectious Diseases 1997;25:584-99.)lAntibiotics are used as“drugs of fear”(Kunin CM Annals 1973;79:555)lSurveys reveal that:25-33%of hospitalized patients receive antibiotics(Arch Intern Med 1997;157:1689-1694)22-65%of antibiotic use in hospitalized patients is inap
3、propriate(Infection Control 1985;6:226-230)lContagious RESISTANCENo equivalent downside to overuse of endoscopy,calcium channel blockers,etc.lMorbidity-drug toxicitylMortalitylCostlBasic Clinical BacteriologylCategories of AntibioticslPharmacology of AntibioticslGram Positive CoccilGram Negative Rod
4、slFastidious GNRlAnaerobeslGram stain:clusterslCatalase pos=StaphlCoag pos=S aureuslCoag neg=variety of specieslChains and pairslCatalase neg=streptococcilClassify by hemolysislType by specific CHOl95%produce penicillinase(beta lactamase)=penicillin resistantlAt PHD 50%of SA are hetero(methicillin)r
5、esistant=MRSA lGlycopeptide(vancomycin)intermediate(GISA)MIC 8-16Eight nationwide(one at PHD)lVRSA reported July 5,2002 MMWRMIC 128S.aureusPenicillin1950sPenicillin-resistantS.aureusMethicillin1970sMethicillin-resistant S.aureus(MRSA)Vancomycin-resistantenterococci(VRE)Vancomycin1990s1997Vancomycini
6、ntermediate-resistantS.aureus (VISA)2002 Vancomycin-resistantS.aureus(n=193)MSSA SSI(n=165)MRSA SSI(n=121)lMany species S.epidermidis most commonlMostly methicillin resistant(65%)lOften contaminants or colonizers use specific criteria to distinguishMajor cause of overuse of vancomycinClin Infect Dis
7、 1999;29:239-244lBeta hemolysis:Group A,B,C etc.lInvasive mimic staph in virulencelS.pyogenes(Group A)Pharyngitis,Soft tissueNon suppurative sequellae:ARF,AGNlS.agalactiae(Group B)Peripartum/NeonatalDiabetic footBacteremia/endocarditis/metastatic focilGroup D(non enterococcal)=S.bovisAssociated with
8、 carcinoma of colonlMany specieslStreptococcus intermedius group Liver abscessEndocarditisGI or pharyngeal floralMost other are mouth flora cause IElFormerly considered Group D Streptococcinow a separate genuslBacteremia/EndocarditislBacteriurialPart of mixed abdominal/pelvic infectionslIntrinsicall
9、y resistant to cephalosporinslNo bactericidal single agentlFermentorslOxidase negativelFacultative anaerobeslEnteric floralNumerous generaEscherischiaEnterobacterSerratia,etclNon-fermentorslOxidase positivelPure aerobeslPseudomonas and AcinetobacterNosocomialOpportunisticInherently resistantlNeisser
10、ia,Hemophilus,Moraxella,HACEKlRequire CO2 for growthlNeisseria must be plated at bedside Chocolate agar with CO2 Ligase chain reaction has reduced number of cultures for N.gonorrhealGram negative rodsBacteroidesFusobacterialGram positive rodsClostridiaProprionobacterialGram positive cocciPeptostrept
11、ococci and peptococcilProduce beta lactamaselEndogenous floralPart of mixed infectionslConfer foul odorlHeterogeneous morphologylFastidiouslNarrow SpectrumActive against only one of the four classeslBroad SpectrumActive against more than one of the classeslBoutiqueActive against a select number with
12、in a classlActive mostly against only one of the classes of bacteriagram positive:glycopeptides,linezolidaerobic gram negative:aminoglycosides,aztreonamanaerobes:metronidazoleGPCGNRFastidAnaerVanc+-only clostridiaLinezolid+-Only gram posAG-+-Aztreon-+-Metro-+lActive against more than one classlGPC a
13、nd anaerobes:clindamycinlGPC and GNR:cephalosporins,penicillins,T/S,newer FQlGPC,GNR and anaerobes:ureidopenicillins BLI,carbapenemslGPC and fastidious:macrolidesStrepOSSAGNRFastidAnaerPen+-+/-+/-Amp/amox+-+/-+/-Ticar+-+/-+Ureid+-+BLI+Carba+GPC non-MRSAGNRFASTIDANAERCeph 1+-Ceph 2+-Cepha-mycin+Ceph
14、3+-Ceph 4+-lJust like the Mall specialty storesspecialty drugslOften like the Mall stores in search of business;drugs in search of diseasesSynercid for VRE faecium,not faecalis,MRSALinezolid VRE,MRSAlID consult neededlMIC=lowest concentration to inhibit growth lMBC=the lowest concentration to killlP
15、eak=highest serum level after a dose lAUC=area under the concentration time curvelPAE=persistent suppression of growth following exposure to antimicrobiallTime above MIC-beta lactams,macrolides,clindamycin,glycopeptidesl24 hour AUC/MIC-aminoglycosides,fluoroquinolones,azalides,tetracyclines,glycopep
16、tides,quinupristin/dalfopristinlPeak/MIC-aminoglycosides,fluoroquinoloneslShould exceed MIC for at least 50%of dose intervallHigher doses may allow adequate time over MIClFor most beta lactams,optimal time over MIC can be achieved by continuous infusion(except unstable drugs such as imipenem,ampicil
17、lin)lAminoglycosides Peak/MIC ratio of 10-12 optimal Achieved by“Once Daily Dosing”PAE helpslFluoroquinolones 10-12 ratio achieved for enteric GNRlPAE helps not achieved for Pseudomonas nor Streptococcus pneumoniae lFor Streptococcus pneumoniae,FQ should have AUIC=30lFor gram negative rods where Pea
18、k/MIC ratio of 10-12 not possible,then AUIC should=125.l-Strong epidemiological evidence that antibiotic use in humans and animals associated with increasing resistancel-Subtherapeutic dosing encourages resistant mutants to emerge;conversely,rapid bactericidal activity discouragesl-Hospital antibiot
19、ic control programs have been demonstrated to reduce resistancep=.001p=.00000.511.522.5Doses/Census Day2000200120020%5%10%15%20%25%30%1999200020012002%Bug/Drug combinations having or=5%increase in resistance%Bug/Drug combinations having or=5%decrease in resistancelDecrease inappropriate fluoroquinol
20、one useStaff educationRestricted reporting lDecrease inappropriate sputum culturesStaff education Laboratory disclaimer lDecrease inappropriate vancomycin levelsEducation about unnecessary peak levels lMonitor surgical site infections and intervene as necessaryImproved timing and administration of p
21、re-op antibioticsclipping not shavingnasal decolonizationchanging pathogens(MRSA,gram-rods)lAutomated protocol-driven antibiotic prescribingComputerized physician order entry “There is only a thin red line of ID practitioners who have dedicated themselves to rational therapy and control of hospital infections”Kunin CID 1997;25:240l2000 BC:Eat this rootl1000 AD:Say this prayerl1800s:Take this potionl1940s:Take penicillin,it is a miracle drugl1980s:Take this new antibiotic,it is betterl?2003 AD:Eat this root
