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Antibiotic Treatment of Syphilis

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Antibiotic Treatment of Syphilis Memling, 15th Century Florence Nightingale in Scutari IGNAZ PHILIPP SEMMELWEIS EFFECTEFFECT OFOF HANDHAND WASHING*WASHING* ONON DEATHSDEATHS DUEDUE TOTO PUERPERALPUERPERAL SEPSISSEPSIS ININ VIENNAVIENNA Date Mortality (%) May 12.2% June 2.38 July 1.30 August 1.89 Average 1.27 (after hand washing) 1.33 (in Second Clinic) *Introduced in May, 1847 by I.P. Semmelweis THETHE FIRSTFIRST ANTIMICROBIALANTIMICROBIAL DRUGS:DRUGS: SULFONAMIDESSULFONAMIDES –– MODIFIEDMODIFIED RAPTURERAPTURE •• 1935,1935, DomagkDomagk reportsreports ProntosilProntosil curescures micemice givengiven lethallethal dosesdoses ofof hemolytichemolytic streptococci.streptococci. •• EncouragingEncouraging resultsresults inin patientspatients withwith pneumococcalpneumococcal pneumoniapneumonia ((equalequal toto serumserum therapy),therapy), meningococcalmeningococcal meningitis,meningitis, erysipelas,erysipelas, mastoiditismastoiditis,, puerperalpuerperal sepsis.sepsis. •• DisappointingDisappointing resultsresults inin streptococcalstreptococcal pharyngitispharyngitis (persistent(persistent colonization,colonization, recurrences,recurrences, diddid notnot preventprevent rheumaticrheumatic fever),fever), andand gramgram--negativenegative infections.infections. •• RapidRapid developmentdevelopment ofof resistanceresistance andand frequentfrequent sideside effects.effects. INITIALINITIAL TREATMENTSTREATMENTS WITHWITH PENICILLINPENICILLIN • 1941 – In February, enough penicillin produced in modified bed pans to treat an Oxford policeman, Albert Alexander, who suffered from widespread Staph/Strep infection. Given 100 U X 3 doses in 24 hr. Dramatic improvement, then relapse. Given 5 more doses recovered from the urine. Ran out of drug. Patient succumbed. – “A remarkable substance grown in bedpans and purified by passage through the Oxford Constabulary.” • Later in February, 1941, enough drug to treat Arthur Jones for a septic hip successfully. • March, 1942, cured Anne Miller at Yale-New Haven Hospital who was dying of puerperal sepsis due to Streptococcus. An Anxious Hour, by Mrs. Alexander Farmer, 1865 SCARLETSCARLET FEVER:FEVER: ANAN EASYEASY TARGETTARGET •• EasilyEasily diagnoseddiagnosed Temp to Strep eradi- Compli- normal cated cations byby rashrash Penicillin 52 hrs. 92% 7% •• CommonCommon diseasedisease (No. 86) in 1940s •• QuarantinedQuarantined inin No Rx 99 hrs. 18% 26% specialspecial wardswards (No. 123) Hirsch et al, 1945 MORTALITYMORTALITY DUEDUE TOTO BACTERIALBACTERIAL ENDOCARDITISENDOCARDITIS BEFOREBEFORE ANTIBIOTICSANTIBIOTICS •• 4343 casescases reportedreported byby LibmanLibman && CellerCeller (1910)(1910) –– allall dieddied withinwithin 44 mos.mos. toto 11 ½½ yrs.yrs. •• 250250 casescases reportedreported byby KelsonKelson && WhiteWhite fromfrom thethe prepre--penicillinpenicillin eraera (1927(1927--1939)1939) –– onlyonly oneone survivor,survivor, whowho dieddied atat 1313 mos.mos. ofof ““rheumaticrheumatic carditiscarditis..”” Kelson & White, 1945 TREATINGTREATING BACTERIALBACTERIAL ENDOCARDITISENDOCARDITIS • 1941- Dawson at Columbia (NYC) made their own penicillin and treated 4 pts for with small doses and short duration – they improved but all subsequently died. • Loewe (Brooklyn) treated 7 pts successfully with heparin and penicillin (higher doses, longer duration) - all survived. • Blake (Yale) recognized that it was the penicillin dose and duration and not the heparin. They treated with penicillin alone at 0.25 M U for 3-4 wks - 11/12 patients survived. • 1948-1951 - Ronald Christie (UK) in MRC trials with 15 centers made the major breakthroughs – showed that higher doses and longer duration of penicillin were critical to successful treatment. Christie, RV, 1948 0.1 0 0.25. 0.51 Christin, RV, 1948 Detail from Syphilis by Richard Tennant Cooper, 1912. Syphilis Deaths, 1933-1960, USA ANTIBIOTICANTIBIOTIC TREATMENTTREATMENT OFOF SYPHILISSYPHILIS •• 19431943 -- JohnJohn F.F. MahoneyMahoney curedcured syphilissyphilis inin rabbitsrabbits andand inin aa fewfew patientspatients withwith penicillin.penicillin. •• 19441944 –– MooreMoore etet al.al. reportedreported inin JAMAJAMA curingcuring 14181418 casescases ofof earlyearly syphilissyphilis –– nono comparisonscomparisons withwith untreateduntreated controls.controls. “The Sick Child”, Edvard Munch, 1907 TUBERCULOSIS NEW CASE AND MORTALITY RATES NEW YORK CITY, 1940-1955 TREATMENTTREATMENT OFOF TUBERCULOSISTUBERCULOSIS WITHWITH ANTIMICROBIALANTIMICROBIAL DRUGSDRUGS StreptomycinStreptomycin –– developeddeveloped byby S.S. WaksmanWaksman inin 19441944 •• JustJust 1010 mos.mos. afterafter isolation,isolation, firstfirst patientpatient waswas treatedtreated successfully.successfully. •• WithinWithin 22 yearsyears (1946),(1946), dangerousdangerous sideside effectseffects (deafness),(deafness), manymany relapsesrelapses andand poorpoor outcomesoutcomes werewere noted.noted. IsoniazidIsoniazid andand TreatmentTreatment ofof TuberculosisTuberculosis •• INHINH synthesizedsynthesized inin 19121912 byby MeyerMeyer && MalleyMalley forfor aa PhDPhD thesis.thesis. NoNo conceptconcept ofof antianti--tbctbc activity.activity. •• InIn 1951,1951, simultaneouslysimultaneously andand independentlyindependently usedused forfor antianti--tbctbc activityactivity inin vitrovitro andand thenthen inin animalsanimals byby scientistsscientists atat HoffmanHoffman--LaRocheLaRoche (USA),(USA), SquibbSquibb (USA)(USA) andand BayerBayer (Germany).(Germany). •• GivenGiven toto patientspatients withinwithin months,months, initiallyinitially atat SeaSea ViewView Hospital,Hospital, andand thenthen atat 22 otherother hospitalshospitals inin USAUSA andand GermanyGermany •• HighlyHighly successfulsuccessful resultsresults reportedreported byby 33 groupsgroups inin 1952.1952. RISING INCIDENCE OF TUBERCULOSIS IN AFRICA 1990 TO 2005 Estimated Incidence of Tuberculosis per 100,000 Population in African Countries in 1990 and 2005. Data are from the World Health Organization. ND denotes no data. NOTNOT JUSTJUST ANYANY ANTIBIOTIC,ANTIBIOTIC, BUTBUT THETHE RIGHTRIGHT ANTIBIOTICANTIBIOTIC ANAEROBICANAEROBIC CANARDSCANARDS OFOF THETHE 1960s1960s •• SmellSmell thatthat E.E. colicoli pus!pus! •• AnaerobesAnaerobes == ClostridiumClostridium •• WhatWhat areare anaerobicanaerobic cultures?cultures? •• TreatmentTreatment ofof peritonitisperitonitis == Penicillin/StreptomycinPenicillin/Streptomycin oror TetracyclineTetracycline Cephalothin/KanamycinCephalothin/Kanamycin INTRAABDOMINALINTRAABDOMINAL ABSCESSESABSCESSES ININ THETHE 1960s1960s •• AltemeierAltemeier reportedreported 540540 IAIA abscessesabscesses fromfrom CincinnatiCincinnati overover aa 1010--yearyear periodperiod duringduring thethe 1960s.1960s. •• Appendicitis,Appendicitis, pancreatitis,pancreatitis, andand diverticulitisdiverticulitis werewere leadingleading sources.sources. •• E.E. colicoli (54%),(54%), BacteroidesBacteroides (17%)(17%) andand anaerobicanaerobic StreptococcusStreptococcus (24%)(24%) werewere thethe leadingleading isolates.isolates. •• MortalityMortality dependeddepended onon thethe sitesite ofof abscess:abscess: AppendicealAppendiceal (2%),(2%), hepatichepatic (28%),(28%), pancreaticpancreatic (44%).(44%). Altemeier et al., Am J Surg, 1973 W.A.W.A. ALTEMEIERALTEMEIER ONON ANTIBIOTICANTIBIOTIC TREATMENT*TREATMENT* ReplyReply (WAA):(WAA): II amam pleasedpleased toto seesee thatthat Dr.Dr. NicholsNichols hashas emphasizedemphasized thethe samesame findings,findings, thatthat is,is, thatthat thethe anaerobesanaerobes areare ofof greatergreater frequencyfrequency andand importanceimportance thanthan areare thethe aerobesaerobes……AsAs farfar asas antibioticantibiotic therapytherapy isis concerned,concerned, wewe stillstill preferprefer thethe combinedcombined useuse ofof penicillinpenicillin andand tetracycline,tetracycline, asas wewe havehave mentionedmentioned inin previousprevious publications.publications. **Discussion of a paper on Intra-abdominal Abscesses – Annual meeting, Society for Surgery of the Alimentary Tract, Chicago, 1972 ClindamycinClindamycin vsvs CephalothinCephalothin PlusPlus KanamycinKanamycin:: FailuresFailures DueDue toto SepticemiaSepticemia oror AbscessAbscess 50 Cephalothin (52 cases) 40 Clindamycin (48 cases) p < 0.05 30 28 22 20 Failures (%) 10 10 2 0 Total failures Total anaerobe failures Thadepalli5/14/2008 et2:11:56 al, 1973 PM 33 ANTIBIOTICANTIBIOTIC PROBESPROBES ININ THETHE ANIMALANIMAL MODELMODEL OFOF INTRAABDOMINALINTRAABDOMINAL INFECTIONINFECTION 100% 98% 100% 90% Mortality 80% Abscess 70% 60% 50% 40% 34% 35% 30% 20% 8% 10% 5% 4% 6% 0% Controls Clindamycin Gentamicin Clinda/Gent (147) (60) (57) (72) MEMEMORABLEMEMEMORABLE QUOTESQUOTES ABOUTABOUT THETHE TRIUMPHTRIUMPH OFOF ANTIBIOTICSANTIBIOTICS 19671967 ((Ascribed to William H. Stewart, US Surgeon General) ““ItIt isis timetime toto closeclose thethe bookbook onon infectiousinfectious diseases,diseases, andand declaredeclare thethe warwar againstagainst pestilencepestilence won.won.”” 19781978 ((Robert Petersdorf, past president of the IDSA) ““EvenEven withwith mymy greatgreat personalpersonal loyaltyloyalty toto InfectiousInfectious Disease,Disease, II cannotcannot conceiveconceive thethe needneed forfor 309309 moremore [graduating[graduating traineestrainees in]in] infectiousinfectious diseasedisease……unlessunless theythey spendspend theirtheir timetime culturingculturing eacheach other.other.”” 19851985 ““TheThe millenniummillennium wherewhere fellowsfellows inin infectiousinfectious diseasedisease willwill cultureculture oneone anotheranother isis almostalmost here.here.”” Walsh McDermott,
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