Medical Microbiology

206 3 GeneralBacteriology

dividualsubstancesinacombinationtherapyareadministeredseparately.

Severaldifferentobjectivescanbepursuedwithcombinationtherapy:

&Broadeningofthespectrumofaction.Inmixedinfectionswithpatho-

gensofvaryingresistance;incalculatedtherapyofinfectionswithunknown,

ornotyetknown,pathogenicfloraandresistancecharacteristics.

&Delayofresistancedevelopment.Intherapyoftuberculosis;whenusing

anti-infectiveagentsagainstwhichbacteriaquicklydevelopresistance.

&Potentiationofefficacy.Insevereinfectionsrequiringbactericidalactiv-

ityatthesiteofinfection.Best-knownexample:penicillinplusgentamicin

intreatmentofendocarditiscausedbyenterococciorstreptococci.

Combiningtheeffectsofanti-infectivedrugscanhaveseveraldifferentef-

fects:

&Nodifference.Thecombinationisnomoreefficaciousthanthemore

activeofthetwocomponentsalone.

&Addition.Summationoftheeffects.

&Synergism.Potentiationoftheeffects.

&Antagonism.Thecombinationislessefficaciousthanoneofthetwo

componentsalone.

Ruleofthumb:combinationsofbacteriostaticswithsubstancesthatare

bactericidalinthecelldivisionphaseonlyoftenresultinantagonism,e.g.,

penicillinplustetracyclineintherapyofpneumococcalpneumonia.

In-vitroinvestigationsofthemechanismofactionofacombinationwhen

usedagainstapathogenusuallyemploytheso-called“checkerboardtitra-

tion”technique,inwhichthecombinatoryeffectsofsubstancesAandB

arecomparedusingacheckerboard-likepattern.

Chemoprophylaxis.........................................

Oneofthemostcontroversialantibioticusesisprophylacticantibiosis.There

arenoclear-cutsolutionshere.Therearecertainsituationsinwhichchemo-

prophylaxisisclearlyindicatedandothersinwhichitisclearlycontraindi-

cated.Themattermustbedecidedonacase-by-casebasisbyweighingpo-

tentialbenefitsagainstpotentialharm(sideeffects,superinfectionswith

highlyvirulentandresistantpathogens,selectionofresistantbacteria).

Chemoprophylaxisisconsideredusefulinmalaria,rheumaticfever,pul-

monarycysticfibrosis,recurringpyelonephritis,followingintensivecontact

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Kayser, Medical Microbiology © 2005 Thieme