Antimicrobial Resistance - Tufts University

548 Pages·2009·5.26 MB·English

Antimicrobial Resistance
in Developing Countries
Anı´bal de J. Sosa Denis K. Byarugaba
l l
Carlos F. Ama´ bile-Cuevas Po-Ren Hsueh
l l
Samuel Kariuki Iruka N. Okeke
l
Editors
Antimicrobial Resistance
in Developing Countries
Foreword by Thomas F. O’Brien
Introductory Preface by the Editors
Guest Preface by Stuart B. Levy
1 3
Editors
Anı´baldeJ.Sosa DenisK.Byarugaba
AllianceforthePrudentUse DepartmentofVeterinaryMedicine
ofAntibiotics(APUA) MakerereUniversity
TuftsUniversity Kampala,Uganda
Boston,MAUSA [email protected]
[email protected]
CarlosF.Ama´bile-Cuevas Po-RenHsueh
Fundacio´nLusaraparala DepartmentofLaboratoryMedicineand
Investigacio´nCientı´fica InternalMedicine
MexicoCity,Mexico NationalTaiwanUniversityHospital
[email protected] Taipei,Taiwan,R.O.C
[email protected]
SamuelKariuki IrukaN.Okeke
KenyaMedicalResearch DepartmentofBiology
Institute(KEMRI),Nairobi, HaverfordCollege
Kenya Haverford,PA,USA
[email protected] [email protected]
ISBN978-0-387-89369-3 e-ISBN978-0-387-89370-9
DOI10.1007/978-0-387-89370-9
SpringerNewYorkDordrechtHeidelbergLondon
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Foreword
Avoiding infection has always been expensive. Some human populations
escaped tropical infections by migrating into cold climates but then had to
procure fuel, warm clothing, durable housing, and crops from a short
growing season. Waterborne infections were averted by owning your own
well or supporting a community reservoir. Everyone got vaccines in rich
countries,whilepeopleinothersgotthemlaterifatall.
Antimicrobialagentsseemedatfirsttobeanexception.Theydidnotneedto
bedeliveredthroughacoldchainandtoeveryone,asvaccinesdid.Theyhadto
begivenonlytoinfectedpatientsandoftenthenasrelativelycheapinjectables
orpillsoffashelfforonlyafewdaystogetastonishingcures.Antimicrobials
notonlywerebetterthanmostotherinnovationsbutalsoreachedmoreofthe
world’speoplesooner.
The problem appeared later. After each new antimicrobial became widely
used, genes expressing resistance to it began to emerge and spread through
bacterialpopulations.Patientsinfectedwithbacteriaexpressingsuchresistance
genesthenfailedtreatmentandremainedinfectedordied.Growingresistance
toantimicrobialagentsbegantotakeawaymoreandmoreofthecuresthatthe
agentshadbrought.
It then proved to be much more resource-intensive to keep patients from
becominginfectedwithandfailingtreatmentfordrug-resistantbacteriathanit
had been to deliver the drugs that had caused the problem. Resource-limited
countriesthathadmanagedtomakeantimicrobialsavailabletotheirinfected
patientscouldnotaffordtodoallthethingsthatwerethenneededtomanage
theantimicrobialresistancethatresulted.
Antimicrobial resistance seems a function of how many bacteria have been
exposed to antimicrobials, for example, so treat only infections that antimi-
crobialscureforaslong,butonlyaslong,asneeded.Treatinganinfectinggerm
withadrugitresistsnotonlyfailsbutalsomakesthatresistantgermspread,so
treatonlywiththedrugthatcanstillkillit.Resistantgermsspreadtoothers,so
identifythemandinterrupttheirspread.
Eachofthesewaystocontrolresistancecostsmuchmorethanithadcostto
distribute the boxes of pills and injectables that had begun the resistance.
Expensive microbiology laboratories in rich countries test whether the germ
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vi Foreword
infectinganypatientisofakindthatantimicrobialagentskill,andifsowhich
agentcouldstillkillit.Thosecountriesthenmakethatagentpromptlyavailable
bykeepingubiquitouscostlystocksofallagents.
Adequate housing and support for personal hygiene may also minimize
interpersonal exchange of resistant bacteria in communities of developed
countries, and clean water limits their ingestion. Many developed countries
feed large amounts of resistance-selecting antimicrobials to food animals,
however,buttheydobantheirresidualsinfoodortheirusetopreservefood.
Lessisknownabouttheseindevelopingcountries
Inbothrichandpoornations,resistantbacteriacausetheirmostfrequent,
costly, and deadly infections in hospitals and intensive care units. In the rich
nations,however,disposableitemscomeintruckloadsfromwarehousestohelp
nurses,andwell-organizedinfectioncontrolteamsslowthespreadofresistant
bacteria between private rooms, while the poorer struggle with shortages of
reusableitemsandonehand-washingsinkforanopenward.
Further promoting resistance in resource-limited countries is a cruel
underlying inequity. They have more of the infections that richer countries
have, e.g., pneumococcal, AIDS, meningococcal, trauma-related, tuberculosis,
shigellosis,plusmanytheydonothave,suchastyphoid,malaria,andcholera.
These require more valid antimicrobial use and also elicit more inadvertent
misusebycomplicatingdiagnosis,thusmakingresistanceworse.
In a developed country, a sick febrile patient has prompt laboratory testing
andcompiledlocaltestresultstopredictdiagnosisandbesttherapyimmediately,
withconfirmationoradjustmentinafewdays.Inanundevelopedcountry,there
willbe fewer or no tests or compiledresults,fewer antimicrobialsavailable for
oftenblindtherapyofmorepossiblediagnosesandsomorechanceoftreatment
failureandfurtherspreadofresistance.
Forallofthesereasons,themanagementofantimicrobial resistance inthe
resource-limitedworld faces specialchallenges and appears to need tools that
arelessresource-intensivethanthosethathaveevolvedinthedevelopedworld.
Affordable strategies and tools to manage antimicrobial resistance in less-
resourced regions may need special effort to develop, but possible examples
canbeconsidered.
Microbiology laboratories in developed countries, for example, using
supply-intensive instruments and highly trained and salaried staff for a huge
menuoftests,becomethemodelofexcellence.Attemptstoduplicatethemina
developing country, however, may deplete the pool of trained professionals,
outrunsupplysources,andpricetestssohighthatfewpatientscanaffordthem
andtheybecome,afterall,largelyunused.
An alternative model might be developed in which a limited set of
inexpensiveessentialtestsusingacommonlistofsuppliescouldbeperformed
by less-extensively but specifically trained workers supported by a web-based
supportandoversightsystem.Thiswouldnotreplaceanycurrentlyfunctioning
laboratoriesbutsupplementthematthenextlowertierofmedicalfacilitiesthat
nowhavenolaboratories.
Foreword vii
Similarly,growthoftheInternetmayprovidecheapwaystoprovideupdated
information on currently prevalent infections and their drug resistances, as
locally compileddata now doindevelopedcountries, and useittoupdateand
disseminate treatment guidelines. Every microbial test result that can be
produced in a resource-limited country should be captured and analyzed to
helpoverviewitsproblemsandupdateresponsestothem.
Eachofthetoolsnowusedtocontrolantimicrobialresistancemightthusbe
reviewedwithdevelopingworldcaregiverstoexplorewaysinwhichtheycould
bemodifiedtobecost-effectiveintheircircumstances.Mightnothospitalsthat
cannot afford a team of infection control nurses, for example, have access to
specialtrainingmaterialsandinformationsupporttohelptheirexistingnursing
staffcarryoutsomeoftheirfunctions?
Such a rethinking of the tools and strategies for controlling antimicrobial
resistance to improve their application in the resource-limited world will not
happenspontaneously.Itwillrequireconcertedandfundedeffortbyspecialists
frombothworlds.Gainingsupportforitmayprovedifficult,moreover,since
thewholeproblemofantimicrobialresistancehasrepeatedlyslippedfromthe
attentionofpublichealthandotherfundingagencies.
The first step in such a needed initiative is to recognize that antimicrobial
resistanceisadifferentandmoredeadlyprobleminthedevelopingworldandto
elaborateindetailalloftheaspectsofthatproblem.Thatiswhatthisbookdoes
andwhyitisimportant.Itcanbeseenasbothaninformativeworkandabasis
foraction.
Boston,Massachusetts ThomasF.O’Brien
Introduction
This book was mainly compiled while we quietly celebrated the 80th
anniversaryofthediscoveryofpenicillin,afactthatformallyinauguratedthe
‘‘era of antibiotics’’ and it will become available during the celebration of the
150th anniversary of Darwin’s On the Origin of Species (and the 200th
anniversary of Darwin himself). These two milestones remind us, on the one
hand, that we have been witnesses to the evolution of bacteria and other
microorganisms from mostly susceptible to mostly resistant to drugs and, on
the other, how little to heart even those of us who are not blinded by
superstitionhavetaken thebasicnotions ofgeneticchangeandselection. But
in addition to the formidable evolutionary forces behind resistance, and the
equallyformidableneglectinputtingourknowledgeofittowork,developing
countrieshavetodealwithawidevarietyofpeculiarconditionsthatfosterthe
emergenceandspreadofresistantgerms.Theseaggravatingfactorsrangefrom
malnutrition to lack of medical services and inadequate medical training and
then to counterfeit drugs and incompetent governments. These traits are not
exclusivetopoorcountries,butcoalesceintheworstpossiblewayshere.There
isanexceptionalneedforrigorousdataonthescaleandspreadofantimicrobial
resistance,aswellasforeffectivemeansforsharingthedataandusingitasan
evidence base for effective containment strategies. In developing countries
where resistance is a prime issue, data are least available, evidence is rarely
collated, and containment interventions have been poorly implemented.
Indeed, the validity of many proposed interventions in developing countries
remainsuntested.
In putting together this book, we tried to assemble an overview of the
magnitude,causes,consequences,andpossibleactionsonmicrobialresistance
indevelopingcountries.Ifthebookappearsbrief,itisbecauseweknowlittle
about this particular side of the problem, as one of the main features of poor
countriesisinsufficientscientificandmedicalresearch,andofopportunitiesto
publishthescarcefindingsin‘‘international’’scientificjournals,whichroutinely
dismiss papers from developing countries because results are ‘‘only of local
interest’’.Therefore,inadditiontopresentinginformationandideas,thebook
explicitly highlights gaps that represent opportunities for research and policy
innovation. High among our priorities has been to obtain data and critique
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x Introduction
fromscholarswhoworknotonbutindevelopingcountriesandtoincludeinput
from a variety of geographic regions. The picture that emerges, although
incomplete, allows the reader to assess the current and emerging threats, the
distinct issues that influence the evolution of resistance, the main problems
caused by resistance, and the potential avenues to tackle at least some of this
complexpanorama.
Preface
Theproblemofantimicrobialresistanceknowsnoboundaries.Drug-resistant
microbesofallkindscanmoveamongpeopleandanimals,fromonecountryto
another—withoutnotice.Fromtheearlystagesofidentifyinganddiscovering
antibiotic resistance, the problem was clearly severe in developing countries
where drug availability was limited and resistance was high. However, it has
been in the developed world, with its abundant resources, where resistance
has been more vigorously studied. Therefore, it is of some interest that out
of a 1981 meeting in the Dominican Republic, where representatives from
developing as well as industrialized countries assembled, came an Antibiotic
MisuseStatementdeclaringtheconsequencesofinappropriateuseofantibiotics,
namely the emergence and spread of antibiotic resistance. The response to the
widecirculationofthestatementledtotheestablishmentoftheAllianceforthe
PrudentUseofAntibiotics(APUA).Thisinternationalorganizationcontinues
today, 27 years later, to champion increased awareness and appropriate
antimicrobial use so as to curtail drug resistance and ‘‘preserve the power of
antibiotics.’’APUAfosterspartnershipsandcommunicationsamongpeoplein
bothdevelopedanddevelopingcountriestoimproveantibioticaccessibilityand
reverseresistance.
This book, edited by Drs. Anibal Sosa and Denis Byarugaba and their
associateeditors,isuniqueinfocusingonantimicrobialresistanceasitrelates
toandthreatensdevelopingcountries.Itiscuriousthatithastakenthislongto
produce a book dedicated to antibiotic resistance in developing parts of the
world.Onecanask‘‘why?’’sinceresistanceisandhasbeensocommonthere.In
fact,whereasresistancehasbeenaddressedforthepastfourdecadesbyexperts
intheindustrializedworld,studiesdescribingtheproblemandthepublichealth
situation in the developing world have lagged behind. Although we have
learned much from studies of the genetics and molecular biology of the
problem from investigations in industrialized countries, it is in developing
countrieswheremorestudiesandeffortsareneeded.With travelencouraging
thetransportofmicrobes,theinformationinthisbookwillhavewide-sweeping
benefit, not only for developing countries but also for the world at large.
Surveillanceofresistanceandthepreventionofresistanceneedattentionona
worldwidebasis.Improvingantibioticuserequiresaglobaleffort.
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