Garp kathmandu jul2016

The Global Challenge of Antimicrobial Resistance

Ramanan LaxminarayanGARP Regional Meeting, Kathmandu

Bacterialdiseasesarestillmajorkillersindevelopingcountriesbecauseoflackofaccesstoantibiotics

O’Brienetal,Lancet2009

Pneumococcalpneumoniadeathsavertablewithimprovedantibioticaccess

Laxminarayanetal,Lancet,2015

Whatareweaskingofantibiotics?

Substituteforimmunization,infectioncontrolandwater/sanitation

South Asia

Substituteforimmunization,infectioncontrolandwater/sanitation

Sub-Saharan Africa

Percentage of Staphylococcus aureus isolates that are methicillin resistant (MRSA) in selected countries, 1999–2014

Source: CDDEP 2015

Depending on the country, resistance to one or more of the following drugs may have been used to test for MRSA: Oxacillin, cefoxitin, flucloxacillin, cloxacillin, dicloxacillin, and methicillin. Intermediate-resistant isolates are included as resistant

CREratesinchildrengrewbetween2000and2012

Loganetal,EID,2015

15

ClonalspreadofS.pneumoniae 23F

Tennessee

Cleveland

Mexico

Colombia

Brazil

ArgentinaUruguay

Chile SouthAfrica

SingaporeMalaysia

ThailandPhilippines

HongKongTaiwan

SouthKoreaSpain

FranceBM42001978?

Finland

Slidecourtesy:KeithKlugman

ResistanceMapwebpage

Resistanceratesinvariouscountriesonglobalmap

Resistanceratescomparisonamongcountries

Wheredoestheburdenofresistancelie?

Neonatalsepsis– 421,000deathsglobally

Mortalityoutcomesareworseinneonateswithresistantinfections

Kayange M,Kamugisha E,MwizamholyaDL,JeremiahS,Mshana SE.2010.Predictorsofpositivebloodcultureanddeathsamongneonateswithsuspectedneonatalsepsisinatertiaryhospital,Mwanza- Tanzania.BMCPediatrics10:39.

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58

369

151

91

55

23

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60

Culture GramReaction ESBL MRSA

Death(%)

Parameter

Positive

Negative

NeonatalCasefatalityratesinIndia(InPress)

LaxminarayanetalLancet,2015

Typhoidandpara typhoid–400,000deaths,16millioncases

Resistanceisincreasingandassociatedwithworseoutcomes• InKenya,proportionofStyphi inKenyathataremultidrugresistantandresistanttonalidixic acidandwithdecreasedsusceptibilitytofluoroquinolones hadrisenfrom1%in2000tonearly25%in2008.

• FluoroquinoloneresistanceisincreasinginIndia(44%)andPakistan(58%).

• Casefatalityratesassociatedwithmultidrug-resistantStyphi insouthAsiaare10%(closetothe12·8%recordedinthepre-antibioticera)LancetInfectDis2005;5:481–93

Surgicalsiteinfections– over400,000deaths

Surgicalsiteinfections

• Thereare92millionsurgeriesinlow-incomecountrieseachyear• 5.5millionsurgicalsiteinfectionsorSSIs(6per100procedures)–aboutathirdofallhealthcareassociatedinfections

• SSIsaretheleadingcauseofinfectioninsettingswithlimitedresources

• MortalityratefromSSIRatesofmortalityfromsurgicalsiteinfectionsare3%intheUSandbetween8and20%inlow-incomecountries

• Between400,000andamilliondeathsfromSSIseachyearwithanincreasingnumbercausedbyresistantpathogens.

Maternaldeathscausedbysepsis– aboutatenthofallmaternaldeaths

Increasingratesofinstitutionaldeliveriesplaceagreaterburdenoninfectionstandardsinhealthcareinstitutions.

Absolute risk reduction (ARR) of infection with antibiotic prophylaxis in common surgical procedures and blood cancer chemotherapy in the USA

Teillant etal,LancetInfectDis,2015

Number of additional infections per year in the USA under a 30% decreased efficacy of antibiotic prophylaxis

Teillant etal,LancetInfectDis,2015

Malaria– 420,000deaths

Riskofmalariamortalityinchildrenunder10wentupbetweentwoandfive-foldinthreepopulationsinSenegalfollowingemergenceofchloroquine resistance.

Anticipatedimpactofdrugresistanceinthenearterm• Neonatalsepsis• Entericpathogens• Surgicalsiteinfections• Maternalmortalityassociatedwithobstetrics• Malaria• Tuberculosis• HIV

Population without access to improved sanitation, by MDG region 2012

Source: WHO/UNICEF 2014

Kyaw MH et al. N Engl J Med 2006;354:1455-1463.

VaccinescanbeeffectiveInvasivediseasecausedbyPneumococciinchildrenundertwodeclinedintheUSpostpneumovaccination

Kyaw MH et al. N Engl J Med 2006;354:1455-1463.

Invasivediseasecausedbynon-susceptiblePneumococci,US

EffectofPCV7introductiononantibioticprescriptionsandambulatorycarevisits

Zhou et al, Pediatrics 2008

EffectofPCV7introductiononantibioticprescriptionsandambulatorycarevisits

Zhou et al, Pediatrics 2008

Antibiotic prescriptions attributable to acute otitis media decreased from 1244 to 722 prescriptions per 1000 person-years – a 41.9% reduction.

LaxminarayanetalLancet,2015

Antibiotic consumption is increasing in developing countries...

Source: Based on data obtained under license from IMS Health MIDAS ™ (January 2005-December 2010); IMS Health Incorporated. All Rights Reserved.

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15000

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25000

BRAZIL, RETAIL INDIA, RETAIL VIETNAM, RETAIL NORWAY, RETAIL USA, RETAIL

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Uni

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Per capita total antibiotic use, retail sector, 2005-2010

2005

2006

2007

2008

2009

2010

-50 – -30 -29 – -20 -19 – -10 -9 – 0 1 – 10 11 – 20 21 – 40 41 – 80 >80 No data

Percentage change in antibiotic consumption per capita 2000–2010*, by country

Source: Van Boeckel et al. 2015 (adapted; based on IMS MIDAS)

*Data for Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama were available only as a group classified as Central America. Similarly, data for Benin, Burkina Faso, Cameroon, Côte d’Ivoire, Gabon, Guinea, Mali, Republic of the Congo, Senegal, and Togo were grouped and classified as French West Africa. The data for these countries represent the estimates for the corresponding regional groupings they belong to. For countries that did not have data available for 2000, the values for the earliest years for which data were available after 2000 were used to calculate the percentage changes. These countries and initial years are Algeria (2002), Bangladesh (2007), Croatia (2005), Netherlands (2005), and Vietnam (2005).

Faropenem consumptionhasincreasedby154%sinceitwasapprovedforuseinIndiain2010

Gandra etal,Clin Inf Dis,2016

Carbapenem consumption in the hospital sector in selected European countries, 1997–2013

ESAC-Net 2015

Non-prescriptionuseofantimicrobialsiscommon

Morganetal,LancetID,2011

Globalavailabilityofcolistin

Wertheim et al, JGAR 2013

Antibioticuseforgrowthpromotionanddiseaseprevention

2/3rds ofthetonnageofantibioticssoldworldwideareusedinagriculture

Numbersofuniqueβ-lactamaseenzymesidentifiedsinceintroductionoffirstβ-lactamantibiotics

• TotalconsumptioninChina- 92700tonsin2013,

• 54000tonsof antibioticsexcretedbyhumanandanimals- muchofthisenteredintothereceivingenvironmentfollowingvariouswastewatertreatmentsinto58riverbasinsofChina

Zhangetal,Env Sci Tech,2015

High-capacityquantitativePCRarraysdetected149uniqueresistancegenesamongallofthefarmsamples,thetop63ARGsbeingenriched192-fold(median)upto28,000-fold(maximum)comparedwiththeirrespectiveantibiotic-freemanureorsoilcontrols.

IncreaseofantibioticresistancegenesamongsoilscollectedatfivesitesinTheNetherlandsfrom1940to2008.

KnappetalEnv Sci Tech,2010

Temporalassociationbetweencontaminationofretailchicken withceftiofur-resistantSalmonellaHeidelbergstrainsandincidenceofceftiofurresistantSalmonellaHeidelberginfectioninhumans

Dutil etal,EID,2010

Global antibiotic consumption in livestock (mg per 10 km2 pixels) 2010

Van Boeckel et al., PNAS, 2015

Log10 [(mg/pixel) + 1]

No data0 - 1 4 - 5 5 - 6 6 - 7 7 - 8 8 - 9 9 - 10 10 - 11

Global antibiotic consumption in livestock (mg per 10 km2 pixels) 2010

Van Boeckel et al., PNAS, 2015

Log10 [(mg/pixel) + 1]

No data0 - 1 4 - 5 5 - 6 6 - 7 7 - 8 8 - 9 9 - 10 10 - 11

Globalconsumptionofantimicrobialsinfoodanimalproduction• estimatedat63,151(±1,560)tonnes in2010• projectedtoriseby67%,to105,596(±3,605)tonnes by2030• hotspotslikeIndiawhereareasofhighconsumption(30kgperkm2)for

industrialpoultryproductionareexpectedtogrow312%by2030

ImageCourtesy ofShutterstock

Slidesaredownloadable@www.cddep.org

MoreontheGlobalAntibioticResistancePartnership@

www.cddep.org/garp