ANTIMICROBIAL RESISTANCE AMONG OTHER BACTERIAL

PATHOGENS OF PUBLIC HEALTHPATHOGENS OF PUBLIC HEALTH IMPORTANCE

Ma. Charmian M. Hufano, M.D., F.P.C.P.Medical Specialist II

Antimicrobial Resistance Surveillance ProgramgResearch Institute for Tropical Medicine

hwhenOnce upon a time…

Alexander Fleming inAlexander Fleming in 1928 accidentally

di PENICILLINdiscovers PENICILLIN

www.nobelprize.org

http//ccat.sas.upenn.edu/goldenage/state/state.htm

Timeline of Antibiotic Deployment and theTimeline of Antibiotic Deployment and the Evolution of Antibiotic Resistance

Clatworthy AE, Pierson E & Hung DT. Nature Chemical Biology 2007;3: 541 - 548.

A i i bi l R iAntimicrobial Resistance

•Antimicrobial resistance occurs when bacteria changes in ways thatbacteria changes in ways that reduces/eliminates the effectiveness

f th d d i d t / tof the drug designed to cure/prevent the infectiont e ect o

http://www.cdc.gov/getsmart/antibiotic-use/anitbiotic-resistance-faqs.html

“S i l f h Fi ”“Survival of the Fittest”

http://www.defra.gov.uk/foodfarm/farmanimal/diseases/vetsurveillance/antimicrobial-res-fig.htm

A i i bi l R iAntimicrobial Resistance

National Institute of Allergy and I f ti DiInfectious Diseases http://www.usc.edu

Antimicrobial Resistance: The Bugs Fight Back

Consequences of Antimicrobial Resistance

• Mortality

• Morbidity- prolonged illness, greater chance of resist organisms to spread to others

• Cost- increase cost of care, newer and more expensive antibioticsantibiotics

•

Li it d O ti f d th h i• Limited Options- few new drugs on the horizon

Antimicrobial Resistance Surveillance ProgramAntimicrobial Resistance Surveillance Program (ARSP)

• World Health Organization (WHO) Working Group on the Regional Information Network on Antimicrobial ResistanceRegional Information Network on Antimicrobial Resistance (1987)

• Department Order No. 339J- Department of Health Created the Antimicrobial Resistance Surveillance Committee (December 1 1988)Committee (December 1, 1988)

• Objective: To provide critical inputs to the DOH’s effort to• Objective: To provide critical inputs to the DOH s effort to promote rational drug use by determining the current status and developing trends on antimicrobial resistance f fof selected bacteria to specific antimicrobials.

Antimicrobial Resistance Surveillance ProgramAntimicrobial Resistance Surveillance Program (ARSP)

1988: Philippine General Hospital (PGH) National Kidney Institute (NKI) Lung Center of the1988: Philippine General Hospital (PGH), National Kidney Institute (NKI), Lung Center of the Philippines (LCP), Research Institute for Tropical Medicine (RITM), San Lazaro Hospital (SLH), Bureau of Research Laboratory (BRL), Far Eastern University (FEU) and Jose Reyes Memorial Medical Center (JRMMC)

1994: Rizal Medical Center (RMC), Governor Celestino Gallares Memorial Medical Center (GMH) and Zamboanga medical Center (ZMC)

1998: Eastern Visayas Regional Medical Center (EVR), Corazon Locsin Montelibano Memorial1998: Eastern Visayas Regional Medical Center (EVR), Corazon Locsin Montelibano Memorial Medical Center (MMH), Vicente Sotto Memorial Medical Center (VSM) and Davao Medical Center (DMC)

2000- Cotabato General Hospital and Medical Center (CMC), Baguio General Hospital and p ( ) g pMedical Center (BGH) , Bicol Regional Teaching and Training Hospital; GonorrheaSurveillance- Pangasinan Provincial Hospital (PPH), Zamboanga del Norte Provincial Hospital (ZPH), Dr. Rafael S. Tumbokon Memorial Hospital (RTH) and Bicol Regional Teaching and Training Hospital (BRT)

2008- Mariano Marcos Memorial Hospital (MAR)and Medical Center and Batangas Regional Hospital (BRH)

2009 Cagayan Valley Medical (CVM) Jose B Lingad Memorial General Hospital (JBL) and2009- Cagayan Valley Medical (CVM), Jose B. Lingad Memorial General Hospital (JBL) and Northern Mindanao Medical Center (NMC)

Antimicrobial Resistance Surveillance ProgramAntimicrobial Resistance Surveillance Program (ARSP)

Pathogens of Public Health ImportancePathogens of Public Health Importance Covered by this Presentation

• Diarrheal DiseasesSalmonella species

• Urinary Tract InfectionsEscherichia coliSalmonella species

Shigella speciesVibrio cholerae

Escherichia coli

• Skin/Lung/BloodstreamVibrio cholerae

• Respiratory Tract Infections

Skin/Lung/Bloodstream Infections

Staphylococcus aureusp yStreptococcus pneumoniae

• Hospital Acquired Infections• Sexually Transmitted 

InfectionsNeisseria gonorrhoeae

InfectionsKlebsiella spp.Pseudomonas aeruginosaNeisseria gonorrhoeae g

ANTIMICROBIAL RESISTANCE SURVEILLANCE PROGRAMSURVEILLANCE PROGRAM

2009 REPORT2009 REPORT

Trends in Antimicrobial Resistance amongTrends in Antimicrobial Resistance among Neisseria gonorrhoeae Isolates 1995-2009 ARSP

E i P hEnteric Pathogens• Diarrhea remains once of the top 5 causes of morbidity

and mortality amongst Filipino children < 5 years old

• Key Bacterial Causes of Diarrhea:Vib i h l1. Vibrio cholera

2. Salmonella sp.Shi ll3. Shigella sp.

World Health Statistics 2010

Trends in Antimicrobial Resistance amongTrends in Antimicrobial Resistance among Vibrio cholera Isolates 1988-2009 ARSP

S l ll I f iSalmonella Infections

Salmonella Infections

Typhoid Fever-S l ll T hi

Diarrhea-NontyphoidalSalmonella Typhi Nontyphoidal Salmonella

Trends in Antimicrobial Resistance amongTrends in Antimicrobial Resistance among Salmonella Typhi Isolates 1988-2009 ARSP

Trends in Antimicrobial Resistance amongTrends in Antimicrobial Resistance among Non-typhoidal Salmonellae 1988-2009 ARSP

YEARYEAR

Trends in Antimicrobial Resistance amongTrends in Antimicrobial Resistance among Shigella spp. Isolates 1988-2009 ARSP

Burden and Epidemiology of Pneumonia• Pneumonia is the leading killer of children under 5 years

of age worldwide.

• Although bacterial infections account for no more than 50% of cases of pneumonia they cause nearly 70% of50% of cases of pneumonia, they cause nearly 70% of deaths due to pneumonia.

WHO report by the Secretariat. Treatment and prevention of pneumonia. March 25, 2010.

WHO Statistics 2009.

Burden and Epidemiology of Pneumonia• Streptococcus pneumoniae and Haemophilus influenzae

are the most common bacteria causing pneumonia and these two organisms account for more than half of allthese two organisms account for more than half of all deaths due to pneumonia in children under five years of age.g

• Penicillin nonsusceptible S. pneumoniae (PNSP) was e c o suscep b e S p eu o ae ( S ) asinitially detected in the 1970s, but resistance to the antimicrobial has since spread worldwide.

WHO report by the Secretariat. Treatment and prevention of pneumonia. March 25, 2010.

Lynch etal. Curr Opin Pulm Med. 2010

Trends in Antimicrobial Resistance among gStreptococcus pneumoniae Isolates 1988-2009 ARSPARSP

E h i hi liEscherichia coli• Most common cause of UTIs

• Other infections: neonatal meningitis, hospital acquired pneumonia, gallbladder and biliary tract infections, skin, b d j i t i f ti d bl d t i f tibone and joint infections and bloodstream infections

Resistance Rates of Escherichia coliResistance Rates of Escherichia coli All Sites 1988-2009

SuperBugs and Hospital-acquired InfectionsStaphylococcus aureus Klebsiella spp and PseudomonasStaphylococcus aureus, Klebsiella spp. and Pseudomonas

aeruginosa

Hospital bugs are exposed to wide range of antibiotics

H it l b i t tHospital bugs are more resistant

-higher mortality rates-higher mortality rates-longer length of hospital stay-higher costg

Cosgrove SE. CID 2006Zoleta etal. Phil J Microbio lnfect Dis 2004

Presumptive Nosocomial InfectionsPresumptive Nosocomial InfectionsARSP 2009 Data from All Sites

# of Isolates 2009 with # of Isolates from % of Isolated# of Isolates 2009 with Date of Admission Data

# of Isolates from Specimens Submitted 48 Hours Admission

% of IsolatedPresumed to Be of Nosocomial Origin

13776 4995 36%Presumptive Nosocomial Infections (N= 4995)

O # f % fOrganism # of Isolates % of Presumed Nosocomial Infections

Klebsiella spp. 1142 23Escherichia coli 850 17Pseudomonas aeruginosa 789 16Enterobacter spp 662 13Staphylococcus aureus 320 6Staphylococcus aureus 320 6Others 683 14

MRSA (Methicillin-Resistant Staphylococcus aureus)

Skin and soft tissue infections, bone infections, pneumonia, catheter-related infections, bloodstream infections

MRSA (Oxacillin) TrendsMRSA (Oxacillin) Trends All ARSP Sites 1998-2009

MRSA: 2009 ARSP and the ANSORPMRSA: 2009 ARSP and the ANSORP Surveillance

MRSA Rates ARSP ANSORP 2009 2004-2006

Over-all 45% 53%

ANSORP (Asian Network for Surveillance of Resistant Pathogens) CountriesANSORP (Asian Network for Surveillance of Resistant Pathogens) Countries participating: Korea, Taiwan, Hong Kong, Thailand, Philippines, Vietnam, India and Sri Lanka.

Song J etal. , J Antimicrob Chemother. 2011

S. Aureus Oxacillin Resistance RatesAll Sites 2009 ARSP

Community-acquired MRSACommunity acquired MRSA

• Skin infections• Younger populationYounger population• No hospital exposureNo previous antibiotic• No previous antibiotic treatmentN i k f f• No risk factors of underlying disease

Distribution of MRSA Isolates Among Admitted gPatients with Date of Admission All ARSP Sites 2009

Admitted Patients with Information on Date of AdmissionDate of Admission

MRSA % MRSAC it A i d 99 57Community Acquired 99 57PresumptiveNosocomial Infection *

74 46Nosocomial Infection *

* Presumptive Nosocomial Infection- “specimen date” was 48 hours after “date of admission”after date of admission

Gram-negative Superbugs and Hospital-Gram negative Superbugs and HospitalAcquired Infections

• Gram-negative bacteria are highly efficient in developing h i f ti i bi l i tmechanisms of antimicrobial resistance

Ab f d d l t ith ti it i t• Absence of new drug development with activity against drug-resistant gram-negative bacteria

• Klebsiella spp. and Pseudomonas aeruginosa –representative of gram-negative hospital pathogensrepresentative of gram-negative hospital pathogens

WHO: Surveillance Standards for Antimicrobial Resistance

Kl b i llKlebsiella spp.

Trends in Resistance of Klebsiella sppTrends in Resistance of Klebsiella spp.1992-2009 ARSP

Trends in Resistance of PseudomonasTrends in Resistance of Pseudomonas aeruginosa 1988-2009 ARSP

100

8090

100

Ciprofloxacin Ceftazidime Imipenem

506070

Ciprofloxacin Ceftazidime Imipenem

304050

0102030

0

AND THE STORY GOESAND THE STORY GOES ONON…Antibiotic resistance now has been universally identified

bli h lth i it d l f ti tas public health priority and necessary plan of action tocombat resistance should be developed.

ANTIMICROBIAL RESISTANCEANTIMICROBIAL RESISTANCE SURVEILLANCE PROGRAMSURVEILLANCE PROGRAM

ARSP A hiARSP AchievementsT th lit f d tTo assure the quality of our data:

The ARSRL participate regularly in International ExternalThe ARSRL participate regularly in International ExternalQuality Assurance Programs for the ARSRL

Sentinel sites’ microbiology laboratories perform cultureand susceptibility tests according to international standards

d f d h l di i l b f hand refer data to the central coordinating laboratory of theprogram

Regular feedback with alert reports for possible outbreaksare reported to the sentinel sitesp

ARSP annual reports from 1988-2009ARSP annual reports from 1988 2009 distributed to relevant stakeholders

Philippine CAP and UTI Guidelines

Philippine National Drug FormularyPhilippine National Drug Formulary

reassessing the national formulary g y assuring that drug supplies are appropriate for needs

ARSP PUBLICATIONS, LOCAL AND INTERNATIONAL

PSMID J l CID J lPSMID Journal CID Journal

ARSP AchievementsARSP AchievementsRelevant researches and publications by Dr. Celia C. Carlos and ARSP staff:staff:• The clinical and molecular epidemiology of an outbreak of multi-drug

resistant typhoid fever in Metro Manila. Abstracts of the 34th ICAACConference, Orlando, Florida, 1994.

• Carriage of antibiotic-resistant pneumococci among Asian children: amultinational surveillance by the Asian Network for Surveillance ofmultinational surveillance by the Asian Network for Surveillance ofResistant of Resistant Pathogens (ANSORP), CID 2001: 32 (15 May):1463-1469.C f• Clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in Asian countries: a study by the Asian Network forSurveillance of Resistant Pathogens, CID 2004: 39 (1 June): 1570-8.

• Epidemiology and clinical outcomes of community-acquired pneumonia inadult patients in Asian countries: a prospective study by the Asian Networkfor Surveillance of Resistant Pathogens International Journal offor Surveillance of Resistant Pathogens. International Journal ofAntimicrobial Agents 31(2):107-114, 2008 (February).

ARSP AchievementsARSP AchievementsRelevant researches and publications by Dr. Celia C. Carlosand ARSP staff:and ARSP staff:

• Antimicrobial susceptibility of Shigella isolates in eight AsianAntimicrobial susceptibility of Shigella isolates in eight Asiancountries, 2001-2004. Journal of Microbiology, Immunologyand Infection 41(2):107-111, 2008 (April).S ill f i i bi l i f S l ll t i• Surveillance of antimicrobial resistance of Salmonella entericaserotype Typhi in seven Asian countries. Epidemiology andInfection 12:1-4, 2008 (May).Infection 12:1 4, 2008 (May).

• Layman’s Guide to Food and Water-borne disease OutbreakResponse. FCA Printhouse, Manila, Philippines, 2010.

• Clinical impact of methicillin resistance on outcome of patientswith Staphylococcus aureus infections: a stratified analysisaccording to underlying diseases and site of infection in aaccording to underlying diseases and site of infection in alarge prospective cohort, J of Infection (2010) 61: 299-306.

ARSP AchievementsARSP AchievementsRelevant researches and publications by Dr. Celia C. Carlos and ARSP staff:ARSP staff:• Spread of methicilin-resistant Staphylococcus aureus between the

community and the hospitals in Asian countries: an ANSORP study. J Antimicrob Chemother (Feb 20 2011)J Antimicrob Chemother (Feb 20, 2011).

• Hospital-based Surveillance to Estimate the Economic Burden of Rotavirus Gastroenteritis in Children Under 5 years of age in the y gPhilippines

• A prospective multinational surveillance of hospital-acquired pneumonia (HAP) and ventilator-associated pneumoniae (VAP) inpneumonia (HAP) and ventilator associated pneumoniae (VAP) in adults in Asian countries: etiology, clinical outcome, and impact of antimicrobial resistance P ti h it l b d lti ti l ill• Prospective, hospital-based, multinational surveillance on antimicrobial resistance and serotypes of Streptococcus pneumoniae and disease burden of pneumococcal infections in Asian countries in the era of pneumococcal conjugate vaccine

ACKNOWLEDGEMENTSACKNOWLEDGEMENTS

THE ENDTHE END