Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.

1. ANTIBIOTIC
RESISTANCE
Dr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care Medicine
Infection Control Fellows Course
Consultant Internal Medicine and Critical Care
Web:- http://www.medicinedoctorinchandigarh.com
Mob:- +91-7508677495

2. Lecture overview
 Definition of multidrug resistance
 History of antibiotics
 How does resistance develop?
 Why is it important?
 Multidrug resistance organisms
(MDROs)
 Control

3. Multidrug-Resistant
Organisms( MDROs)
 Microorganisms that are resistant to one or
more classes of antimicrobial agents. MDRSP
refers to isolates resistant to 2 or more of
the following antibiotics: penicillin, second-
generation cephalosporins, macrolides,
tetracycline, and
trimethoprim/sulfamethoxazole
CDC: Management of Multidrug-Resistant Organisms in Healthcare Settings, Healthcare Infection Control Advisory Committee, Jane D. Siegel et. al. pg 7-
12

4. History of antibiotics
 1928: Penicillin first discovered by Alexander
Fleming
 Chain and Florey, helped develop penicillin into
a widely available medical product

5. History of antibiotics
 1943- Drug companies begin mass
production of penicillin
 1944 – U.S. Military takes Penicillin to
the battlefield

6. History of antibiotics
 1945, Fleming, Chain and Florey awarded the
Nobel Prize in Physiology and Medicine
 After 2nd World War many more antibiotics
were developed
 Today about 150 types

8. History of antibiotics
 Many experts were confident the tide
had turned in the war against bacterial
infections
 1969, the then US Surgeon General,
William Stewart, boldly told the US
Congress it was time to "…close the
books on infectious diseases."

9. March 1942
A 33 year-old lady lay dying of streptococcal
sepsis in Connecticut, USA
Best efforts of doctors fail to clear the
bloodstream infection
Doctors manage to obtain small amount of
newly discovered penicillin which when
injected cautiously, clears the streptococci from
the blood
The patient miraculously survives. And lives up
to 90 years

10. November 2011
A 16 year-old girl is being treated for pneumonia caused
by Klebsiella pneumonia in Ivy Hospital Mohali
Despite best medical care – ALL antibiotics available for
klebsiella , treating physicians unable to clear the
patient’s blood
The patient dies, still with bloodstream infection

11. We have come almost
full circle and arrived at a
point as frightening as
the pre-antibiotic era

12. Dr.T.V.Rao MD 12

13. How does resistance develop?

14. A variety of mutations can lead to antibiotic resistance
Mechanisms of antibiotic resistance
1. Enzymatic destruction of drug
2. Prevention of penetration of drug
3. Alteration of drug's target site
4. Rapid ejection of the drug
Resistance genes are often on plasmids or transposons that can
be transferred between bacteria

16. BACTERIA MUTATE TO PROTECT
THEMSELVES FROM ANTIBIOTIC

17. THE MUTATED BACTERIA EVENTUALLY THERE ARE MORE
SURVIVE AFTER THE ANTIBIOTIC-RESISTANT
ANTIBIOTICS ARE GONE BACTERIA THAN NON-
RESISTANT

18. Why is Resistance a Concern?
Resistant organisms are becoming commonplace
Bacterial resistance often results in treatment failure and
increased mortality and cost
The problem is no longer confined to the hospital setting
Bacterial resistance will continue to worsen if not
addressed
There are no antibiotics on the immediate horizon with
activity against these multi-drug resistant pathogens

19. Number of New Molecular Entity (NME) Systemic Antibiotics Approved
by the US FDA Per Five-year Period, Through 3/11.
Clin Infect Dis. 2011;52:S397-S428

20. Risk factors for acquisition of
MDROs
 ICU stay
 Previous exposure to antimicrobial agents
 Underlying diseases
 Dialysis
 Invasive devices
 Recurrent admissions to hospital
 Nursing home
 Previous colonization of a multidrug-resistant
organism
 Advanced age

21. How do patients acquire
MDRO’s?
 Select out the resistant strains due to
repeated courses of antibiotics
 Spread from person to person
 environment
 hands of HCW
 patient equipment
 contact with patient

22. Resistance is accelerated through
inappropriate use of antimicrobials
–Standard treatment guidelines not provided
–Provided but not adhered to
50 % prescriptions are inappropriate
–Drugs not accessible
50% populations in developing countries do not have access
–Accessible but poor quality or expensive
–Inadequate monitoring
50% of patients do not adhere to recommended regimen
–Irrational self-administration or prescription
–Extensive use for therapeutic and growth promotion in animals
50% of national antibiotic consumption is for non-therapeutic
purposes in animals

24. Multi-drug resistant
organisms
 Gram positive organisms
 MRSA
 VRE
 Gram negative organisms
 ESBLs
 CRE

25. MRSA
 NNIS (2004) – 60% of S. aureus are methicillin resistant
 Nosocomial
 mecA gene encodes low affinity for PBP resulting in resistance to all
beta-lactams
 Usually multi-drug resistant
 Community-acquired
 More virulent – Panton-Valentine leukocidin
 Skin and soft tissue infections in children and young adults
 Usually susceptible to non beta-lactam drugs

27. VRE
 Non-existent as recently as 1989
 NNIS report (2004) – 30% of all enterococcal isolates are
resistant
 Mediated by vanA and vanB genes resulting in alteration of
target site
 Clonal spread via poor infection control

29. Resistance in Gram negatives
 Acinetobacter
 Uncommon in most U.S. medical centers
 Incidence as high as 10% in some geographic
locations
 Carbapenems are drug of choice
 Pseudomonas aeruginosa
 Multi-drug resistance increasing nationwide
 Fluoroquinolones: 29% resistance (NNIS 2004)
 Beta-lactams: metallo-beta-lactamase producing strains
have been reported

30. ESBLs a growing concern
Resistant to all penicillins, cephalosporins, and aztreonam
Carbapenems are the drug of choice
Fluoroquinolone resistance
NNIS 2004 report: 8% E.coli resistant
Chromosomal and plasmid mediated alterations in target site
or decreased access to target
Carbapenem resistance
Klebsiella pneumoniae carbapenemase
Metallo-beta-lactamases
ampC beta-lactamase + loss of outer membrane channels

31. IVY HOSPITAL ANTIBIOGRAM
(DEC 2010 - MAR 2011)
LACTOSE FERMENTING GNB (E. coli,
Klebsiella spp., Citrobacter spp., Enterobacter spp., etc.)
TOTAL= 112 isolates

32. Percentage break up OF LFGNB( n= 112)

33. NON LACTOSE FERMENTING GNB
(Acinetobacter spp, Pseudomonas spp. etc)
TOTAL = 55 ISOLATES

35. Staphylococcus aureus
(Total 21 isolates)

37. Prevention of antimicrobial
resistance
 Prevent Infection
 Vaccinate
 Remove catheters
 Diagnose and Treat Infection Effectively
 Isolate the pathogen
 Target the pathogen
 Access the experts

38. Prevention of antimicrobial
resistance
 Appropriate prescribing of antibiotics
 Only prescribe antibiotics when necessary
 Use local data
 Treat infection, not contamination
 Treat infection, not colonisation
 Stop treatment when infection is cured or
unlikely

39. Prevention of antimicrobial
resistance
 Surveillance:
 Moniters trends in resistance patterns,
incidence of MDROs, emerging MDROs
 Locally, regionally, nationally, internationally
 Moniters effectiveness of interventions

40. Prevention of transmission to
other patients
 Spread from person to person
 Environment, hands of HCW, patient
equipment, contact with patient
 Hand hygiene
 Environmental cleaning

41. Antibiotic Stewardship Program
 Optimal selection, dosage, and duration of
antimicrobial treatment that
 Results in the best clinical outcome for the treatment or
prevention of infection
 With minimal toxicity to the patient and
 With minimal impact on subsequent resistance

42. Antibiotic Stewardship Program
 Involves
 Prescribing antimicrobial therapy only when it is
beneficial to the patient
 Targeting therapy to the desired pathogens
 Using the appropriate drug, dose, and duration

43. Antibiotic Policy : To Minimise
Antibiotic Resistance
 Appropriate Use of Antibiotics and specific guidelines e.g.
Therapy Recommendations
 In serious infections; start with ultra-broad antibiotic then de-
escalate to narrow spectrum depending on culture report
 Limit use of Broad Spectrum Antibiotics where possible
 Antibiotic cycling/rotation