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.
Introduction to bacterial resistance to antibiotics, types of resistance, brief explaining & examples
The lecture was presented at Al-Mahmoudiya General Hospital at Wed, 17th Nov. 2021
Represented & updated as part of the training course for fresh appointed pharmacist at 16/5/2023
updated statistics about antimicrobial resistance,causes and mechanism of antimicrobial resistances, national antimicrobial policy, national antimicrobial surveillance, new delhi b metallo-lactamase-1 bacteria
FLOW OF THE SEMINAR
1. Definition – antibiotic resistance, Multi-resistance, cross-resistance in antibiotics
2. Evolution of resistance
3. Impact of resistance
4. The scenario of resistance: Global, India
5. Factors causing resistance
6. Mechanisms of resistance: Intrinsic and Acquired
7. Acquired mechanism of resistance
8. Quorum sensing
9. Mechanism of resistance in commonly used antibiotics
10. Methods for determining the resistance
11. Strategies to contain resistance
12. Antibiotic stewardship
13. Role of Pharmacologist
14. Initiatives undertaken by India to control resistance
Introduction to bacterial resistance to antibiotics, types of resistance, brief explaining & examples
The lecture was presented at Al-Mahmoudiya General Hospital at Wed, 17th Nov. 2021
Represented & updated as part of the training course for fresh appointed pharmacist at 16/5/2023
updated statistics about antimicrobial resistance,causes and mechanism of antimicrobial resistances, national antimicrobial policy, national antimicrobial surveillance, new delhi b metallo-lactamase-1 bacteria
FLOW OF THE SEMINAR
1. Definition – antibiotic resistance, Multi-resistance, cross-resistance in antibiotics
2. Evolution of resistance
3. Impact of resistance
4. The scenario of resistance: Global, India
5. Factors causing resistance
6. Mechanisms of resistance: Intrinsic and Acquired
7. Acquired mechanism of resistance
8. Quorum sensing
9. Mechanism of resistance in commonly used antibiotics
10. Methods for determining the resistance
11. Strategies to contain resistance
12. Antibiotic stewardship
13. Role of Pharmacologist
14. Initiatives undertaken by India to control resistance
Antimicrobial resistance is the ability of a microorganism (like bacteria, viruses, and some parasites) to stop an antimicrobial (such as antibiotics, antivirals, and antifungals) from working against it.
Mechanism Antibiotic Resistance
Intrinsic (Natural)
Acquired
Chromosomal
Extra chromosomal
Intrinsic Resistance
Lack target : No cell wall; innately resistant to penicillin
2. Drug inactivation: Cephalosporinase in Klebsiella
3. Innate efflux pumps:
It is an active transport mechanism. It requires ATP.
Eg. E. coli, P. aeruginosa
Altered target sites
PBP alteration
Ribosomal target alteration
Decreased affinity by target modification
Beta-lactamase
Beta-lactamases are enzymes produced by bacteria that provide resistance to β-lactam antibiotics such as penicillins, cephamycins, and carbapenems
Major resistant Pathogen
1. PRSP- Penicillin resistant Streptococcus pneumoniae2. MRSA/ORSA- Methicillin-resistant Staphylococcus Aureus (Super bug)3. VRE -Vancomycin-Resistant Enterococci4. Carbapenem resistant pseudomonas aeruginosa5. Carbapenem resistant Carbapenem resistant 6. Extended spectrum beta-lactamase (ESBL)-producing bacteria
Antimicrobial resistance is the ability of a microorganism (like bacteria, viruses, and some parasites) to stop an antimicrobial (such as antibiotics, antivirals, and antifungals) from working against it.
Mechanism Antibiotic Resistance
Intrinsic (Natural)
Acquired
Chromosomal
Extra chromosomal
Intrinsic Resistance
Lack target : No cell wall; innately resistant to penicillin
2. Drug inactivation: Cephalosporinase in Klebsiella
3. Innate efflux pumps:
It is an active transport mechanism. It requires ATP.
Eg. E. coli, P. aeruginosa
Altered target sites
PBP alteration
Ribosomal target alteration
Decreased affinity by target modification
Beta-lactamase
Beta-lactamases are enzymes produced by bacteria that provide resistance to β-lactam antibiotics such as penicillins, cephamycins, and carbapenems
Major resistant Pathogen
1. PRSP- Penicillin resistant Streptococcus pneumoniae2. MRSA/ORSA- Methicillin-resistant Staphylococcus Aureus (Super bug)3. VRE -Vancomycin-Resistant Enterococci4. Carbapenem resistant pseudomonas aeruginosa5. Carbapenem resistant Carbapenem resistant 6. Extended spectrum beta-lactamase (ESBL)-producing bacteria
‘Antibiotic Ireland’ Antimicrobial Resistance A Major Cause for ConcernImproper Prescribing or Patient’s Misconceptions, Expectation and Pressure on Dr’s to prescribe ?
a research presentation done by Augustine Mwaawaaru Level 400) and Matthew Frimpong Antwi (Level 300) students of( Presbyterian University College-Ghana on Antimicrobial resistance and the way foeward in Ghana. contact 0261825262
‘Antibiotic Ireland'. Antimicrobial Resistance: A Major Cause for Concern. I...Theresa Lowry-Lehnen
‘Antibiotic Ireland’: Antimicrobial Resistance A Major Cause for Concern. Improper Prescribing or Patient’s Misconceptions, Expectation and Pressure on Dr’s to prescribe ?
Vasculitis syndrome an approach -and-basic principles of treatmentSachin Verma
Vasculitides are a hetrogenous group of conditions characterized by inflammation and necrosis of blood vessels.
A broad group of syndromes may result from this process,since any type,size, and location of vessel may be involved.
Type 2 dm gdm new updates & guidelinesSachin Verma
Type 2 diabetes is a multifactorial disorder characterised by progressive pancreatic beta-cell dysfunction and insulin- resistance, leading to relative insulin deficiency, chronic hyperglycaemia, and various complications.
The treatment options for this disorder, which aim at correcting one or other of the two major pathophysiological mechanisms, have been hamstrung by unacceptable side-effects, lack of patient acceptability, and loss of efficacy over time.
Tuberculosis suspect. Productive cough for more than 2 weeks, which may be accompanied by other respiratory symptoms and/or constitutional symptoms
Case of tuberculosis. A definite case of TB or one in which a health worker (clinician or other medical practitioner) has diagnosed TB and has decided to treat the patient with a full course of TB treatment.
Any person given treatment for TB should be recorded as a case. Incomplete “trial” TB treatment should not be given as a method for diagnosis.
Proteinuria – early indicator of renal disease
Increases the risk of renal impairment, hypertension & cardiovascular disease.
Proteinuria of 1+ or more persisting on 2 subsequent dipstick tests at weekly intervals – requires further investigations.
Causes of transient proteinuria to be excluded
Vertigo –the dizzy patient an evidence-based diagnosis and treatment strategySachin Verma
Vertigo is a symptom of illusory movement and not a diagnosis .It is due to asymmetry of vestibular system due to damage or dysfunction of the
Labyrinth and vestibular nerve, or
Central vestibular structures in the brainstem
Urine examination how to approach final.ppt1Sachin Verma
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.
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.
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.
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.
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.
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.
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.
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.
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
7.
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
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
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
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
26.
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
28.
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
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
Editor's Notes
By 1946, 6% of S. aureus strains were resistant to penicillin By 1960 up to 60% of S. aureus strains were resistant to penicillin