This document discusses antibiotic resistance and its management. It defines antibiotic resistance as when microorganisms become resistant to drugs that previously treated infections from them. It outlines various mechanisms of antibiotic resistance in microorganisms and lists priority resistant bacteria. It also discusses superbugs and different strategies to manage antibiotic resistance like prudent antibiotic use, infection control, developing new drugs, and reducing agricultural overuse of antibiotics.

1. By- Animesh Gupta
JR- III medicine

2. Introduction:
 The drug concentration at the site of infection must inhibit the
organism but also must remain below the level that is toxic to
human cells. If this can be achieved, the microorganism is
considered sensitive; if not, the microorganism is considered
resistant to the drug.
 WHO defines antimicrobial resistance as a microorganism's
resistance to an antimicrobial drug that was once able to treat an
infection by that microorganism.
Goodman and Gilman Manual of Pharmacology and Therapeutics.11th edition

4. Mechanism OfAction OfAntibiotics
 Inhibit cell wall synthesis:
 β-Lactam antibiotic:- Penicillins, Cephalosporins,
 Glycopeptide antibiotics:- Vancomycin, Teicoplanin
 Polypeptide antibiotics:- Bacitracin.
 Leakage from cell membranes:
 Polypeptides:- Polymyxin B, Colistin, Bacitracin.
 Polyenes:- Amphotericin B, Nystatin.
 Inhibit protein synthesis:
 Aminoglycosides:- Streptomycin, Gentamicin,
 Tetracyclines:- Doxycycline, tigecycline
 Nitrobenzene derivative:- Chloramphenicol
 Macrolide antibiotics:- Erythromycin,
 Lincosamide antibiotics:- Clindamycin
 Oxazolidinone:- Linezolid, Tedizolid

5. Mechanism OfAction OfAntibiotics
 Inhibit DNA gyrase
 Fluoroquinolones- Ciprofloxacin
 Interfere with DNA function(RNA polymerase inhibitors)
 Rifampicin.
 Destroy DNA
 Nitroimidazoles:- Metronidazole
 Interfere with intermediary metabolism:
 Sulfonamides and related drugs:- Sulfonamides, Sulfones (Dapsone (DDS),
Paraaminosalicylic acid (PAS))
 Diaminopyrimidines:- Trimethoprim, Pyrimethamine,

6. Godfrey S. Bbosa et al. Antibiotics/antibacterial drug use, their marketing and promotion during the post-antibiotic golden age and their
role in emergence of bacterial resistance Vol.6 No.5(2014), Article ID:43142,16 pagesDOI:10.4236/health.2014.65059

7. Mechanism Of Resistance
 Reduced entry of antibiotic into pathogen
 Enhanced export of antibiotic by efflux pumps
 Release of microbial enzymes that destroy the antibiotic
 Alteration of microbial proteins that transform pro-drugs to the effective
moieties
 Alteration of target proteins
 Development of alternative pathways to those inhibited by the antibiotic

8. Sundsfjord A et al. Genetic methods for detection of antimicrobial resistance. APMIS 2004 Nov-Dec;112(11-12):815-37

9. Superbugs
 The term “superbugs” refers to microbes with
enhanced morbidity and mortality due to multiple
mutations endowing high levels of resistance to the
antibiotic classes specifically recommended for their
treatment; the therapeutic options for these microbes
are reduced, and periods of hospital care are extended
and more costly.
Julian Davies et al. Origins and Evolution of Antibiotic ResistanceMicrobiol Mol Biol Rev. 2010 Sep; 74(3): 417–433.
doi: 10.1128/MMBR.00016-10

10. Superbugs
 Priority 1: Critical
 Acinetobacter baumannii carbapenem-resistant
 Pseudomonas aeruginosa, carbapenem-resistant
 Enterobacteriaceae, carbapenem-resistant, ESBL-producing
 Priority 2: High
 Enterococcus faecium, vancomycin-resistant
 Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and
resistant
 Helicobacter pylori, clarithromycin-resistant
 Campylobacter spp., fluoroquinolone-resistant
 Salmonellae, fluoroquinolone-resistant
 Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant
 Priority 3: Medium
 Streptococcus pneumoniae, penicillin-non-susceptible
 Haemophilus influenzae, ampicillin-resistant
 Shigella spp., fluoroquinolone-resistant
https://www.statnews.com/2017/02/27/who-list-bacteria-antibiotic-resistance

11. Superbugs
 What is NDM-1?
 NDM-1 stands for New Delhi metallo- beta- lactamase.
 The gene was named after New Delhi, the capital city of India, as it
was first described by Yong et al. in 2009 in a Swedish national who
fell ill with an antibiotic-resistant bacterial infection that he acquired
in India . The infection was unsuccessfully treated in a New Delhi
hospital, a carbapenem-resistant Klebsiella pneumoniae strain
bearing the novel gene was identified. The authors concluded that the
new resistance mechanism clearly arose in India
 The enzyme is active against other compounds that contain beta-
lactam ring like, penicillins, cephalosporins and the carbapenems.
 Some gram negative Enterobacteriaceae bacteria (notably Escherichia
coli and K. pneumoniae) that makes them resistant to virtually all
beta- lactams, including carbapenems.

12. Mycobacteria
 Multi- drug resistant
 Combined resistance to Rifampicin and Isoniazid
 Extensively - drug resistant
 Combined resistance to at least
 Isoniazid
 Rifampicin
 A fluoroquinolone (ofloxacin, levofloxacin, or moxifloxacin)
 A second- line injectable drugs (capreomycin, kanamycin or
amikacin)

13. Revised National Tuberculosis Control Programme. Guidelines on Programmatic Management of Drug Resistant TB (PMDT) in India

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15. Factors ForAntibiotic Resistance
Antibiotic
Resistance
Environmental
Drug
Related
Prescriber
related
Patient
related

16. Environmental
 Lack of sanitation Facilities
 Lack of immunisation coverage
 Environmental antibiotic pollution
 Poorly monitored infection control in hospitals
 Growing antibiotic use in the animal sector as growth
supplements

18. Drug Related
 Over the counter availability of antibiotics without
prescription
 Counterfeit and substandard drug causing sub-
optimal blood concentration
 Irrational fixed dose combination of antibiotics
 Availability of few new antibiotics
Laxminarayan R et al. Antibiotic Resistance in India: Drivers and Opportunities for Action PLoS Med 13(3): e1001974. doi: 10.
1371/journal. pmed. 1001974

20. Patient Related
 Poor adherence of dosage Regimens
 Self-medication
 Lack of education and awareness
 Poverty
 Lack of sanitation habits

21. Prescriber Related
 Inappropriate use of available drugs
 Over- prescription of antibiotics
 Lack of current knowledge and training
 Increased empiric poly-antimicrobial use
 Lack of more rapid and accurate diagnostic
methods
Ventola CL. The Antibiotic Resistance Crisis Part 1: Causes and Threats. P&T®. April 2015. Vol. 40 No. 4

23. Management OfAntibiotic Resistance
Center for Disease Dynamics, Economics & Policy. 2015. State of the World’s Antibiotics, 2015.

24. Management OfAntibiotic Resistance
 Prevent Transmission of Bacterial Infections
 Diligent hand hygiene before and after all patient interactions that
take place during the delivery of health care
 Disinfection of the health care environment and patient-care
equipment
 Development of new vaccines can be effective in limiting the
transmission of resistant bacterial infections. For e.g. The new
Streptococcus pneumoniae vaccine in 2010.
 Improving access to clean water and sewerage systems, and ensuring a
safe and healthful food supply
 Establishment of regulations governing the discharge of antimicrobial
waste into the environment for prevention of environmental
antibiotic pollution.

25. Management OfAntibiotic Resistance
 Adopt Antibiotic Stewardship Programs
 guide all prescribers in administering antibiotics correctly.
 Making a commitment to use antibiotics only when needed.
 Choose the proper drug, and administer the medication at the
appropriate dose and duration in every case.
 Requires an interdisciplinary team, system innovation,
educational intervention, and feedback provided to health
care workers.
 Improve patient care, shorten hospital stays, and reduce health
care facilities’ pharmacy costs.
Ventola CL et al. The Antibiotic Resistance Crisis Part 2: Management Strategies and New Agents P&T®, May 2015.Vol. 40 No. 5

26. Management OfAntibiotic Resistance
 Improving Health Care Delivery
 Implementation of more rapid, accurate diagnostic methods.
 Discouraging extended regimens i.e. Optimize therapeutic regimens
e.g. using biological markers like C-reactive protein or procalcitonin
(PCT) to better facilitate therapeutic decisions.
 Encourage development and use of guidelines and treatment
algorithms to foster appropriate use
 Institution a combination therapy instead of a single agent if
necessary.
 Preferring a narrow spectrum agent for initial empirical therapy

27. Microbiologist
Physician
Bacterial
sensitivity test
Treat Infection
Regular interaction between an infectious disease
specialist/microbiologist and the health care
practitioners for establishment of microbiological
diagnosis.

28. Management OfAntibiotic Resistance
 Reduce And Eventually Phase Out Antibiotic
Use In Agriculture
 Require obligatory prescriptions for all antimicrobials used for
disease control in food animals.
 Monitor resistance to identify emerging health problems and
take timely corrective actions to protect human health.
 Create national systems to monitor antimicrobial usage in
food animals.
 Develop guidelines for veterinarians to reduce overuse and
misuse of antimicrobials in food animals.
WHO Global Strategy for Containment of Antimicrobial Resistance

29. Management OfAntibiotic Resistance
 Educating Patients And The General
Community
 The importance of measures to prevent infection, such as
immunization, vector control, use of bed nets, etc.
 Simple measures that may reduce transmission of infection in
the household and community, such as hand washing, food
hygiene, etc.
 Encourage appropriate and informed health care seeking
behaviour.
 Suitable alternatives to antimicrobials for relief of symptoms
and discourage patient self-initiation of treatment.

30. Management OfAntibiotic Resistance
 National Governments And Health Systems
Initiatives
 Establish an effective registration scheme for dispensing
outlets.
 Surveillance of resistance, antimicrobial usage and disease
burden.
 Establish and maintain updated national standard treatment
guidelines (STGs) and encourage their implementation.

31. Management OfAntibiotic Resistance
 Establish an Essential Drugs List (EDL) consistent with the
national STGs and ensure the accessibility and quality of these
drugs.
 Limit the availability of antimicrobials to prescription-only status,
except in special circumstances when they may be dispensed on
the advice of a trained health care professional.
 Ensure that only antimicrobials meeting international standards
of quality, safety and efficacy are granted marketing
authorization.
 Enhance immunization coverage and other disease preventive
measures, thereby reducing the need for antimicrobials.

32. Management OfAntibiotic Resistance
 Research And Development Of New
Antibiotics
 Baxdela (delafloxacin) tablets and injection:-
 A fluoroquinolone by Melinta Therapeutics
 Approved June 2017
 For the treatment of Acute bacterial skin and skin structure infections,
community and hospital-acquired bacterial pneumonia, uncomplicated
gonorrhoea, complicated UTIs and intra-abdominal infections
 Vabomere (meropenem and vaborbactam):-
 Approved August 2017
 A combination of Meropenem & Vaborbactam, a beta-lactamase inhibitor
that protects meropenem from beta-lactamases such as Klebsiella
pneumoniae carbapenemase, by The Medicines Company
 For the treatment of complicated urinary tract infections.

33. Management OfAntibiotic Resistance
 Teixobactin
 First of a new class of antibiotics discovered by iChip
technology to grow previously impossible-to-culture microbe
that produces teixobactin, Eleftheria terrae in January 2015.
 Mode of action- inhibiting peptidoglycan biosynthesis.
 Activity against Gram-positive (but not Gram-negative)
organisms and mycobacteria.