Antibacterial resistance is a major global problem as many bacterial infections are becoming increasingly difficult to treat due to antibiotic resistance. There are two main issues - increased antibiotic resistance among bacteria and a declining antibiotic pipeline. Bacteria are developing resistance to existing antibiotics, especially gram-negative rods, leaving some infections with no effective treatment options. Meanwhile, the development of new antibiotics has slowed dramatically in recent years. Novel approaches are being explored to address the antibiotic resistance crisis, such as developing antibiotics from non-culturable bacteria and using bacteriophages and their gene products. However, the problem of antibiotic resistance worldwide remains serious without action.
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
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
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.
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
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
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.
Resistance to antibiotics is one of the main important facts that most nations are working on. Actually, in USA, it is considered as a health problem to solve. Why it happens? Here is a review to answer this.
updated statistics about antimicrobial resistance,causes and mechanism of antimicrobial resistances, national antimicrobial policy, national antimicrobial surveillance, new delhi b metallo-lactamase-1 bacteria
Antibiotics Resistance is a new issue in Microbiology-Medicine aspects, taken from Lange Review of Medical Microbiology, this purpose is for education only
Antibiotic resistance,introduction, cause, mechanism and solution of Antibiot...Dr. Sharad Chand
A illustrative representation of the antibiotic resistance, its introduction, cause, mechanism, examples and possible solutions of the antibiotic resistance. with pictorial illustrations for better understanding.
Resistance to antibiotics is one of the main important facts that most nations are working on. Actually, in USA, it is considered as a health problem to solve. Why it happens? Here is a review to answer this.
updated statistics about antimicrobial resistance,causes and mechanism of antimicrobial resistances, national antimicrobial policy, national antimicrobial surveillance, new delhi b metallo-lactamase-1 bacteria
Antibiotics Resistance is a new issue in Microbiology-Medicine aspects, taken from Lange Review of Medical Microbiology, this purpose is for education only
Antibiotic resistance,introduction, cause, mechanism and solution of Antibiot...Dr. Sharad Chand
A illustrative representation of the antibiotic resistance, its introduction, cause, mechanism, examples and possible solutions of the antibiotic resistance. with pictorial illustrations for better understanding.
AMR & Alternative Stratergies - MicrobiologySijo A
Antibiotic resistance poses one of the most important health challenges of the 21st century.
The rise of multidrug-resistant bacteria has already led to a significant increase in human disease and death.
The U.S. Centers for Disease Control and Prevention estimates that approximately 2.8 million people worldwide are infected with antibiotic-resistant bacteria, accounting for 35,000 deaths each year in the U.S. and 700,000 deaths around the globe.
A study of antibiotic resistance of Extended-Spectrum Beta-Lactamases produci...Premier Publishers
Background: Extended-Spectrum Beta-Lactamases - producing Enterobacteriaceae are common in hospitals. This study aims to describe the antibiotic resistance of these bacteria and their associated demographic and clinical factors. Methods: It was a prospective study of 73 isolates of Extended-Spectrum Beta-Lactamases - producing Enterobacteriaceae for a period of six months from July to December 2019 in the laboratory of Befelatanana. Results: This study showed 73 (6.3%) isolates of Extended-Spectrum Beta-Lactamases- producing Enterobacteriaceae, represented by 25 (34.2%) isolates of Klebsiella spp, 24 (32.9%) isolates of Escherichia coli, 22 (30.1%) isolates of Enterobacter spp and 2 (2.7%) isolates of Proteus spp. The antibiotic resistance of these bacteria varied from 0% to 100% for all of the antibiotics tested. Resistance to aminoglycosides ranged from 0% (amikacin) to 69.9% (gentamycin). Resistance to quinolones ranged from 43.8% (levofloxacin) to 76.7% (nalidixic acid). Similarly, 60 (82.2%) isolates were resistant to cotrimoxazole and 25 (34.2%) isolates to chloramphenicol. Patients under 20 years (57.1%) (p=0.03), men (52.2%)(p=0.11; NS), patients with respiratory samples (83.3%)(p=0.004), with pus (61.9%)(p=0.02) and hospitalized in surgery and intensive care units (68.4%)(p=0.0009) were the most affected by these enterobacteria. Conclusion: Extended-Spectrum Beta-Lactamases - producing Enterobacteriaceae are responsible for severe infections and the majorities are multi-resistant bacteria.
Keywords: Beta-lactamase, Enterobacteriaceae, antibiotic resistance, amikacin, imipenem.
Antimicrobial stewardship to prevent antimicrobial resistanceGovindRankawat1
India is among the nations with the highest burden of bacterial infections.
India is one of the largest consumers of antibiotics worldwide.
India carries one of the largest burdens of drug‑resistant pathogens worldwide.
Highest burden of multidrug‑resistant tuberculosis,
Alarmingly high resistance among Gram‑negative and Gram‑positive bacteria even to newer antimicrobials such as carbapenems.
NDM‑1 ( New Delhi Metallo Beta lactamase 1, an enzyme which inactivates majority of Beta lactam antibiotics including carbapenems) was reported in 2008
Antibiotic resistance a global concern part iiRohan Jagdale
Bacteria, not humans or animals, become antibiotic-resistant. These bacteria may infect humans and animals, and the infections they cause are harder to treat than those caused by non-resistant bacteria.
Antibiotic resistance leads to higher medical costs, prolonged hospital stays, and increased mortality.
The world urgently needs to change the way it prescribes and uses antibiotics. Even if new medicines are developed, without behaviour change, antibiotic resistance will remain a major threat. Behaviour changes must also include actions to reduce the spread of infections through vaccination, hand washing, practising safer sex, and good food hygiene.
Herbal antimicrobials are considered as an important alternative to antibiotic and probable tools to mitigate emerging antimicrobial-drug-resistance (AMR). However, it is difficult to accept that microbes may not adapt to herbal antimicrobials as rapidly as to antibiotics. This is now well documented that herbal antimicrobial resistance is also common among common pathogenic microbes and genes are now known to encode herbal drug-resistance too. This lecture gives description how resistance to conventional antimicrobials impacts susceptibility of microbes for herbal antimicrobials. Lecture Scheduled on 21st February 2023, In: Antimicrobial Resistance (AMR) in Foodborne pathogens” sponsored under the ICAR-NAHEP-CAAST project by the MAFSU, Mumbai Veterinary College, at the Division of Veterinary Public Health, ICAR-IVRI from 20th February to 25th February, 2023.
Prevalence and Characterisation of Beta Lactamases in Multi Drug Resistant Gr...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Background: The widespread use of antibiotics has resulted in emergence of community-acquired antibiotic resistance among uropathogens in outpatient’s population. This constitutes an impediment in the management of urinary tract infection (UTI) in both community and hospital settings. Objective: The aim of this study was to determine the current antibiotic resistance trends, extended spectrum beta-lactamase (ESBL) production and plasmid profile of uropathogens from outpatients. Methods: A total of 370 mid-stream urine samples were collected and cultured by standard methods. Isolated uropathogens were identified using appropriate biochemical methods. The modified Kirby Bauer disk method was used for antibiotic susceptibility test. The ESBL-producing uropathogens were identified and their plasmid DNA extraction and curing were carried out by standard methods. Results: About 35.7% and 32.7% of uropathogens were multi-drug resistant and ESBL-producing respectively. There was higher prevalence of ESBL-production among isolates from female patients (62.5%) when compared to that from male patients (37.5%). The isolated uropathogens were most resistant to Cefotaxime, and most sensitive to Imipenem. Resistance to antibiotics by ESBL-producing uropathogens was found to be plasmid-mediated. Conclusion: Community acquired Uropathogens from outpatients were multidrug resistant due to ESBL production localized on plasmids, a probable cause of treatment failures experienced in Uyo.
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.
Environmental Transmission of Antimicrobial ResistancePranab Chatterjee
This is the second lecture I took for the MPH students at the Indian Institute of Public Health, Delhi, as a part of the Environmental Health module. In this lecture I introduce the students to the basics of AMR and some common modes and routes of transmission of the same through the environment.
ANTIMICROBIAL RESISTANCE PATTERNS AMONG ACINETOBACTER BAUMANNII ISOLATED FROM...inventionjournals
Acinetobacter baumannii (Ab) is a troublesome and increasingly problematic healthcareassociated pathogen, especially in critical care unit (ICU) and cardiovascular internal medicine (CIM). This organism has a capacity for long-term survival in the hospital environment. This study aimed to investigate the drug resistance patterns of Ab strains isolated from Thongnhat Dongnai General Hospital and the relationships between Ab isolations with clinical wards and year of patients. The antibiotic susceptibility of 279 Ab isolates for aminoglycosides, fluro-quinolons, cephalosporins, carbapenems, colistin and bactrim was determined using Kirby-Bauer disk diffusion method. The minimum inhibitor concentration (MIC) of 146 Ab isolates for Meropenem was determined using E-test method according to CLSI guide-line. A total 279 A. baumannii strains out of 1,976 positive isolates were collected from various specimens during study period. Among Ab-positive specimens, the most isolated specimen was sputum (26.6%, χ 2 =161.705 p<0.000),><0.000)><0.000),><0.000). Among 279 Ab isolated, resistance from 53.16% – 63.52% to aminoglycosides, 23.6% – 68.58% to fluroquinolons, 59.61% to 97.93% to cephalosporins, 60.27% to 80.7% to carbapenem, 10.53% to 66.48% to antibiotic combinations, 0.75% to colistin and 61.71% to bactrim. Among 146 multidrug-resistant Ab, 53.42% MICmeropenem ≥ 32 μg/ml and only 18.49% strains were susceptible to Meropenem. Due to the high antimicrobial resistance to two clinical wards (ICU and CIM) and carbapenems by disk agar diffusion test and E-test; we must focus on both a wiser use of antimicrobials and the prevention of infection. Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to eliminate major outbreaks in the future.
ANTIMICROBIAL RESISTANCE PATTERNS AMONG ACINETOBACTER BAUMANNII ISOLATED FROM...inventionjournals
Acinetobacter baumannii (Ab) is a troublesome and increasingly problematic healthcareassociated pathogen, especially in critical care unit (ICU) and cardiovascular internal medicine (CIM). This organism has a capacity for long-term survival in the hospital environment. This study aimed to investigate the drug resistance patterns of Ab strains isolated from Thongnhat Dongnai General Hospital and the relationships between Ab isolations with clinical wards and year of patients. The antibiotic susceptibility of 279 Ab isolates for aminoglycosides, fluro-quinolons, cephalosporins, carbapenems, colistin and bactrim was determined using Kirby-Bauer disk diffusion method. The minimum inhibitor concentration (MIC) of 146 Ab isolates for Meropenem was determined using E-test method according to CLSI guide-line. A total 279 A. baumannii strains out of 1,976 positive isolates were collected from various specimens during study period. Among Ab-positive specimens, the most isolated specimen was sputum (26.6%, χ 2 =161.705 p<0.000),><0.000)><0.000),><0.000). Among 279 Ab isolated, resistance from 53.16% – 63.52% to aminoglycosides, 23.6% – 68.58% to fluroquinolons, 59.61% to 97.93% to cephalosporins, 60.27% to 80.7% to carbapenem, 10.53% to 66.48% to antibiotic combinations, 0.75% to colistin and 61.71% to bactrim. Among 146 multidrug-resistant Ab, 53.42% MICmeropenem ≥ 32 μg/ml and only 18.49% strains were susceptible to Meropenem. Due to the high antimicrobial resistance to two clinical wards (ICU and CIM) and carbapenems by disk agar diffusion test and E-test; we must focus on both a wiser use of antimicrobials and the prevention of infection. Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to eliminate major outbreaks in the future
Antibiotic selection /certified fixed orthodontic courses by Indian dental ...Indian dental academy
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Antibiotic selection /certified fixed orthodontic courses by Indian dental ...
Anti Microbial Resistance (AMR)
1.
2. Antibacterial resistance worldwide
Optimism of the early period of antimicrobial discovery
Tempered by the emergence of bacterial strains with resistance to
therapeutics
We enter an era where bacterial infections (bloodstream infections
and ventilator-associated pneumonia) → no longer be successfully
treated with Antibiotics.
We now face a dramatic challenge resulting from two combined
problems:
First, microorganisms are becoming extremely resistant to
existing antibiotics, in particular Gram-negative rods (e.g.,
Escherichia coli, Salmonella spp, Klebsiella spp, Pseudomonas
aeruginosa, Acinetobacter spp), which are resistant to almost all
currently available antibiotics in some settings.
Second, the antibiotic pipeline has become extremely dry
4. Emergence and dissemination of new
mechanisms of resistance, e.g., novel
extended-spectrum beta-lactamases
(ESBL) and carbapenemases . The
spread of the new resistance gene, the New
Delhi metallo-betalactamase (NDM-1), or
other carbapenemases in
Enterobacteriacae is alarming because
these “superbugs” are resistant to most
available antibiotics and can disseminate
worldwide very rapidly, in particular as a
consequence of medical tourism
Ref: Ready for a world without antibiotics? The Pensières
Antibiotic Resistance Call to Action by Jean Carlet in
Antimicrobial Resistance and Infection Control 2012
http://www.aricjournal.com/content/1/1/11
6. Europe
In Europe, the European Centre for Disease
Prevention and Control (ECDC) reported that
25,000 people die each year from antibiotic-
resistant bacteria.
Multidrug-resistant organisms (MDROs) result in
massive extra healthcare costs and productivity
losses of at least 1.5 billion euros each year in
Europe (Ref: Combating Antimicrobial Resistance: 2011 is the year of
“No action today, No cureTomorrow”
by Daxesh M.P, in Indian Journal of
Pharmacy Practice )
7. USA
In the USA, the annual cost of AMR in hospitals is
estimated at more than US$ 20 billion.
In the US, two thirds of deaths due to bacterial
infections are caused by Gram-negative bacteria
The Canadian Committee on Antibiotic Resistance
developed a model that suggested resistant infections
add $14 to $26 million in direct hospitalization costs
to health care cost in Canada
10. ASIA
ESBL-producing bacteria are frequently causing
infections in newborns. In an Indian hospital,
Klebsiella and E.coli were the most common Gram-
negative bacteria among infants with BSIs. About
33% of ESBL-infections were deadly in spite of
available newer antibiotics and other supportive care.
In a study from Pakistan, 37 of 78 newborns (less
than 6 days old) with infections due to Acinetobacter
died within a short time frame. 71% of the bacteria
were resistant to all antibiotics except polymyxin.
Ref: A fact sheet from ReAct - Action on Antibiotic Resistance,www.reactgroup.org, May 2012
11. Initiatives Worldwide
AMR became an important issue in the 1960s when resistance
plasmid and transmissibility were detected.
WHO recognized global AMR threat in 1998
WHO developed the Global Strategy for the containment of
Antimicrobial Resistance in 2001
WHO and member states observed 2011 as the year of
Antimicrobial resistance to building momentum for
rational use of antibiotics: No action today, No cure
tomorrow
The World Health Organization (WHO estimates that up to
40% of health care costs are related to procurement of
medicines.
13. INDIA
ESBL & MBL Prevalence in India:
In 2008-2010, P aeruginosa more resistant against
ceftazidime [53.17%]
Increased resistance to cephotaxime- 50.79%, netilmicin
45.23%, gentamicin - 38.09%, amikacin -36.50%,
ciprofloxacin- 46.82% and piperacillin- 41.26 %.
Among 126 Pseudomonas aeruginosa , 22.22% were ESBL
producers. 69 % strains were resistant to carbapenem.
MBLs in the imipenem resistant isolates was 62.5%.
The study suggested that the carbapenem resistance in P.
aeruginosa was mediated predominantly via MBL
production.
(Source: and MBL Mediated Resistance in Aeruginosa, by Durwas Peshattiwar et al,of
Clinical and Diagnostic Research. 2011)
14. As per a latest report, ESBL production rate was
70% in E. coli and 60% in Klebsiella spp. in
India respectively for the year 2010. (Source: Detection of
TEM and SHV genes in coli pneumoniae in a tertiary care hospital from India, by
Sharma, J et al, J Med )
Very recently in 2011, TEM and CTX-M were
predominantly found in E. coli (39.2%) and
among the Klebsiella spp., TEM, SHV and CTX-
M occurred together in 42.6% of the isolates.
(Source: Correlation of TEM, SHV and CTX-M extended-spectrum beta
lactamases among Enterobacteriaceae with their vitro susceptibility, Manoharan,
A et al, Journal of Medical Microbiology 2011)
16. Dwindling Trend of Antibiotics
Ref: Policy Responces to the growing threat of Antibiotic Resistance in extending the cure.org
17. The FDA approved new antibiotics in the past years (those
with novel mechanisms of action are shaded) (Ref: Policy Responces to
the growing threat of Antibiotic Resistance in extendingthecure.org)
18. Reasons of Dwindling Trend
The antibiotic pipeline is drying up for foll. reasons:
It is intrinsically difficult to find new antibiotics with
novel mechanisms of action.
A high cost/benefit and risk/benefit ratio (length of
development, low selling prices, and short treatments)
discourage pharmaceutical companies from investment.
There is strong competition with other drugs already
on the market. While resistance is an emerging problem,
low-priced generic antibiotics on the market are still
effective in treating most infections and are used as first-
line therapy.
19. Regardless of the reasons → companies have to
deal with the reality → there are less new
products being approved → therefore they are
failing to achieve their potential to provide
treatment for patients and commercial benefits to
their companies.
20. Treatment of ESBL‐producing organisms has become
limited by increasing resistance. However, over 95% of
ESBL‐ producing Enterobacteriaceae are still
susceptible to certain antibiotics → carbepenems,
amikacin, tigecycline and β‐lactam/β‐lactamase inhibitor
combinations.
In some clinical studies, fosfomycin and nitrofurantoin
prove to be good alternatives for urinary tract infections
22. Novel approaches to developing new
antibiotics for bacterial infections
After more than 50 years of success, the pharmaceutical
industry is now producing too few antibiotics, particularly
against Gram-negative organisms, to replace antibiotics that
are no longer effective for many types of infection.
Genomics, non-culturable bacteria, bacteriophages and
non-multiplying bacteria may also be a source of novel
compounds.
23. Current methods of antibiotic development:
Natural compounds: non-culturable bacteria as target:
Bacteria produce antibiotics that kill or inhibit the replication of competitors. To
date, marketed antibiotics such as streptomycin have been derived from bacteria
that grow on artificial solid or liquid media. Marketed antibiotics have not been
isolated from non-culturable bacteria, since growth on solid media has been an
essential step to the development antibiotics. Now, it is possible to clone large
fragments of non-culturable bacterial genomes and to express them using
recombinant DNA technology
The genomics revolution:
Genomics is used to select potential antibacterial targets and can also be used to
provide insights into, for example, pathogenesis and antibiotic resistance.
GlaxoSmithKline used a genomics-derived, targetbased approach to
antibiotic discovery for 7 years, in which they examined more than 300 genes
and employed 70 highthroughput screening campaigns, but did not develop an
antibiotic into the market (Payne et al., 2007).
24. Bacteriophages
Bacteriophages and their fragments kill bacteria. It is estimated that every 2
days, half of the world’s bacterial population is destroyed by bacteriophages
Bacteriophages have been used as antibacterials in humans in some countries
of the world. Indeed, in the last century, just before the introduction of
penicillin and sulpha drugs, phage preparations were sold in the United
States of America. Even as far as in 2001, bacteriophages were used in
the former Soviet Union to treat patients with infectious diseases.
The development of phage gene products is another potential route for new
antibacterials. Phage lysins, have potential uses as antibacterials for human
use. A particularly interesting finding is that lysins may be active against
non-multiplying bacteria and biofilms. This could help in the treatment
of, for example, catheter-associated infections.
Currently, there is a lack of good human clinical trial results, although
animal studies suggest that in certain circumstances, bacteriophage therapy
may be useful.
25. Non-multiplying bacteria as targets:
Bacteria exist in two different states in a clinical infection, such as
tuberculosis, bacterial endocarditis, biofilms and streptococcal sore throat.
The states are described as multiplying (logarithmic phase) and non-
multiplying (sometimes called stationary phase, dormant or latent).
Currently marketed antibiotics are bacteriostatic for non-multiplying bacteria,
although some of them, such as the penicillins, are highly bactericidal for
multiplying organisms.
The advantage of an antibiotic that is bactericidal for nonmultiplying
bacteria is that the duration of therapy may be shortened. This
presumes that all the multiplying and nonmultiplying target bacteria are
quickly killed by an antibiotic or by a combination of compounds.
(Ref: Novel approaches to developing new antibiotics for bacterial infections
by ARM Coates and Y Hu in British Journal of Pharmacology (2007)
27. The need for new generations of anti-infective
agents, and in particular new antibacterial agents,
is constant, as the emergence of resistance is largely a
question of when and not if ?
Current antibiotics include the fourth generation of
beta lactams and the third generation of macrolides.
However, significantly new approaches and
strategies for breakthrough molecules have not
been forthcoming.
28. There are examples of recent strategies for
development of adjunctive antibiotic therapies that
overcome microbial resistance and thus rejuvenate the
existing arsenal of drugs.
Recent studies → demonstrated potential of compounds
that inhibit the action of the repressor protein implicated
in ethionamide resistance → stimulating activation of the
drug and thereby restoring the activity of the antibiotic
for treatment of Mycobacterium tuberculosis.
Such specific interference with regulators or signal
transduction mechanisms involved in antibiotic resistance
or virulence → new toolbox for novel combinations of
antimicrobial drugs with adjuvant molecules lacking
intrinsic antibiotic activity.
29. Adjuvant strategies for potentiation of
antibiotics to overcome antimicrobial resistance
(Michel Pieren and Marcel Tigges, Current Opinion in Pharmacology 2012,
www.sciencedirect.com)
The most important defence mechanisms utilized by
bacteria to neutralize antibiotic drug action comprise
Upregulation of active efflux and downregulation of
outer membrane permeability thus inhibiting intracellular
accumulation of the drug,
Antibiotic target mutation,
Enzymatic detoxification of the drug, and
Compensatory pathways that bypass the drug target.
30. Combination therapy regularly used by clinicians
→ suffers from side effects, difficult dosing and the
potential selection of multidrug resistant
phenotypes.
Therefore, combination of an antibiotic with a
non-toxic adjuvant compound → preferable.
Potential points of intervention for such an
adjuvant compound could be → (i) signal
integration and processing, (ii) regulation of
virulence and resistance gene expression, (iii)
activity of effector molecules
31. Prospective Study for Antimicrobial Susceptibility of
Escherichia coli Isolated from Various Clinical Specimens in
India (Manu Chaudhary and Anurag Payasi in J Microb Biochem Technol 4: 157-
160. doi:10.4172/1948-5948.1000088)
Microbial efficacy of a new Antibiotic Adjuvant Entity (AAE),
which is a combination of a non-antibiotic adjuvant Ethylenediamine
Tetraacetic Acid disodium (EDTA) along with β-lactam and β-
lactamase inhibitor, altogether termed as ceftriaxone plus EDTA
plus sulbactam (CSE1034) was studied and compared.
Results obtained in the current research clearly demonstrate the
good in-vitro activity of ceftriaxone plus EDTA plus sulbactam
(CSE1034) against ESBLs, as well as MβLs producing E. coli.
However, penems exhibited in-vitro activity against only ESBLs
producing E. coli.
Hence, in case of infection with MβLs producing E. coli,
ceftriaxone plus EDTA plus sulbactam (CSE1034) can be of drug
of choice for the treatment.