This document discusses several topics related to antibiotics and antibiotic resistance:
1. It notes that self-medication with antibiotics in too small doses can lead to antibiotic-resistant bacteria spreading between individuals.
2. It provides classifications of different types of antibiotics including 50 penicillins, 71 cephalosporins, and lists other common classes.
3. It discusses the evolution of antibiotic resistance through enzymes and plasmids, noting increasing resistance to later generation cephalosporins over time.
I have few drugs which are commonly being used in ICU. The slide contains information related to drug storage, Dosage, Use, Usual concentration use, and things to do and not to do with drug use.
While MIC is a good measure of antibiotic activity, it is static and reflects in vitro activity. PK and PD of the drug needs to be considered together with MIC if we wish to obtain an in vivo prediction of drug action and success.
I have few drugs which are commonly being used in ICU. The slide contains information related to drug storage, Dosage, Use, Usual concentration use, and things to do and not to do with drug use.
While MIC is a good measure of antibiotic activity, it is static and reflects in vitro activity. PK and PD of the drug needs to be considered together with MIC if we wish to obtain an in vivo prediction of drug action and success.
Almost 100% of injections are being given in unsafe conditions in our country, whether it is govt or private hospitals. please go through a few guidelines.
Laboratory offering TDM for Immunosuppressive Drugs needs to understands their pharmacodynamics & clinical applications so that the results value add in the patient care
Antibiotic stewardship explained in one presentation, which can be helpful to the medical field beginners and students as well as thorough information can be obtained regarding the subject matter.
Objectives:
1. To understand the purpose of implementing an antimicrobial stewardship program (ASP)
2.To recall the core elements of hospital and outpatient antibiotic stewardship programs as defined by the CDC
3. To recognize key interventions that an antimicrobial stewardship program can implement in both the hospital and community settings
Adaptation and Implementation of Evidence-Based Clinical Practice Guidelines for Antibiotic Prophylaxis in Surgery in King Saud University Hospitals in Riyadh, Saudi Arabia
Almost 100% of injections are being given in unsafe conditions in our country, whether it is govt or private hospitals. please go through a few guidelines.
Laboratory offering TDM for Immunosuppressive Drugs needs to understands their pharmacodynamics & clinical applications so that the results value add in the patient care
Antibiotic stewardship explained in one presentation, which can be helpful to the medical field beginners and students as well as thorough information can be obtained regarding the subject matter.
Objectives:
1. To understand the purpose of implementing an antimicrobial stewardship program (ASP)
2.To recall the core elements of hospital and outpatient antibiotic stewardship programs as defined by the CDC
3. To recognize key interventions that an antimicrobial stewardship program can implement in both the hospital and community settings
Adaptation and Implementation of Evidence-Based Clinical Practice Guidelines for Antibiotic Prophylaxis in Surgery in King Saud University Hospitals in Riyadh, Saudi Arabia
Microbiology is the study of microorganisms.
The overall theme of the Microbiology course is to study the relationship between microbes and our lives.
Microorganisms (microbes) are organisms that are too small to be seen with the unaided eye, and usually require a microscope to be seen.
This relationship involves harmful effects such as diseases and food spoilage as well as many beneficial effects.
All new antibacterial agents which have been approved after the year 2000 have been described along with their mechanism of action, development of resistance, spectrum of activity and the stage of developmental in case of yet to be approved drugs.
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
3. Self Medication
• The greatest possibility of evil in self-
medication is the use of too small doses so
that instead of clearing up infection, the
microbes are educated to resist penicillin and
a host of penicillin-fast organisms is bread
out which can be passed to other individuals
and from them to other until they reach
someone who gets a septicemia or a
pneumonia which penicillin cannot save.
Sir AlexanderFlemming
Dr.T.V.Rao MD 3
5. Evolution of Enzymes
Plasmid-Mediated TEM and SHV
b-Lactamase
Third-Generation
Ampicillin Cephalosporins
1965 1970s 1980s 1987 2000
1983
1963
TEM-1
TEM-1 ESBL >120 ESBLs
Reported in ESBL in
E coli in Worldwide
28 Gram- Europe
S paratyphi United
Negative
States
Species
Dr.T.V.Rao MD 5
6. Development of anti-microbials
ertapenem
tigecyclin
The development daptomicin
linezolid
of anti-infectives … telithromicin
quinup./dalfop.
cefepime
ciprofloxacin
aztreonam
norfloxacin
imipenem
cefotaxime
clavulanic ac.
cefuroxime
gentamicin
cefalotina
nalidíxico ac.
ampicillin
methicilin
vancomicin
rifampin
chlortetracyclin
streptomycin
pencillin G
prontosil
1920 1930 1940 1950 1960
Dr.T.V.Rao MD 1970 1980 1990 2000 6
7. 1962 and 2000, no major classes of
antibiotics were introduced
Fischbach MA and Walsh CT Science 2009
Dr.T.V.Rao MD 7
8. A Changing Landscape for
Numbers of Approved Antibacterial Agents
18
16
Number of agents approved
14
12
Resistance
10
8
6
4
2
0
0
1983-87 1988-92 1993-97 1998-02 2003-05 2008
Bars represent number of new antimicrobial agents approved by the FDA during the period listed.
Infectious Diseases Society of America. Bad Bugs, No Drugs. July 2004; Spellberg B et al. Clin Infect Dis. 2004;38:1279-1286;
New antimicrobial agents. Antimicrob Agents Chemother. 2006;50:1912
10. Antibiotics
• Biology and Society
About 50% of the antibiotics produced
today are used in the livestock industry.
What impact does this have on the
treatment of human diseases?
Dr.T.V.Rao MD 10
11. ANTIMICROBIAL RESISTANCE:
The role of animal feed antibiotic additives
• 48% of all antibiotics by weight is added to
animal feeds to promote growth. Results
in low, sub therapeutic levels which are
thought to promote resistance.
• Farm families who own chickens feed
tetracycline have an increased incidence of
tetracycline resistant fecal flora
Dr.T.V.Rao MD 11
12. Prescribing an antibiotic
Is an antibiotic necessary ?
What is the most appropriate
antibiotic ?
What dose, frequency, route and
duration ?
Is the treatment effective ?
Dr.T.V.Rao MD 12
13. How are antibiotics overused or
Misused?
• Seven out of ten Americans receive
antibiotics when they seek
treatment for a common cold!
Only one-third of patients use
antibiotics the way doctors tell them.
• This allows bacteria to become
resistant by not killing them
completely. Dr.T.V.Rao MD 13
14. Antibiotic Prescribing
Children are real Concern
• Antibiotics were
prescribed in 68% of
acute respiratory tract
visits – and of those,
80% were unnecessary
according to CDC
guidelines
• Children are of
particular concern
because they have the
highest rates of
Dr.T.V.Rao MD 14
antibiotic use.
15. We too Contribute for Creating
Drug Resistance
• Every time a person
takes antibiotics,
sensitive bacteria are
killed, but resistant
microbes may be left to
grow and multiply.
Repeated and improper
uses of antibiotics are
primary causes of the
increase in drug-
resistant bacteria.
Dr.T.V.Rao MD 15
16. The consequences of antibiotic
resistance
• Increased morbidity & mortality
– “best-guess” therapy may fail with the patient’s
condition deteriorating before susceptibility results
are available
– no antibiotics left to treat certain infections
• Greater health care costs
– more investigations
– more expensive, toxic antimicrobials required
– expensive barrier nursing, isolation, procedures, etc.
• Therapy priced out of the reach of some
third-world countries
16 Dr.T.V.Rao MD
17. Costs Associated with
Increased Bacterial
Resistance
• ↑Treatment failures
• ↑Morbidity and mortality
• ↑Risk of hospitalization
• ↑Length of hospital stays
• ↑Need for expensive and broad
spectrum antibiotics
Dr.T.V.Rao MD 17
18. Social factors fuelling resistance
• Poverty encourages the development of
resistance through under use of drugs
– Patients unable to afford the full course of
the medicines
– Sub-standard & counterfeit drugs lack
potency
• Globalization, increased travel and
trade ensure that resistant strains
quickly travel elsewhere. So does excessive
18
promotion. Dr.T.V.Rao MD
19. Developed countries Overuse
• In wealthy countries, resistance is emerging
for the opposite reason – the overuse of
drugs.
• Unnecessary demands for drugs by patients
are often eagerly met by health services and
stimulated by pharmaceutical promotion
• Overuse of antimicrobials in food production
is also contributing to increased drug
resistance.
Dr.T.V.Rao MD 19
20. Classification of Pencillins
• Natural
Benzyl penicillin
Phenoxymethyl penicillin Penicillin v
Semi synthetic and pencillase resistant
1 Methicillin
2 Nafcillin
3 Cloxacillin
4 Oxacillin
5 Floxacillin
Dr.T.V.Rao MD 20
21. Macrolides,Azalides,Ketolides
• Contain macro cyclic
lactone ring
Erythromycin. Is
popularly used drug
• Other drugs
Roxithromycin,Azithromy
cin
• Inhibits the protein
synthesis.
• Used as alternative to
pencillin allergy patients.
Dr.T.V.Rao MD 21
23. Cephalosporins
• Like penicillin acts
similar
• Products of the molds
of genus
Cephalosporium
except cefoxilin
• Divided into 4
generation of
Cephalosporins
depending on the
spectrum of activity.
Dr.T.V.Rao MD 23
24. Major generations of
Cephalosporins
• Cephalosporins are divided into 3 generations:
• 1st generation: Cephalexin, cefadroxil,
cephradine
• 2nd generation: Cefuroxime, cofactor
• 3rd generation: cefotaxime, Ceftazidime,
cefepime - these give the best CNS penetration
• 4th generation Cephalosporins are already
available
Dr.T.V.Rao MD 24
25. Different Generations of
Cephalosporins
• Cephalosporins are
grouped into
"generations" based on
their spectrum of
antimicrobial activity. The
first Cephalosporins were
designated first
generation while later,
more extended spectrum
Cephalosporins were
classified as second
generation
Cephalosporins.
Dr.T.V.Rao MD 25
26. 5th Generation Cephalosporins
• Ceftaroline is a new intravenous (IV)
cephalosporin that was FDA-approved
October 2010. It is labelled for the
treatment of adults with infections
caused by susceptible bacteria,
specifically skin and skin structure
infections (SSSIs) caused by methicillin-
sensitive
Dr.T.V.Rao MD 26
27. 5th Generation Cephalosporins
• Staphylococcus aureus (MSSA), methicillin-
resistant S aureus (MRSA), Streptococcus
pyogenes, Streptococcus agalactiae,
Escherichia coli, Klebsiella pneumoniae, or
Klebsiella oxytoca; and community acquired
pneumonia (CAP) caused by Streptococcus
pneumoniae (with or without concurrent
bacteraemia), MSSA, E coli, Haemophilus
influenza, K.pneumoniae, or K oxytoca
Dr.T.V.Rao MD 27
28. Ceftaroline is effective …
• Ceftaroline is a fifth generation
cephalosporin with excellent
activity against GPCs including
MRSA & DRSP Affinity for all PBPs
including PBP 2’ and PBP 2X Not
ESBL stable, Not active against
Non fermenters
Dr.T.V.Rao MD 28
29. Irrational Use of Third Generation
Cephalosporins
• Several studies have
demonstrated that patterns
of antibiotic usage greatly
affect the number of
resistant organisms which
develop. Overuse of broad-
spectrum antibiotics, such
as second- and third-
generation Cephalosporins,
generate resistant strains.
Dr.T.V.Rao MD 29
30. Advantages with Newer generations
• Each newer generation of cephalosporins
has significantly greater gram-negative
antimicrobial properties than the
preceding generation, in most cases with
decreased activity against gram-positive
organisms. Fourth generation
cephalosporins, however, have true
broad spectrum activity
Dr.T.V.Rao MD 30
31. Other Beta-lactams include
• Other beta-lactams include:
• Aztreonam: a monocytic beta-
lactam, with an antibacterial
spectrum which is active only against
Gram negative aerobes, including
Pseudomonas aeruginosa, Neisseria
meningitides and N. gonorrhoea.
Dr.T.V.Rao MD 31
32. How are Carbapenems Used?
Uses by Clinical Syndrome Use by Clinical Isolate
• Bacterial meningitis Acinetobacter spp.
Pseudomonas aeruginosa
• Hospital-associated
Alcaligenes spp.
sinusitis
Enterobacteriaceae
• Sepsis of unknown origin Mogenella spp.
• Hospital-associated Serratia spp.
pneumonia
Enterobacter spp.
Citrobacter spp.
ESBL or AmpC + E. coli
and Klebsiella spp.
Reference: Sanford Guide MD
Dr.T.V.Rao 32
34. Emerging Carbapenem Resistance in
Gram-Negative Bacilli
• Significantly limits treatment options for
life-threatening infections
• No new drugs for gram-negative bacilli
• Emerging resistance mechanisms,
carbapenemases are mobile,
• Detection of carbapenemases and
implementation of infection control practices
are necessary to limit spread
Dr.T.V.Rao MD 34
35. Daptomycin (Cubicin®)
• New drug class (lipopeptide)
• Rapidly bactericidal
• New mechanism of action: acts by
binding to cell membrane and disrupting
the cell membrane potential
• No cross resistance
• Dose: 4-6 mg/kg once daily
36. Other drugs
• Imipenem: a
carbapenem with a
broader spectrum of
activity against Gram
positive and negative
aerobes and
anaerobes. Needs to
be given with
cilastatin to prevent
inactivation by the
kidney.
Dr.T.V.Rao MD 36
37. Quinolones
• Quinolones are the first
wholly synthetic
antimicrobials. The
commonly used
Quinolones.
• Act on the DNA gyrase
which prevents DNA
polymerase from
proceeding at the
replication fork and
consequently stopping
synthesis.
Dr.T.V.Rao MD 37
38. Aminoglycosides
• Aminoglycosides are group of
antibiotics in which amino
sugars liked by glycoside bonds
• Eg Streptomycin,
• Act at the level of Ribosome's
and inhibits protein synthesis
• Other Aminoglycosides –
Gentamycin,
neomycins,paromomycins,tobr
amycins Kanamycins and
spectinomycins
Dr.T.V.Rao MD 38
40. Tetracycline's
• Broad spectrum antibiotic
produced by Streptomyces
species
• 1. Oxytetracycle,
chlortetracycle and
tetracycline
• Tetracyclnes are bacteriostatic
drugs inhibits rapidly
multiplying organisms
• Resistance develops slowly
and attributed to alterations
in cell membrane permeability
to enzymatic inactivation of
the drug
Dr.T.V.Rao MD 40
41. Other Antimicrobial agents
• Lincomycins
Clindamycin
resembles Macrolides
in biting site and
antimicrobial activity.
Streptogramins
Quinpristin /
dalfopristin
useful in gram
positive bacteria
Dr.T.V.Rao MD 41
42. Antibiotics in Anaerobes
• Major anaerobes –
Anaerobic cocci,
clostridia and
Bactericides are
susceptible to Benzyl
pencillin
• Bact.fragilis as well as
many other anaerobes
are treatable with
Erythromycin,Lincomycin,
tetracycline and
Chloramphenicol
• Clindamycin is effective
against many strains of
Bacteroides
Dr.T.V.Rao MD 42
43. Metronidazole in Anaerobic
Infections
• Since the discovery of
Metronidazole in 1973
since then it was
identified as leading
agent anaerobes.
• But also useful in treating
parasitic infections
Trichomonas,
Amoebiasis and other
protozoan infections.
Dr.T.V.Rao MD 43
44. Treatment of N. gonorrhoea
• Only current CDC-recommended options for treating
N. gonorrhoea infections are from a single class of
antibiotics, the cephalosporins.
– Ceftriaxone, available only as an injection, is the
recommended treatment for all types of gonorrhea
infections (i.e., urogenital, rectal, and pharyngeal).
– Cefixime is the only oral agent recommended for
treatment of uncomplicated urogenital or rectal gonorrhea
Reduced susceptibility to cefixime being described in
Japan and other countries
45. Drug Resistance
• In spite discovery of several
antibiotics several
microorganisms attained
resistance.
• The major factor contributing
to persistence of infectious
disease has been the
tremendous capacity of
microorganisms for
circumventing the action of
inhibitory drugs.
• The drug resistance continues
to be a threat for usefulness of
the chemotherapeutic agents.
Dr.T.V.Rao MD 45
46. Inappropriate Antibiotic Use
Use of antibiotics
with no clinical
indication (eg, for
viral infections)
Use of broad
spectrum antibiotics
when not indicated
Inappropriate choice
of empiric antibiotics
Dr.T.V.Rao MD 46
47. Multi Drug resistant pathogens
• If a bacterium carries
several resistance
genes, it is called
multiresistant or,
informally, a
superbug. The term
antimicrobial
resistance is
sometimes use to
explicitly encompass
organisms other than
bacteria MD
Dr.T.V.Rao 47
48. Extended-Spectrum β-Lactamases
• β-lactamases capable of conferring bacterial resistance to
– the penicillins
– first-, second-, and third-generation
cephalosporins
– aztreonam
– (but not the cephamycins or carbapenems)
• These enzymes are derived from group 2b β-lactamases (TEM-1, TEM-2,
and SHV-1)
– differ from their progenitors by as few as
one AA Dr.T.V.Rao MD 48
49. Antibiotic Resistance
Threat to Humans and Animals
• Antibiotic resistance has
become a serious
problem in both
developed and
underdeveloped nations.
By 1984 half of those
with active tuberculosis
in the United States had a
strain that resisted at
least one antibiotic. In
certain settings, such as
hospitals and some
childcare location
Dr.T.V.Rao MD 49
50. Carbapenemases
• Ability to hydrolyze penicillins, cephalosporins,
monobactams, and carbapenems
• Resilient against inhibition by all commercially viable ß-
lactamase inhibitors
– Subgroup 2df: OXA (23 and 48) carbapenemases
– Subgroup 2f : serine carbapenemases from molecular class
A: GES and KPC
– Subgroup 3b contains a smaller group of MBLs that
preferentially hydrolyze carbapenems
• IMP and VIM enzymes that have appeared globally, most
frequently in non-fermentative bacteria but also in
Enterobacteriaceae
Dr.T.V.Rao MD 50
51. K. pneumonia carbapenemases)
• KPCs are the most
prevalent of this
group of enzymes,
found mostly on
transferable plasmids
in K. pneumonia
• Substrate hydrolysis
spectrum includes
cephalosporins and
carbapenems
Dr.T.V.Rao MD 51
52. Consequences of Antibiotic drug
Resistance
• People infected with drug-resistant organisms
are more likely to have longer and more
expensive hospital stays, and may be more
likely to die as a result of the infection. They
require treatment with second- or third-
choice drugs that may be less effective, more
toxic, and more expensive. This means that
patients with an antimicrobial-resistant
infection may suffer more and pay more for
treatment. (Issues with Insurance)
Dr.T.V.Rao MD 52
53. Emerging Trends in Antibiotic
Resistance
• Reports of methicillin-resistant
Staphylococcus aureus (MRSA)—a
potentially dangerous type of staph bacteria
that is resistant to certain antibiotics and
may cause skin and other infections—in
persons with no links to healthcare systems
have been observed with increasing
frequency in the United States and
elsewhere around the globe.
Dr.T.V.Rao MD 53
54. Gram negative bacteria a great threat
• Multi-drug resistant
Klebsiella species
and Escherichia coli
have been isolated
in hospitals
throughout the
United States.
• It is a Universal
phenomenon
Dr.T.V.Rao MD 54
55. WHAT NEXT
• Indian hospitals have reported very high
Gram-negative resistance rates, with very high
prevalence of ESBL (Extended Spectrum Beta
Lactamases) producers and also high
carbapenem resistance rates. Increasing
carbapenem resistance will invariably result in
increased usage of colistin, currently the last
line of defence, with a potential for colistin-
resistant and Pan Drug Resistant bacterial
infections. Dr.T.V.Rao MD 55
56. Fungi too becoming resistant
• Antimicrobial
resistance is
emerging among
some fungi,
particularly those
fungi that cause
infections in
transplant patients
with weakened
immune systems. Dr.T.V.Rao MD 56
57. Resistance in Virus
• Antimicrobial
resistance has also
been noted with
some of the drugs
used to treat human
immunodeficiency
virus (HIV) infections
and influenza.
Dr.T.V.Rao MD 57
58. Parasites too are Problematic
• The development of
antimicrobial resistance to
the drugs used to treat
malaria infections has been
a continuing problem in
many parts of the world for
decades. Antimicrobial
resistance has developed to
a variety of other parasites
that cause infection.
•
Dr.T.V.Rao MD 58
59. Identification of The Etiological
Agent
Laboratory diagnosis
Interpretation of the report
What is isolated is not necessarily the
pathogen
Was the specimen properly collected ?
Is it a contaminant or colonizer ?
Sensitivity reports are at best a guide
Dr.T.V.Rao MD 59
60. Limitations of combination of antibiotics
• The role of combination
antimicrobial therapy for
the prevention of resistance
is limited to those situations
in which there is
A high organism load
A high frequency of
mutational resistance
during therapy.
• Classic examples are
tuberculosis or HIV
infection.
Dr.T.V.Rao MD 60
61. Problems With Improper Use of
Antibiotics
• They don’t help the patient at all
• Expense: 75% of outpatient antibiotics are used for
respiratory infections
• Patient expectations: why no better?
• Side effects: diarrhea, rash, allergy
• Development of resistance: the antibiotic
won’t work when you really DO need it for a
bacterial infection
Dr.T.V.Rao MD 61
62. WHO global strategy on reducing the
antibiotic resistance
• The WHO Global Strategy for
Containment of Antimicrobial
Resistance identifies the
establishment and support of
microbiology laboratories as a
fundamental priority in guiding
and assessing intervention
efforts. Dr.T.V.Rao MD 62
63. Importance of local antibiotic
Resistance data
Resistance patterns vary
From country to country
From hospital to hospital in the same
country
From unit to unit in the same hospital
Regional/Country data useful only
for looking at trends NOT guide
empirical therapy
Dr.T.V.Rao MD 63
64. Streamlining or De-Escalation
of Therapy
–On the basis of culture and sensitivity
reports we can more effectively target
the causative pathogens, by elimination
of redundant combination therapy
–Resulting in decreased Ab exposure and
substantial cost savings
Dr.T.V.Rao MD 64
65. Continuous Medical Education
• Training and educating
a Must ..
health care professionals on
the appropriate use of
antibiotics must include
appropriate selection,
dosing, route, and duration
of antibiotic therapy. To
ensure that training and
education is working, there
should be extensive
collaboration between the
antibiotic stewardship and
hospital infection prevention
and control teams.
Dr.T.V.Rao MD 65
66. Antibiotic Pressure and Resistance in Bacteria
What factors promote their development and spread ?
Alteration of normal flora
Practices contributing to misuse of antibiotics
Settings that foster drug resistance
Failure to follow infection control principles
Dr.T.V.Rao MD 66
67. Practices Contributing to
Misuse of Antibiotics
Inappropriate specimen selection and
collection
Inappropriate clinical tests
Failure to use stains/smears
Failure to use cultures and susceptibility tests
Dr.T.V.Rao MD 67
68. Settings that Foster Drug Resistance
Hospital
Intensive care units
Oncology units
Dialysis units
Rehab units
Transplant units
Burn units
Dr.T.V.Rao MD 68
69. What Is Antimicrobial Stewardship?
• A combination of infection control and antimicrobial
management
• Mandatory infection control compliance
• Selection of antimicrobials from each class of drugs that does
the least collateral damage
• Collateral damage issues include
– MRSA
– ESBLs
– C difficile
– Stable derepression
– MBLs and other carbapenemases
– VRE
• Appropriate de-escalation when culture results are available
Dellit TH, et al. Clin Infect Dis. 2007;44:159-177.
Dr.T.V.Rao MD 69
70. IDSA Guidelines – Definition of
Antimicrobial Stewardship
• Antimicrobial stewardship is an activity that
promotes
– The appropriate selection of antimicrobials
– The appropriate dosing of antimicrobials
– The appropriate route and duration of
antimicrobial therapy
Dr.T.V.Rao MD 70
71. The Primary Goal of
Antimicrobial Stewardship
• The primary goal of antimicrobial stewardship is to
– Optimize clinical outcomes while minimizing unintended
consequences of antimicrobial use
• Unintended consequences include the following
– Toxicity
– The selection of pathogenic organisms, such as C difficile
– The emergence of resistant pathogens
Dr.T.V.Rao MD 71
72. Practices Contributing to
Misuse of Antibiotics
Inappropriate specimen selection and collection
Inappropriate clinical tests
Failure to use stains/smears
Failure to use cultures and susceptibility tests
Dr.T.V.Rao MD 72
73. Identification of The Etiological
Agent
Laboratory diagnosis
Interpretation of the report
What is isolated is not necessarily the
pathogen
Was the specimen properly collected ?
Is it a contaminant or colonizer ?
Sensitivity reports are at best a guide
74. Implementation of WHONET CAN HELP TO MONITOR
RESISTANCE
• Legacy computer
systems, quality
improvement teams, and
strategies for optimizing
antibiotic use have the
potential to stabilize
resistance and reduce
costs by encouraging
heterogeneous
prescribing patterns and
use of local susceptibility
patterns to inform
empiric treatment.
Dr.T.V.Rao MD 74
75. Growing importance of
WHONET
• World over antimicrobial
resistance is a major
public health problem.
The WHONET software
program puts each
laboratory data into a
common code and file
format, which can be
merged for national or
global collaboration of
antimicrobial resistance
surveillance
Dr.T.V.Rao MD 75
76. Whonet helps us in ……
• The understanding of the
local epidemiology of
microbial populations;
the selection of
antimicrobial agents; the
identification of hospital
and community
outbreaks; and the
recognition of quality
assurance problems in
laboratory testing.
Dr.T.V.Rao MD 76
77. Drugs Under Development
PRSP, MRSA,VISA,VRE
• Lipopetides (Daptomycin: narrow
therapeutic index)
• Glycyclines
• Glycopeptides (Vancomycin analogues)
• Fluoroquinolones
• Macrolides/Ketolides
• Evernimicin (trials on hold)
Dr.T.V.Rao MD 77
78. Physicians Can Impact
Other clinicians
Patients
Optimize patient evaluation Optimize consultations with
Adopt judicious antibiotic other clinicians
prescribing practices Use infection control measures
Immunize patients Educate others about judicious
use of antibiotics
Dr.T.V.Rao MD 78
79. A good clinical practice saves antibiotics
• Treatment should be
limited to bacterial
infections, using
antibiotics directed
against the causative
agent, given in optimal
dosage, interval and
length of treatment, with
steps taken to ensure
maximum patient
compliance with the
treatment regimen and
only when the benefit of
treatment outweighs the Dr.T.V.Rao MD 79
80. Continuous Medical Education a Must
..
• Training and educating health
care professionals on the
appropriate use of antibiotics
must include appropriate
selection, dosing, route, and
duration of antibiotic therapy.
To ensure that training and
education is working, there
should be extensive
collaboration between the
antibiotic stewardship and
hospital infection prevention
and control teams
Dr.T.V.Rao MD 80
81. Chennai Declaration
• The Chennai Declaration wants India to take
urgent initiatives to formulate an effective
national policy to control the rising trend of
antimicrobial resistance and to ban on over-the-
counter sale of antibiotics.
• Chennai: ‘The Chennai Declaration: A roadmap to
tackle the challenge of antimicrobial resistance’
published in the latest edition of Indian Journal of
Cancer has recommended to make it mandatory
to set up an Infection Control Team (ICT) in all
hospitals.
Dr.T.V.Rao MD 81
82. Educating the Educated
• The recommendations include offering Post-
MD/DNB (internal medicine) sub-specialisation in
Infectious Diseases at all post-graduate centres
that offer sub-speciality training, compulsory
training in infection control and infectious
diseases training in under-graduate and post
graduate curriculum in all specialities. The
Medical Council of India should introduce one-
week antibiotic stewardship and infection control
training in the third, fourth and final year of
MBBS and two-week training at the PG level.
Dr.T.V.Rao MD 82
83. Creating a Task force
• Recommending the setting up of a National
Task Force to guide and supervise the regional
and State infection control committees, the
paper suggests that the National Accreditation
Board for Hospitals & Healthcare Providers
(NABH) insist on strict implementation of
hospital antibiotic and infection control policy,
during hospital accreditation and re-
accreditation processes.
Dr.T.V.Rao MD 83
85. Good hand washing practices still reduces
antibiotic resistance and spread
Dr.T.V.Rao MD 85
86. Conclusions
Antibiotic resistance is a major
problem world-wide
Resistance is inevitable with use
No new class of antibiotic introduced
over the last two decades
Appropriate use is the only way of
prolonging the useful life of an
antibiotic
Dr.T.V.Rao MD 86