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Dr.T.V.Rao MD
ANTIBIOTICS
SUCCESS AND FAILURES
WHAT IS OUR ROLE
ANTIBIOTICS
• We didn’t have antibiotics before the 1940s.
• Alexander Fleming helped to develop the first
antibiotic from a mold.
• Antibiotics work to kill infecting bacteria.
• Natural variations exist within bacterial populations
that make some bacteria resistant to antibiotics.
• Abuse of antibiotics promotes the development of
antibiotic-resistant bacteria.
A DISCOVERY BY ACCIDENT
• A fungal spore that the wind might have
blown into his lab while Fleming was on
vacation in 1928, forever changed the
course of medicine...
• A. Fleming named the substance Penicillin,
after the mould Pencillium notatum – but
was unable to isolate the substance
• In the late 1930s and early 1940s, E. Chain
& H. Florey managed to produce larger
amounts of penecillin, and ran successful
trials on mice
• Nobel prize in 1945
• 50 penicillin's
• 71 cephalosporins
• 12 tetracycline's
• 8 aminoglycosides
• 1 monobactam
• 5 Carbapenems
• 9 macrolides
• 2 streptogramins
• 3 dihydrofolate
reductase inhibitors
• 1 oxazolidinone
• 5.5 quinolones
ANTIBIOTIC BRANDS
1920 1930 1940 1950 1960 1970 1980 1990 2000
ertapenem
tigecyclin
daptomicin
linezolid
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
The development
of anti-infectives …
Development of anti-microbials
DR.T.V.RAO MD 5
ANTIBIOTIC USE AND MISUSE
•During the 1940s and 1950s antibiotics were extremely
effective
•They were (and still are) widely prescribed, often for
medical conditions that did not require them
•Antibiotics started to be used in agriculture: dosing cattle
with antibiotics increases yield, and battery farming
relies on antibiotics to control infection
•By the 1970s the World was awash with antibiotics.
EVOLUTION OF RESISTANCE
•Antibiotic use represents a strong selection pressure
•If a population of bacteria with a few resistant individuals
is exposed to a lethal antibiotic, the susceptible bacteria
will die, but the resistant bacteria will survive
•In an environment with a lot of antibiotic use, resistance
alleles spread rapidly
•The problem is compounded by horizontal gene transfer
and by cross-resistance
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?
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
CHRONOLOGY OF DEVELOPMENT OF
ANTIBIOTIC RESISTANCE
Antibiotic Year introduced Resistance identified
Penicillin 1942 1940
Streptomycin 1947 1947
Tetracycline 1952 1956
Erythromycin 1955 1956
Gentamicin 1967 1970
Vancomycin 1956 1987
PRESCRIBING AN ANTIBIOTIC
 Is an antibiotic necessary ?
 What is the most appropriate
antibiotic ?
 What dose, frequency, route and
duration ?
 Is the treatment effective ?
• 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
antibiotic use.
ANTIBIOTIC PRESCRIBING
CHILDREN REAL CONCERN
• Every time a person
takes antibiotics,
sensitive bacteria are
killed, but resistant
germs may be left to
grow and multiply.
Repeated and improper
uses of antibiotics are
primary causes of the
increase in drug-
resistant bacteria.
WE TOO CONTRIBUTE FOR
CREATING DRUG RESISTANCE
ANTIBIOTIC PRESSURE AND RESISTANCE IN
BACTERIA
WHAT HAPPENED TO S. AUREUS ?
• Reports of increasing use of third gen
cephalosporins and quinolones related to
emergence of MRSA.
• Some data suggest that quinolones enhance
expression of methicillin resistance in SA in vitro
• Outbreaks of MRSA have been reduced by curbing
antibiotic use: especially of cephalosporins
Antimicrobial Resistance:
Key Prevention Strategies
Optimize
Use
Prevent
Transmission
Prevent
Infection
Effective
Diagnosis
& Treatment
Pathogen
Antimicrobial-Resistant Pathogen
Antimicrobial
Resistance
Antimicrobial Use
Infection
Susceptible Pathogen
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.
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
 Inappropriate specimen selection and collection
 Inappropriate clinical tests
 Failure to use stains/smears
 Failure to use cultures and susceptibility tests
Practices Contributing to
Misuse of Antibiotics
 Intensive care units
 Oncology units
 Dialysis units
 Rehab units
 Transplant units
 Burn units
HOSPITAL
Settings that Foster Drug Resistance
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.
• Multi-drug resistant
Klebsiella species
and Escherichia coli
have been isolated
in hospitals
throughout the
United States.
• It is a Universal
phenomenon
GRAM NEGATIVE BACTERIA A
GREAT THREAT
• Antimicrobial
resistance is
emerging among
some fungi,
particularly those
fungi that cause
infections in
transplant patients
with weakened
immune systems.
FUNGI TOO BECOMING RESISTANT
• Antimicrobial
resistance has also
been noted with
some of the drugs
used to treat human
immunodeficiency
virus (HIV) infections
and influenza.
RESISTANCE IN VIRUS
• 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.
•
PARASITES TOO ARE PROBLEMATIC
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
WHO GLOBAL STRATEGY ON REDUCING THE
ANTIBIOTIC RESISTANCE
DR.T.V.RAO MD 26
• 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.
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
WHONET DOCUMENTATION
WHY WE NEED IT
ADOPTION OF WHONET
• To enhance the local use of data for local
needs: clinical decision support, antimicrobial
use policy, infection control and outbreak
detection, identifying laboratory test
performance, and characterization of local
microbial and resistance epidemiology
• To promote local, national, regional, and global
collaborations through the exchange of data
and sharing of experiences
WHAT IS WHONET
DR.T.V.RAO MD 30
• WHONET is a free software developed by the WHO
Collaborating Centre for Surveillance of Antimicrobial
Resistance for laboratory-based surveillance of infectious
diseases and antimicrobial resistance.
• The principal goals of the software are:
• 1 to enhance local use of laboratory data; and
• 2 to promote national and international collaboration
through the exchange of data.
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 31
WHONET SUPPORTS SURVEILLANCE IN OVER 90
COUNTRIES INDICATED BELOW IN RED.
DR.T.V.RAO MD 32
US – NEW ANTIBACTERIAL AGENTS
Year No. Approved Agents
1991 20± Multiple agents
1992 3 Temafloxacin, lomefloxacin, cefpodoxime
1993 1 Piperacillin/Tazobactam
1994 0 Lowest number of new agents (22) since 1988
1995 2 Dirithromycin, ceftibutin
1996 4 Meropenem, levofloxacin, sparfloxacin, Cefepime
1997 2 Grepafloxacin, Trovafloxacin
1998 0 Rivaled 1994
1999 3 Dalfopristin/quinupristin, gatifloxacin, moxifloxacin
2000 1 Linezolid
2001 2 Ertapenem, ceftidoren
2002 0 89 drugs approved, no antibacterial agents
2003 2 Daptomycin, gemifloxacin
• 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.
WHONET HELPS US IN ……
DR.T.V.RAO MD 34
CLINICIANS AND MICROBIOLOGIST CAN DO
ANALYSIS OF THE DATA THEMSELVES
DR.T.V.RAO MD 35
• WHONET has a user-friendly interface permitting many
types of analysis. Options include isolate line-listings and
summaries, such as organism frequencies over time,
antimicrobial susceptibility test statistics, zone diameter
antibiotic scatterplots and regression curves, and
antibiotic resistance and MIC histograms, profile line
listings and summaries.
WHONET also has a number of alert features which
permit the detection of unlikely or important results
as well as possible community outbreaks of bacterial
or non-bacterial species.
ALL THE DOCUMENTED RESULTS ARE
ANALYZED IN WHONET
• The heart of WHONET is
a software package
designed to collect the
results of antibiotic
resistance tests.
Researchers /
Microbiologists feed the
results into a computer
and look for trends
DR.T.V.RAO MD 36
CLINICIANS CAN ACCESS DATA OF THEIR PATIENTS
ANYTIME IN THE COMPUTER JUST WITH CLICK OF THE
MOUSE
DR.T.V.RAO MD 37
OUR LABORATORY REPORTS ARE DOCUMENTED IN
DIGITAL FORMAT WITH WHONET
• 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.
IMPLEMENTATION OF WHONET CAN HELP
TO MONITOR RESISTANCE
DR.T.V.RAO MD 39
ANTIBIOTICS SAVE LIVES
SAVE ANTIBIOTICS FROM MISUSE
DR.T.V.RAO MD 40
PHYSICIANS CAN IMPACT
Other clinicians
Patients
Optimize patient evaluation
Adopt judicious antibiotic
prescribing practices
Immunize patients
Optimize consultations with
other clinicians
Use infection control measures
Educate others about
judicious use of antibiotics
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
• Program file created by Dr .T.V.Rao MD for basic
understanding on Antibiotics' its role misuse
consequences for benefit of Medical and
Paramedical Professionals in the Developing
countries
• Email
• doctortvrao@gmail.com

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Antibiotics Success and Failures what is our role by Dr.T.V.Rao MD

  • 1. Dr.T.V.Rao MD ANTIBIOTICS SUCCESS AND FAILURES WHAT IS OUR ROLE
  • 2. ANTIBIOTICS • We didn’t have antibiotics before the 1940s. • Alexander Fleming helped to develop the first antibiotic from a mold. • Antibiotics work to kill infecting bacteria. • Natural variations exist within bacterial populations that make some bacteria resistant to antibiotics. • Abuse of antibiotics promotes the development of antibiotic-resistant bacteria.
  • 3. A DISCOVERY BY ACCIDENT • A fungal spore that the wind might have blown into his lab while Fleming was on vacation in 1928, forever changed the course of medicine... • A. Fleming named the substance Penicillin, after the mould Pencillium notatum – but was unable to isolate the substance • In the late 1930s and early 1940s, E. Chain & H. Florey managed to produce larger amounts of penecillin, and ran successful trials on mice • Nobel prize in 1945
  • 4. • 50 penicillin's • 71 cephalosporins • 12 tetracycline's • 8 aminoglycosides • 1 monobactam • 5 Carbapenems • 9 macrolides • 2 streptogramins • 3 dihydrofolate reductase inhibitors • 1 oxazolidinone • 5.5 quinolones ANTIBIOTIC BRANDS
  • 5. 1920 1930 1940 1950 1960 1970 1980 1990 2000 ertapenem tigecyclin daptomicin linezolid 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 The development of anti-infectives … Development of anti-microbials DR.T.V.RAO MD 5
  • 6. ANTIBIOTIC USE AND MISUSE •During the 1940s and 1950s antibiotics were extremely effective •They were (and still are) widely prescribed, often for medical conditions that did not require them •Antibiotics started to be used in agriculture: dosing cattle with antibiotics increases yield, and battery farming relies on antibiotics to control infection •By the 1970s the World was awash with antibiotics.
  • 7. EVOLUTION OF RESISTANCE •Antibiotic use represents a strong selection pressure •If a population of bacteria with a few resistant individuals is exposed to a lethal antibiotic, the susceptible bacteria will die, but the resistant bacteria will survive •In an environment with a lot of antibiotic use, resistance alleles spread rapidly •The problem is compounded by horizontal gene transfer and by cross-resistance
  • 8. 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?
  • 9. 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
  • 10. CHRONOLOGY OF DEVELOPMENT OF ANTIBIOTIC RESISTANCE Antibiotic Year introduced Resistance identified Penicillin 1942 1940 Streptomycin 1947 1947 Tetracycline 1952 1956 Erythromycin 1955 1956 Gentamicin 1967 1970 Vancomycin 1956 1987
  • 11. PRESCRIBING AN ANTIBIOTIC  Is an antibiotic necessary ?  What is the most appropriate antibiotic ?  What dose, frequency, route and duration ?  Is the treatment effective ?
  • 12. • 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 antibiotic use. ANTIBIOTIC PRESCRIBING CHILDREN REAL CONCERN
  • 13. • Every time a person takes antibiotics, sensitive bacteria are killed, but resistant germs may be left to grow and multiply. Repeated and improper uses of antibiotics are primary causes of the increase in drug- resistant bacteria. WE TOO CONTRIBUTE FOR CREATING DRUG RESISTANCE
  • 14. ANTIBIOTIC PRESSURE AND RESISTANCE IN BACTERIA WHAT HAPPENED TO S. AUREUS ? • Reports of increasing use of third gen cephalosporins and quinolones related to emergence of MRSA. • Some data suggest that quinolones enhance expression of methicillin resistance in SA in vitro • Outbreaks of MRSA have been reduced by curbing antibiotic use: especially of cephalosporins
  • 15. Antimicrobial Resistance: Key Prevention Strategies Optimize Use Prevent Transmission Prevent Infection Effective Diagnosis & Treatment Pathogen Antimicrobial-Resistant Pathogen Antimicrobial Resistance Antimicrobial Use Infection Susceptible Pathogen
  • 16. 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.
  • 17. 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
  • 18.  Inappropriate specimen selection and collection  Inappropriate clinical tests  Failure to use stains/smears  Failure to use cultures and susceptibility tests Practices Contributing to Misuse of Antibiotics
  • 19.  Intensive care units  Oncology units  Dialysis units  Rehab units  Transplant units  Burn units HOSPITAL Settings that Foster Drug Resistance
  • 20. 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.
  • 21. • Multi-drug resistant Klebsiella species and Escherichia coli have been isolated in hospitals throughout the United States. • It is a Universal phenomenon GRAM NEGATIVE BACTERIA A GREAT THREAT
  • 22. • Antimicrobial resistance is emerging among some fungi, particularly those fungi that cause infections in transplant patients with weakened immune systems. FUNGI TOO BECOMING RESISTANT
  • 23. • Antimicrobial resistance has also been noted with some of the drugs used to treat human immunodeficiency virus (HIV) infections and influenza. RESISTANCE IN VIRUS
  • 24. • 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. • PARASITES TOO ARE PROBLEMATIC
  • 25. 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
  • 26. WHO GLOBAL STRATEGY ON REDUCING THE ANTIBIOTIC RESISTANCE DR.T.V.RAO MD 26 • 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.
  • 27. 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
  • 29. ADOPTION OF WHONET • To enhance the local use of data for local needs: clinical decision support, antimicrobial use policy, infection control and outbreak detection, identifying laboratory test performance, and characterization of local microbial and resistance epidemiology • To promote local, national, regional, and global collaborations through the exchange of data and sharing of experiences
  • 30. WHAT IS WHONET DR.T.V.RAO MD 30 • WHONET is a free software developed by the WHO Collaborating Centre for Surveillance of Antimicrobial Resistance for laboratory-based surveillance of infectious diseases and antimicrobial resistance. • The principal goals of the software are: • 1 to enhance local use of laboratory data; and • 2 to promote national and international collaboration through the exchange of data.
  • 31. 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 31
  • 32. WHONET SUPPORTS SURVEILLANCE IN OVER 90 COUNTRIES INDICATED BELOW IN RED. DR.T.V.RAO MD 32
  • 33. US – NEW ANTIBACTERIAL AGENTS Year No. Approved Agents 1991 20± Multiple agents 1992 3 Temafloxacin, lomefloxacin, cefpodoxime 1993 1 Piperacillin/Tazobactam 1994 0 Lowest number of new agents (22) since 1988 1995 2 Dirithromycin, ceftibutin 1996 4 Meropenem, levofloxacin, sparfloxacin, Cefepime 1997 2 Grepafloxacin, Trovafloxacin 1998 0 Rivaled 1994 1999 3 Dalfopristin/quinupristin, gatifloxacin, moxifloxacin 2000 1 Linezolid 2001 2 Ertapenem, ceftidoren 2002 0 89 drugs approved, no antibacterial agents 2003 2 Daptomycin, gemifloxacin
  • 34. • 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. WHONET HELPS US IN …… DR.T.V.RAO MD 34
  • 35. CLINICIANS AND MICROBIOLOGIST CAN DO ANALYSIS OF THE DATA THEMSELVES DR.T.V.RAO MD 35 • WHONET has a user-friendly interface permitting many types of analysis. Options include isolate line-listings and summaries, such as organism frequencies over time, antimicrobial susceptibility test statistics, zone diameter antibiotic scatterplots and regression curves, and antibiotic resistance and MIC histograms, profile line listings and summaries. WHONET also has a number of alert features which permit the detection of unlikely or important results as well as possible community outbreaks of bacterial or non-bacterial species.
  • 36. ALL THE DOCUMENTED RESULTS ARE ANALYZED IN WHONET • The heart of WHONET is a software package designed to collect the results of antibiotic resistance tests. Researchers / Microbiologists feed the results into a computer and look for trends DR.T.V.RAO MD 36
  • 37. CLINICIANS CAN ACCESS DATA OF THEIR PATIENTS ANYTIME IN THE COMPUTER JUST WITH CLICK OF THE MOUSE DR.T.V.RAO MD 37
  • 38. OUR LABORATORY REPORTS ARE DOCUMENTED IN DIGITAL FORMAT WITH WHONET
  • 39. • 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. IMPLEMENTATION OF WHONET CAN HELP TO MONITOR RESISTANCE DR.T.V.RAO MD 39
  • 40. ANTIBIOTICS SAVE LIVES SAVE ANTIBIOTICS FROM MISUSE DR.T.V.RAO MD 40
  • 41. PHYSICIANS CAN IMPACT Other clinicians Patients Optimize patient evaluation Adopt judicious antibiotic prescribing practices Immunize patients Optimize consultations with other clinicians Use infection control measures Educate others about judicious use of antibiotics
  • 42. 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
  • 43. • Program file created by Dr .T.V.Rao MD for basic understanding on Antibiotics' its role misuse consequences for benefit of Medical and Paramedical Professionals in the Developing countries • Email • doctortvrao@gmail.com