ANTIBIOTICS

SUCCESS AND FAILURES

Dr.T.V.Rao MD

ANTIBIOTICS
We didnt 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

ANTIBIOTIC BRANDS
50 penicillin's
71 cephalosporins

9 macrolides
2 streptogramins

12 tetracycline's
8 aminoglycosides 1 monobactam 5 Carbapenems

3 dihydrofolate reductase inhibitors

1 oxazolidinone 5.5 quinolones

Development of anti-microbials
The development
of anti-infectives

ertapenem tigecyclin daptomicin linezolid telithromicin quinup./dalfop. cefepime ciprofloxacin aztreonam norfloxacin imipenem cefotaxime clavulanic ac. cefuroxime gentamicin cefalotina nalidxico ac. ampicillin methicilin vancomicin rifampin chlortetracyclin streptomycin pencillin G

prontosil

1920
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1940

1950

1960

1970

1980

1990

2000
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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
Penicillin Streptomycin Tetracycline Erythromycin Gentamicin

Year introduced
1942 1947 1952 1955 1967

Resistance identified
1940 1947 1956 1956 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 ?

ANTIBIOTIC PRESCRIBING CHILDREN 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 antibiotic use.

WE TOO CONTRIBUTE FOR CREATING DRUG RESISTANCE

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 drugresistant bacteria.

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:
Susceptible Pathogen Pathogen Antimicrobial-Resistant Pathogen
Prevent Transmission

Key Prevention Strategies

Prevent Infection

Antimicrobial Resistance
Optimize Use

Infection
Effective Diagnosis & Treatment

Antimicrobial Use

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

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

Settings that Foster Drug Resistance

HOSPITAL

Intensive care units

Oncology units

Dialysis units
Rehab units

Transplant units
Burn units

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 infectionsin persons with no links to healthcare systems have been observed with increasing frequency in the United States and elsewhere around the globe.

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

FUNGI TOO BECOMING RESISTANCE

Antimicrobial resistance is emerging among some fungi, particularly those fungi that cause infections in transplant patients with weakened immune systems.

RESISTANCE IN VIRUS
Antimicrobial resistance has also been noted with some of the drugs used to treat human immunodeficiency virus (HIV) infections and influenza.

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.

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

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.
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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
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.
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GROWING IMPORTANCE OF
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
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WHONET

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WHONET SUPPORTS SURVEILLANCE IN OVER 90 COUNTRIES INDICATED BELOW IN RED.

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US NEW ANTIBACTERIAL AGENTS

Year 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 No. Approved 20 3 1 0 2 4 2 0 3 1 2 0 2 Multiple agents Temafloxacin, lomefloxacin, cefpodoxime Piperacillin/Tazobactam Lowest number of new agents (22) since 1988 Dirithromycin, ceftibutin Meropenem, levofloxacin, sparfloxacin, Cefepime Grepafloxacin, Trovafloxacin Rivaled 1994 Dalfopristin/quinupristin, gatifloxacin, moxifloxacin Linezolid Ertapenem, ceftidoren 89 drugs approved, no antibacterial agents Daptomycin, gemifloxacin Agents

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.

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CLINICIANS AND MICROBIOLOGIST CAN DO ANALYSIS OF THE DATA THEMSELVES

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.
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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

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CLINICIANS CAN ACCESS DATA OF THEIR PATIENTS ANYTIME IN THE COMPUTER JUST WITH CLICK OF THE MOUSE

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OUR LABORATORY REPORTS ARE DOCUMENTED IN DIGITAL FORMAT WITH WHONET

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.

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ANTIBIOTICS SAVE LIVES SAVE ANTIBIOTICS FROM MISUSE

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PHYSICIANS CAN IMPACT

Patients
Other clinicians

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

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

 Programme Created by Dr.T.V.Rao MD for Medical, Paramedical and Health Care Workers in the Developing World
Email
doctortvrao@gmail.com