Dr.T.V.Rao MD

ANTIBIOTICSSUCCESS AND FAILURES

ANTIBIOTICSSUCCESS AND FAILURES

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

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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 Year introduced Resistance identifiedPenicillin 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 PRESCRIBINGCHILDREN 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

PreventTransmission

PreventInfection

EffectiveDiagnosis& Treatment

PathogenAntimicrobial-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 RESISTANCE

• 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

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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.

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 DOCUMENTATIONWHY 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

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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.

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

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

US – NEW ANTIBACTERIAL AGENTSYear 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

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• 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 ……

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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.

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

OUR LABORATORY REPORTS ARE DOCUMENTED IN

DIGITAL FORMAT WITH WHONET

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• 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

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ANTIBIOTICS SAVE LIVESSAVE ANTIBIOTICS FROM MISUSE

PHYSICIANS CAN IMPACT

O th er clin ician s

Patients

Optimize patient evaluation Adopt judicious antibiotic

prescribing practicesImmunize patients

Optimize consultations with other clinicians

Use infection control measuresEducate 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