Dr.T.V.Rao MD   1
Fleming and Penicillin         Dr.T.V.Rao MD   2
Self Medication• The greatest possibility of evil in self-  medication is the use of too small doses so  that instead of c...
Antibiotic brands•   50 penicillins          • 9 macrolides•   71 cephalosporins        • 2 streptogramins•   12 tetracycl...
Evolution of Enzymes         Plasmid-Mediated TEM and SHV                                      b-Lactamase                ...
Development of anti-microbials                                                                                            ...
1962 and 2000, no major classes of  antibiotics were introduced                     Fischbach MA and Walsh CT Science 2009...
A Changing Landscape for             Numbers of Approved Antibacterial Agents                                        18   ...
Dr.T.V.Rao MD   9
Antibiotics• Biology and Society  About 50% of the antibiotics produced   today are used in the livestock industry.     Wh...
ANTIMICROBIAL RESISTANCE:    The role of animal feed antibiotic additives• 48% of all antibiotics by weight is added to  a...
Prescribing an antibiotic Is an antibiotic necessary ? What is the most appropriate  antibiotic ? What dose, frequency,...
How are antibiotics overused or           Misused?• Seven out of ten Americans receive  antibiotics when they seek  treatm...
Antibiotic Prescribing           Children are real Concern• Antibiotics were  prescribed in 68% of  acute respiratory trac...
We too Contribute for Creating      Drug Resistance                      • Every time a person                        take...
The consequences of antibiotic               resistance     • Increased morbidity & mortality       – “best-guess” therapy...
Costs Associated with         Increased Bacterial             Resistance• ↑Treatment failures• ↑Morbidity and mortality• ↑...
Social factors fuelling resistance     • Poverty encourages the development of       resistance through under use of drugs...
Developed countries Overuse• In wealthy countries, resistance is emerging  for the opposite reason – the overuse of  drugs...
Classification of Pencillins• Natural   Benzyl penicillin   Phenoxymethyl penicillin Penicillin v Semi synthetic and penci...
Macrolides,Azalides,Ketolides• Contain macro cyclic  lactone ring  Erythromycin. Is  popularly used drug• Other drugs  Rox...
Dr.T.V.Rao MD   22
Cephalosporins• Like penicillin acts  similar• Products of the molds  of genus  Cephalosporium  except cefoxilin• Divided ...
Major generations of               Cephalosporins• Cephalosporins are divided into 3 generations:• 1st generation: Cephale...
Different Generations of           Cephalosporins• Cephalosporins are  grouped into  "generations" based on  their spectru...
5th Generation Cephalosporins• Ceftaroline is a new intravenous (IV)  cephalosporin that was FDA-approved  October 2010. I...
5th Generation Cephalosporins• Staphylococcus aureus (MSSA), methicillin-  resistant S aureus (MRSA), Streptococcus  pyoge...
Ceftaroline is effective …• Ceftaroline is a fifth generation  cephalosporin with excellent  activity against GPCs includi...
Irrational Use of Third Generation          Cephalosporins• Several studies have  demonstrated that patterns  of antibioti...
Advantages with Newer generations• Each newer generation of cephalosporins  has significantly greater gram-negative  antim...
Other Beta-lactams include• Other beta-lactams include:• Aztreonam: a monocytic beta-  lactam, with an antibacterial  spec...
How are Carbapenems Used?Uses by Clinical Syndrome        Use by Clinical Isolate• Bacterial meningitis             Acine...
Spectrum of Activity            Strep spp. &     Entero-        Non-Drug                                                  ...
Emerging Carbapenem Resistance in        Gram-Negative Bacilli• Significantly limits treatment options for  life-threateni...
Daptomycin           (Cubicin®)• New drug class (lipopeptide)• Rapidly bactericidal• New mechanism of action: acts by  bin...
Other drugs• Imipenem: a  carbapenem with a  broader spectrum of  activity against Gram  positive and negative  aerobes an...
Quinolones• Quinolones are the first  wholly synthetic  antimicrobials. The  commonly used  Quinolones.• Act on the DNA gy...
Aminoglycosides• Aminoglycosides are group of  antibiotics in which amino  sugars liked by glycoside bonds• Eg Streptomyci...
Dr.T.V.Rao MD   39
Tetracyclines• Broad spectrum antibiotic  produced by Streptomyces  species• 1. Oxytetracycle,  chlortetracycle and  tetra...
Other Antimicrobial agents• Lincomycins    Clindamycin   resembles Macrolides   in biting site and   antimicrobial activit...
Antibiotics in Anaerobes• Major anaerobes –  Anaerobic cocci,  clostridia and  Bactericides are  susceptible to Benzyl  pe...
Metronidazole in Anaerobic               Infections• Since the discovery of  Metronidazole in 1973  since then it was  ide...
Treatment of N. gonorrhoea• Only current CDC-recommended options for treating  N. gonorrhoea infections are from a single ...
Drug Resistance• In spite discovery of several  antibiotics several  microorganisms attained  resistance.• The major facto...
Inappropriate Antibiotic Use   Use of antibiotics    with no clinical    indication (eg, for    viral infections)   Use ...
Multi Drug resistant pathogens• If a bacterium carries  several resistance  genes, it is called  multiresistant or,  infor...
Extended-Spectrum β-Lactamases• β-lactamases capable of conferring bacterial resistance to    – the penicillins    – first...
Antibiotic Resistance       Threat to Humans and Animals• Antibiotic resistance has  become a serious  problem in both  de...
Carbapenemases• Ability to hydrolyze penicillins, cephalosporins,  monobactams, and carbapenems• Resilient against inhibit...
K. pneumonia carbapenemases)• KPCs are the most  prevalent of this  group of enzymes,  found mostly on  transferable plasm...
Consequences of Antibiotic drug            Resistance• People infected with drug-resistant organisms  are more likely to h...
Emerging Trends in Antibiotic         Resistance• Reports of methicillin-resistant  Staphylococcus aureus (MRSA)—a  potent...
Gram negative bacteria a great threat                         • Multi-drug resistant                           Klebsiella ...
WHAT NEXT• Indian hospitals have reported very high  Gram-negative resistance rates, with very high  prevalence of ESBL (E...
Fungi too becoming resistant• Antimicrobial  resistance is  emerging among  some fungi,  particularly those  fungi that ca...
Resistance in Virus                • Antimicrobial                  resistance has also                  been noted with  ...
Parasites too are Problematic• The development of  antimicrobial resistance to  the drugs used to treat  malaria infection...
Identification of The Etiological                Agent           Laboratory diagnosis Interpretation of the report What...
Limitations of combination of antibiotics• The role of combination  antimicrobial therapy for  the prevention of resistanc...
Problems With Improper Use of           Antibiotics• They don’t help the patient at all• Expense: 75% of outpatient antibi...
WHO global strategy on reducing the          antibiotic resistance• The WHO Global Strategy for  Containment of Antimicrob...
Importance of local antibiotic         Resistance data Resistance patterns vary   From country to country   From hospit...
Streamlining or De-Escalation          of Therapy–On the basis of culture and sensitivity reports we can more effectively ...
Continuous Medical Education•   Training and educating                           a Must ..    health care professionals on...
Antibiotic Pressure and Resistance in Bacteria   What factors promote their development and spread ? Alteration of normal...
Practices Contributing to      Misuse of Antibiotics   Inappropriate specimen selection and    collection   Inappropriat...
Settings that Foster Drug Resistance Hospital    Intensive care units    Oncology units    Dialysis units    Rehab uni...
What Is Antimicrobial Stewardship?• A combination of infection control and antimicrobialmanagement• Mandatory infection co...
IDSA Guidelines – Definition of        Antimicrobial Stewardship• Antimicrobial   stewardship is an activity thatpromotes–...
The Primary Goal of           Antimicrobial Stewardship• The primary goal of antimicrobial stewardship is to– Optimize cli...
Practices Contributing to      Misuse of Antibiotics   Inappropriate specimen selection and collection   Inappropriate c...
Identification of The Etiological                Agent           Laboratory diagnosis Interpretation of the report What...
Implementation of WHONET CAN HELP TO MONITOR                   RESISTANCE                              • Legacy computer  ...
Growing importance of                   WHONET• World over antimicrobial  resistance is a major  public health problem.  T...
Whonet helps us in ……• The understanding of the  local epidemiology of  microbial populations;  the selection of  antimicr...
Drugs Under Development       PRSP, MRSA,VISA,VRE• Lipopetides (Daptomycin: narrow  therapeutic index)• Glycyclines• Glyco...
Physicians Can Impact                                 Other cliniciansPatientsOptimize patient evaluation        Optimize ...
A good clinical practice saves antibiotics• Treatment should be  limited to bacterial  infections, using  antibiotics dire...
Continuous Medical Education a Must                ..• Training and educating health  care professionals on the  appropria...
Chennai Declaration• The Chennai Declaration wants India to take  urgent initiatives to formulate an effective  national p...
Educating the Educated• The recommendations include offering Post-  MD/DNB (internal medicine) sub-specialisation in  Infe...
Creating a Task force• Recommending the setting up of a National  Task Force to guide and supervise the regional  and Stat...
Are we overusing Antibiotics  Dr.T.V.Rao MD                84
Good hand washing practices still reduces    antibiotic resistance and spread                  Dr.T.V.Rao MD             85
Conclusions Antibiotic resistance is a major  problem world-wide Resistance is inevitable with use No new class of anti...
Antibiotics save LivesSave Antibiotics from Misuse            Dr.T.V.Rao MD      87
Dr.T.V.Rao MD   88
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  1. 1. Dr.T.V.Rao MD 1
  2. 2. Fleming and Penicillin Dr.T.V.Rao MD 2
  3. 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
  4. 4. Antibiotic brands• 50 penicillins • 9 macrolides• 71 cephalosporins • 2 streptogramins• 12 tetracyclines • 3 dihydrofolate• 8 aminoglycosides reductase• 1 monobactam inhibitors• 5 Carbapenems • 1 oxazolidinone • 5.5 quinolones Dr.T.V.Rao MD 4
  5. 5. Evolution of Enzymes Plasmid-Mediated TEM and SHV b-Lactamase Third-GenerationAmpicillin 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. 6. Development of anti-microbials ertapenem tigecyclinThe 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. 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. 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
  9. 9. Dr.T.V.Rao MD 9
  10. 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. 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. 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. 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. 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. 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. 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 countries16 Dr.T.V.Rao MD
  17. 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. 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 excessive18 promotion. Dr.T.V.Rao MD
  19. 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. 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. 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
  22. 22. Dr.T.V.Rao MD 22
  23. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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
  33. 33. Spectrum of Activity Strep spp. & Entero- Non-Drug Anaerobes MSSA bacteriaeae fermentorsImipenem + + + +Meropenem + + + + LimitedErtapenem + + activity +Doripenem + + + +
  34. 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. 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. 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. 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. 38. Aminoglycosides• Aminoglycosides are group of antibiotics in which amino sugars liked by glycoside bonds• Eg Streptomycin,• Act at the level of Ribosomes and inhibits protein synthesis• Other Aminoglycosides – Gentamycin, neomycins,paromomycins,tobr amycins Kanamycins and spectinomycins Dr.T.V.Rao MD 38
  39. 39. Dr.T.V.Rao MD 39
  40. 40. Tetracyclines• 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 69. What Is Antimicrobial Stewardship?• A combination of infection control and antimicrobialmanagement• Mandatory infection control compliance• Selection of antimicrobials from each class of drugs that doesthe 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 availableDellit TH, et al. Clin Infect Dis. 2007;44:159-177. Dr.T.V.Rao MD 69
  70. 70. IDSA Guidelines – Definition of Antimicrobial Stewardship• Antimicrobial stewardship is an activity thatpromotes– The appropriate selection of antimicrobials– The appropriate dosing of antimicrobials– The appropriate route and duration ofantimicrobial therapy Dr.T.V.Rao MD 70
  71. 71. The Primary Goal of Antimicrobial Stewardship• The primary goal of antimicrobial stewardship is to– Optimize clinical outcomes while minimizing unintendedconsequences 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. 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. 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. 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. 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. 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. 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. 78. Physicians Can Impact Other cliniciansPatientsOptimize patient evaluation Optimize consultations withAdopt judicious antibiotic other cliniciansprescribing practices Use infection control measuresImmunize patients Educate others about judicious use of antibiotics Dr.T.V.Rao MD 78
  79. 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. 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. 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. 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. 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
  84. 84. Are we overusing Antibiotics Dr.T.V.Rao MD 84
  85. 85. Good hand washing practices still reduces antibiotic resistance and spread Dr.T.V.Rao MD 85
  86. 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
  87. 87. Antibiotics save LivesSave Antibiotics from Misuse Dr.T.V.Rao MD 87
  88. 88. Dr.T.V.Rao MD 88
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