Antimicrobial Resistance

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Antimicrobial Resistance

• Steven M Gordon
• Dept of Infectious Disease
• Cleveland Clinic

Cleveland Clinic Journal of MedicineVolume 65,
Number 5, May 1998
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Bacterialcidal Mechanism
Cell Membrane
Cell Wall
Mitochondria
DNA
RibosomalComplex
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Bacterialcidal Mechanism

• Damaging or inhibiting synthesis of the bacterial
  cell wall (penicillins, cephalosporins,
  monobactams, carbapenems, bacitracin, vancomycin,
  cycloserine, fosfomycin)
• Damaging or inhibiting synthesis of the cell
  membrane (polymyxins)

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Bacterialcidal Mechanism

• Metabolizing or inhibiting DNA synthesis of
  nucleic acids (rifampin, nitrofurantoins,
  nitromidazoles)
• Modifying ribosomal energy metabolism
  (sulfonamides, trimethroprim, dapsone, isoniazid)

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Bacterialcidal Mechanism

• Inhibiting ribosomal protein biosynthesis
  (aminoglycosides, tetracyclines, chloramphenicol,
  erythromycin, clindamycin, spectinomycin,
  mupirocin, fusidic acid)

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Acquired Bacterial Resistance
Virus
Plasmid
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Acquired Bacterial Resistance

• Receiving a plasmid bearing a resistance gene
  from another bacterium directly
• Receiving a resistance gene from other bacterium
  by viral transfection
• Chromosomal mutation
• DNA scavenged from dead bacteria

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Antibiotic Resistance
Antibiotic
Alteredbinding site
Inactivebinding site
Enzymeinactivation
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Antibiotic Resistance

• Creating enzymes that destroy antibiotic
  molecules
• Making the cell wall less permeable
• Altering the binding site of the antibiotic
• Crating a second, inactive site for the antibiotic

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Loss of Antibiotic Resistance

• Antibiotic resistant bacteria are at a selective
  disadvantage - they must expend energy and
  resources to manufacture proteins that confer
  resistance
• The prevalence of resistant bacteria declines
  after antibiotics are withdrawn

Lancet 19701213-1215
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Enterococcus faecalisEnterococcus faecium

• Largely resistant to penicillin and
  aminoglycosides
• Vancomycin resistance increased from 0.3 in 1989
  to 10 in 1995
• streptogamin Synercid (quinupristin-dalfopristin)
  can treat vacomycin resistant E faecium but not E
  faecalis

Infect Control Hosp Epidemiol 199516105-113
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Neisseria gonorrhoeae

• Until 1992 almost all N gonorrhoeae strains were
  susceptible to fluroquinolone antibiotics,
  including ciprofloxacin
• From 1992 to 1994, 7.4 of isolates in Cleveland
  were resistant to ciprofloxacin

Ann Intern Med 1996125465-470
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Streptococcus pneumoniae

• Emerging resistance to penicillin is a great
  concern
• Affects patients in all age groups, especially
  the elderly and the young
• 20 of community-acquired S pneumoniae pneumonia
  are resistant
• 21 of children in a day care found to carry
  resistant strains

J Infect Dis 19921661346-1353
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Overprescription

• Antibiotics offer little benefit in treating
  colds, URI, or bronchitis
• account for 31 of antibiotic prescriptions in
  ambulatory care
• more than 50 of patients with one of these
  conditions walked out with a prescription for an
  antibiotic

Br J Gen Pract 199444400-404 JAMA
1995273214-219JAMA 1997 278901-904
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Inappropriate Prescription

• Prolonged cough occurs commonly inpatients with
  viral respiratory infections, and does not
  necessarily indicate the need for antibiotics
• A positive urine culture in a patient with a
  Foley catheter may be meaningless if the patient
  has no fever and feels well

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Inappropriate Prescription

• Culturing skin in patients with decubitus ulcers
  and treating all organisms isolated is not
  necessary
• Coagulase-negative stahylococcus isolated from
  one of two blood cultures probably represents a
  contaminant, and does not requite treatment

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Antibiotics in Feedlots

• 40 of antibiotics production goes into the
  livestock feed as prophylaxis
• Encourages microbial resistance in chickens,
  agricultural workers, and consumers

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Need for Change

• Prescribe fewer antibiotics
• Prescribe antibiotics that target as narrow a
  range of bacteria as possible
• Observe the often ignored basics of infection
  control - hand washing

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Advice to Physicians

• Wash hands thoroughly between patients visits
• Do not give antibiotics when not needed, even if
  patients ask for them
• When possible, prescribe antibiotics that target
  only a narrow range of bacteria computerized
  system may help
• Isolate hospital patients with multi-drug
  resistant infections
• Familiarize yourself with local data on
  antibiotic resistance

Sci Am March 1998278(3) 46-53
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Advice to Patients

• Do not demand antibiotics
• when given antibiotics, take them exactly as
  prescribed and complete the full course of
  treatment do not hoard pills for later use
• Wash fruits and vegetables thoroughly avoid raw
  eggs and undercooked meat, especially in ground
  form
• Use soaps and other products with antibacterial
  chemicals only when protecting a sick person
  whose defenses are weakened

Sci Am March 1998278(3) 46-53
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Please Visit
www.healthsci.tufts.edu/apua/pract.htm
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References

• Antimicrobial resistance an ecological approach
  to growing threat.Gordon SM, Cleve Clin J Med.
  199865232-235
• Antimicrobial-drug resistance.Gold HS,
  Moellering RC. N Engl J Med. 19963351445-1453
• Control of infection due to Klebsiella aeruginosa
  in a neurological unit by withdrawal of all
  antibiotics. Lancet 19701213-1215.