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ANTIMICROBIAL RESISTANCE

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ANTIMICROBIAL RESISTANCE Prof. Khalifa Sifaw Ghenghesh Each class of antimicrobial agent has a unique mode of action. Some antibiotics differ in their action on Gram ... – PowerPoint PPT presentation

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Title: ANTIMICROBIAL RESISTANCE


1
ANTIMICROBIAL RESISTANCE
  • Prof. Khalifa Sifaw Ghenghesh

2
  • Each class of antimicrobial agent has a unique
    mode of action.
  • Some antibiotics differ in their action on
    Gramve and Gram-ve bacteria due to the
    difference in the cell wall structure of such
    bacteria.
  • Other antibiotics are active on both types of
    bacteria gtgt Broad spectrum antibiotics.

3
Site of action of some antimicrobial agents
  • Agent Site of action
  • --------------------------------------------------
    -----------------
  • Penicillins Cell wall
  • Cephalosporins Cell wall
  • Glycopeptides Cell wall
  • Tetracyclines Ribosome
  • Aminogylcosides Ribosome
  • Macrolides Ribosome
  • Rifamycins RNA synthesis
  • Sulphonamides Folate metabolism
  • Quinolones DNA synthesis

4
  • Antimicrobial agents can be classified to
  • Bacteriostatic
  • Inhibits growth and multiplication of bacteria.
  • Bactericidal
  • Kills bacteria.

5
Bacterial Mechanisms of Antibiotic Resistance
6
1. Production of enzymes that destroy the
antibiotic before it reaches its target.
  • b-lactamases
  • In G -ve
  • b-lactam drug enters the cell through the porin
    channels where it encounters the b-lactamases in
    the periplasmic space.
  • b-lactamases destroy the b-lactam molecules
    before they reach their PBP targets.
  • In G ve
  • b-lactamases excreted extracellularly. Thus
    b-lactam drugs are inactivated outside the cell.

7
2. The cell wall becomes impermeable to
antibiotics.
  • G ve bacteria may become resistant to b-lactam
    drugs by developing permeability barriers.
  • This caused by altered porin channels that no
    longer allow the entrance and passage of drug
    molecules into the cell.

8
3. Alteration of the target site by mutation
  • PBP alteration through mutation in Gve bacteria.
  • The b-lactam can no longer bind to it and the
    cell becomes resistant to the drug.
  • Also occurs in G ve bacteria.

9
4. Possession of an efflux pump
  • Efflux pump is a channel in the cell that
    actively exports tetracycline molecules and other
    drugs out of the cell as fast as they are
    transported or diffuse into the cell.
  • The antibiotic can not reach its target.

10
5. Alteration of specific metabolic pathways
  • By mutation or acquisition of genes encoding an
    alternative metabolic pathway so that the drug
    can not exert an effect.

11
Intrinsic Resistance
  • Escherichia coli intrinsically resistant to
    vancomycin because vancomycin is too large to
    pass through porin channels.
  • Gram ve bacteria have no porins and thus are not
    intrinsically resistant to vancomycin.

12
Acquired Resistance
  • Susceptible bacteria can acquire resistance to
    antibiotics by
  • 1. Genetic mutation
  • During multiplication of G -ve bacteria one cell
    undergoes a mutation to streptomycin for example.
  • When the population of cells is exposed to
    streptomycin only the mutant streptomycin-resistan
    t cell survives.
  • This resistant cell now multiplies and a
    streptomycin-resistant population arises.

13
  • 2. Acquisition of resistance
  • By Conjugation
  • When two bacterial cells are in close proximity a
    bridge-like structure (Pilus) forms between them.
  • If one of the cell carries a plasmid encoding
    ampicillin resistance gene this plasmid can be
    transferred to the other cell.
  • By Transformation
  • Gram-ve bacteria encounter a fragment of DNA
    contains a gentamicin-resistance gene. This gene
    has been released from a Gr ve bacteria during
    cell lysis.
  • The DNA fragment is taken into the cell during
    transformation.
  • The gene is incorporated into hosts chromosome
    by recombination.

14
Some examples of b-lactamases in
Enterobacteriaceae
  • Plasmid mediated TEM-1, TEM-2 and SHV-1.
  • Confer resistance to ampicillin and other
    penicllins.
  • Inhibited by calvulanic acid.
  • As level of expression of broad spectrum
    b-lactamases, increases resistance to other
    b-lactams occurs.

15
Extended Spectrum Beta-Lactamases (ESBLs)
  • Mutations of the genes encoding TEM-1, TEM-2 and
    SHV-1 b-lactamases results in the production of
    b-lactamases known as ESBLs.
  • Found in E. coli, Klebsiella pneumoniae and other
    G ve bacilli.
  • Hydrolyse
  • All penicillins
  • All cephalosporins (except cephramycin) and
    aztreonam.
  • Inhibited by b-lactamase inhibitors (e.g
    clavulanic acid).

16
  • Resistance to antimicrobial drugs is a major
    problem that inflicts the whole world.
  • The problem is still worse in developing
    countries where lack of antimicrobial-resistance
    surveys and control policies are the norm.

17
Methicillin-resistance (MRSA) among Staphylcoccus
aureus isolated from different cities in Libya
  • City Source No MRSA
  • tested
  • --------------------------------------------------
    -----------------------------
  • Tripoli and Clinical samples 218 25
  • Misulata
  • Benghazi Nares 238 24
  • (HCW, Pts, GP)
  • Misurata Nares 601 26
  • (HCW, Pts, GP)
  • --------------------------------------------------
    -----------------------------
  • Daw et al. 1996 El-Gadi 2000 Ghenghesh and
    Sanalla (2001)

18
Resistance of Shigella isolated from children
with and without diarrhea in Tripoli to
antibiotics (1992-1993).
  • Antibiotic resistant
  • (n11)
  • --------------------------------------------------
    -----------------------------------
  • Ampicillin 36
  • Ceftriaxone 0.0
  • Chloramphenicol 27
  • Ciprofloxacin 0.0
  • Gentamicin 0.0
  • Kanamycin 9
  • Nalidixic acid 0.0
  • Norfloxacin 0.0
  • Streptomycin 91
  • Trimethoprim-
  • sulphamethoxazole 64
  • --------------------------------------------------
    ---------------------------------Ghenghesh et al
    1997.

19
Resistance of enterobacteria isolated from
different sources in Tripoli to antibiotics
(1991-1993)
  • Antibiotic resistant
  • (n215)
  • --------------------------------------------------
    ----------------
  • Ampicillin 58
  • Chloramphenicol 26
  • Gentamicin 06
  • Kanamycin 29
  • Tetracycline 66
  • Trimethoprim- 28
  • sulphamethoxazole
  • --------------------------------------------------
    ----------------
  • Ghenghesh et al. 1994.

20
Resistance of Escherichia coli isolated from
urinary tract infections in Benghazi to
antibiotics (1996)
  • Antibiotic Hospital acquired Community
    acquired (n62) (n148)
  • --------------------------------------------------
    -----------------------------------Ampicillin 5
    2(84) 111(75)Carbenicillin 53(85) 117(79)C
    ephaloridine 22(35) 53(36)Chloramphenicol 3
    7(60) 67(45)Gentamicin 19(31)
    27(18)Nalidixic acid 3(5)
    15(10)Nitrofurantoin 4(6)
    10(7)Tetracycline 45(73) 121(82)Trimethoprim
    52(84) 120(81) sulphamethoxazole
  • --------------------------------------------------
    ----------------------------------() Tobgi et
    al 2001

21
Resistance of Salmonella species isolated from
children with diarrhoea in Zliten (2001) to
antibiotics.
  • Antibiotic No. () resistant
  • (n23)
  • --------------------------------------------------
    -----------------------------------
  • Ampicillin 23 (100)
  • Amoxicillincalvulanic acid 22 (95.7)
  • Cefoxitin 20 (87)
  • Gentamicin 18 (78.3)
  • Doxycycline 21 (91.3)
  • Chloramphenicol 22 (95.7)
  • Nalidixic acid 1 (4.3)
  • Norfloxacin 0 (0.0)
  • Trimethoprim-sulphamehtoxazole 1 (4.3)
  • --------------------------------------------------
    -----------------------------------
  • Ghenghesh et al. 2002

22
Resistance of different bacterial pathogens
isolated from ice cream in Tripoli
  • resistant
  • Antibiotic Gram-negative Gram-positive
  • (n48) (n67)
  • --------------------------------------------------
    -----------------------------------
  • Ampicillin 83 90
  • Amoxicillin- 40 45
  • clavulanic acid
  • Cefuroxime 25 NT
  • Ciprofloxacin 0.0 6
  • Gentamicin 0.0 12
  • Tetracycline 19 24
  • TMP-SMZ 12.5 25
  • --------------------------------------------------
    -----------------------------------
  • Ghenghesh et al. 2003 NTnot tested

23
ESBLs-producing Escherichia coli and Klebsiella
pneumoniae isolated from different clinical
samples in Tripoli
  • Organism No ESBLs
  • tested
  • --------------------------------------------------
    ------------
  • E. coli 383 8.6
  • K. pneumoniae 209 15.3
  • --------------------------------------------------
    ------------
  • Total 592 9.3
  • --------------------------------------------------
    ------------
  • Gebreel and Ghenghesh 2005.

24
THE PROBLEM
  • The high prevalence of resistant bacteria in
    Libya seems to be related to antibiotic usage
  • Easy availability without prescription at drug
    stores,
  • Injudicious use in hospitals, and
  • Uncontrolled use in animal husbandry.

25
CONCLUSION
  • The problem of antibiotic resistance is very
    serious in Libya, as it appears to be on the
    increase, particularly with the emergence of
    resistance to newer drugs that include the
    fluoroquinolones (e.g. ciprofloxacin) among the
    clinically important bacterial species.

26
RECOMMENDATIONS
  • It is urgently required
  • To ban the sale of antibiotics without
    prescription,
  • To use antibiotics more judiciously in hospitals
    by intensive teaching of the principles of the
    use of antibiotics, and
  • To establish better control measures of
    nosocomial infections.
  • Regulation of antimicrobials for other than human
    use is also required.
  • These issues are not easy to address and require
    the collective action of health authorities, the
    pharmaceutical community, health care providers,
    and consumers
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