ANTIMICROBIAL CHEMOTHERAPY Pit Stop

LINA C. CASIPLE-AMSUA, M.D.

July 24, 2013 This bacterium is lysing
Group 4 because an antibiotic
disrupted its cell wall.
Antimicrobial Drugs
Why doesnt the antibiotic
Chemotherapy: The use of drugs to treat a disease
lyse human cells?
Antimicrobial drugs: Interfere with the growth of
microbes within a host
Selective Toxicity
Antibiotic: Of biological origin. Produced by a microbe,
inhibits other microbes.
Chemotherapeutic agent: synthetic chemicals
Today distinction blurred many newer an0bio0cs Features of Antimicrobial Drugs
are biological products that are: Selective toxicity: Drug kills pathogens without damaging
o chemically modified or the host.
o chemically synthesized Antimicrobial action: bacteriostatic vs. bacteriocidal
Antimicrobials Activity spectrum: broad-spectrum vs. narrow-spectrum
One of the most important discoveries in the history Tissue distribution, metabolism, and excretion BBB,
of humankind Unstable in acid; half-life duration
Antibiotics have become both a boon and a bane
Importance of proper and rational use of antibiotics CLASSES OF ANTIBIOTICS
Beta lactams
The History of Chemotherapy o Penicillins
Paul Ehrlich and Sacachiro Hata developed o Cephalosporins
Salvarsan (Arsphenamine) against syphilis in 1910. o Carbapenems
The concept of chemotherapy, which was to treat o Monobactams
microbial diseases, was born. Aminoglycosides
Sulfa drugs (sulfanilamide) was discovered in 1932 Macrolides
against Gram + bacteria Tetracyclines
1928: Fleming discovered penicillin Fluoroquinones
1940: Howard Florey and Ernst Chain performed Others
first clinical trials of penicillin. o Chloramphenicol
o Cotrimaxazole
Where do antimicrobials come from? o Glycopeptides
Gram-positive rods o Oxazolidinozole
Bacillus subtilis Bacitracin
Paenibacillus polymixia Polymixin Mechanism of Action of Antibiotics
Actinomycetes
Streptomyces nodosus Amphotericin B
Streptomyces venezuelae Chloramphenicol
Streptomyces aureofaciens Chlortetracycline and
tetracycline
Saccharopolyspora Erythromycin
erythraea
Streptomyces grisues Neomycin
Micromonospora purpurea Streptomycin
Gentamycin
Fungi
Cepaholosporium spp Cephalosporins
Penicillium griseofulvum Griseofulvin
Penicillium ichrysogenum Penicillin
The Action of Antimicrobial Drugs
1. Inhibition of cell wall synthesis: penicillins,
cephalosporins, bacitracin, vancomycin
2. Inhibition of protein synthesis: chloramphenicol,
erythromycin, tetracyclines, streptomycin
3. Inhibition of nucleic acid replication and transcription:
quinolones, rifampin
4. Injury to plasma membrane: polymixin B
5. Inhibition of synthesis of essential metabolites:
sulfonilamide, trimethoprim
General Mechanisms of Action
Inhibition of cell wall synthesis
Inhibition of protein synthesis
Inhibition of nucleic acid synthesis
Alteration of cell membrane function
INHIBITION OF BACTERIAL CELL WALL SYNTHESIS
PEPTIDOGLYCAN/MURAMIC ACID
Provides support, shape and rigidity
Protects cell from physical stresses
Injury to the cell wall causes lysis
Inhibitors of cell wall synthesis
-lactams
antibiotics structurally related because of the
presence of the beta lactam ring
e.g. penicillins, cephalosporins
Glycopeptides vancomycin
Cycloserine
Bacitracin
The -lactams penicillins, cephalosporins are structurally
similar to the terminal peptides that participate in the final
stages of cross linking of peptidoglycan
The -lactams penicillins, cephalosporins
bacterial transpeptidases and other enzymes called penicillin-
binding proteins (PBPs)
Bind the penicillin instead of the peptide chains
Prevent cross linkages
Unstable Bacterial Cell Wall
The -lactams penicillins, cephalosporins
Also trigger membrane-associated autolytic enzymes that
destroy bacterial cell wall
Antibacterial Antibitotics
Inhibitors of Cell Wall Synthesis:
Penicillin
Natural and semisynthetic penicillins contain -
lactam ring
Natural penicillins
Produced by the Penicillim are effective against
Gram + cocci and spirochetes
 Semisynthetic penicillins: made in laboratory by
adding different side chains onto -lactam ring
penicillinase-resistant and broader spectrum of
activity

Penicillinase (-lactamase): Bacterial enzyme that

destroys natural penicillins
Penicillinase-resistant penicillins: methicillin, oxacillin
and nafcillin MRSA
Extended-spectrum penicillins: Ampicilin, amoxicillin;
new: carboxypenicillins and ureidopenicillins (also good
against P. aeruginosa) OTHER -LACTAM ANTIBIOTICS

Monobactams (Aztreonam)
Binds primarily to protein-binding protein 3 (PBP 3) of
Gram(-) aerobes

Carbapenems (Imipenem, Meropenem, Ertanpenem,

Doripenem)
Binds to PBP 1 and PBP 2 of G(- )and G(+) causing cell
Cephalosporins deformity and lysis
Fungi of genus Cephalosporium 4 Genera0ons of
cephalosporins
1. First Generation: narrow spectrum, gram (+)
2. Second Generation: extended spectrum includes
gram
3. Third Generation: includes pseudomonads; mostly
injected, some oral
4. Fourth Generation: mostly extended spectrum

Structure and mode of action resembles penicillin

1. More stable to bacterial -lactamases than
penicillins
2. Broader spectrum used against penicillin-resistant
strains The -lactams therefore:
Prevent peptidoglycan synthesis by targeting PBPs or
transpeptidases and inhibiting cross-linkages of murein
units

NON- -LACTAM ANTIBIOTICS

Cycloserine
Inhibits reactions that incorporate alanine into cell wall
precursor
 Mechanisms of Antibacterial Resistance: Bata-Lactam
Antibiotics

A peek at antibiotic resistance penicillinase

Antibiotic Resistance
A variety of mutations can lead to antibiotic resistance
Glycopepetides e.g. vancomycin Mechanisms of antibiotic resistance
Bind to terminal D-ala-D-ala residues, prevent o Enzymatic destruction of drug
incorporation into growing peptideglycan o Prevention of penetration of drug
Spectrum of activity limited to G(+) organisms o Alteration of drugs target site
o Rapid ejection of the drug
Resistance genes are often on plasmids or transposons
that can be transferred between bacteria.

Bacteria Fight Back

Mechanism 1 Production of -lactamases

Penicillinase and cephalosporinase (-lactamases)

Hydrolyze the -lactam ring of -lactams antibiotics.

Bacitracin
Prevents dephosphorylation of phosphorylipid carrier
which prevents regeneration of carrier necessary for
subunit to be transported to the cell wall which prevents
regeneration of carrier spectrum limited to G+ organisms

Mechanism 2 Alteration of target site PBPs

Non- -lactams therefore:
Methicillin-resistant staphylococci synthesize an
Target the peptide side chain portion where alanine is
additional PBP
incorporated (cycloserine, vancomycin)
o Can continue cell wall synthesis even if other
Target the phospholipid carrier that brings the murein
PBPs are inhibited.
subunits to the cell wall to be linked with other subunits
Penicillin-resistant Streptococcus pneumonia mutate to
(bacitracin)
change their PBPs
o -lactams cannot bind
Mechanism 3 Altering access to the target site -lactam Resistance

Decreased permeability porin reduction

(Source: page 372 of Jawetz Medical Microbiology)
In Gram(-) bacteria, -lactams have to go through
protein channels (porins) in the outer membrane to
target the PBPs
Mutation in porin genes decrease permeability = PBPs
cannot be targeted by beta-lactams
Efflux broad specificity efflux pumps
Inactivation beta-lactamase enzymes
Target site modification -
Sciences counter-response: -lactamase inhibitors
Clavulanic acid
Inhibits -lactamases of staphylococci and many G(-)
bacteria
Acts by forming an irreversible acyl enzyme complex with
the -lactamase, leading to loss of enzyme activity
Used in combination with amoxicillin as Co-amoxiclav

Inhibition of Protein Synthesis

Inhibition of protein synthesis by antibiotics

Mechanism 4 Efflux of -lactam drug out of bacterial cell

Gram- bacteria pumps out the antibiotic in the
periplasmic space

Therefore, bacterial resistance mechanisms to cell wall drugs

consist of:
Inactivate the -lactam drug by attacking the -lactam
ring
Modify the target site by altering PBPs
Decrease permeability by preventing access to PBPs via
porins
Efflux mechanism Diagram indicating the different points at which
chloramphenicol, the tetracyclines and streptomycin can
exert their activities
 Chloramphenicol binds to 50s portion and inhibits
formation of peptide bond; principally bacteriostatic
Tetracycline interferes with attachment of tRNA to
mRNA-ribosome complex
resistance to sulfonamides: widespread bacterial cell
produce an alternative enzyme to dihydropteroate
synthetase
spectrum of activity: primarily Gram- organisms
except Pseudomonas

Streptomycin changes shape of 30s portion,

causing code on mRNA to be read incorrectly

Inhibition of Bacterial PROTEIN SYNTHESIS

o Agents that act on the ribosomal units of bacteria
o 30s subunit: aminoglycosides, tetracycline,
glycyclines (tigecycline), oxazolidones (linezolid)
o 50s subunit: chloramphenicol, macrolides/azalides,
clindamycin, streptogramins

Trimethoprim
inhibits the production of THF (tetrahydrofolic) by
inhibiting the enzyme DHF (dihydrofolate) reductase
Resistance: bacteria produce new DHF reductases with
altered affinity for trimethoprim!

Aminoglycosides binds to 30s tRNA and disable them

Aminoglycosides cause misreading
Tetracycline inhibits binding of tRNA on 30s subunit
Erythromycin inhibits translocation
Clinadamycin and chloramphenicol inhibit binding site of
tRNA on 50s subunit side

Inhibition of NUCLEIC ACID SYNTHESIS

1. Inhibition of PRECURSOR synthesis

Sulfonamides and Trimethoprim
block the synthesis of tetrahydrofolic acid which
is required as methyl donor in the synthesis of
adenine, guanine and thymine

Sulfonamide
is a structural analogue of p-aminobenzioc acid
(PABA)
PABA + pteridine
= dihydopteroic acid

Tetrahydrofolic acid
sulfonamides compete with PABA for the active site
of enzyme dihydropteroate synthetase
 Spectrum of activity of trimethoprim
Given alone active against gram- bacilli (ex.
Pseudomonas), especially for UTIs
In combination with a sulfonamide (cotrimoxazole)
causes synergism wide range of UTIs and
Salmonella typhi. Also for Pneumocystis carinii
pneumonia, nocardiosis and chancroid
o lowered affinity for rifampin
Spectrum of activity: Mycobacteria
prophylaxis for meningococcal and Haemophilus
meningitis
Different mechanism on viruses, blocks a late
stage in the assembly of poxviruses
Alteration of Cytoplasmic MEMBRANE FUNCTION- bacterial

2. Inhibition of DNA replication

Quinolones

blocks bacterial DNA synthesis by
inhibiting DNA gyrase (topoisomerase
enzymes that play key roles in DNA
replication and repair): prevents
unwinding of DNA (This modification
causes DNA fragmentation of the
microorganism since other enzymes are
continually active) POLYMIXIN (Colistin)
Inhibition of fungal DNA synthesis Has positively-charged free amino acids which acts
like a cationic detergent to damage the
o Flucytosine phospholipid structure of the cell membrane

Is converted to fluorouracil which Holes in the cell membrane cell death
inhibits thymidylate synthetase needed Resistance: chromosomal alteration of membrane
for forming thymidine needed for DNA structure
synthesis Spectrum of activity: gram (-) organisms except

Additional :Another mechanism is its Proteus spp.
conversion into 5-
fluorodeoxyuridinemonophosphate
which damages RNA synthesis Polymixin consists of detergent-like cyclic

Active against yeasts only (Candida, peptides that selectively damage membranes
Cryptococcus) containing phosphatidylethanolamine, a major
o Griseofulvin component of bacterial membranes.

Inhibits mitotic activity and chitin
(fungal wall) synthesis Daptomycin

Active against dermatophytes A lipopetide, used for MRSA, is also cell membrane acting
Binding to cell membrane in a calcium-ion dependent
manner causing depolarization of bacterial membrane
Dermatophytes are 3 classes of fungi
potential causing intracellular potassium release.
(Microsporum, Epidermophyton and Trichopyton)
Used also for kin and soft tissue infections by gram-
that cause skin diseases due to their ability to obtain
positive bacteria (those resistant to -lactam agents and
nutrients from keratinized material such as skin, hair
vancomycin)
and nails

3. Inhibition of RNA polymerase / Inhibition of mRNA ALTERATION OF CYTOPLASMIC MEMBRANE FUNCTION

synthesis FUNGAL
Rifampicin
Polyenes (Amphotericin B, Nystatin)
Rifamycin (Rifampin)
Bind with the ergosterol in fungal membranes = leakage
Block mRNA synthesis by blocking bacterial DNA
Amphotericin B is used for systemic fungal infections
dependent RNA polymerase
Nystatin is used only in topical formulations. Due to its
Resistance: mutation of RNA polymerase target
-7 5 high toxicity, It cannot be IV. It can be given orally due to
that occurs with a high frequency (10 -10 )
the low absorption of the drug through mucocutaneous
causing bacterial infections treated solely by
membranes such as the gut and the skin.
rifampin to fail
Azoles (fluconazole, ketoconazole, clotrimazole, miconazole,
itraconazole, voriconazole)
Inhibit ergosterol synthesis by blocking the enzyme: 14-
demethylase thereby stopping the demethylation of
precursor lanosterol
Uses:
o clotrimazole, miconazole topical
o ketoconazole wide range of fungal disease
o fluconazole Candida infections
o voriconazole new agent for invasive Aspergillosis
and Candida bacteremia
Origin of Drug Resistance
Agents that act on the cytoplasmic membrane
act like cationic detergents to target the phospholipid
component, causing holes in the membrane polymixins
target the ergosterol component of the fungal
cytoplasmic membrane
o Polyenes bind to sterol = holes
o Azoles inhibit sterol synthesis
OTHER AGENTS
Metronidazole
Is reduced by protozoan and bacterial cells resulting
intermediate products damage DNA
Active only against:
o Giardia, Trichomonas and Entamoeba
o Anaerobes including Bacteriodes fragilis,
Clostridium tetani
o Poxviruses
Cross resistance
Resistance to Antibiotics
According to Jawetz
1. Production of enzymes that destroy the active
form of the drug
2. Changes in the outer membrane, decreasing the
drugs permeability
3. Development of altered receptors by the
microorganism
4. Development of altered metabolic pathway
5. Development of an altered form of the enzyme
targeted by the drug causing less inhibition to
the enzyme
A. Non- genetic
1. Metabolically inactive (non-multiplying)
microorganism that are phenotypically resistant
to the drug but their offspring is susceptible to
the drug (for drugs that are require active
replication of organisms for their antimicrobial
action)
2. Loss of the target structure
3. Microorganisms can infect host at sites where
the drugs are excluded or are not active
B. Genetic
1. Chromosomal

Spontaneous mutation in a locus that
controls the susceptibility of the drug
2. Extrachomosomal

Plasmids carry genes that cause
resistance to the drug can be
introduced to microorganism

Resistance to one drug could cause
resistance to other durgs that share the
same mechanism of action

Problems to solve:
o Infection?
o Where?
o Organism?
o Effective Drug?

 Type of infection- community acquired? Hospital?

 Site
 Bug- Gram(+)? Gram (-)?
 Drug

Limitation to Drug Resistance

Resistance to Antibiotics 1. Maintaining sufficiently high levels of the drug in the
tissues that inhibit both the original population and
1. Blocking entry
the first-step mutants
2. Inactivating enzymes
2. Simultaneous administration of 2 drugs that do not
3. Alteration of target molecule
cause cross resistance
4. Efflux of antibiotic
3. Avoiding exposure of microorganisms to a particularly
valuable drug by limiting its use especially in
hospitals
CHOICE OF ANTIMICROBIAL AGENTS o A 25 year old with sore throat, coryza, headache and
Nature and site of infection low grade fever
Probable organism
o Antimicrobial resistance in the local setting ANTIMICROBILA UTILIZATION
Pk/Pd (Pharmacokinetics/Pharmacodynamics) POTENTIAL PROBLEM: Inappropriate antibiotic use
o Route of administration
o Patient tolerability and side effects CONSEQUENCES OF INAPPROPRIATE ANTIBIOTIC USE
Availability and affordability Superinfection
Unwanted adverse reactions
Factors in Antibiotic Selection Waste of efforts and resources
Spectrum Increase in total cost of therapy
Tissue penetration  Emergence of antimicrobial resistance
Antibiotic resistance
Safety profile
Cost

How are antibiotics used?

Empiric therapy treating the most likely pathogen;
often broad spectrum
Definitive therapy based on culture and sensitivity
tests; shifting to a narrower spectrum
Antibiotic prophylaxis

Effects of Combinations of Drugs

Synergism occurs when the effect of two drugs together
is greater than the effect of either alone.
Antagonism occurs when the effect of two drugs
together is less than the effect of either alone.
Additive
Indifference
Clinical Uses of Important Antibiotics
When choosing an antibiotic, consider:
PHARMACODYNAMICS what the drug does to the Penicillins
body/bacteria Penicillin G streptococcal infections, clostridial
Desirable Effects infections (tetanus, gas gangrene). Spirochetal infections
o Cidal vs static (syphilis, leptospirosis), meningococcemia, anaerobic
o Concentration vs time dependent killing infections
o Post-antibiotic effect
AminoPCNs
Undesirable Effects
PRSP Oxacillin, Nafcillin sensitive staphylococcal
o Allergy
infections
o Toxicity
Ureidopenicillins Ticarcillin, Piperacillin -lactamase
Also consider:
producing Gram bacteria including Pseudomonas
Pharmacokinetics what the body does to the drug
aeruginosa
Absorption food, drug interaction
Combination with -lactams inhibitor (sulbactam,
Distribution does it go where it needs to get in the
clavulanic acid, tazobactam) restores original spectrum
right concentration?
Well distributed to tissue increase CNS/CSF
Metabolism
Excretion Renal? Hepatic? Half-life? Hypersensitivity reactions may occur
Cross-reactivity and cross-sensitivity occur (beta-lactam
Clinical Cases allergy)
o A 20 year old female with acute exudative tonsillitis,
bilateral
o A 60 year old diabetic with pneumonia. Bilateral lung
infiltrates on chest X-ray
o A 5 year old girl with acute suppurative meningitis
Cephalosporins
1 cephalosporin
o cephazolin, cephalexin
o used in skin/soft tissue infections, URTI
2 cephalosporin
o Cefuroxime- RTIs, UTI
o Cefaclor- RTI
3 cephalosporin
O Ceftriaxone- broad range of uses including typhoid
fever, CNS infections, infective Endocarditis,
complicated gonococcal infections; long half-life,
intracellular action
O Cefotaxime- similar to ceftriaxone
o Ceftazidine and cefoperazone- extended gram()
coverage including Pseudomonas aeruginosa
4 cephalosporin
O Cefepime- enhanced G(+) and G() coverage,
including P. aeruginosa, used in serious infections
New cephalosporin
O Increased activity against resistant G(+) cocci:
Penicillin-susceptible S. pneumoniae (PSP),
Methicillin-resistant Staphylococcus aureus (MRSA),
Vancomycin-resistant enterococci (VRE): cefditoren,
ceftarolne, ceftobiprole
Cross-reacts with penicillin = 5%
Monobactam (Aztreonam)
Contains a monocyclic beta-lactam ring
Resistant to beta-lactamases
Active vs G(-) bacteria, poorly vs G(+)
Has similar spectrum with Aminoglycosides but without
the nephro and ototoxicity
Carbapenems
Broad G(-) coverage, G(-) and anaerobes
Imipenem-
o resistant to beta-lactams but is degraded by a
dihydropeptidase in renal tubules
o Cilastatin peptidase inhibitor, used with imipenem
to avoid degradation
o Serious infections, hospital acquired infections,
resistant bugs
o Can cause seizures especially in renal failure patient
Meropenem- similar to imipenem, less seizure SE and
does not require cilastatin
Ertapenem longer half-life so can be given once daily,
no anti-pseudomonal coverage
Doripenem- newest, greater activity vs Pseudomonas
Carbapenems have no activity against Stenotrophomonas
maltrophilia
Aminoglycosides
Highly active vs G(-), including Pseudomonas, staph and
enterococci
Ototoxic and nephrotoxic
More active at alkaline than acid pH
Higher levels in urine than in serum
Often used in combination with cell active drugs to attain
synergism (sepsis, Infective endocarditis, etc)
Does not cross the blood brain barrier
Amikacin, Gentamicin, Tobramycin, Streptomycin
Quinolones
Fluoroquinolones are clinically used
Spectrum: enteric G(-) , Staphylococcus aureus,
Pseudomonas aeruginosa, Haemophilus influenzae,
atypical (Chlamydia, Legionella), mycobacteria
Useful in treatment of GUT and RT infections
Typhoid fever Ciprofloxacin, Ofloxacin
Levofloxacin, Moxifloxacin RTIs
Not recommended for children 18 and below
Macrolides
Consists of Erythromycin, the azalides (Clarithromycin,
Azithromycin), the ketolides (Telithromycin)
Used as an alternative in beta-lactam allergy
For atypical pneumonia (Legionella, mycoplasma,
chlamydia)
Azithromycin increased tissue concentration and half-
life, 3 day therapy, alternative therapy for gonorrhea and
Salmonella typhi
Erythromycin extolate (ilosone) discovered in Iloilo
Tetracyclines
Doxycycline used in Leptospirosis (mild cases and
prophylaxis): for Chlamydia trachomatis urethritis,
syphilis, cholera, mycoplasma
Not to be given to children < 6 yo, it deposits in bones
and teeth
Tigecycline new agent active vs MRSA, enteric G- but
not Pseudomonas, Enterococci, Bacteroides fragilis
Used for complicated soft tissue and abdominal
infections
OTHER ANTIBIOTICS
Chloramphenicol
used for typhoid fever, CNS infections
can cause anemia and aplastic anemia
Vancomycin
used for MRSA, Coagulase (-) staph, enterococci
oral vancomycin used for antibiotic associated
pseudomembranous colitis secondary to Clostridium
difficile
Daptomycin-- used for soft tissue infections and infective
endocarditis (IE) caused by MRSA
Televancina glycolipopeptide for Vancomycin-
Intermediate Staphylococcus aureus (VISA), Vancomycin-
Resistant Staphylococcus aureus (VRSA), MRSA
Streptogramins Quinopristin/Dalfopristin: used for MRSA,
Penicillin resistant Streptococcus pneumonia (PRSP), VRE
Oxazolidones Linezolid; used for MRSA, VRE; may be given
IV or po
Colistin Polymixin E; may be used to treat Multi Drug
Resistant G(-): Acinetobacter baumanii, Pseudomonas,
Klebsiella
Anti-mycobacterial Drugs
Isoniazid
inhibits synthesis of mycolic acid
pyridoxine analog
can cause peripheral neuritis
Mueller-Hinton agar medium
Antibiotic impregnated paper disks
Uniform inoculation of pure bacterial culture
Agar Disk Diffusion Method determines susceptibility of
an organism to a series of antibiotics: Kirby-Bauer Test
More sophisticated methods available for clinical labs
E Test (Epsilometer test)
- is a laboratory test used by microbiologists to
determine whether or not a specific strain
of bacterium or fungus is susceptible to the action of
a specific antibiotic

Ethambutol
may cause visual disturbances, ototoxic

Rifampin
inhibits bacterial RNA synthesis
also active vs Staphylococcus, some G (-), poxviruses

Pyrazinamide
Given in intensive phase of TB treatment
Can cause hepatotoxicity, hyperuricemia Broth Dilution Test

Antibiotic Susceptibility Tests Diffusion tests

Diffusion Method

Kirby-Bauer Method

When to use combination therapy?

For synergism against resistant bacteria and serious

infections
To prevent emergence of drug resistance
To shorten the course of the therapy
 Mixed infections 8. Treat infection, not colonization use antimicrobial
Examples: wisely
o TB therapy isonicotinylhydrazine (INH), Rifampicin 9. Know when to say "no" to vanco
Pyrazinamide 10. Stop treatment when cured
o Pseudomonas aeruginosa beta-lactam + 11. Isolate the pathogen - prevent transmission
aminoglycoside 12. Break the chain
o Staphylococcus Endocarditis beta-lactam+
aminoglycoside Sources: Doc Amsuas Slides; Jawetz Chapter 28

Mechanisms of Resistance Edited by: Ange

A variety of mutations can lead to antibiotic resistance
Misuse of antibiotics selects for resistant mutants.
Misuse includes:
o using out-dated or weakened antibiotics
o Using antibiotics for common cold and other
inappropriate conditions
o Using antibiotics in animal feed
o Failing to complete the prescribed regimen
o Using someone elses leftover prescription
Resistance genes are often on plasmids or transposons
that can be transferred between bacteria

Infections caused by drug resistant microbes

Neisseria gonorrhea from sulfonamides to penicillin
rd
(PCN), now only treated by 3 gen cephalosporins (a new
resistant strain emerging in Japan)
Staphylococcus aureus MRSA, a superbug in many
countries, most new drugs address this problem
Vancomycin Resistant Enterococci (VRE)
Carbapenem Resistant Acinetobacter baumanii (CRAB)
Pseudomonas aeruginosa can be treated only with few
antibiotics: ceftazidine, ciprofloxacin, cefoperazone,
cefepime, carbapenems, and aminoglycosides
E.coli Extended-Spectrum Beta-Lactamase (ESBL) and
carbapenemase producing
TB Multi-drug resistant (MDR), Extensively drug-
resistant (XDR)

12 Steps to Prevent Antimicrobial Resistance

1. Vaccination
2. Get the catheters out prevent infections
3. Target the pathogen
4. Access the experts diagnose and treat effectively
5. Practice antimicrobial control
6. Use local data
7. Treat infection, not contamination use antimicrobial
wisely