Anda di halaman 1dari 4

Microbiology 3.5 Dra.

Beltran
ANTIMICROBIALS Sept. 16, 2013

OUTLINE INHIBITORS OF CELL WALL SYNTHESIS AND FUNCTION


I. Introduction PENICILLIN
a. Antimicrobials vs. Antibiotics  Prototypical beta lactam antimicrobial
b. How Antimicrobial Drugs Work  Acts on beta lactam group found on the outer membrane of the
c. Common Antimicrobial Agents bacterial cell wall
II. Inhibitors of Cell Wall Synthesis and Function  Blocks the transpeptidase cross-linking of bacteria
a. Penicillin  Activates the autolytic enzymes present
b. Cephalosphorins  Bind to penicillin binding protein (PBP) in the outer membrane
III. Inhibitors of Protein Synthesis
a. Aminoglycosides
b. Tetracyclines
c. Macrolides
IV. Inhibition of Nucleic Acid Synthesis
a. Floroquinolones
V. Other Antimicrobial Drugs
a. Carbapanems  Coverage
b. Vancomycin o Broad-spectrum antibiotic
VI. Genetic Alterations  Gram (+) cocci
a. Antimicrobial Resistant Etiology Pneumonia /  Streptococcus pneumoniae
b. Altered Expression of Protein in Drug-Resistant Organism respiratory  Streptococcus pyogenes
infections  Streptococcus viridans group
OBJECTIVES  Gram (+) bacilli
1. Give an overview of antibiotic agents.  Bacillus anthracis (anthrax)
2. Discuss the mechanism of action of antibiotics.  Corynebacterium diphtheriae (diphtheria)
3. Enumerate the different types and their clinical use.  Gram (-) cocci
4. Explain the emergence of resistance to antimicrobial drugs.  Neisseria meningitides (meningitis)
o Penicilling IV used for meningitis
INTRODUCTION
 Anaerobes
ANTIMICROBIALS VS. ANTIBIOTICS
 Clostridium perfringes
 Antimicrobials – for all kinds organisms
 Spirochetes
o Antiviral
 Treponema pallidium (syphilis)
o Antiparasitic
 Treponema pertenue (yaws)
o Antifungal
 Use now limited due to resistance
o Antibacterial
 Resistance due to:
 Antibiotics – refer only to antibacterials
o Beta lactamase/penicilinase – cleaves the beta lactam ring
HOW ANTIMICROBIAL DRUGS WORK  Adverse Effects
o Hypersensitivity reactions (like rashes)
 3 Major Targets of Common Antimicrobial agents
o Hemolytic anemia (rare)
1. Cell wall
 Block cell wall synthesis and function
PENICILLINASE-RESISTANT PENICILLIN
 Ex. Beta lactam antibiotics (Penicillins, cephalosporins),
glycopeptides (vancomycin), bacitracin  Methicillin, nafcillin, dicloxacillin
2. Ribosomes  Narrow spectrum – more targeted on Gram (+) bacteria
 Block peptidoglycan synthesis  REMEMBER: “Use NAF for STAPH”
 Inhibition of protein synthesis  EXCEPT: MRSA – Methicillin-Resistant Staphylococcus aureus
 Ex. Tetracyclines & aminoglycosides (30S ribosomes), o Resistant due to altered penicillin binding protein target sites
lincosamides, macrolides, streptogramins,  Use of nafcillin group limited due to hypersensitivity reactions
chloramphenicol (50S ribosomes)  Use of methicillin limited due to interstitial nephritis
3. Bacterial DNA
 Inhibition of nucleic acid synthesis AMINOPENICILLINS
 Ex. Fluoroquinolones, Novobiocin, Nitroimidazoles Ampicillin, amoxicillin
(metronidazole), Nitrofurans  Wide-spectrum
o Gram (+) bacteria and Gram (-) rods
COMMON ANTIMICROBIAL AGENTS o Same with penicillin, but more potent, especially when
1. Penicillins combined with clavulanic acid, since it protects against
2. Cephalosporins β-lactamase
3. Tetracyclines  REMEMBER: Ampicillin is AMPED UP PENICILLIN
4. Aminoglycosides
5. Macrolides  HELPSS kill enterococci
6. Fluoroquinolones o H. influenza
7. Others o E. coli
o Listeria monocytogenes
o Proteus mirabilis

Group 14 | Ompoc, Opena, Openiano, Ortiz, Oxemer Page 1 of 4


Micro 3.5

o Salmonella Treatment for


o Shigella Gram (+) COCCI Gram (-) Gram (-) RODS
(eg. respiratory COCCI
 Some still have β-lactamase resistance, especially when NOT
infections) (eg. STDs)
combined with clavulanic acid
Streptococcus Neisseria Enterobacter aerogenes
BETA-LACTAMASE INHIBITORS pneumoniae gonorrhea E. coli
Streptococcus Haemophilus influenzae
 REMEMBER: CAST pyogenes Proteus mirabilis
o Clavulanic Acid Anaerobic
 Co-amoxiclab – amoxicillin + clavulanic acid streptococci *Pseudomonas
o Sulbactam aeruginosa (EXCEPTION:
 Ampisul – ampicillin + sulbactam only covered by
o Tazobactam Ceftazidime!)
 Piperacillin + tazobactam rd
*3 generation Ceph are also treatment for meningitis and gonorrhea
ANTI-PSEUDOMONALS
 Extended-spectrum penicillins 4TH GENERATION Cephalosphorins
o Have additional coverage aside from what is covered by Cefepime
penicillin  Pseudomonas aeruginosa (not covered by -encompasses the others (1st-3rd gen, only differs in Susceptibility)
regular penicillin) -limited use because of: Hypersensitivity, Vit K deficiency
o Gram (-) rods
o Susceptible to penicilinase (can bypass penicilinase)  Which antibiotics to use??? e.g. meningitis
combined with CAST
 Reserved against particularly devastating bacteria, mostly in Remember to:
immunocompromised patients (elderly, diabetic, etc) -Ask if child, adult, immunocompromised (for meningitis, can still
 Same MOA as penicillin but with wider spectrum use Penicillin since its cheaper)
-Still get patient history
CEPHALOSPHORINS PENICILL
 beta lactam drugs that inhibits cell wall synthesis INHIBITORS OF PROTEIN SYNTHESIS
- ribosome is the center for protein synthesis in cells, which is also true for
 less susceptible to pecillinase
bacteria
 5 groups/generations
- 30s ribosomal subunit, 50s ribosomal subunit
1ST GENERATION Cephalosphorins REMEMBER: Buy AT 30, CCEL at 50
Cefazolin, Cephalexin 30S inhibitors 50s inhibitors
Aminoglycosides Cloramphenicol
Treatment for
Tetracyclines Clindamycin
Gram (+) COCCI: Gram (-) RODS: PEcK
Stapylococcus aureus Proteus mirabilis
Erythromycin
Staphylococcus epidermis E.coli Linezolid
Streptococcus pneumoniae Klebsiella pneumoniae
Streptococcus pyogenes 30S INHIBITOR: AMINOGLYCOSIDES
Anaerobic streptococci  characterized by a hexose ring attached to various amino sugars
by glycosidic linkages
2ND GENERATION Cephalosphorins  MOA: binds with 30s ribosomal unit
Cefoxitin, Cefaclor, Cefuroxime  very narrow spectrum of coverage
 Members of the Group:
Treatment for: o Gentamycin
REMEMBER: HEN PEcKS o Neomycin
o Amikacin
H. influenzae o Tobramycin
Enterobacter o Streptomycin
Neisseria spp (Gram - cocci) - REMEMBER: "Mean Gnats"
P. mirabilis (Gram - rods) (aMEANoglycosides, GNATS)
E. coli  Spectrum of Activity:
K. pneumoniae o Aerobes only - only works for bacteria with an Oxygen-
Serratia marcescens Dependent Transport System
o Cannot kill anaerobes
3RD GENERATION cephalosphorins o Mostly for Gram (-) rods: Brucella, Klebsiella species
Ceftriaxone, Cefotaxime, Ceftazidime (respiratory infections)
o Gram (+) cocci: Enterococcus species, Streptococcus
agalactiae (GI infections)

Group #14 | Ompoc, Opena, Openiano, Ortiz, Oxemer Page 2 of 4


Micro 3.5

 ADR: very toxic o UTI, and GI tract infections


o Nephrotoxicity  Contraindications include:
o Teratogenicity o Children less than 18 years old
o Ototoxicity (streptomycin)
o Pregnancy
30S INHIBITOR: TETRACYCLINES
OTHER ANTIMICROBIAL DRUGS
Tetracycline, Doxycycline, Demeclocycline, Minocycline
CARBAPANEMS
 Includes Imipenem, Meropenem, Doripenem, Ertapenem
Treatment for
 Used mostly as Empiric Therapy
Gram (+) bacilli Bacillus anthracis
 It has broad spectrum activity that are resistant to β-lactamase.
Gram (-) rods Brucella species
Vibrio cholerae  Always given with Cilastin to prevent renal degradation.
Anerobic organisms Clostridium perfingens  Β-lactamase producing.
Clostridium tetani  Reserved for devastating disease (hospital life threatening
Mycoplasma Mycoplasma pneumoniae infections).
Chlamydia  Given to prevent development of resistance.
Rocky mountain spotted fever  Effective against gram positive and gram negative bacteria.
 Also effective against anaerobes( P. aeurginosa) and
Adverse reaction: TERATOGENIC (not for pregnant patients) Pseudomonas.
50S INHIBITOR: MACROLIDES  Toxicity: GI distress, skin rash, CNS toxicity.
 characterized by a macrocyclic lactone ring attached to deoxy VANCOMYCIN
sugars  Inhibits synthesis of bacterial cell wall by blocking polymerization
 MOA: block the translocation of 50s ribosomal subunit to prevent of the disaccharide pentapeptide units via Transglycosidase.
protein synthesis  Bactericidal
 wide spectrum of coverage  Drug of choice for serious drug resistant gram positive organisms,
 first line treatment after penicillins including methicillin--‐resistant Staphylococcus, Penicillin--‐
o when there is penicillin allergies or resistance to beta resistant pneumococci, and Clostridium Difficile
lactams Adverse effects:
 Members of the Group:  Thrombophlebitis at the IV injection site, fever, chills
o Erithromycin  Nephrotoxic
o Azithromycin  Ototoxic (tinnitus, high tone hearing loss,deafness)
o Clarithromycin  Serious hypersensitivity reactions
 Spectrum of Activity: o “Red man” syndrome – diffuse flushing due to rapid IV
Gram (+) cocci/rods Staphylococcus aureus, infusion
Streptococcus pneumoniae (atypical pneumonia)  There is also hypotension and maculopapular rash on chest
Streptococcus pyogenes (sore throat) o Pain and spasm syndrome
Corynebacterium diptheriae o Hypotension
Gram (-) cocci/rods Moraxella catarrhalis
GENETIC ALTERATIONS
Campylobacter jejuni
Haemophilus influenzae (atypical pneumonia),  It is a battle between us and the microorganisms, perhaps the
Legionella pneumophila most obvious example of evolution in action. Evolution is the
Neisseria meningitidis (meningitis) reason why bacteria are able to adapt in every antimicrobial we
throw at them.
Treponema pallidum
Chlamydia trachomatis (STDs)

INHIBITION OF NUCLEIC ACID SYNTHESIS


FLOROQUINOLONES
 Targets DNA gyrase(topoisomerase II).
o Results in the prevention of formation of nucleic acid
 Includes Ciprofloxacin, Ofloxacin, Norfloxacin, Sparfloxacin,
Levofloxacin, and Moxifloxacin.
Gram (+) bacilli Bacillus anthracis.
(excellent activity)
Gram (-) rods E. coli, H. influenza, K.
(bactericidal activity) pneumonia, Legionella
pneumophilia, Proteus
mirabilis, P. aeruginosa,
Shigella species and
Enterobacter species
 Adverse effects include:
o Diarrhea- common How resistance affects patients. The bacteria with drug resistance can
o Headache multiply and become the predominant bacteria that cause the infection.

Group #14 | Ompoc, Opena, Openiano, Ortiz, Oxemer Page 3 of 4


Micro 3.5

ANTIMICROBIAL RESISTANCE ETIOLOGY  If we are not able to kill the resistant strains, they become
A. Natural/Biological Causes dominant. Rendering us few available drugs to use against them.
1. Mutation  As in multidrug resistant TB
 A mutated DNA of normal bacteria can cause replication and
ALTERED EXPRESSION OF PROTEIN IN DRUG-RESISTANT ORGANISIM
will definitely multiply the number of resistant bacteria
 Microbes reproduce by dividing every few hours  evolve
rapidly and adapt quickly to new environmental conditions

 Drug resistance may be mediated by a variety of mechanisms,


such as:
o Lack of or an alteration in an antibiotic target site
Mutations- During replication, some bacteria will mutate and these o Lowered penetrability of the drug due to decreased
mutations can lead to drug resistance. permeability
o Increased efflux of the drug, or presence of antibiotic-
2. Gene transfer inactivating enzymes
 Microbes also acquire genes from each other, including drug-
resistant genes 1. Modification of target sites
 Through two mechanisms:  Alteration of an antibiotic’s target site through mutation can
o Pili confer organismal resistance to one or more related
o Plasmids: even drug resistant genes are acquired antibiotics.
 Once genetic material is transferred, bacteria can now divide  For example, S. pneumoniae resistance to β-lactam
and multiply. antibiotics involves alterations in one or more of the major
 This is a faster way compared to mutation bacterial penicillin-binding proteins, resulting in decreased
binding of the antibiotic to its target.
2. Decreased accumulation
 Decreased uptake or increased efflux of an antibiotic can
confer resistance because the drug is unable to attain access
to the site of its action in sufficient concentrations to injure or
kill the organism.
 For example, gram-negative organisms can limit the
penetration of certain agents, including β-lactam antibiotics,
tetracyclines, and chloramphenicol, as a result of an
alteration in the number and structure of porins (channels) in
the outer membrane.
 Also, the presence of an efflux pump can limit levels of a drug
in an organism.
3. Enzymatic inactivation
 The ability to destroy or inactivate the antimicrobial agent
can also confer resistance on microorganisms.
 Examples of antibiotic-inactivating enzymes include:
o β-lactamases (“penicillinases”) that hydrolytically
inactivate the β-lactam ring of penicillins,
Mechanism of gene transfer. cephalosporins, and related drugs
o Acetyltransferases that transfer an acetyl group to the
3. Selective Pressure antibiotic, inactivating chloramphenicol or
 In the presence of an antimicrobial, microbes either are killed or aminoglycosides
survive o Esterases that hydrolyze the lactone ring of macrolides.
 Survivors will replicate and their progeny will quickly become the
dominant type throughout the microbial population

Group #14 | Ompoc, Opena, Openiano, Ortiz, Oxemer Page 4 of 4