ANTIBIOTICS AND

RESISTANCE

Prepared by: Kevin John C. Jaugan, RMT, MLS

(ASCPi)
 ANTIBIOTICS
●Are chemical substances
produced by
microorganisms that
inhibit the growth of other
microorganisms
● Bactericidal Agents- agents that kill bacteria
● Bacteriostatic Agents- agents that inhibit bacteria
● Minimum Inhibitory Concentration- lowest concentration of
antibiotic that inhibits the growth of bacteria
● Minimum Bactericidal Concentration- lowest concentration of
antibiotic that kills the bacteria
● Antibiotic Interactions:
❖Autonomous or Indifferent- results obtained with two combined
drugs is equal to the result with the most effective drug by itself
❖Antagonistic- result with two drugs is significantly less than the
autonomous result; combined action is less than that of the more
effective agent when used alone
❖Additive- result with two combined drugs is equal to the sum of
the actions of each drug when used alone/separately
❖Synergistic- results with two drugs is significantly greater than
the sum of both effects; drug combination has an effect which is
both qualitatively and quantitatively different from that of the
single components
 DEFINITION OF TERMS: BACTERIAL
RESISTANCE TO ANTIMICROBIAL AGENTS
● Biologic resistance: refers to changes that result in the
organism being less susceptible to an antimicrobial agent
than has been previously observed
● Clinical resistance: occurs when antimicrobial
susceptibility has been lost to such an extent that the drug
is no longer effective for clinical use
● Environmentally-mediated antimicrobial resistance:
resistance that directly results from physical or chemical
characteristics of the environment that either directly alter
the antimicrobial agent or alter the microorganisms’s
normal physiologic response to drugs. Examples- pH,
anaerobic atmosphere, cation (Mg and Ca) concentrations,
thymidine content
 … continuation
● Microorganism-mediated antimicrobial resistance:
resistance due to genetically encoded traits of the
microorganism. They can be intrinsic or acquired:
❑Intrinsic, Inherent or Natural- results from normal
genetic, structural or physiological state or
microorganism, predictable resistance. Examples-
Aerobic bacteria are naturally resistant to metronidazole;
Pseudomonas aeruginosa are naturally resistant to
sulfonamides, trimethoprim, tetracycline and
chloramphenicol; Enterococci are naturally resistant to
aminoglycosides
❑Acquired- results from altered cellular physiology and
structure caused by changes in a microorganism’s usual
genetic make up; unpredictable type; resistance can be
 substitutions in the DNA sequences
…transfer:
● Gene continuation
Mechanisms
1. VERTICAL INHERITANCE OR GENE TRANSFER –
inheritance of parenteral genes
2. LATERAL OR HORIZONTAL TRANSFER- movement of
genes from one organism (donor) to another (recipient); can be
through:
a. Conjugation- requires donor cell and recipient cell contact to
transfer one strand of DNA; makes use of pili
b. Transduction- transfer of bacterial genes through
bacteriophage (virus that infects bacteria)
c. Transformation- direct uptake of “naked” donor DNA by
recipient cell, may be natural or forced; cells that take up the
naked DNA are known as “competent”
 REACTIONS TO
UNTOWARD
●Hypersensitivity
reactions
●Toxicity
●Suppression of normal
flora
 CLINICAL AND LABORATORY
FINDINGS MAY OCCUR AS A RESULT
OF:
● Failure to drain pus collection or to remove
foreign bodies
● Drug not effectively reaching the site of
infection
● Development of drug-resistant mutants
● More than one organism causing the
infection but only one being affected by
therapy
● New infection or a superinfection setting in
after original infection controlled
 INHIBITS PROTEIN SYNTHESIS
A. Tetracycline- inhibits protein synthesis at 30s ribosomal subunit
▪ Tetracycline, minocycline, demeclocycline, oxytetracycline,
doxycycline
B. Aminoglycoside- inhibits protein synthesis at 30s ribosomal
subunit
▪ Streptomycin- Streptomyces griseus
▪ Tobramycin- Streptomyces tenebrarius
▪ Neomycin- Streptomyces fradiae
▪ Kanamycin- Streptomyces kanamycetius
▪ Amikacin/Amikin- semisynthetic, derived from kanamycin
▪ Gentamicin- Micromonospora purpurea
▪ Netilmicin- Micromonosporum inyoensis
▪ Spectinomycin
C. Chloramphenicol- inhibits protein synthesis at 50s ribosomal
D. Lincosamide- inhibits protein synthesis at 50s
… continuation
ribosomal subunit
▪ Lincomycin- from Streptomyces lincolnensis
▪ Clindamycin
E. Macrolide- inhibits protein synthesis at 50s
ribosomal subunit
▪ Erythromycin- Streptomyces erytheus
▪ Clarithromycin
▪ Azithromycin
▪ Dirithromycin
F. Fusidic acid
 INHIBITS DNA SYNTHESIS
A. Quinolones
i. Nalidixic acid
ii. Fluoroquinolones
• Enoxacin, Ofloxacin, Ciprofloxacin, Norfloxacin,
Moxifloxacin, Galifloxacin
B. Rifampicin
C. Sulfonamides
D. Trimethoprim
 INHIBITS CELL MEMBRANE
1. Polyene Antibiotics
a. Amphotericin B
b. Nystatin
c. Candicidin
d. Natamycin
e. Griseofulvin
2. Polymyxin
3. Imidazoles
❖BETA-LACTAMS
INHIBITS CELL WALL SYNTHESIS
1. Penicillin
a. Natural Penicillin- from Penicillum notatum
▪ Penicillin G- benzyl penicillin
▪ Penicillin V- phenoxymethylpenicillin
▪ Benzathine Penicillin
b. Penicillinase-Resistant Penicillin
▪ Methicillin, Nafcillin, Oxacillin, Cloxacillin, Dicloxacillin
c. Extended Spectrum Penicillin
▪ Aminopenicillins
▪ Carboxypenicillins
▪ Ureidopenicillins/Acyclaminopenicillins
▪ Penicillin co-drugs (Augmentin, Timetin, Tazocin, Unasyn)
Cephalosphorin C
a. …continuation
First generation Cephalosphorin
▪ Cephalothin, Cephapirin, Cephalexin, Cephradine,
Cefadroxil, Cefazolin
b. Second generation Cephalosphorin
▪ Cefamandole, Cefoxitin, Cefuroxime, Cefonicid, Ceforanide,
Cefotetan, Cefaclor
c. Third generation Cephalosphorin
▪ Cefoperazone, Cefotaxime, Ceftriaxone, Moxalactam,
Ceftizoxime, Ceftazidime, Cepexime
d. Fourth generation Cephalosphorin
▪ Cefepime, Cefpiron
3. Carbapenem- Imipenem
4. Monobactam- Aztreonam, Tigemonam
 … continuation
❖ GLYCOPEPTIDES
1. Vancomycin- from Streptomyces orientalis;
can cause Red Man Syndrome
2. Teicoplanin

❖ BACITRACIN
❖ CYCLOSERINE
VACCINES
VACCINES
●Biological preparation meant to
provide or improve immunity to
a particular disease
●Provides artificial active
immunization
 TYPES OF VACCINES:
➢ Killed Virus Vaccine: vaccine that contains killed virus; i.e. Salk
vaccine (injected polio vaccine), Hepa-A and B vaccine
➢ Live attenuated Virus Vaccine: contains live but weakened virus;
i.e. Rabies vaccine, MMR, Varicella, Rotavirus
➢ Toxoids: toxins that were modified to become non-toxic; injected as
to an individual to stimulate production of antibodies; i.e. Tetanus
and Diphtheria
➢ Subunit Vaccines: presents an antigen to the immune system
without introducing viral particles, whole or otherwise; can be
produced by isolating a specific protein from a virus and
administering this by itself; i.e. recombinant Hepa-B vaccine
➢ Conjugate: can be created by covalently attaching a poor
(polysaccharide) antigen to a carrier protein (preferably from the
same microorganism), thereby conferring the immunological
attributes of the carrier to the attached antigen; i.e. Haemophilus
 CHARACTERISTICS KILLED LIVE
VACCINE VACCINE
NUMBER OF DOSES MULTIPLE SINGLE

NEED FOR ADJUVANT YES NO

DURATION OF IMMUNITY SHORTER LONGER

EFFECTIVENESS OF PROTECTION LOWER GREATER

IMMUNOGLOBULINS PRODUCED IgG IgA and IgG

MUCOSAL-IMMUNITY PRODUCED POOR YES

CELL-MEDIATED IMMUNITY PRODUCED POOR YES

RESIDUAL VIRULENT VIRUS IN VACCINE POSSIBLE NO

REVERSION TO VIRULENCE NO POSSIBLE

EXCRETION OF VACCINE VIRUS AND NO POSSIBLE

TRANSMISSION TO NON-IMMUNE
CONTACTS
INTERFERENCE BY OTHER VIRUSES IN NO POSSIBLE
HOST
STABILITY AT ROOM TEMPERATURE HIGH LOW