ANTIMICROBIAL THERAPY

Fasilitator : Dr. Sunarjati Sudigdoadi,dr. SpMK,

MSc.
Akhmad Mustafa, dr. (Urologi)
Farry, dr. (Orthopaedi dan Traumatologi)
Dedi Farokka, dr. (Bedah Umum)
Erwin Wijatmiko (Bedah Saraf)

WHAT IS THE ANTIMICROBIAL ??

An Antimicrobial is an agent that kill
microorganisms or inhibits their growth
An Antimicrobial consist of :
1. Antibacterial, are used against bacteria
2. Antifungi, are used against fungi
3. Antiviral, are used against viral

HISTORICAL OF ANTIMICROBIAL AGENT

Antimicrobial drugs have caused a dramatic
change not only of the treatment of infectious
diseases but of a fate of mankind
The first antimicrobial agent in the world was
salvarsan, a remedy for syphilis that was synthesized
by Ehrlich in 1910

 In 1935, sulfonamides were developed by Domagk and

other researchers.These drugs were synthetic
compounds and had limitations in terms of safety and
efficacy.
In 1928, Fleming discovered penicillin. He found that
the growth of Staphylococcus aureus was inhibited in a
zone surrounding a contaminated blue mold (a fungus
from the Penicillium genus) in culture dishes, leading to
the finding antibiotic was named penicilin
Cephems were developed in the 1960s, and came into
widespread use. Cephems are classified into several
generations according to their antimicrobial spectra.

THE STORY OF ANTIMICROBIALS DISCOVERY OF SOME

SURGICALLY IMPORTANT ANTIMICROBIAL CLASSIES
Antibiotic
classes

Targeted approaches
Empirical screening
Nalidixic acid
Fluoroquinolones
Fusidic acid
Mupirocin
Erythromycin
Newer macrolides
Rifamycin
Trimethoprim
lactamase inhibitors
Vancomycin
Carbapenems
Bacitracin
Monobactams
Cephalosporin
Semi-synthetic penicillins
Chloramphenicol
and cephalosporins
Neomycin
Newer aminoglycosides
Penicillin Streptomycin
Prontosil Chlortetracycline Newer tetracyclines

1910 1920 1930 1940 1950 1960 1970 1980 1990 2000
Adapted from Knowles 1997

SUCCESSFUL ANTIMICROBIAL THERAPY IS

BASED ON 4 PRINCIPLES:-

1. Identification and characteristic of the

pathogen(s), includes its antimicrobial
sensitivity and selection of a drug based on
the sites of infection
2. Effective concentration of the indicated
antimicrobial agent for sufficient period at
the site of infection.

3. A dose rate, frequency and route of

administration of the antimicrobial agent, as well
as duration of therapy, that maximizes the
likelihood of a cure, prevents relapse and
minimizes the risk of resistance without causing
any harmful drug induced effects in the animal.
4. Specific and appropriate supportive therapy to
enhance the animals ability to overcome the
infection and associated disease condition

CLASSIFICATION OF ANTIBACTERIAL DRUGS

Classification of antibacterial drugs that are major use in
medicine
Are of six major classes of antibiotics:
1. Aminoglycosides (Streptomycin, neomycin, Kanamycin,
gentamicin) .
2. Cephalosporins (ceftriaxone, cefotaxime, etc.
3. Macrolides (erythromycin,clindamycin, spiramycin,
azithromycin)
4. Penicillins (amoxicillin, Benzylpenicillns, Cloxacillin,
aminobenzyl-penicillins )
5. Quinolones (nalidixic acid, ciprofloxacin, levofloxacin etc)
6. Tetracyclines (oxytetracycline, Tetracyclines and Doxycline etc.

CLASSIFICATION AND ANTIBIOTIC

MECHANISMS OF ACTION
Inhibition of cell membrane synthesis: B-lactams
such as penicillins penems and carbapenems
cephalosporins.
Alteration of membrane permeability: Polymyxin B
and colistin, nystatin and amphotericin
Inhibition of nucleic acid metabolism: rifampicin
(RNA synthesis), quinolones (DNA synthesis)

ANTIBIOTICS SPECTRUM OF
COVERAGE
Narrow Spectrum effective against
a few organisms
Broad Spectrum effective against
many organisms

TYPES OF ANTIBIOTIC
Bactericidal
kills the infecting organisms
Bacteriostatic
Slow their growth

Protein synthesis
inhibition
Macrolides
erythromyci
n
midecamyci
n, etc.
Chlorampheni
col

Aminoglycosid
es kanamycin
dibekacin
amikacin
streptomycin
Tetracycline
s
Cytoplasmic
membrane
inhibition
Polypeptides
polymixin B,
etc.

Cell wall
synthesis
inhibition
FOM
(Fosfomycin)
Cephems
cephalosporin
s
cephamycins
Inhibition of nucleic
acid synthesis

Penicillins
penicilin-G
ampicillin
cloxacillin,
etc.

DNA synthesis
inhibition Quinolones
RNA synthesis
inhibition rifampicin

CLASSIFICATION OF CHEMOTHERAPEUTIC
AGENTS BY MECHANISM OF ACTION
Herdiman T Pohan, Jakarta 2005

PENICILLIN
MOA: Inhibition of cell wall synthesis
Resistance: Common and due to Blactamase production
Toxicity: Hypersensitivity can occur

 The b-lactam antibiotics are useful and frequently prescribed

antimicrobial agents that share a common structure and
mechanism of action inhibition of synthesis of the bacterial
peptidoglycan cell wall.
This class includes penicillins G and V, which are highly active
against susceptible gram-positive cocci;
penicillinase-resistant penicillins such as nafcillin which are
active against penicillinase-producing Staphylococcus aureus
ampicillin and other agents with an improved gram-negative
spectrum, especially when combined with a b-lactamase
inhibitor; and extended-spectrum penicillins with activity against
Pseudomonas aeruginosa, such as piperacillin.

CEPHALOSPORINS
group of Beta-Lactam antibiotics similar to penicillins but more
stable to many B-lactamases; thus has broader spectrum

MOA: Inhibits BACTERIAL CELL WALL Synthesis

BACTERICIDAL
Elimination: Renal (70% via Glomerular Filtration &
Tubular Secretion)
*except Ceftriaxone (Biliary)
Caution: Nephrotoxicity

FIRST GENERATION CEPHALOSPORINS

Cefazolin, Cephalexin, Cefadroxil

Good activity against gram (+) organisms
Gram (-) activity limited
Used in skin infections, soft tissue
Adverse reactions: Seizures, GI upset, colitis,
rash, leucopenia

Spectrum of Activity
Class

G (+)

G (-)

Beta Lactatamase
Stability

First Gen

+++

+/-

Easily hydrolyzed

Second
Gen

++

Third Gen

+/-

++

++

Fourth Gen

+++

+++

+++

2ND GENERATION CEPHALOSPORINS

- good activity against Gram (+), less
active than 1st gen
- enhanced Gram (-) activity
- covers some anaerobes
Cefuroxime
Cefoxitin
Cefaclor

CLINICAL USES
Activity against B-lactamase producing H.
influenzae & M. catarrhalis = treatment for sinusitis,
otitis & LRTIs
Activity against anaerobes (ex: Cefoxitin) =
treatment for intra-abdominal infections
(peritonitis, diverticulitis) & GYN infections (pelvic
inflammatory disease)
Activity against S. aureus = treatment of skin & soft
tissue infections

 Cefuroxime crosses blood-brain barrier =

treatment for meningitis (though less effective than
3rd gen drugs)

Cefuroxime also has activity against B

lactamase- producing K. pneumoniae =
treatment for Community-Acquired
Pneumonia

THIRD GENERATION
CEPHALOSPORINS
Very good gram (-) activity & pseudomonas activity.
Used to treat RTIs, UTIs, bacteremia, meningitis, FUO.
Ceftriaxone
Cefotaxime
Ceftazidime
Cefepime
Cefixime

CLINICAL USES
serious infections caused by :
Klebsiella
Enterobacter
Proteus

Providencia
Serratia
Haemophilus
Ceftriaxone is the therapy of choice for all forms of gonorrhea and for severe
forms of Lyme disease. The third-generation cephalosporins cefotaxime or
ceftriaxone are used for the initial treatment of meningitis in
nonimmunocompromised adults and children older than 3 months of age

FOURTH-GENERATION
CEPHALOSPORINS

Cefepime and cefpirome are fourth-generation cephalosporins

Cefepime is stable to hydrolysis by many of the previously identified plasmidencoded b-lactamases

active against many Enterobacteriaceae that are resistant to other

cephalosporins via induction of type I b-lactamases
cefepime has comparable or greater in vitro activity than cefotaxime against
H.influenzae, N. gonorrhoeae, and N. Meningitidis
The fourth-generation cephalosporins are indicated for the empirical
treatment of nosocomial infections where antibiotic resistance owing to
extended-spectrum b-lactamases or chromosomally induced b-lactamases
are anticipated. For example, cefepime has superior activity against
nosocomial isolates of Enterobacter, Citrobacter, and Serratia spp. compared
with ceftazidime and piperacillin

OTHER BETA-LACTAM ANTIBIOTICS

Carbapenems are b-lactams that contain a fused blactam ring and a five-membered ring system that
differs from the penicillins in being unsaturated and
containing a carbon atom instead of the sulfur atom.
This class of antibiotics has a broader spectrum of
activity than do most other b-lactam antibiotics
E.g: imipenem, meropenem, aztreonam, ertapenem
Clinical use: empiric therapy for serious infection in GI
gtract, GU tract, skin infection and bone infection

Aminoglycosides
- Administration: IM, IV, Topical
- Mode of action: Inhibition of bacterial protein synthesis
Resistance:
Due to bacterial enzymes decreasing drug transport in the organism.
- Toxicity: Vertigo, deafness, renal

Tetracycline
- Administration: Oral
- Mode of action: Inhibition of bacterial protein synthesis
- Antibacterial activity: Mycoplasma, Chlamydia, urethritis
- Toxicity: Gastric irritation, diarrhea, inhibition of bone
development, yellow staining of teeth.

Metronidazole
- Administration: Oral, IV, Rectal
- Mode of action: Inhibition of DNA synthesis
- Antibacterial activity: Anaerobic infections in abdominal
and gynecological lesions
- Toxicity: Gastric irritation, metallic taste
Macrolides
- Administration: Oral, IV
- Mode of action: Inhibition of protein synthesis
- Antibacterial activity: Atypical microorganism
- Toxicity: Gastric irritation

MECHANISM OF

ANTIMICROBIAL RESISTANCE
Production of structure altering or inactivating
enzymes e.g lactamase.
Alteration of penicillin binding protein.
Altered DNA gyrase targets.
Mutational change or acquisition of resistance
encoding genetic material.

EMERGENCE OF RESISTANCE IS
DUE TO:

Misuse of antimicrobial agents.

Increased use of invasive devices and
procedures.
Greater number of susceptible host.
Lapses in infection control.

IMPORTANCE OF ANTIBIOTIC
RESISTANCE
Infections/communicable diseases are a
major cause of mortality and morbidity
worldwide
Rapid increase in organisms resistance to
commonly used antibiotics
Many common pathogens are resistant to a
variety of -lactam agents

ROLE OF -LACTAM ANTIBIOTICS IN

INFECTIOUS DISEASES
-Lactams are the most frequently prescribed antibiotics
Cephalosporins are one of the most frequently prescribed subclasses of lactams

Mechanisms of bacterial resistance to -lactam antibiotics

Reduced affinity for target binding proteins (penicillin-binding proteins)

Increased production of -lactamases
Reduced permeability of outer membrane
(Gram-negative organisms only)
Increased efflux of antibiotic

Sulbactam/Cefoperazone:
Achieves and sustains high therapeutic concentrations
in many tissues/fluids after IV/IM administration
No evidence of accumulation after multiple dosing
Suitable for use in elderly patients, children and individuals
with mild-to-moderate renal impairment
Low level of drugdrug interactions
Sulbactam is less likely to induce -lactamase than
clavulanic acid

PROFILAKSIS ANTIMICROBIAL
consists of the administration of an antimicrobial agent or
agents prior to initiation of certain specific types of surgical
procedures in order to reduce the number of microbes that
enter the tissue or body cavity
By definition, prophylaxis is limited to the time prior to and
during the operative procedure; in the vast majority of cases
only a single dose of antibiotic is required, and only for
certain types of procedures (see Surgical Site Infections)

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