CHEMOTHERAPEUTIC

MEDICINE

ARJO SURJANTO
SCHOOL OF NURSERY
BANDUNG POLYTECHNIC OF
HEALTH
 CHEMOTHERAPEUTICS
HYSTORY
1847 : IGNAZ SEMMELWEIS INTRODUCED Ca-hypochloride as
desinfectant. He was not know about anti infection mechanism
1863 : LOUIS PASTEUR Published his study about fermentation
and spoilage process
Based on Pasteur study : JOSEPH LISTER Conditioned carbol
spray on surgery works
1876 : ROBERT KOCH Demonstrated microorganism as an
infection caused. He developed coloring technical in microorganism
1893 :EMIL von BEHRING Introduced diphtheria serum,
prophylaxis and general serum therapy
PAUL ERLICH : Primary develop selective toxicity innovate
Salvarsan as medicine of syphilis and trypanosoma disseases
1928 : ALEXANDER FLEMING Discovered Penicillin, an antibiotics
of Penicillium notatum
1932-1934 : GERARD DOMAGK Discovered bacteriostatic action
of sulphonamides
1940 : ERNEST CHAIN and partners Primary isolated penicillin
DEFINITION CHEMOTHERAPEUTICS
GERMICIDE ANTIMICROBE
CHEMOTHERAPEUTICS Medicine
exterminated microbe. It used to
systemic and gained from
synthetically process ANTICEPTIC
ANTIMICROBE Medicine
exterminate pathogenic microbe DESINFECTANT
GERMICIDE Medicine exterminate
SANITIZER
germ
ANTIBIOTICS Medicine gained SULPHONAMIDE
from microbe that could exterminate
other microbes ANTIBIOTICS
ANTICEPTICS Antimicrobe
substance used to topically
DESINFECTANT Antimicrobe substance used to health instrument
that purposed to prevent ceptic condition
SANITIZER Specially desinfectant that used to decrease microbe
population until to save grade
SULPHONAMIDE Antimicrobe of p-aminobenzenesulphonate
derivate used to or topically application to prevent and cure several
infection deseases
SELECTIVE TOXICITY As toxic as to microbes, but relatively non
toxic to human body
 ANTIMICROBE, MICROBE AND
HOST INTERACTION
AM
2 1
B C
1 2
1
M A H
2
A. Interaction between microbe host
1. Pathogenity M as disease causal to H
2. Immunity of H eradicate M
B. Interaction between antimicrobe microbe
1. AM activity (bacteriostatical or bactericidal effects) eradication M
2. Sensitivity or resistance M to AM
C. Interaction between antimicrobe host
1. Drug pharmacokinetics on host
2. Drug pharmacodynamics on host
 ANTIMICROBE MECHANISM OF
AB : Polymyxine
ACTION AB :
& Pollien 2 1 Penicilline,
Cephalosphorine,
AC : surface Bacitracine,
active agent Vancomycine,
Rystocetine,
Folic acid synthesis Cyclocerine
Protein synthesis
4 3
SULPHONAMIDE :
5 AB :
Sulphons,
Aminoglycoside,
Trimethoprim, p- AB :
Macrolide,
aminosacylic acid, Rifampycine,
Lyncomycine,
nalidixate acid
Tetracycline,
Chloramphenicol,
Novobiocine,
Puromycine
 RESISTANCE OF MICROBE
PATERN 1 : There have never became
significant resistance (Streptococcus pyogenes
A group to Penicilline)
PATERN 2 : Shifting from sensitive to less
sensitive but not full resistance (Gonococcus
still sensitive to Penicilline 0.06 mcg/ml in blood
level)
PATERN 3 : Resistance character in exactly high
grade clinical problem occur (several
staphylococcus resistance to Penicilline G)
SCHEME OF MICROBE RESISTANCE
RESISTANCE

NON GENETIC GENETIC CROSS

NATURAL ACQUISITION
RESISTANCE RESISTANCE

INDUCTION REMOVAL SPONTANEUS

RESISTANCE MUTATION

TRANSFORMATION CONJUGATION TRANSDUCTION

 TERM OF AM RESISTANCE
Resistance of microbe is a specific character
where its existence is not be interfered by
antimicrobe
There is natural mechanism to survive
Non genetic resistance of microbe is resistance because
of rest condition (metabolic inactivity) persisters
bacteria
When its activity come back bacteria should be
sensitive to antimicrobe again

BACK
 ANTIMICROBE HOST INTERACTION
UNEXPECTED REACTION

ALLERGY IDIOSYNCRACY
REACTION REACTION

independent to drug dose independent to drug dose

Occur all of AB involve body Difference of allergy genetic caused, it is not
immunity system body immunity system

Reaction urticaria (light) until Example : aplastic anemia on chloramphenicol

anaphylactic shock (deep) therapy

BIOLOGICAL AND
TOXIC REACTION METABOLICAL CHANGE
Toxic effect could occur by all of AB REACTION
Dose dependent of AM Disturbance of microflora harmony
Predilexion of targeted organ by AM Disturbance of nutrition or metabolic
Biotransformation could increase or decrease Super infection might be occur
drug toxicity
 SULPHONAMIDE
Sulphonamides sensitive to Gram + and several of Gram
(Streptococcus pyogenes group A, staphilococcus, pneumococcus,
several strain of b anthracis, c diphteriae, h influenzae, h ducreyi, brucella,
v cholerae, p pestis, nocardia, actinomyces, donovania granulomatis,
viruses caused thrachome, limphogranuloma venereum and inclusion
conjunctivitis, meningococcus, coli,proteus mirabilis etc.)
Sulphonamides resistance to enterococcus, a lot of gonococcus,
several strains of menicoccus, spirochaeta, mycoplasma, richettsia,
mycobacteria, fungi and a lot of salmonella and shigella
They act to competitively eradicate PABA needed bacteria to its folic acid
synthesis it have to high dose administration and its act as
bacteriostatic
Body immunity is going to play important role to support its anti bacteria
action. Blood, pus and damage tissue products would inhibition of
medicine activity
Resistance could inhibition by :
- High dose administration
- As fast as therapy when diagnose determined
- Use the medicine when it selected as drug of choice
- Combination medicines therapy when needed
THE POSOLOGI OF SULPHONAMIDE
The safely administration of sulphonamide is oral pathways
(rapid absorption and maximal concentration in blood level
would be achieved 3 or 4 hours after taken)
In the case of lack of oral administration, parentheral pathways
(i.m. or i.v.) would be chosen
Topical usage should not be chosen because of its bad yielding
and dangerous sensititation, except application of sodium
sulphacetamid eye ointment or lotion in conjungtiva
Generally, it taken 150 mg/kg BW for children and 3 -5 gram/kg
BW daily for adult
Almost of 70% of drugs reabsorbed in renal vessels they
might be made crystalluria, haematuria and obstruction
It be prevented by application of more water soluble
sulphonamides (sulphisoxazol, trisulphapyrimidin), keep urine
in alkaline condition, more drinking and polysulphonamide
regime application (trimetoprim-sulphametoxazol)
THE SULPHONAMIDE AND
TRYMETHOPRIM ACT
PABA
Dihydropteroic Competition between
syntace sulphonamide and PABA
Dihydro folic acid
Dihydro folic Trymethoprim
reductace
Tetrahydro folic
acid

Purine

DNA
 UNEXPECTED REACTION
Sulphonamides could occur several side effects,
like allergy and the others because of its toxicity
All of sulphonamides are cross allergenics
The manifestation of side effects are skin rash,
photosensitivity, urticaria, nausea, vomiting,
diarrhea, urination disorder, stomatitis,
conjunctivitis, arthritis, haematopoietic disorder,
exfoliative dermatitis, Steven-Jones syndrome,
psychosis, etc
Other unexpected reaction is rickettsia growing
stimulated by sulphonamides
 PUBLIC HEALTH AND MEDICAL
ASPECT
Sulphonamides could made and distributed in
low cost therefore constitute main anti microbe
in under develop country
Sulphonamides remain useful for medication of
urine channel infection, but resistance appearing
decrease it
Topical application of sulphonamides (skin, eye)
in a large scale support public sensitivity
TRIMETHOPRIM - SULPHAMETHOXAZOL
Trymethoprim is taken combine with sulphamethoxazole because of
the same of their half time. The combination would reduce their toxic
effect, and potentate their anti microbial action of each compound
Trymethoprim sulphamethoxazole combination is optimal in ratio 1
:5
The optimal dose trymethoprim 80 mg and sulphamethoxazole 400
mg would be administered orally against pneumonia, enteritis,
salmonella infection, urogenital infection, prostatitis, etc.
The last regimen could be taken parentherally against deep
pneumonia complication in AIDS patient, gram sepcis, shigellosis,
urogenital infection in case oral administration could not taken. The
ampoul of 5 ml contain trymethoprim 80 mg + sulfamethoxazole 400
mg. Adult dose is 6 12 ampouls devided 3 or 4 times a day
The optimal dose sulphonamide 6 8 g a day and pyrimethamine
50 mg would be administrated orally against parasitic infection
Combination of pyrimethamine sulphonamide against parasitic
infection. Administration of sulphonamide 6 8 g daily combine with
pyrimethamine 50 mg daily in the case of leismahniasis and
toxoplasmosis. Other combination of pyrimethamine
sulphonamide (Fransidar) cure m. falsiparum
SULPHONAMIDE PREPARATION
Trisulfa tablet KF, Sulphonamide multiple,
Trisulphapyrimidine (combine of SD, SMer
and SMez). Oral adult dose is 500 mg
(total sulphonamide)
Sulfaguanidin KF : sulphonamide for
infection in stomach
Co-trimoxazole (OGB, Bactrim, Kaftrim,
Septrim etc) use for upper respiration tract
infection, etc.
 ANTIBIOTICS

First AB invention is reported by Fleming in 1929 when he

found that staphylococcus colony lyses to Penisillium
contaminant
Antibiotics might be bacteriostatical or bactericidal action
There are antibiotics action:
- inhibition of cell shield synthesis (bacithracin,
cephalosporin, cyclocerin, penicillin, vankomycin)
- inhibition of cell membrane function (amphotericin, azoles,
polien, polymixin)
- Inhibition of protein synthesis (aminoglycoside, tetracycline,
macrolide, chloramphenicol, lincomycine)
- inhibition of nucleic acid synthesis (quinolon, pyrimetamin,
rifampicine, sulfonamide, trymethoprim)
 PENICILLINE AND ITS DERIVATES (1)
Penicilline and cephalosporin are called betalactam antibiotics because
of lactam ring on their chemical structure.
Generally, anti bacterial mechanism of -lactam AB is cell shield damage
Na-penicilline crystal is represented in 1600 unit/mg (1 unit = 0.6 ug; 1
million units of penicilline = 0.6 g), other semi synthetic of penicilline in
grams
Resistance of penicilline occur in bacteria s aureus, h influenzae, certain
staphilococcus, listeria, mycoplasma form
Penicilline and cephalosporin are rapid absorbed and wide distributed
Penicilline G or other penicilline 3-6 g parentheral in devided dose i. m. or
infusion caused blood level concentration in 1 -10 unit (0.6 6 ug/ml)
Slow-release penicilline benzathin penicilline G could hold out more
than 0.03 unit/ml on ten days and more than 0.005 unit/ml on 3 weeks on
single dose i. m. 0.75 g (1.2 million unit). The same evidence occur in
procaine penicilline which its benefit blood level hold out in 12 24
hours.
Generally, its concentration in tissue is same as blood level. Less
concentration found in eyes, prostate and central nerve system.
However, in the case of meningitis or other cerebral membrane
inflamation penicilline concentration should more than 0.2 ug/ml with
parentheral intake 12 g
 PENICILLINE AND ITS DERIVATES (2)
Excretion is going on kidney to urine and slightly to others (ex: sputum and breast
milk)
Almost all penicilline should be administered out of meal time, because of its binding
and acid inactivation in stomach, especially oxacilline. However, amoxycilline could
be administered in or on meal time
Penicilline G is drug of choice for infection caused pneumococcus, streptococcus,
meningococcus, staphilococcus without -lactamase, and GO, tryponema pallidum
and other spyrochaeta, bacillus anthraxis and other gram + bacilla, actinomyces,
listeria and bacteriodes (expect b fragilis)
Usual dose is 0.6 10 million unit (0.36 6 g) daily intermittent intra venous
Pen V is oral penicilline, it recommended in light case like respiratory tract infection,
especially pediatric (pharyngitis, otitis, sinusitis) with usual dose 1 4 g daily in
devided dose
Ampicilline, amoxycilline, karbenicilline, tycharcilline, piperacylline, mezlocilline,
azlocilline are more active than penicilline G in gram bacteria, but inactivated by
beta lactamase enzym
Ampicilline and amoxycilline had an activity and spectrum almost same, but
amoxycillin more absorbed in intestine. Therefore, oral administration 3 x 250 500
mg a day amoxycilline is equal to administration ampicilline 4 times daily. These
medicines indicated to urinary tract infection by gram coliformis bacteria and
secondary mix infection on respiratory tract.
Ampicilline is drug of choice to h influenzae by i. v. administration 300 mg/kg body
weigh a day.
Ampicilline should not effective to enterobacter, pseudomonas and proteus .
Bacampicilline could release ampicilline in digest tract. It is orally administered twice
a day 400 800 mg for the same indication to ampicilline.
 PENICILLINE AND ITS DERIVATES (3)
Karbenycilline is almost same with ampicilline, but more effective to
pseudomonas and proteus.
Single administration of karbenycilline could cause resistance on
pseudomonas colony. It recommended combination intake with
aminoglycoside administration. For example, in the case of pseudomonas
sepsis (burn wound, immunosupresive patient) is needed 12 30 g/day i.v.
(300 500 mg/kg body weigh daily) of karbenycilline combine to 5 7
mg/kg body weigh/day of gentamycine i.m.
Tycarcilline had an activity almost the same to karbenycilline, but in less
dose
-lactam ring on this group (ampicillin, amoxycilline etc) could protected
from lysis or damage by -lactamase enzyme when administered together
to -lactamase inhibitor like clavulanic acid, sulbactam or tazobactam
Seriously side effect of penicilline consumption is hypersensitivity.
All penicillines are sensitization and cross reaction. All preparation contain
penicilline (included food or cosmetics) could induce sensitization. Allergy
should expressed as specific anaphylactic shock, urticaria, joint swollen,
seriously pruritis, respiratory disorder in 7 12 days after consumption,
skin rash, mouth lesion, interstitial nephritis, eosinophilia, hemolytic
anemia and other hematology disorder, and vasculity
Toxicity : All penicillines irritate CNS and increase neuron exibility. High
dose consumption per oral cause digestive disorder like nausea, vomit and
diarrhea
CEPHALOSPORINE AND ITS DERIVATES (1)

Cephalosporine is produced by Cephalosporium fungi,

and its chemical structure resemble penicilline
Natural activity of anti microbial is relatively lower,
however substitution or addition of various R 1 or R2 made
its anti microbial activity more effective.
Traditionally, cephalosphorine is devided into 3 main
group or generation
The first generation (narrow spectrum) are cephadroxil,
cephazoline, cephalexine, cephalotine, cephapyrine and
cephadrine
The second generation (intermediate spectrum) are
cephachlor, cephamandol, cephmethazol, cephonizide,
cephoranid, cephoxitine, cephpodoxim, cephprozil,
cephuroxim, loracarbef
The third generation (wide spectrum) are cephixim,
cephoperazon, cephotaxim, cephotetane, cephtazidim,
cephtizoxim, cephtriaxon
CEPHALOSPORINE AND ITS DERIVATES (2)

Cephalosporine first generation had a sensitivity to gram + coccus (included

pneumococcus, streptococcus viridan, group of streptococcus A hemoliticus
and S aureus); gram (E coli, Klebsiella pneumoniae, Proteus mirabilis; and
anaerob coccus (Peptococcus, Peptostreptococcus)
Various absorbtion of intestine are found in cephalexin, cephadrine, and
cephadroxil. Oral dose 500 mg yield 15-20 ug/ml blood level. Usual dose
cephradine and cephalexine is 250 500 mg 4 times a day. Oral
administration is usage for urinary infection, little wound caused
staphylococcus or little infection caused polybacteria
Intravenous administration of 1 g of cephazoline produce the peak of blood
level 90 120 ug/ml, while cephalotine or cephapyrine only 40 60 ug/ml.
Usual dose cephazoline for adult is 1 -2 intra venous per 8 hours (50 -100
mg/kg body weigh/day) and cephalotin or cephapyrine 1 2 g intra venous
per 4 6 hours(50 200 ug/kg body weigh/day). Their excretion pass
through kidney. The first generation of Cephalosporine is drug of choice for
surgical prophylaxis especially cephazoline. Intra venous injection might be
alternative for infection because of its less toxicity. Therefore, it is drug of
choice for K pneumoniae and patient with light hypersensitivity of penicilline
Intramusculus administration is rare because of its painful
CEPHALOSPORINE AND ITS DERIVATES (3)
Spectrum the second generation of cephalosporin is the same to the
first with addition of wide gram (Enterobacter, Klebsiella included
strain resistant of cephaloxine-, positive indol Proteus).
Cephamandol, cephuroxim, cephonisid, cephoranid sensitive to H
influenzae
Oral administration could given by cephachlor, axethyl cephuroxim,
cephprozil, cephpodoxim and lorakabef. Adult dose 10 -15 mg/kg
body weigh/day into 2-4 administration, while children 20-40 mg/kg
bw/day until 1 g a day
Infusion intra venous 1 g, serum concentration could reach 75 125
ug/ml. However, cephonisid could reach 200 250 ug/ml. There are
half time difference among these medicines. Long half time medicine
injected with less frequency (cephuroxim 0.75 1.5 g per 8-12 hours,
cephothetan 1 2 g per 8 12 hours, cephonisid or cephoranid 1 2
g p 12 24 hours, cephprozil 500 mg per 24 hours
Cephachlor indicate to sinusitis, and otitis media for patient resistant
amoxycilline or ampicilline because its activity to H influenzae and
Moraxella cattarrhalis.
Cephuroxim recommended to meningitis. It might be this medicine
could passed to brain barrier
Cephoxitin and cephothetan used in infection of mix anaerob
(peritonitis, diverticulitis) because of their activity to anaerob bacteria
 CEPHALOSPORINE AND ITS DERIVATES (4)
Cephalosporine third generation had a wide activity of gram and its ability to reach
CNS
Its spectrum covered Enterobacter, Citrobacter, S marcescens, and Providencia, strain
Haemophilus and Neisseria produced beta-lactamase. Cephtazidin and cephoperazon
had a powerful activity to P aeruginosa. Cephtizoxim and Moxalatam had an enough
activity to B fragilis
After intravenous administration 1 g of drug, blood level reach 60 140 ug/ml. Its good
distributed in body and tissue liquid (included cerebrospinalis liquid)
Cephtriaxon (half time 7 8 hours) could injected per 12 24 hours in 15 30 mg/kg
bw/day (but in meningitis 30 50 mg/kg bw/day devided per 12 hours. Cephoperazon
(half time 2 hours) could injected per 8 12 hours in 25 100 mg/kg bw/day. Others
(half time 1 -1.7 hours) could injected per 6 8 jam in 2 12 g/day depend light or deep
infection
Oral administration should be given in cephixim (400 mg twice a day) for respiratory or
urinary tract infection
Cephoperazon and cephtriaxon excretion would pass to bile. Therefore, dose adjustment
should not needed in kidney failure. Others excreted via kidney, however dose
adjusment should needed
Clinical application used in meningitis (except caused by P aeruginosa). Other potential
indication is unknown sepsis
Side effects:
Reaction of allergy is almost same to penicilline.
Toxicity of cephalosporin contain methylthiotetrazol (cephamandol, moxalactam,
cephmetazol, cephotetan, cephoperazon) might caused hypo prothrombinemia and
blood anomaly
 OTHER BETA LACTAM (1)
MONOBACTAM

Monobactam is medicine with beta-lactam monocyclic ring in its

chemical structure.
Monobactam resistance to -lactamace and active to gram
bacillus (included Psedumonas and Serratia), otherwise inactive to
gram + and anaerob
The first monobactam is azthreonam which its activity almost same
to aminoglycoside.
Usual dose of azthreonam is 1 2 g per 8 hours intra venous
(serum concentration reach 100 ug/ml). Its half time is 1 2 hours,
more and more when renal failure found.
Clients had penicillines allergy could tolerate azthreonam
Usually skin rash occur in long therapy, also increase of
transaminace serum. Staphilococcus and enterococcus super
infection could become
 OTHER BETA LACTAM (2)
BETA LACTAMACE INHIBITOR
CLAVULANIC ACID, SULBACTAM, TAZOBACTAM
Their chemical structure are resemble to beta-lactam, but their anti bacterial are
not potent. However, they are potent -lactamace inhibitor that could protect
hydrolysis of -lactam ring of penicillines
Therefore, combination clavulanic acid amoxycilline or ticarcilline is
recommended to manage upper respiratory tract infection especially caused H
influenzae
Sulbactam ampicilline combination is effective to upper tract of respiratory
infection

CARBAPENEM
Carbapenem is new class medicine which its chemical structure resemble to
beta-lactam. First carbapenem extensively studied is imipenem, that had wide
spectrum with activity to gram , gram + and anaerob bacteria. This medicine is
resistance to beta lactamase but inactivated to dihydropeptodase in renal tube
administration with cilastatin (dihydropeptidase) is recommended.
Imipenem is well penetrated to body liquid and tissues included cerebrospinalis
liquid. Usual dose is 0.5 1 g intravenous per 6 jam (half time one hour). Dose
should be minimize in the case of renal insufficiency, and addition dose could be
taken after hemodyalisis.
General side effect of imipenem is nausea, vomitting, diarrhea, allergy in
infusion. High dose could promote attack to renal failure patient. Patient who
penicilline allergy might be allergy imipenem too.
Imipenem aminoglycoside might effective to cure neutropenical fever
 CHLORAMPHENICOL (1)
Chloramphenicol is very bitter colorless crystal, and first
commercially synthetic antibiotics (first isolation in 1947, and first
synthetic production in 1949)
Chloramphenicol has a bacteriostatics for almost gram + bacteria
in concentration 1 10 ug/ml, and gram bacteria in 2 5 ug/ml,
and rickettsia.
Bacterisidal action of chloramphenicol show up to H influenzae,
Neisseria meningitis and several strain of Bacteroides and
Salmonela
Lot of cell population sensitively to chloramphenicol contain
resistant mutant resistance bacteria. The resistant plasmid
could moved to another medicines (chloramphenicol, tetracycline,
streptomycin etc)
The resistance via plasmid to chloramphenicol happened because
of chloramphenicol acethyltransferace produced bacteria which
inactivated medicine. Therefore, microorganism resistance contain
plasmid forms high level
Chloramphenicol crystal should completely rapid absorbed. Daily
dose 2 g per oral produce bloodlevel 8 ug/ml.
Chloramphenicol palmitate usually given to children up to 50 mg/kg
BW/day per oral should be hydrolysis on intestine to free
chloramohenicol but blood level rarely more than 10 ug/ml
 CHLORAMPHENICOL (2)
Chloramphenicol succinate usually given parentheral. Dose of 25 50
mg/kg BW/day intra venous or intra muscle produce free
chloramphenicol (by hydrolysis) which its blood level lower than blood
level oral origin. After absorption, chloramphenicol severe distributed to
all body tissues and liquids, included cerebrospinalis liqiud indication
to infection of CNS
Because of its toxicity and existence others, nowadays,
chloramphenicol is indicated to:
1. Somatic salmonella infection (lot of salmonella strain is resistance and
cotrimoxazol often used)
2. Seriously infection of h influenzae (meningitis, epiglottis, or pneumonia)
3. Infection of meningococcus or pneumococcus on CNS that
hypersensitive of beta lactam medicines
4. Anaerobic or mix infection on CNS (like cerebral abscess)
5. Rarely, as an alternative drug to tetracycline on seriously rickettsia
infection
Sometimes chloramphenicol administered topically (like eye infection)
because of its severe spectrum of antibacteria and its penetration in eye
tissues and aqueous humor. However, there is ineffective in clamidia
infection
 CHLORAMPHENICOL (3)
Dose for salmonelosis (typhus or parathyphus fever) is 2 3 g a day per oral
during 14 21 days. Long therapy reduce relapse frequency. This program is
suitable for severe rickettsia infection or Rocky Mountain fever.
Dose for meningitis caused H influenzae or laringotracheitis or pneumonia is
chloramphenicol 50 100 mg/kg BW/day per oral or i.v. during 8 14 days
Since appearing of chloramphenicol resistance of Haemophilus strain
cephtriaxon and cephotaxin became drug of choice
Sometimes combination of chloramphenicol 2 g daily and aminoglycoside (ex.
amycasin 15 mg/kgBW a day) should be chosen as living injury caused lower
intestine sepsis
Sometimes it usually taken to cerebritis, cerebral absces or unknown
meningitis. Usually dose for adult is 50 mg/kg BW daily in 4 doses. It useful to
other sepsis caused bacteroides and severe meliodosis
When consumption reach 1.5 2.5 g daily sometimes appear nausea, vomit,
and diarrhea. This phenomenon is rarely for children. After 5 10 days
consumption membrane mucouse candidiasis (mouth and vagina)
Consumption more than 50 mg/kg BW/day could appearing of erythrocyte
maturation after blood level over than 25 30 ug/ml for 1 2 weeks. It is signed
by appearing of vacuole nucleus erythrocyte in spinal cord, anaemia, and
reticulocytopenia. This disturbances is reversible
Aplastic anaemia might appears as idiosyncracy. Aplastic anaemia could
appear since of repeatedly consumption. Leukemia might follow aplastic
anaemia
 CHLORAMPHENICOL (4)

Neonatus had not sufficient mechanism of

degradation and detoxification of chloramphenicol.
Since infant is given 75 mg/kg BW daily,
chloramphenicol would accumulated gray babby
syndrome with a vomit, faint, hypothermia, grey,
shock and collapse. Caution should be taken with
decrease dose of chloramphenicol up to or less than
50 mg/kg BW daily and 30 mg/kg BW a day for
premature
Chloramphenicol could extend half time and increase
blood level of phenitoin, tolbutamide, chlorpropamide
and warfarin.
Chloramphenicol would precipitate other medicines
antagonis for penicilline and aminoglycoside
Because of its severe spectrum and lack of clarity of
toxicity excessive usage aplastic anaemia wave
almost totally prohibition
 TETRACYCLINE (1)
Chlortetracycline isolated from Streptomyces aureofaciens introduce
in 1948. Oxytetracycline isolated from S rimosus introduce in 1950 and
tetracycline (be obtained as catalytic dehalogenitation) in 1953.
Demeclocycline is obtained by demethylation of chlortetracycline
Tetracycline is bacteristatic for almost all gram + and gram bacteria,
included anaerob, rickettsia, clamidia, mycoplasma, L form and
several protozoa like amoeba
The difference of efficacy is depend on its absorption, distribution,
and excretion, and the other hand is cell sensitivity of microbe
isolate laboratory test is very important
Nowadays, several gram bacteria (Pseudomonas, proteus and
coliform) are resistance to tetracycline. Tetracycline resistance usually
move by plasmid. By severe application severe resistance to
tetracycline, even sensitive microbe (like pneumococcus, bacteroides)
Tetracycline is almost irregular absorption in digestive tract, only 30%
of chlortetracycline, 60 80% of tetracycline, oxytetracycline and
demeclosin, and 90 100% of doxycycline and minocycline distributed
in body tissues and liquid. Best yielding of absorption happens in
empty upper intestine. Ca++, Mg++, Fe++, Al+++, especially in milk,
antacide and pH alkaline.
Excretion of tetracycline passed through bile and urine. Tetracycline
should be bound to protein and Ca and it could pass through placenta
barrier and breast milk
 TETRACYCLINE (2)
Tetracycline is drug of choice for infection caused
Mycoplasma pneumoniae, clamidia, rickettsia and
several spirochaeta. This medicine also usually used for
mix infection connected to respiratory tract (like sinusitis
and bronchitis)
It might used to various of gram and gram + bacteria
(included vibrio and perhaps cholera)
Tetracycline effectives to almost all of clamidia infection
included sexual interchange diseases
Others application are in acne, urogenital tract infection,
bronchitis with exacerbation, Lyme disease, repeated
fever, and leptospirosis. Doxicycline effectives as
leptospirosis prophylaxis.
In brucellosis, tularemia, and pest tetracycline
aminoglycoside combination gives a good yielding.
Tetracycline usually using in protozoa infection as
Entamoeba hystolitica or Plasmodium falsiparum
 TETRACYCLINE (3)
Minimum oral dose is 0.25 g of tetracycline HCl 4 times a day for adult or
equivalent to 20 mg/kg BW/day for children. This amount is rapid
excretion
In the case of severity systemic infection, recommended dose is 2-3 times
of minimum oral dose during 3 5 days. However, 10 14 days is
recommended for clamidia infection on urogenital tract
Effective minimum daily doses for demeclocycline or metacycline are 600
mg, doxycycline is 100 mg, and minocycline is 300mg
Tetracycline should not be taken with milk, antacide, and or ferro
sulphate. It should not be taken to gravid women or children under 8
Daily tetracycline HCl 250 500 mg usually application on acne
medication for a long time (month to month)
Several tetracyclines are presented in i.v. application with dose 0.1 0.5 g
every 6 12 hours for adult and 10 -15 mg/kg BW/day for children
Intra muscle injection usually avoid because of its sickness and
inflammation reaction. It be taken because of condition (like rickettsia
patient in comma condition)
Hypersensitivity reaction (drug fever, skin rash) of tetracycline is rarely.
Lot of side effect are caused of direct toxicity of medicine or change of
microbe flora
Tractus digestivus side effects are nausea, vomiting, and diarrhea
because local irritation. It should not recommended to consume
medicines on empty stomach
 TETRACYCLINE (4)
After a few days oral administration, tetracycline could change normal flora.
Psedomonas, Proteus, Staphilococcus, resistance coliform, clostridia, and
Candida could stick out. Pseudomembrane entero colitis connected
Clostridium difficile, or staphilococcus had to known and cured by
vancomycine per oral
Tetracycline should not be given to gravid women, infant, or children
because of its dental and bone deposit. Bone deposit could inhibit body
growth and deformity, while dental deposit could coloring it.
Tetracycline might be disturb liver function, especially in liver insufficiency.
Liver necrosis was reported in application of 4 g daily intra venous
Except doxycycline, tetracyclines could deposit on liver until toxic
concentration in liver fungtion disorder clients
Intra muscle injection could cause local irritation, while intra venous cause
vena thrombosis.
Photosensitization appears in systemic tetracycline administration,
especially for reddish blonde hair
Vestibular reaction (dizziness, vertigo, nausea and vomiting) appear after
consumption of 200 400 mg/day of minocycline
Large scale application in hospitals causes tetracycline resistance organism
as an super infection agent. Large scale application on veterinary appears
large distribution of super infection agents.
On the other hand, tetracycline is very profitable, not only controlling the
present infection, but it very useful for initial medication of acute
exacerbation on chronic bronchitis and keep a lot of people still health and
workable
 AMINOGLYCOSIDE
Aminoglycoside is a group of bactericide medicines origin
from various species of Streptomyces and had a similarity
on chemical, antimicrobial, pharmacology and toxic effects.
In fact, there are streptomycine, neomycine, kanamycine,
amycasine, gentamycine, tobramycine, cysomycine,
nethylmycine, etc. All of this medicines are inhibit protein
synthetic of bacteria and has a lack of various of weakness
connected of its resistance
All of aminoglycoside had an autotoxic and nephrotoxic
adjustable dose should be taken for clients with kidney
insufficiency
Aminoglycoside is wide application to fight gram enteric
bacteria (especially bacteriemia), sepsis, or endocarditis.
Aminoglycoside is bactericide for sensitive organism via
irreversible inhibitation of protein synthetic
Aminoglycoside is not or less absorption from digestive
tract.
Excretion pass trough faeces
 STREPTOMYCINE
Nowadays, its application limited during 5 days because of
rapid appearing resistance of sensitive bacteria isolate.
Streptomycine had rarely use in initial therapy on Koch. On late
tbc, milier spread, meningitis, or heavy infection of organs,
streptomycine could be taken on 0.5 1 g (30 mg.kg BW/day) by
intra muscle injection in combination with other antibacteria.
This combination apply week by week or month by month, start
with daily and then 2 times a week.
On non tbc infection (pest, tularemia, and usually brucelosis),
streptomycine applied 1 g/day (15 mg/ml/day for children) per
i.m., while tetracycline per oral.
Application of penicilline combine to aminoglycoside could
eradication of bacteria (exp.: endocartitis infection caused
streptococcus faecalis, bacteremia)
Fever, skin rash, and others might appear during consumption
of streptomycine
Seriously toxic effect is disturbance of vestibular vertigo
function and lost of body balanced, partial recovery usually
happen when consumption is stopped
Streptomycine is used during pregnancy could cause deafness
 GENTAMYCINE
Gentamycine sulphate 2 10 ug/ml inhibit staphilococcus, coliform, and
other gram -. Combination with carbenicyline or ticarcyline could increase
synergism and bactericide activity to Pseudomonas, Proteus, Enterobacter,
Klebsiella, other gram -, and S viridans and S faecalis.
Many streptococcus resistance to gentamycine because of medicine failure
to reach ribosome of germ
Nowadays, gentamycine and tobramycine applied in heavy infection (like
sepsis and pneumonia) in combination with cephalospurine or penicilline.
Dose of 5 7 mg/kb BW/day i.m. or i.v. for every medicine (gentamycine
cephalospurine or penicilline). Gentamycine or tobramycine penicilline G
combination applied for bactericidal activity in endocarditis caused S
viridans or S faecalis
Monitoring of vestibular vertigo should be taken, especially on client with
kidney failure. Serum concentration of gentamycine could be essay by direct
enzymatic or radioimmunoassays
Cream, ointment, or solution of gentamycin sulphate 0.1 0.3% applied in
burn injury, wound or skin lesion, and infection prophylaxis on i.v. catheter.
Gentamycin sulphate 1 10 mg/day intratechal applied for meningitis.
Gentamycine intratechal is toxic for neonatus. Epidural absces, after
aspiration, dropped by gentamycine 20 mg/day during 10 days
Side effects are almost similar with streptomycine. Lost of sense of hearing
could happen, sometimes severe and irreversible
 POLYMIXINE
Polymixine is base polypeptide that active to gram bacteria
Because of its nephrotoxicity almost all of polymixine should not applied
especially polymixine B and E
Polymixine is bactericide for many gram bacteria included Pseudomonas
in 1 5 ug/ml blood level. Polymixine adhere on cell membrane of bacteria
rich of fosfatidylethanolamine and disturb osmotic nature and transport
mechanism on membrane. Gram + organism, Proteus and Neisseria, is very
resistance
Polymixine would not absorbed from intestine. Excretion mainly pass
through kidney and high concentration could reach in urine. Disturbance of
excretion should be present in clients with kidney insufficiency
Nowadays, polymixine is using in topical application. Solution of
polymixine B sulphate 1 -10 mg/ml could given on infected surface,
injected in pleura and joint cavity as sub conjunctive, and inhalation as
aerosol. Total dose should not exces 2.5 mg/kg BW/day
Polymixine 0.5 mg/g of ointment combine to bacitracin and or neomycine
usually spreading it on lesion of infected skin surface. This medicine also
given per oral to press aerob gram from intestinal flora
Local reaction and hipersensitivity is rarely. Systemic concentration of
polymixine could cause paresthesia, dizzyness, and incoordination. This
symptom is reversible. High blood level (>30 ug/ml) could cause respiratory
paralysis, that recoverable by consumption of calcium gluconate.
Absorption of polymixine could cause proteinuria and hematuria as a sign
of tube disturbance. On kidney insufficiency N retention could happen