Chloromphenicol

7/31/2019 Chloromphenicol

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CHLORAMPHENICOL

PROF DR SHAH MURAD

[email protected]
mailto:[email protected]:[email protected]


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Broad spectrum antibiotic usuallybacteriostatic sometimes bactericidalagainst certain species ofmicroorganisms, when given in highconcentration

Chloramphenicol interferes with theprotein synthesis.


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Mechanism of Action

Chloramphenicol inhibits protein synthesis inbacteria, to a lesser extent, in eukaryotic cells.

Drug penetrates bacterial cells by facilitated diffusion

Primarily acts by binding reversibly to 50S ribosomalsub-unit. (competes macrolides and clindamycin)

Prevents binding of amino-acids containing end ofamino-acyl tRNA to receptor site on 50S ribosomalsub-unit.

The interaction between peptidyl transferase and itsamino acid substrate can not occur and peptide bond


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Eukaryotic erythropoietic cells aresensitive to Chloramphenicolbecause it can inhibit mitochondrial

protein synthesis (70S). (cytoplasmicis 80S)


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Spectrum Of activity

Bacteriostatic wide spectrum antibiotic

Bactericidal for certain sp. E.g., H.Influenzae >>>>>>


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H. Influenzae causes bacteremia,pneumonia, and acute bacterialmeningitis.

On occasion, it causes cellulitis,osteomyelitis, epiglottitis, and infectiousarthritis

otitis media, eye infections(conjunctivitis), and sinusitis in childrenassociated with pneumonia.


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Meningeococcal infections, like N.meningitidis, Meningococcemia(dissiminated intravascularcoagulation >>>>>> causingnecrotic tissue damage)


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Strp. pneumoniae


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More than 95% of the following Gram-ve bacteria are inhibited: >>>>>>>

H. influenzae,

N. meningitidis,

N. gonorrhoeae,

Brucella,

Bordetella pertussis.


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Spectrum

Anaerobic bacteria including G-vecocci, clostridium and G-ve rodsincluding B. Fragilis.

Active against Mycoplasma,chlamydia and rickettsiae.


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E. Coli, Klebsiella pneumoniae ( moststrains)

Proteus mirabilis and indole-positive

Proteus. (50%) Vibrio Cholera

Shigella and salmonella resistant tomultiple drugs including Chloramphenicol

are on the rise Of special concern is increasing

prevalence of multiple drug-resistantstrains of salmonella serotype typhi


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Resistance:

Resistance develops due toenzymatic deactivation ofchloramphenicol by a plasmid-

encoded acetyl-transferase


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Pharmacokinetics

Dose: 50 100mg/kg/d

Available in oral -- Chloramphenicol,Chloramphenicol palmitate.. >>>>

Absorbed rapidly from GIT. Parenteral Chloramphenicol succinate.

Di ib i


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Distribution: Well distributed in body fluids, CSF etc.

May accumulate in brain tissue

Present in bile, milk and crosses placental barrier Penetrates aqueous humor after sub-conjunctival

injection


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Elimination Elimination is primarily through the liver,

it is converted to inactive glucuronide,with this metabolite as well as

chloramphenicol itself is excreted inurine by filtration secretion.

Dose need not to be adjusted in renal

patients BUT checked in patients withimpaired liver functions


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Therapeutic Uses

Therapy with chloramphenicol must belimited to infections for which thebenefits of drug-use out weigh the risks

of potential toxicity

When other antibiotic areavailable which are less toxicand equally effective, then

the should be referred.


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Typhoid: (and other salmonella infections)

It i i t t d i th t t t


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It is an important drug in the treatmentof salmonella infections but with timethere are many resistant organismproduced and moreover much saferdrugs are available .

3rd generation Cephalosporins andquinolones are used

If chloramphenicol is used its given 1g 6 hourly for 4 weeks to treat typhoid


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Bacterial Meningitis

Excellent activity in meningitis caused by H.Influenza, it is bactericidal and better thanampicillin.

3rd generation cephalosporins are now useddue to less toxicity but chloramphenicolremains alternative for treatment ofmeningitis when Beta Lactams are

contraindicated.


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Anaerobic-infections

Chloramphenicol is effective againstanaerobic bacteria

Used for the treatment of serious

intraabdominal infections or brainabscesses. (alternative available)


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Rickettsial infections:

Tetracyclines are more preffered agentsbut chloramphenicol can be used as an

alternative treatment in epidemictyphus, murine, scrub and recrudescenttyphus as well as Q. fever


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Rocky mountain spotted fever,

Chill


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Chills

Confusion

Fever

Headache

Muscle pain

Rash -- usually starts a few days after the fever;

first appears on wrists and ankles as spots thatare 1 - 5 mm in diameter, then spreads to mostof the body. About one-third of infected peopledo not get a rash.


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Diarrhea

Light sensitivity

Hallucinations

Loss of appetite Nausea

Thirst

Vomiting


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Diagnostic tests

Antibody titer

Complete blood count (CBC)

Kidney function tests (RFTs)

Partial thromboplastin time (PTT) Prothrombin time (PT)

Skin biopsy taken from the rash to check for R. rickettsii

Urinalysis to check for blood or protein in the urine (urineDR)


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Brucellosis

Tetracyclines are more effective whentetracyclines are contraindicatedchloramphenicol may be used.


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Adverse Effects


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Hematological Toxicity:The most important adverse effect of

chloramphenicol is on the bone marrow.

It causes bone marrow depression, aplasticanemia which may lead to fatal pancytopenia.


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The drug should never be used, however,in undefined situations or in diseasesreadily, safely and effectively treatable

with other antimicrobial agents.


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Hypersensitivity reactions

Relatively uncommon, macular orvesicular skin rashes occur

Fever may appear simultaneously or as

a sole manifestation.


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Toxic & irritative effects

Nausea, vomiting, unpleasant taste,diarrhea and perineal irritation mayfollow oral administration.

RARE: blurring of vision, digitalparesthesia, optic neuritis in children.


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Fatal toxicity in neonatesspecially premature babies

exposed to high dose Grey Baby Syndrome.


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Greybabysyndrome

seen in neonates and

receiving high doses of

CHLORAMPHENICOL


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Toxic blood levels of chloramphenicol occursdue to :

inadeqaute conjugation of

chloramphenicol with glucuronic

acid because of inadequateactivity of glucuronyl transferase

in the newborn liver and

decreased renal excretion of the

chloramphenicol


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The infant is cyanosed,

is acidotic,

has cold peripheries has the signs of all of marked

hypotonia, poor feeding, vomiting,

loose stools and a distendedabdomen


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Similar condition seen in adults as well if the areaccidentally exposed to high dose.

Death occurs in 40 % cases, those who recover

show no sequelae


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Drug Interactions

Chloramphenicol inhibits micorsomalcytochrome P450 enzyme thus mayprolong the half-lives of drugs

metabolized by this enzyme. E.g.,Warfarin, dicumarol, phenytoin,chlorpropamide, tolbutamide.


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Phenobarbital chronic use andRifampin acute administrationshorten the half-life of

chloramphenicol >>>>>>>>may be due to enzyme inductionand may result in sub

therapeutic concentrations ofthe drug.


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THERAPEUTICS


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TYPHOID FEVER

The patient feels weak, cold and tired.

Headache, backache, diarrhea, constipation, loss ofappetite

Temperature rises and remains high for about 10-14days.

Body temperature typically rises in the evening anddrops in the morning.


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Skin eruptions appear, tongue becomesdry and gets white patches in the center,which causes oily taste in mouth and

inflamed bones.

Fever comes down gradually by the end

of fourth week.

C f T h id F


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Causes of Typhoid Fever

Poor sanitation, contaminated water andinfected milk are some of the main factorsresponsible for typhoid.

Flies contaminate the food with germs. Peoplecarrying the germs can also spread the diseaseif they prepare or serve food.

Wrong dietary habits and faulty lifestyle lead to

accumulation of toxic waste in the body andpromotes typhoid fever.

Typhoid is common in people who eat more

meat and meat products.

The type of salmonella most commonly


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The type of salmonella most commonlyassociated with infections in humans is callednontyphoidal salmonella >>>>> It is carried

by chickens, cows, and reptiles such as turtles,lizards, and iguanas.

Another, rarer form of salmonella, typhoidalsalmonella (typhoid fever), is carried only byhumans and is usually transmitted throughdirect contact with the fecal matter of an

infected person >>>>>> This kind ofsalmonella infection can lead to high fever,abdominal pain, headache, malaise, lethargy,skin rash, constipation, and delirium.

It occurs primarily in developing countries

C l d di i


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Commonly used medicines

Ciprofloxacin Oral

Cephalosporins mostly parenteral administration

Amoxicillin Oral

Ampicillin Oral, ampicillin sodium IV

Sulfamethoxazole-trimethoprim Oral

Sulfamethoxazole-trimethoprim IV

Chloramphenicol sod succinate IV

on armaco og ca


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on armaco og caManagement

Complete bed rest is essential.

Patient should be kept on a liquid diet

of orange, barley juice and milk. Orange juice, especially, hastens

recovery as it increases energy,

promotes body immunity andincreases urinary output.

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Chloromphenicol