|Trade names||Pentamycetin, Chloromycetin, others|
| Routes of|
|Topical (eye drops), by mouth, IV, IM|
|Elimination half-life||1.6–3.3 hours|
|Excretion||Kidney (5–15%), faeces (4%)|
|ECHA InfoCard|| 100.000.262 |
|Chemical and physical data|
|Molar mass||323.1320 g/mol g·mol−1|
|3D model (JSmol)|
Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections.This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, and typhoid fever. Its use by mouth or by injection is only recommended when safer antibiotics cannot be used. Monitoring both blood levels of the medication and blood cell levels every two days is recommended during treatment.
An antibiotic is a type of antimicrobial substance active against bacteria and is the most important type of antibacterial agent for fighting bacterial infections. Antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics.
Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. The affected eye may have increased tears or be "stuck shut" in the morning. Swelling of the white part of the eye may also occur. Itching is more common in cases due to allergies. Conjunctivitis can affect one or both eyes.
Meningitis is an acute inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or altered consciousness, vomiting, and an inability to tolerate light or loud noises. Young children often exhibit only nonspecific symptoms, such as irritability, drowsiness, or poor feeding. If a rash is present, it may indicate a particular cause of meningitis; for instance, meningitis caused by meningococcal bacteria may be accompanied by a characteristic rash.
Common side effects include bone marrow suppression, nausea, and diarrhea.The bone marrow suppression may result in death. To reduce the risk of side effects treatment duration should be as short as possible. People with liver or kidney problems may need lower doses. In young children a condition known as gray baby syndrome may occur which results in a swollen stomach and low blood pressure. Its use near the end of pregnancy and during breastfeeding is typically not recommended. Chloramphenicol is a broad-spectrum antibiotic that typically stops bacterial growth by stopping the production of proteins.
Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. The risk is especially high in cytotoxic chemotherapy for leukemia.
Gray baby syndrome is a rare but serious side effect that occurs in newborn infants following the accumulation of antibiotic chloramphenicol.
Hypotension is low blood pressure, especially in the arteries of the left sided systemic circulation. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. A systolic blood pressure of less than 90 millimeters of mercury or diastolic of less than 60 mm Hg is generally considered to be hypotension. However, in practice, blood pressure is considered too low only if noticeable symptoms are present.
Chloramphenicol was discovered after being isolated from Streptomyces venezuelae in 1947. 26 It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world of an intravenous dose is about US$0.40–1.90. In the United States an intravenous dose costs about $41.47.Its chemical structure was identified and it was first artificially made in 1949, making it the first antibiotic to be made instead of extracted from a micro-organism. :
Streptomyces venezuelae is a species of soil-dwelling Gram-positive bacterium of the genus Streptomyces. S. venezuelae is filamentous. In its spore-bearing stage, hyphae perfuse both above ground as aerial hyphae and in the soil substrate. Chloramphenicol, the first antibiotic to be manufactured synthetically on a large scale, was originally derived from S. venezuelae. Other secondary metabolites produced by S. venezuelae include jadomycin and pikromycin.
A health system, also sometimes referred to as health care system or as healthcare system, is the organization of people, institutions, and resources that deliver health care services to meet the health needs of target populations.
The original indication of chloramphenicol was in the treatment of typhoid, but the now almost universal presence of multiple drug-resistant Salmonella typhi has meant it is seldom used for this indication except when the organism is known to be sensitive.
In low-income countries, the WHO no longer recommends oily chloramphenicol as first-line to treat meningitis, but recognises it may be used with caution if there are no available alternatives.
In the context of preventing endophthalmitis, a complication of cataract surgery, a 2017 systematic review found moderate evidence that using chloramphenicol eye drops in addition to an antibiotic injection (cefuroxime or penicillin) will likely lower the risk of endophthalmitis, compared to eye drops or antibiotic injections alone.
Endophthalmitis is an inflammation of the interior of the eye. It is a possible complication of all intraocular surgeries, particularly cataract surgery, with possible loss of vision and the eye itself. Infectious cause is the most common and various bacteria and fungi have been isolated as the cause of the endophthalmitis. Other causes include penetrating trauma, allergic reaction, and retained intraocular foreign bodies. Intravitreal injections expose patients to the risk of endophthalmitis, but with an incidence rate usually less than .05%.
A cataract is a clouding of the lens in the eye which leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry vision, halos around light, multiple images of a single object, trouble with bright lights, and trouble seeing at night. This may result in trouble driving, reading, or recognizing faces. Poor vision caused by cataracts may also result in an increased risk of falling and depression. Cataracts cause half of all cases of blindness and 33% of visual impairment worldwide. It is the leading cause of preventable blindness in the world.
Cefuroxime, sold under the brand name Zinacef among others, is an antibiotic used to treat and prevent a number of bacterial infections. These include pneumonia, meningitis, otitis media, sepsis, urinary tract infections, and Lyme disease. It is used by mouth or by injection into a vein or muscle.
Chloramphenicol has a broad spectrum of activity and has been effective in treating ocular infections such as conjunctivitis, blepharitis etc. caused by a number of bacteria including Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli. It is not effective against Pseudomonas aeruginosa. The following susceptibility data represent the minimum inhibitory concentration for a few medically significant organisms.
Each of these concentrations is dependent upon the bacterial strain being targeted. Some strains of E. coli, for example, show spontaneous emergence of chloramphenicol resistance.
Three mechanisms of resistance to chloramphenicol are known: reduced membrane permeability, mutation of the 50S ribosomal subunit, and elaboration of chloramphenicol acetyltransferase. It is easy to select for reduced membrane permeability to chloramphenicol in vitro by serial passage of bacteria, and this is the most common mechanism of low-level chloramphenicol resistance. High-level resistance is conferred by the cat-gene; this gene codes for an enzyme called chloramphenicol acetyltransferase, which inactivates chloramphenicol by covalently linking one or two acetyl groups, derived from acetyl-S-coenzyme A, to the hydroxyl groups on the chloramphenicol molecule. The acetylation prevents chloramphenicol from binding to the ribosome. Resistance-conferring mutations of the 50S ribosomal subunit are rare.
Chloramphenicol resistance may be carried on a plasmid that also codes for resistance to other drugs. One example is the ACCoT plasmid (A=ampicillin, C=chloramphenicol, Co=co-trimoxazole, T=tetracycline), which mediates multiple drug resistance in typhoid (also called R factors).
As of 2014 some Enterococcus faecium and Pseudomonas aeruginosa strains are resistant to chloramphenicol. Some Veillonella spp. and Staphylococcus capitis strains have also developed resistance to chloramphenicol to varying degrees.
The most serious side effect of chloramphenicol treatment is aplastic anaemia. This effect is rare and sometimes fatal. The risk of AA is high enough that alternatives should be strongly considered. Treatments are available but expensive. No way exists to predict who may or may not get this side effect. The effect usually occurs weeks or months after treatment has been stopped, and a genetic predisposition may be involved. It is not known whether monitoring the blood counts of patients can prevent the development of aplastic anaemia, but patients are recommended to have a baseline blood count with a repeat blood count every few days while on treatment.Chloramphenicol should be discontinued if the complete blood count drops. The highest risk is with oral chloramphenicol (affecting 1 in 24,000–40,000) and the lowest risk occurs with eye drops (affecting less than one in 224,716 prescriptions).
Thiamphenicol, a related compound with a similar spectrum of activity, is available in Italy and China for human use, and has never been associated with aplastic anaemia. Thiamphenicol is available in the U.S. and Europe as a veterinary antibiotic, but is not approved for use in humans.
Chloramphenicol may cause bone marrow suppression during treatment; this is a direct toxic effect of the drug on human mitochondria. g has been given. The anaemia is fully reversible once the drug is stopped and does not predict future development of aplastic anaemia. Studies in mice have suggested existing marrow damage may compound any marrow damage resulting from the toxic effects of chloramphenicol.This effect manifests first as a fall in hemoglobin levels, which occurs quite predictably once a cumulative dose of 20
Leukemia, a cancer of the blood or bone marrow, is characterized by an abnormal increase of immature white blood cells. The risk of childhood leukemia is increased, as demonstrated in a Chinese case–control study,and the risk increases with length of treatment.
Intravenous chloramphenicol use has been associated with the so-called gray baby syndrome.This phenomenon occurs in newborn infants because they do not yet have fully functional liver enzymes (i.e. UDP-glucuronyl transferase), so chloramphenicol remains unmetabolized in the body. This causes several adverse effects, including hypotension and cyanosis. The condition can be prevented by using the drug at the recommended doses, and monitoring blood levels.
Fever, macular and vesicular rashes, angioedema, urticaria, and anaphylaxis may occur. Herxheimer's reactions have occurred during therapy for typhoid fever.
Headache, mild depression, mental confusion, and delirium have been described in patients receiving chloramphenicol. Optic and peripheral neuritis have been reported, usually following long-term therapy. If this occurs, the drug should be promptly withdrawn.
Chloramphenicol is extremely lipid-soluble; it remains relatively unbound to protein and is a small molecule. It has a large apparent volume of distribution and penetrates effectively into all tissues of the body, including the brain. Distribution is not uniform, with highest concentrations found in the liver and kidney, with lowest in the brain and cerebrospinal fluid.The concentration achieved in brain and cerebrospinal fluid is around 30 to 50% of the overall average body concentration, even when the meninges are not inflamed; this increases to as high as 89% when the meninges are inflamed.
Chloramphenicol increases the absorption of iron.
Chloramphenicol is metabolized by the liver to chloramphenicol glucuronate (which is inactive). In liver impairment, the dose of chloramphenicol must therefore be reduced. No standard dose reduction exists for chloramphenicol in liver impairment, and the dose should be adjusted according to measured plasma concentrations.
The majority of the chloramphenicol dose is excreted by the kidneys as the inactive metabolite, chloramphenicol glucuronate. Only a tiny fraction of the chloramphenicol is excreted by the kidneys unchanged. Plasma levels should be monitored in patients with renal impairment, but this is not mandatory. Chloramphenicol succinate ester (an intravenous prodrug form) is readily excreted unchanged by the kidneys, more so than chloramphenicol base, and this is the major reason why levels of chloramphenicol in the blood are much lower when given intravenously than orally.[ citation needed ]
Chloramphenicol passes into breast milk, so should therefore be avoided during breast feeding, if possible.
Plasma levels of chloramphenicol must be monitored in neonates and patients with abnormal liver function. Plasma levels should be monitored in all children under the age of four, the elderly, and patients with renal failure. Because efficacy and toxicity of chloramphenicol are associated with a maximum serum concentration, peak levels (one hour after the intravenous dose is given) should be 10–20 µg/ml with toxicity > 40 µg/ml; trough levels (taken immediately before a dose) should be 5–10 µg/ml.
Administration of chloramphenicol concomitantly with bone marrow depressant drugs is contraindicated, although concerns over aplastic anaemia associated with ocular chloramphenicol have largely been discounted.
Chloramphenicol is a potent inhibitor of the cytochrome P450 isoforms CYP2C19 and CYP3A4 in the liver.Inhibition of CYP2C19 causes decreased metabolism and therefore increased levels of, for example, antidepressants, antiepileptics, proton-pump inhibitors, and anticoagulants if they are given concomitantly. Inhibition of CYP3A4 causes increased levels of, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, azole antifungals, tricyclic antidepressants, macrolide antibiotics, SSRIs, statins, cardiac antiarrhythmics, antivirals, anticoagulants, and PDE5 inhibitors.
Chloramphenicol is antagonistic with most cephalosporins and using both together should be avoided in the treatment of infections.
Chloramphenicol is a bacteriostatic by inhibiting protein synthesis. It prevents protein chain elongation by inhibiting the peptidyl transferase activity of the bacterial ribosome. It specifically binds to A2451 and A2452 residuesin the 23S rRNA of the 50S ribosomal subunit, preventing peptide bond formation. Chloramphenicol directly interferes with substrate binding in the ribosome, as compared to macrolides, which sterically block the progression of the growing peptide.
Chloramphenicol was first isolated from Streptomyces venezuelae in 1947 and in 1949 a team of scientists at Parke-Davis including Mildred Rebstock published their identification of the chemical structure and their synthesis, making it the first antibiotic to be made instead of extracted from a micro-organism. 26:
In 2007, the accumulation of reports associating aplastic anemia and blood dyscrasia with chloramphenicol eye drops lead to the classification of “probable human carcinogen” according to World Health Organization criteria, based on the known published case reports and the spontaneous reports submitted to the National Registry of Drug-Induced Ocular Side Effects.
In many areas of the world an intravenous dose is about US$0.40–1.90.In the United States it costs about $3.60 per dose in oral tablet form at wholesale.
Chloramphenicol is available as a generic worldwide under many brandnamesand also under various generic names in eastern Europe and Russia, including chlornitromycin, levomycetin, and chloromycetin; the racemate is known as synthomycetin.
Chloramphenicol is available as a capsule or as a liquid. In some countries, it is sold as chloramphenicol palmitate ester (CPE). CPE is inactive, and is hydrolysed to active chloramphenicol in the small intestine. No difference in bioavailability is noted between chloramphenicol and CPE.
Manufacture of oral chloramphenicol in the U.S. stopped in 1991, because the vast majority of chloramphenicol-associated cases of aplastic anaemia are associated with the oral preparation. No oral formulation of chloramphenicol is now available in the U.S.
In molecular biology, chloramphenicol is prepared in ethanol.
The intravenous (IV) preparation of chloramphenicol is the succinate ester, because pure chloramphenicol does not dissolve in water. This creates a problem: Chloramphenicol succinate ester is an inactive prodrug and must first be hydrolysed to chloramphenicol; however, the hydrolysis process is often incomplete, and 30% of the dose is lost and removed in the urine. Serum concentrations of IV chloramphenicol are only 70% of those achieved when chloramphenicol is given orally. mg/kg/day when administered IV to achieve levels equivalent to the oral dose.For this reason, the dose needs to be increased to 75
Oily chloramphenicol (or chloramphenicol oil suspension) is a long-acting preparation of chloramphenicol first introduced by Roussel in 1954; marketed as Tifomycine, it was originally used as a treatment for typhoid. Roussel stopped production of oily chloramphenicol in 1995; the International Dispensary Association has manufactured it since 1998, first in Malta and then in India from December 2004.
Oily chloramphenicol was first used to treat meningitis in 1975and numerous studies since have demonstrated its efficacy. It is the cheapest treatment available for meningitis (US$5 per treatment course, compared to US$30 for ampicillin and US$15 for five days of ceftriaxone). It has the great advantage of requiring only a single injection, whereas ceftriaxone is traditionally given daily for five days. This recommendation may yet change, now that a single dose of ceftriaxone (cost US$3) has been shown to be equivalent to one dose of oily chloramphenicol.
Chloramphenicol is still used occasionally in topical preparations (ointments and eye drops) for the treatment of bacterial conjunctivitis. Isolated case reports of aplastic anaemia following use of chloramphenicol eyedrops exist, but the risk is estimated to be of the order of less than one in 224,716 prescriptions.In Mexico, this is the treatment used prophylactically in newborns.
Although its use in veterinary medicine is highly restricted, chloramphenicol still has some important veterinary uses.It is currently considered the most useful treatment of chlamydial disease in koalas. The pharmacokinetics of chloramphenicol have been investigated in koalas.
Although unpublished, recent research suggests chloramphenicol could also be applied to frogs to prevent their widespread destruction from fungal infections.It has recently been discovered to be a life-saving cure for chytridiomycosis in amphibians. Chytridiomycosis is a fungal disease, blamed for the extinction of one-third of the 120 frog species lost since 1980.
Ampicillin is an antibiotic used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B streptococcal infection in newborns. It is used by mouth, by injection into a muscle, or intravenously. Like all antibiotics, it is not useful for the treatment of viral infections.
Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used during pregnancy to prevent Group B streptococcal infection in the newborn, as well as to improve delayed stomach emptying. It can be given intravenously and by mouth. An eye ointment is routinely recommended after delivery to prevent eye infections in the newborn.
Vancomycin is an antibiotic used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant Staphylococcus aureus. Blood levels may be measured to determine the correct dose. Vancomycin is also recommended by mouth as a treatment for severe Clostridium difficile colitis. When taken by mouth it is very poorly absorbed.
Aplastic anaemia is a rare disease in which the bone marrow and the hematopoietic stem cells that reside there are damaged. This causes a deficiency of all three blood cell types (pancytopenia): red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia). Aplastic refers to the inability of stem cells to generate mature blood cells.
Gentamicin, sold under brand name Garamycin among others, is an antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. It is not effective for gonorrhea or chlamydia infections. It can be given intravenously, by injection into a muscle, or topically. Topical formulations may be used in burns or for infections of the outside of the eye. In the developed world, it is often only used for two days until bacterial cultures determine what specific antibiotics the infection is sensitive to. The dose required should be monitored by blood testing.
Levofloxacin, sold under the trade names Levaquin among others, is an antibiotic. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. It is available by mouth, intravenously, and in eye drop form.
Azithromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumonia, traveler's diarrhea, and certain other intestinal infections. It may also be used for a number of sexually transmitted infections, including chlamydia and gonorrhea infections. Along with other medications, it may also be used for malaria. It can be taken by mouth or intravenously with doses once per day.
Colistin, also known as polymyxin E, is an antibiotic produced by certain strains of the bacteria Paenibacillus polymyxa. Colistin is a mixture of the cyclic polypeptides colistin A and B and belongs to the class of polypeptide antibiotics known as polymyxins. Colistin is effective against most Gram-negative bacilli.
Rifampicin, also known as rifampin, is an antibiotic used to treat several types of bacterial infections, including tuberculosis, Mycobacterium avium complex, leprosy, and Legionnaires’ disease. It is almost always used together with other antibiotics, except when given to prevent Haemophilus influenzae type b and meningococcal disease in people who have been exposed to those bacteria. Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended. Rifampicin may be given either by mouth or intravenously.
Ceftriaxone, sold under the trade name Rocephin, is an antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joint infections, intra-abdominal infections, skin infections, urinary tract infections, gonorrhea, and pelvic inflammatory disease. It is also sometimes used before surgery and following a bite wound to try to prevent infection. Ceftriaxone can be given by injection into a vein or into a muscle.
Meropenem, sold under the brandname Merrem among others, is a broad-spectrum antibiotic used to treat a variety of bacterial infections. Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax. It is given by injection into a vein.
Ceftazidime, sold under the brand names Fortaz among others, is an antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections, meningitis, pneumonia, sepsis, urinary tract infections, malignant otitis externa, Pseudomonas aeruginosa infection, and vibrio infection. It is given by injection into a vein or muscle.
Cefaclor, sold under the trade name Ceclor among others, is a second-generation cephalosporin antibiotic used to treat certain bacterial infections such as pneumonia and infections of the ear, lung, skin, throat, and urinary tract. It is also available from other manufacturers as a generic.
Tigecycline is an antibiotic for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as Staphylococcus aureus, Acinetobacter baumannii, and E. coli. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance.
Cefotaxime is an antibiotic used to treat a number of bacterial infections. Specifically it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, sepsis, gonorrhea, and cellulitis. It is given either by injection into a vein or muscle.
Flucytosine, also known as 5-fluorocytosine (5-FC), is an antifungal medication. It is specifically used, together with amphotericin B, for serious Candida infections and cryptococcosis. It may be used by itself or with other antifungals for chromomycosis. Flucytosine is used by mouth and by injection into a vein.
A drug of last resort (DoLR) is a pharmaceutical drug that is tried after all other drug options have failed to produce an adequate response in the patient. Drug resistance, such as antimicrobial resistance or antineoplastic resistance, may make the first-line drug ineffective, especially with multidrug-resistant pathogens or tumors. Such an alternative may be outside of extant regulatory requirements or medical best practices, in which case it may be viewed as salvage therapy.
Clinafloxacin is an investigational fluoroquinolone antibiotic. Despite its promising antibiotic activity, the clinical development of clinafloxacin has been hampered by its risk for inducing serious side effects.