Chloramphenicol is a bacteriostatic antimicrobial agent
that was originally derived from the bacterium Streptomyces venezuelae
and introduced into clinical practice in 1949, under the trade name
Chloromycetin. It was the first antibiotic to be manufactured synthetically on a
It is a broad-spectrum antibiotic, and is
cheap and easy to manufacture, a condition that make it a frequently used
antibiotic in low income countries. Chloramphenicol, also known as
chlornitromycin, is effective against a wide variety of Gram-positive and
Gram-negative bacteria, including most anaerobes. Due to resistance and safety
concerns, it is no longer a first-line agent for any infection in developed
nations, although it is used topically for eye infections. Nevertheless, the
global problem of advancing bacterial resistance to newer drugs has led to
renewed interest in its use. In low-income countries, chloramphenicol is
still widely used because it is inexpensive and readily available.
The action of chloramphenicol against
enterobacteria is largely bacteriostatic, but against some bacteria, including
the Gram-positive cocci, it may display quite potent bactericidal activity. The
drug also possesses the important properties of diffusing well into
cerebrospinal fluid and of penetrating into cells, a very useful feature in the
treatment of diseases such as typhoid, typhus, and other conditions where
intracellular bacteria are involved. Resistance to chloramphenicol is generally
uncommon, although resistant strains of the typhoid bacillus, Salmonella
enterica, serotype Typhi, cause serious problems in areas of the world where
the disease is endemic. Strains of Haemophilus influenzae that are
resistant to chloramphenicol are also encountered with increasing frequency.
Chloramphenicol use is
limited by the risk ofpotentially fatal aplastic anaemia and has
carved a role as reserve drug for use in life-threatening infections
caused by bacteria resistant to safer compounds.
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. Chloramphenicol may be used as a second-line agent in
the treatment of tetracycline-resistant cholera.
Because of its excellent
penetration (far superior to any of the
chloramphenicol remains the first choice treatment for
staphylococcal brain abscesses. It is also useful in the treatment
of brain abscesses due to mixed organisms or when the causative
organism is not known.
Chloramphenicol is active against the three
main bacterial causes of meningitis:
and Haemophilus influenzae.
In the West, chloramphenicol remains the drug of choice in the
treatment of meningitis in patients with severe
cephalosporin allergy and GPs are
recommended to carry intravenous chloramphenicol in their bag. In
low income countries, the WHO recommend that oily chloramphenicol be
used first-line to treat meningitis.
Chloramphenicol has been used in the U.S. in the initial
empirical treatment of children with fever and a petechial rash, when the differential
diagnosis includes both
as well as Rocky Mountain spotted fever, pending the results of
Chloramphenicol is also effective against
which has led to its being considered for treatment of vancomycin-resistant enterococcus.
The most serious adverse effect associated with chloramphenicol treatment is
bone marrow toxicity, which may occur in two distinct forms: bone marrow
suppression, which is a direct toxic effect of the drug and is usually
reversible, and aplastic anemia, which is idiosyncratic (rare, unpredictable,
and unrelated to dose) and in general fatal.
Aplastic anaemia is the most serious adverse event of chloramphenicol. This
adverse event is rare and is generally fatal: there is no treatment and no way
of predicting its occurence. The event usually occurs weeks or months after
chloramphenicol treatment has been stopped, and may have a genetic origin. 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 blood
count check twice weekly while on treatment. The highest risk of this adverse
event is associated with oral chloramphenicol (affecting 1 in
24,000–40,000) and the lowest risk occurs with eye drops (affecting less than
1 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, and is not approved for use in
Bone marrow suppression
Treatment with chloramphenicol may causes bone marrow
suppression as direct toxic effect of the drug on human mitochondria. The
effect is identified by a fall in hemoglobin levels, which occurs quite
predictably following the administration of a cumulative dose of 20g. Anaemia is
fully reversible once the drug is removed from circulation and is not predictive
of the risk of developing aplastic anaemia. Studies in mice have suggested that
existing marrow damage may be worsened by marrow damage resulting from the toxic
effects of chloramphenicol.
There is an increased risk of childhood leukemia, as demonstrated in a Chinese
case-controlled study, and the risk increases with length of treatment.
Gray baby syndrome
Intravenous chloramphenicol use can cause the gray baby syndrome. This
phenomenon occurs in newborn infants because they do not yet have fully
functional liver enzymes (i.e. UDP-glucuronyl transferase) and chloramphenicol
is not adequately metabolized. 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.
1. Falagas, M. E.; Grammatikos, A. P.;
Michalopoulos, A. (October 2008). "Potential of old-generation antibiotics to
address current need for new antibiotics". Expert Review of Anti Infective
Therapy 6 (5): 593–600.
2. Rich, M.; Ritterhoff, R.; Hoffmann, R.
(December 1950). "A fatal case of aplastic anemia following chloramphenicol
(chloromycetin) therapy". Annals of Internal Medicine 33 (6): 1459–1467.
3. Nagao, T.; Mauer, A. (July 1969).
"Concordance for drug-induced aplastic anemia in identical twins". New England
Journal of Medicine 281 (1): 7–11.
4. Holt, R. (1967). "The bacterial degradation
of chloramphenicol". Lancet 289 (7502): 1259–1260.
5. Wallerstein, R.; Condit, P.; Kasper, C.;
Brown, J.; Morrison, F. (June 1969). "Statewide study of chloramphenicol therapy
and fatal aplastic anemia". JAMA 208 (11): 2045–2050.
6. Lancaster, T.; Stewart, A. M.; Jick, H.
(1998). "Risk of serious haematological toxicity with use of chloramphenicol eye
drops in a British general practice database". British Medical Journal 316
7. Yunis AA (September 1989). "Chloramphenicol
toxicity: 25 years of research". Am. J. Med. 87 (3N): 44N–48N.
8. Morley, Alec; Trainor, Kevin; Remes, Judith
(1 April 1976). "Residual Marrow Damage: Possible Explanation for Idiosyncrasy
to Chloramphenicol". British Journal of Haematology 32 (4): 525–532.
9. Shu, X.; Gao, Y.; Linet, M.; Brinton, L.;
Gao, R.; Jin, F.; Fraumeni, J. (October 1987). "Chloramphenicol use and
childhood leukaemia in Shanghai". Lancet 2 (8565): 934–937.
10. McIntyre, J.; Choonara, I. (2004). "Drug
toxicity in the neonate". Biology of the Neonate 86 (4): 218–221.