"DOUBLE TYPHOID" was a dreaded diagnosis in the 60s in India. My younger brother who was probably 12 or 13 years old went to visit my Uncle in Culcutta and when he came back had a very high fever.
the use of Double typhoid was interpreted by different people differently.
for some it was a relapse of the same typhoid with in shoe rt time of getting over the first infection for other it was an infection from typhi and para typhi infection in the same patient.
Any way at that time only Chloramphenicol was the effective antibiotic available for typhoid fever treatment.
He suffered for quite a few days with high fevers before recovering.
he had a big growth spurt after this fever infact he is the tallest and heaviest of all us 4 brothers.
Chloramphenicol was supposedly associated with this deadly disease called aplastic anemia. so after lot of controversy and discussion this drug was almost banned in most countries and we lost a good weapon against the most common of infectious diseases in developing countries.
I always wondered why no other formulations with the similar structure as chloramphenicol were ever introduced .
"antique case reports leave doubt as to whether marrow failure in benzene workers was not often myelodysplasia rather than aplastic anemia. Unpredictable marrow failure in the setting of routine medical drug use is devastating to the patient and physician and has serious legal ramifications in pharmaceutical development. The study of idiosyncratic drug reactions, by definition so extremely rare, is difficult. That genetic differences in drug metabolism, especially in detoxification of reactive intermediate compounds, likely underlie susceptibility is thus poorly supported by experimental data. Overrepresentation of deletions in the drug metabolizing glutathione-S-transferase genes (GSTM1, GSTT1, which would increase concentrations of toxic drug intermediates) have been observed in some series.7,8 Nevertheless, no satisfactory mechanisms have been developed for the most notorious pharmaceutical, chloramphenicol, or for other heavily inculpated agents such as penicillamine or gold. Many drugs on “black lists” also more commonly cause mild marrow suppression. Regular but only modest destruction of marrow cells may sometimes be a prerequisite for a much more infrequent immune response to an exposed neoantigen. There is little demographic or clinical difference between patients with idiopathic aplastic anemia and those with an assumed drug etiology. Claims of permanent aplastic anemia after idiosyncratic exposure to minuscule quantities of chloramphenicol, as in ophthalmic solutions, may reflect observation and reporting biases rather than extreme sensitivity to a hidden metabolite. Conversely, very few chemotherapeutic agents, despite being designed as cell poisons and administered in milligram or gram quantities, directly result in irreversible marrow destruction without obvious effects on other organs.
If one takes a look at the case of vancomycin
We can realize that some toxic byproducts were the reason for the toxicity of earlier versions of vancomycin so much so this drug was discarded as an antibiotic . it was taken off the shelf dusted and manufactured in a more pure form and it is now one of the live saving Antibiotics.
"Despite the constantly increasing need for new antimicrobial agents, antibiotic drug discovery and development seem to have greatly decelerated in recent years. Presented with the significant problem of advancing antimicrobial resistance, the global scientific community has attempted to find alternative solutions; one of the most promising ones is the evaluation and use of old antibiotic compounds. Due to the low-level use of many of the old antibiotic compounds, these have remained active against a large number of currently prevalent bacterial isolates. Thus, clinicians are beginning to re-evaluate their use in various patient populations and infections, despite the fact that they were previously thought to be less effective and/or more toxic than newer agents. A number of old antibiotic compounds, such as polymyxins, fosfomycin, fusidic acid, cotrimoxazole, aminoglycosides and chloramphenicol, are re-emerging as valuable alternatives for the treatment of difficult-to-treat infections. The availability of novel genetic and molecular modification methods provides hope that the toxicity and efficacy drawbacks presented by some of these agents can be surpassed in the future."
read the full article here
the use of Double typhoid was interpreted by different people differently.
for some it was a relapse of the same typhoid with in shoe rt time of getting over the first infection for other it was an infection from typhi and para typhi infection in the same patient.
Any way at that time only Chloramphenicol was the effective antibiotic available for typhoid fever treatment.
He suffered for quite a few days with high fevers before recovering.
he had a big growth spurt after this fever infact he is the tallest and heaviest of all us 4 brothers.
Chloramphenicol was supposedly associated with this deadly disease called aplastic anemia. so after lot of controversy and discussion this drug was almost banned in most countries and we lost a good weapon against the most common of infectious diseases in developing countries.
I always wondered why no other formulations with the similar structure as chloramphenicol were ever introduced .
"antique case reports leave doubt as to whether marrow failure in benzene workers was not often myelodysplasia rather than aplastic anemia. Unpredictable marrow failure in the setting of routine medical drug use is devastating to the patient and physician and has serious legal ramifications in pharmaceutical development. The study of idiosyncratic drug reactions, by definition so extremely rare, is difficult. That genetic differences in drug metabolism, especially in detoxification of reactive intermediate compounds, likely underlie susceptibility is thus poorly supported by experimental data. Overrepresentation of deletions in the drug metabolizing glutathione-S-transferase genes (GSTM1, GSTT1, which would increase concentrations of toxic drug intermediates) have been observed in some series.7,8 Nevertheless, no satisfactory mechanisms have been developed for the most notorious pharmaceutical, chloramphenicol, or for other heavily inculpated agents such as penicillamine or gold. Many drugs on “black lists” also more commonly cause mild marrow suppression. Regular but only modest destruction of marrow cells may sometimes be a prerequisite for a much more infrequent immune response to an exposed neoantigen. There is little demographic or clinical difference between patients with idiopathic aplastic anemia and those with an assumed drug etiology. Claims of permanent aplastic anemia after idiosyncratic exposure to minuscule quantities of chloramphenicol, as in ophthalmic solutions, may reflect observation and reporting biases rather than extreme sensitivity to a hidden metabolite. Conversely, very few chemotherapeutic agents, despite being designed as cell poisons and administered in milligram or gram quantities, directly result in irreversible marrow destruction without obvious effects on other organs.
If one takes a look at the case of vancomycin
We can realize that some toxic byproducts were the reason for the toxicity of earlier versions of vancomycin so much so this drug was discarded as an antibiotic . it was taken off the shelf dusted and manufactured in a more pure form and it is now one of the live saving Antibiotics.
"Despite the constantly increasing need for new antimicrobial agents, antibiotic drug discovery and development seem to have greatly decelerated in recent years. Presented with the significant problem of advancing antimicrobial resistance, the global scientific community has attempted to find alternative solutions; one of the most promising ones is the evaluation and use of old antibiotic compounds. Due to the low-level use of many of the old antibiotic compounds, these have remained active against a large number of currently prevalent bacterial isolates. Thus, clinicians are beginning to re-evaluate their use in various patient populations and infections, despite the fact that they were previously thought to be less effective and/or more toxic than newer agents. A number of old antibiotic compounds, such as polymyxins, fosfomycin, fusidic acid, cotrimoxazole, aminoglycosides and chloramphenicol, are re-emerging as valuable alternatives for the treatment of difficult-to-treat infections. The availability of novel genetic and molecular modification methods provides hope that the toxicity and efficacy drawbacks presented by some of these agents can be surpassed in the future."
read the full article here
AN OLD FRIEND REVISITS: CHLORAMPHENICOL OPTIC NEUROPATHY
Abstract
"A 66-year-old woman presented in October 2011 with bilateral visual failure of subacute onset. She has Rheumatoid Arthritis, treated with methotrexate (since 2002), etanercept (2003–2009). A right knee replacement was revised and underwent 6 washouts for persistent infection. Antibiotics included vancomycin, amoxicillin, and daptomycin. Chloramphenicol 4 g daily was started in June 2011 (14 weeks before visual loss). 10 days after onset of visual loss she had visual acuity of 3/24 (Snellen) bilaterally, hyperaemic optic discs and centrocaecal scotomas. The control Ishihara plate could not be read. Toxic optic neuropathy secondary to chloramphenicol was suspected; chloramphenicol had been stopped on Day 6 of visual symptoms. 4 weeks after stopping chloramphenicol acuity was 6/5 (right), 6/6 (left) and visual fields normal, but Ishihara colour plates impaired at 8/13 bilaterally. At the onset of visual symptoms she developed paraesthesiae of limbs which also improved. Examination showed L5 dermatomal loss to pinprick and abnormal proprioception at the toes. From 1950 to 1988 approximately 40 cases of chloramphenicol optic neuropathy were reported, but only two in the past 12 years. This case highlights the potential pitfalls of older generation antibiotics and unfamiliar adverse effects. This may become more pertinent as antibiotic resistance increase."
I was happy to see this article
I was happy to see this article
Synthesis and evaluation of chloramphenicol homodimers: molecular target, antimicrobial activity, and toxicity against human cells.
let us hope one of the grandchildren of chloramphenicol will save our great grandchildren
No comments:
Post a Comment