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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1965-5-1
pubmed:abstractText
Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have described a comparison of four regimens (three of isoniazid alone and one of isoniazid plus PAS) in the treatment of pulmonary tuberculosis and an investigation of the serum isoniazid levels in the patients concerned. The present report studies the emergence of isoniazid-resistant organisms in these patients during treatment. All patients with an unsatisfactory response to treatment yielded resistant cultures, showing that the isoniazid dosage was never too low to inhibit sensitive organisms. From the degree of resistance of the first resistant cultures and of the six-month cultures from the patients treated with isoniazid alone it was concluded that resistance emerged in two stages. In the first stage, very earlyin treatment, highly resistant mutant bacilli grew freely whatever the isoniazid dosage, but mutants of lower resistance were prevented from growing to an extent dependent on the peak isoniazid concentration in the serum. Consequently, when the isoniazid dosage was increased the proportion of patients with resistant organisms decreased, since fewer low-resistance strains were able to develop. In the second stage, organisms with relatively low resistance continued to multiply, though still partially inhibited by isoniazid, and became more resistant, particularly in slow inactivators. The first-stage events determined the results of treatment since, once resistance had emerged, its extent was unrelated to the patient's eventual progress. These findings emphasize the importance of early intensive chemotherapy and adjustment of the isoniazid dosage according to peak serum concentrations rather than concentrations measured three or six hours after the dose. Concomitant administration of PAS prevented emergence of isoniazid resistance in many patients and in others delayed its emergence and reduced its degree, possibly because growth in the second stage was slow.
pubmed:commentsCorrections
pubmed:keyword
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
OM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0042-9686
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
273-94
pubmed:dateRevised
2010-10-26
pubmed:meshHeading
pubmed:year
1964
pubmed:articleTitle
THE EMERGENCE OF ISONIAZID-RESISTANT CULTURES IN PATIENTS WITH PULMONARY TUBERCULOSIS DURING TREATMENT WITH ISONIAZID ALONE OR ISONIAZID PLUS PAS.
pubmed:publicationType
Journal Article