International Orthopaedics (SICOT) (1992) 16:67-68 International Orthopaedics

© Springer-Verlag 1992

The penetration of drugs into the lesions of spinal tuberculosis

K. Kumar

Department of Orthopaedics, Krishna Institute of Medical Sciences, Karad Maharashtra State, India

Summary. The concentration of antituberculous drugs in blood and pus from tuberculous spinal le- sions was measured initially, and again after 3 to 5 months of treatment in 4 cases. The pre- and post- chemotherapy drug concentrations were almost the same. This indicated that healing does not interfere with the penetration of the drugs into the lesion.

R6sum6. Les concentrations des drogues antituber- culeuses au niveau mOme des ldsions ostdo-articu- laires ont 6t6 mesur~es chez quatre malades aprbs 3 ~ 5 mois de chimioth6rapie sp~cifique. On a constat6 que les concentrations dans le sang et dans le pus tuberculeux ~taient pratiquement les m6mes avant et aprbs chimiothdrapie, sans difference significative (test de Wilcoxon: p >0.5). Ceci d6montre que la gu6rison des ldsions tuberculeuses par la chimio- thdrapie sp6cifique n'influence pas la p6ndtration de ces drogues dans les rdgions ostdo-articulaires at- teintes.

Introduction

The ability of antituberculous drugs to reach the site of osteoarticular lesions, when given adequate con- centration, has been demonstrated by several work- ers in animal experiments and in humans [1, 2, 3, 5, 7]. There is, however, very little information avail- able on the reassessment of drug concentration at the site of lesions after a period of chemotherapy [6]. It has been presumed that the concentration is likely to diminish as healing occurs by fibrosis. The aim of this study is to determine the drug concentration before and after chemotherapy.

Material and methods

Ten patients with tuberculosis of the spine and psoas abscesses (7 unilateral, 3 bilateral) were included; 6 were male and 4 female, aged between 15 and 37 years of age. One of the bilateral psoas abscesses communicated in the midline.

Streptomycin sulphate was given by intramuscular injection (25 mg/kg body weight, not exceeding 1 g/day). Ethambutal chloride (25 mg/kg body weight) was taken by mouth before meals for 2 consecutive days. On the second day, 3 h after the drugs were given, pus and blood were aspirated from the psoas abscesses. Special care was taken to avoid mixing blood with pus. Enough pus was withdrawn to measure the drug concentra- tion, but some was left for further aspiration.

After the initial analysis, the patients were put on streptomy- cin, isoniazide and ethambutol. Three to five months later, the drug concentrations were again estimated in blood and pus. Standard techniques were used with broth dilution and micro- biological assay for streptomycin and chemical assay for etham- butol.

Results

In spite of leaving pus behind after the first aspira- tion, four abscesses absorbed, so only six cases were left in whom the drug concentration could be esti- mated a second time. In these the pus, which had been thick and difficult to aspirate, had become thin and straw coloured. Technical mistakes in the esti- mation occurred in two cases, leaving only four to be considered. Table 1 gives their details. In these the pre- and post-chemotherapy concentration of drugs was almost the same with no significant difference (Wilcoxon 's test p >0.5).

Discussion

This type of study is difficult because of the large number of variables present, and other workers have produced results which have varied f rom patient to

68 K. Kumar: Penetration of drugs in lesions of spinal tuberculosis

Table 1. Concentration of drugs in four patients before and after antitubercular drugs (gg/ml)

Streptomycin Ethambutol

Serum Tubercular cold abscess Serum Tubercular cold abscess

Range Average Median Range Average Median R a nge Average Median R a nge Average Median

Initialconcen- 8-32 18.2 16.0 1-16 9.0 8.0 2-16 8.2 8.0 1.2-9.5 2.9 2.5 tration

Concentration after 3-5 months 4-32 16.6 8.0 1-16 0.1 4.0 4.5-12.5 6.4 8.0 3.2-10.5 4.6 4.4 of chemotherapy

patient [2, 3, 4, 6, 7]. There were similar variations in our cases and, therefore the range of concentration is given in Table 1 and, as the numbers were small, the nonparametric statistical Wilcoxon test was used.

In this study the abscesses were not completely aspirated on the first occasion, and antituberculous drugs were not instilled into the cavity. This is not recommended in normal clinical practice, when ab- scesses should be completely aspirated and an anti- tuberculous drug instilled. In spite of this the ab- scesses absorbed in four cases after 3 to 5 months of treatment, indicating that there had been a good re- sponse to the drugs.

In the six abscesses which refilled, the thick pus had become thin which was an indication of a good response.

The results of the four cases reported in this paper clearly show that the drugs penetrated the fibrous tissue surrounding the tuberculous spinal lesions at a therapeutically adequate concentration.

References

1. Barclay WR, Ebert RH, LeRoy GV, Mantheir RO, Roth LJ (1953) Distribution and excretion of radioactive isoniazide in tuberculous patients. J Am Med Ass 151: 1384-1388

2. Fellander M, Hiertonn T, Willmark G (1952) Studies on the concentration of streptomycin in the treatment of bone and joint tuberculosis. Acta Tuberculosis Scand 27: 176-189

3. Hever E, Risko T (1960) Studies on streptomycin levels of blood and abscesses. Acta Tuberculosis Scand 38:40-50

4. Katayama R, Hami Y, Oyak K, Tanaka J, Maruno E (1954) The chemotherapy of bone and joint tuberculosis, Ann Tuber- culosis 5 :59-94

5. Lindberg L (1967) Experimental skeletal tuberculosis in guinea pigs. Acta Orthop Scand (Suppl) 98

6. Tuli SM, Kumar K, Sen PC (1977) Penetration of antitubercu- lar drugs in clinical osteoarticular tubercular lesions. Acta Orthop Scand 48: 362- 368

7. Tuli SM, Mishra S (1983) Penetration of antitubercular drugs in cold abscesses of skeletal tuberculosis and in tuberculous joint aspirates. Ind J Orthop 17: 14-18