65, 3^ Correspondence^ 375

Histoid leprosy originally described byWade (") is a variam of lepromatous lep-rosy. It is characterized by the developmentof fiou, hemispheric, dome-shaped, well-delineei nodules ou an apparently normal-looking skin. Many cases occur during a re-lapse after dapsone monotherapy or mayarise per se without any prior chemother-apy. The nodules tend to arise in unusualbody sites, such as the lower back, loins oraxillae or over the chest and neck (')•

Clinicai and histopathological features ofthe nodules in our patient suggested a diag-nosis of histoid leprosy. The lesions ap-peared as a relapse of lepromatous leprosy,probably due to inadequate dosage and du-ration of dapsone monotherapy. The possi-bility of infection with dapsone-resistantMvcobacterium leprae also exists in ourcase, although we could itot prove it due tothe lack of facilities for animal inoculationstudies. WHO/MDT resulted in completeclinicai cure of leprosy in this patient. al-though a few dead bacilli persisted at thesue of the nodules.

Another interesting feature observed Iterewas the presence of histoid nodules ou thelip mucosa. Unlike the nose lesions whichwere skin-colored and appeared in clusters,the lip lesions were discrete and coppery-red. This color variation is probably due to

the increased vascularity and decreasedmelanization of the lip mucosa. Involve-mem of the mucous membrane is quite ou-usual in histoid leprosy, although rarelynodules have been reported to develop onthe mucosal surface of the hard palate andglans penis (2), and may also occur in thenasal mucosa (4).

—K. Pavithran, M.B.B.S., M.D., D.V.D.,M.N.A.M.S.

Professor of Derinuto-VenereologyMedical College HospitalCalicut 673 008Kerala, índia

REFERENCES• PrAnzokA•r, R. E. and RANiti, G. Clinicai leprosy.

In: Leprosy. 2nd edn. Hastings, R. C., ed. Edin-burgh: Churchill Livingstone, 1994, pp. 237-287.

2. RIN1ANUJAN1, K. and IZANtu, G. Wade's histoid lep-romatous leprosy: report of a clinica] study. Lepr.Ilidia 41 (1969) 293-297.

3. WAiw, 11. W. The histoid variety of lepromatousleprosy. Int. J. Lepr. 31 (1969) 129-142.

4. WADE, 11. W. and Toi.ENT18(), J. C. The histoid va-riety of lepromatous leprosy. (Abstract) Int. J. Lepr.31 (1963) 608-609.

5. W110 STUDY GRour. Chemotherapy of leprosy forcontrol programmes. Geneva: W'orld Ilealth Orga-nitation, 1982. Tech. Rep. Ser. 675.

Minimal Inhibitory Concentrations of Lomefloxacinand Minocycline Against Drug-Sensitive and

Drug-Resistant lsolates of M. tuberculosisCompared on L-J and 7H11 Media

To THE EDITOR:

Rifampin derivatives, 13-lactam antibi-otics with 13-lactamase inhibitors, and fluo-roquinolones are the newer and highlypromising drugs against tuberculosis.Among them, little is known about the ac-tivity of lomefloxacin, a new difluoropiper-azinyl quinolone '1), and minocycline,a long-acting tetracycline derivative, againstMrcobacterium tuberculosis. Minocyclinehas beco studied with respect to its effect ouM. leprae only

In the present study, we have tested a to-tal of 97 M. tuberculosis strains for theirsusceptibility to lomefloxacin and minocy-cinte by the minimal inhibitory concentra-tion (MIC) method using both Lowenstein-Jensen (L-J) medium and 7H11 medium tosee if the high protein content of L-Jmedium would have any effect on theMICs. The strains tested included 46 M. tu-berculosis strains resistant to S (strepto-mycin) H (isoniazid) R (rifampin) /HR and51 susceptible to SHR isolated from pa-tients. Their susceptibility to ciprolloxacin

2 4 8 16 32 Total

o O 5O 4 I() 4 O 18O 7 5 O 14

O 4 9 O 14

2 8 23 18 O 51

4^8^I 6^32^Total

O48^O16^O

Total

5^O^O-)^7^5i^6^4-3^3^8

11^16^17

O^

5o^

15O^

1214

46

376^ International Journal Leprosy^ 1997

TABU: I. Frequeney distributionMICs^lomejlexacin on L-1 and 71111against 46 drug-resistant (S111?/111?) and 51drug-sensitive (SHR) strains o/ M. tubercu-losis.

L-J^71111

MICJur/mi

No.SIIR/I IR

res.strains

No.SI IRseus.

strains

No.SI IR/11R

res.strains

No.SIIRsens.

strains

0.5 O 0 O O1.0 0 0 o o2.0 1 5 54.0 II 8 14 188.0 16 -t3 13 14

16.0 17 18 14 1432.0 O

Total 46 51 46 51

and ofloxacin had been determine(' previ-ously in our Centre (17).

Lomefloxacin (Torrent Phamaceuticals)and minocycline ICyanamid of GreatBritain Limited (Lederle), kindly providedby Dr. M.D. Gupte, Officer-in-Charge,CJ1L Field Una, Avadil at the final concen-trations of 16.0, 8.0, 4.0, 2.0, 1.0, 0.5 and0.25 pg/ml, and 64, 32, 16, 8, 4, 2 and 1pg/ml, respectively, were tested in L-Jmedium and 7H11 medium containing oleieacid-albumin-dextrose (OADC) enrichmentusing standard procedures. The inoculatedmedia were incubated at 37°C with the7H11 plates kept in 5% CO„ and read at theend of 4 weeks. The lowe.St concentrationof the drug which inhibited growth to <20colonies compared to at least ++ (numerousdiscrete colonies) growth on drug-freemedium was taken as the minimal in-hibitory concentration (MIC).

RESUVI'S AND DISCUSSION

Lomefloxacin. The MIC for the stan-dard A/. tuberculosis strain 1-137Rv was 4pg/inlon l,-J and 2 pg/mlon 71-111. For theother strains, the ram2e of MICs was 2-32pg/ml on L-J and 2:--16 pg/ml on 71-111(Table 1). A highly significam differencebetween the mean MICs of lomelloxacin onL-J and 71111 was observed. MICs beinggenerally higher on L-J. Of the 46 resistamstrains, 16 had the same MICs on L-J and71111, 22 had higher MICs on L-J and only8 had lower MICs on L-J (Table 2). Si mi-larly, of the 51 sensitive strains. 21 had thesame MICs on L-J and 71-111, 23 had higherM1Cs on L-J while only 7 had lower MICson L-J. The geometric mean MICs forSHR/IR-resistant and SIIR-sensitive strainswere 0.84 and 0.82, respectively, on 71-111,and 0.94 for both resistam and sensitivestrains on L-J. The differences in MICs onL-J and 7H II NVCI-C highly significam forboth resistam and sensitive strains together(p = 0.0013), for resistam strains alone (p =0.0209) and for sensitive strains alone (p =0.0251). It lias been reported earlier that theMICs of quinolones (norfloxacin, per-floxacin, ciprolloxacin and ofloxacin) maynot vary much when the agar or broth dilu-tion methods are used (15).

Fluoroquinolones have promising iii vitroactivity and low toxicity and no crossresis-lance has been reported between fluoro-quinolones and other anti-tuberculosisdrugs (''). In earlier salines comparing theactivities of different fluoroquinolones, theactivity of lomelloxacin has either been less(l") or lias compared favorably ("). In thepresent study, the MICs of lomelloxacin(geometric mean MIC 0.94) were signiti-cantly higher than those of ciprotioxacin

TAI31E 2. Comparison 0/ lhe MICs (ag/m1) lomello.vacin ou L-J and on 7H I I media.

MICs on L-1MIC on

SI 13Z/111Z-resistam strains

SI IR-sensitive strains7H11

65, 3^ Correspondence^ 377

(geometric mean MIC 0.3) and ofloxacin(geometric mean MIC 0.3) on L-J for thesame strains reported in an earlier studyfrom this Centre (17). The MIC rang,ed from2-16 pg/m1 for lomefloxacin compared to1-4 pg/m1 for ciprofloxacin and ofloxacinfor the same strains. However, these con-centrations of lomefloxacin are probablywithin the leveis achieved in tissues andmacrophages because of its pharmacoki-netic features, which include a high degreeof tissue distribution, a lack of significammetabolism, good oral absorption, longserum half-life, good tolerance on oral ad-ministration, and high tissue and intracellu-lar concentrations '3). Thus, the ac-tivity of lomefloxacin against M. tuberculo-sis merits further study.

Minocycline. The MIC of minocyclinewas >64 iitg/m1 for ali of the strains testedboth on L-J and 7H11. There was more than1+ growth (>100 colonies) of ali the strainstested even at the concentration of 64 pg/mlof minocycline, indicating no activity at aliof this drug at these concentrations againstthe M. tuberculosis strains tested. There isto date very meager information on the ac-tivity of minocycline against mycobacteriaother than AI. leprae. In an earlier report, of5 M. tuberculosis strains tested, 4 were in-hibited at 6.5 pg/ml, and all 5 at 12.5 pg/mlwhen Ogawa egg medium was used ('').The serum levei is about 2 g/m1 after a sin-gle oral dose of 150 mg of minocycline.Thus, the results of the present study sug-gest that minocycline may not be useful inLhe treatment of tuberculosis.

SUMMARYThe in ritro activity of lomefloxacin and

minocycline was tested as:;ainst 46 strains oftuberculosis resistam to streptonnycin

(S), isoniazid (H) and rifiimpin (R) or SHRand 51 strains sensitive to SHR by the min-imal inhibitory concentration (MIC) methodon two different media, namely, Lowen-stein-Jensen (L-J) and Middlebrook 7H 1 1.The results of the study showed that, irre-spective of the medium used, minocyclinehad little activity against the strains testedand the MIC N,vas >64 pg/ml. The MIC oflomefloxacin in 7H11 mediu tu ranged from2 to 16 pg/ml. There were highly significamdifferences in the MICs of lomelloxacin in

L-J compared with 7H11. The results sug-gest that the activity of lomeiloxacinagainst M. tuberculosis merits further study.

—T. Kamala, Ph.D.Daniel Herbert, Ph.D.P. Venkatesan, Ph.D.

C. N. Paramasivan, Ph.D.Department of BacteriologyTuberculosis Research Center(Inchai, Council of. Medical Research)Spur 7ank RoadChetput, Madras 600 031, índia

Reprint requests to Dr. Paramasivan atLhe above address or FAX 91-44-8262135.

REFERENCES• BALDwiN, D. R., Wisu, R., ANDREws, J. M.,

M. and IlomnsouRNE, D. Comparative bron-cboalveolar concentrations of ciprolloxacin andlornetIoxacin following oral administration.Respir. Med. 87 (1993) 5-95-601.

2. B1:1.1.1VEAU, P., NIGHTINGALE, C. H., QUINTIANI, R.,CRowE, H. and Gousn, G. Oral eiprolloxacin,olloxacin, and lomelloxacin as abem:uives to in-travenous antimierobial therapy. Conn. Med. 57(1993) 539-545.

3. DiA0, Y., LU, J., Li , L., ZI111, X. D., ii, G. andWANG, E. 1-1. [Pharmacokinetics and relativebioavailability of lomelloxacin, preparations in 10healthy Chi nese volunteers.] Chung Kno Yao Lilisueh Pau 14 (1993) 247-249.

4. FAJARDo, T. T. JR., VII.I.AIII:RMOSA, L. G., DELACRui., E. C., AitAins, R. M., FRANim.Au, S. G.and WALsii, G. P. Minocycline in lepromatousleprosy. Int. J. Lepr. 63 (1995) 8-17.

5. FREENIAN, C. D., NIcol.Au, D. E, B1:1.I.IVEAU, E P.and NIGWINGALE, C. H. Lomeiloxacin clinicai pilar-maeokinetics. Clin. Pharmacokinet. 25 (1993) 6-19.

6. GinsuR, R. H., FUKUDA, K., BYRD, S., MURRAY, L.P., Sal, P., TSANG, M. and RE,, T. H. A clinicaitrial of minocycline 01 lepromatous leprosy. Br.Med. J. 304 (1992) 91-92.

7. GI:1,BER, R. 1-1., MURRAY, L. P., Siu, P., TSANG, M.and RI:,, T. 11. Efticaey of minocycline in singledose and ai 100 nig daily for Iepromatous leprosy.Int. J. Lepr. 62 (1994) 568-573.

8. .11,13., JANIET, P., PERANI, E. G., BoiuN, P. andGRossur, J. II. Powerful bacterieidal activities ofclaritbromyein and nnnocycline against Mycobac-terium leprae in lepromatous leprosy. J. In fect.Dis. 168 (1993) 188-190.

9. KAVI, J., SioNu, J., ANDRims, J. M., Asnos', J. R andR. Tissue penetration and pbarmacokinetics

of loinelloxacin following multiple doses. For. J.Clin. Microbiol. Infect. Dis. 8 ( 989) 168-170.

378^ International lournal of Leprosy^ 1997

10. KAwAIIARA, S., KAmisAKA, K., 'FADA, A., NAKADA,11., MrsitimA, Y., Y ()sintam, S., MATtitIYAN1A, T.,KIIIATA, M. and NAGARII, J. 110 ritro activities ofnewly developed quinolones, fleroxacin, lume-Iloxaein tind sparfloxacin against Mycobartermin

taberru/oxis. Kekkaku 66 (1991)429-431.II. Mwia, K. II. and FALA, J. A. Loinefloxacin, mi-

erobiologie assessinent and unique properties.Ant. J. Med. 92 (1992) 585-625.

12. PARENT1, F. New experimental drugs for the treta-incuto! tuberculosis. Rev. Infect.1)is. 11 Suppl. 2(1989) S479—S483.

13. l'EREA, E. J., (;ARciA, 1. and PASCUAL, A. Com-parative penetration of lomefloxttein and otherquinolones itm) human phatzocytes. Am. J. Med.92 (1992) 485-515.

14. PliazsimoNi, C., 15/10Rmitucci, V., BORNIGIA, 8., Dl:

SIO, G. and S('Ai.P,L, G. ht titio aetivity of thenew quinolone lomelloxacin against Myeebac-

niberculoxis. Am. Rev. Respir. Dis. 146(1992) 1445-1447.

15. TExits-MAtaaAN, J., NloRmEiti:, M., FouRcm.:, J.and RiawAR, C. In litro activity oi newquinolones against eighty-six isolates of myeohae-teria. Eur. J. (lin. Mierobiol. 6(1987) 583-586.

16. TstIKANIURA, M. lo vitro antimyeobacterial activ-ity^minocycline. Tuberele 61 (1980) 37-38.

17. VIINKATARANIAN, R, PARAMASIVAN, C. N. andPRAIIIIIKAR, R. lii vitro aetivity of ciprofloxacinand olloxacin against South 1ndian isolates of My-

cobacterium rubereuhtsix. Indian J. Tuberc. 41(1994) 87-90.