Bull. Org. mond. Sante Bull. Wid Hith Org. 1969,19,4025-640, 257-262

Antibiotic Sensitivity of Gonococcal Strains Isolated in the South-East Asia and Western Pacific Regions in 1961 68*

ALICE REYN I

A decreasing susceptibility of gonococcal strains to penicillin and other antibiotics has been observed in most parts ofthe world, including the WHO South-East Asia and W"estern Pacific regions. In the Neisseria Department, Statens Seruminstitut, Copenhagen, the antibiotic sensitivity ofabout 100 gonococcal strainsfrom these regions has been determined. The strains wvere collected during 2 periods, one in 1961 (Ceylon and the Philippines), the other in 1967-t8 (Thailand, Taiwan, Viet-Nam and Hong Kong). It was found that the incidence of gonococcal strains with decreased susceptibility to penicillin and most of the more generally used antibiotics is increasing in these regions. The distribution of the 50 % inhibitory concentrations of penicillin, tetracycline, streptomycin and spiramvcin was similar for the strains isolated in the Philippines in 1961 andfor those from the other areas in 1967-68, namely, strains with "normal sensitivity" were lacking. Most of the strains collected in 1961 were fully sensitive to chloramphenicol and erythromycin, whereas about 25 % of the strains collected in 1967-68 were only moderately sensitive to chloramphenicol, and about 75 % were moderately sensitive to erythronmycin; 1 strain was resistant to erythromycin. Only 10 % of these strains were sensitive to all the antibiotics employed. In contrast to these findings, several authors report an increasing susceptibility of the gonococcal strains in northern Europe. Possible explanations.for the reversion to " normal sensitivity'" are discussed briefly.

The author has examined the recent literature Yogeswari (1966) found that 45.6 % of 150 relating to studies on the sensitivity of various strain gonococcal strains isolated at random showed of gonococci in the WHO South-East Asia and decreased in vitro sensitivity to penicillin. In a limited Western Pacific regions to antibiotics; the amount of group of 25 strains they observed " a trend towards published work on this topic is, however, limited. positive correlationship in the in vitro parallel Using a commercial brand of impregnated antibiotic sensitivities of penicillin, streptomycin and chloro- discs, Suvanamalik & Arnau (1964--66) tested a mycetin ". In 1967, Ho & Chang found that about series of gonococcal cultures isolated in Bangkok, 30% of the gonococcal strains from Taiwan had a Thailand. They concluded that " some strains exist minimal inhibitory concentration (MIC) greater than which have or develop a relative resistance to 0.2 International Unit (IU) of penicillin per ml, and penicillin and other antibiotics ". Barile, van Zee & that about 7 % of the total isolates showed an MIC Yaguchi (1959) and Tawes (1966) reported on of 2 IU per ml. They compared their results with gonococcal strains, isolated from American soldiers those of Tai & Han (1960) who found that 5 % of the operating in Japan and Korea, that were less strains examined showed relatively low susceptibility susceptible to penicillin. In Madras, India, Chacko & to penicillin. Ho & Chang (1967) concluded that the incidence of gonococcal strains relatively resistant to * This study was supported by grants from the World antibiotics was likely to increase in Taiwan. In Health Organization. Australia, Smith & Levey (1967) observed that 44% 1 WHO International Reference Centre for Gonococci, Neisseria Department, Statens Seruminstitut, Copenhagen, of 104 gonococcal strains isolated in Sydney and Denmark. Newcastle in 1966 showed a decreased susceptibility

2296 257 7 258 A. REYN to penicillin as compared with strains isolated before clinical information concerning the origin of the 1954. It may also be relevant to mention that Warren strains is not yet available, but most of the strains (1968) found that the percentage of gonococcal were said to have been picked out at random. strains partially resistant to penicillin was signifi- cantly higher in an overseas infection group than in RESULTS the local infection group and infection " elsewhere " General features in the United Kingdom. Warren's material was from All except I of the 87 strains were fully sensitive or Southampton during the years 1958 to 1965. moderately sensitive to sulfathiazole, chlorampheni- col, erythromycin, nalidixic acid and kanamycin. MATERIAL AND METHODS Only 20 strains (23 %) were sensitive to penicillin, and these were also sensitive to streptomycin and Altogether, 108 gonococcal strains from the tetracycline. Of these multisensitive strains, 16 were South-East Asia and Western Pacific regions have isolated in 1961 in Ceylon, and the remaining 4 were been examined in the Neisseria Department. In 1961, isolated in 1967, 2 in Hong Kong and 2 in Thailand. 65 strains from the Philippines' and Ceylon 2 were However, it must be remembered that the strains tested against sodium benzylpenicillin, dihydro- designated as less sensitive to penicillin are, in fact, streptomycin and tetracycline (Reyn, 1963). Recent- sensitive provided that a sufficiently high dosage of a ly, another series of strains was received from these suitable penicillin is used. The strain most resistant regions, namely, 12 strains from Bangkok, Thai- to penicillin had IC50 = 2.4 IU (1.4 ,ug) per ml, with land,3 16 from Hong Kong,4 9 from Taipei, Taiwan,5 a corresponding MIC of 4.0 IU (2.4 ,ug) per ml and 6 from Saigon, Viet-Nam.6 The sensitivity (50% (strain 307 from Hong Kong, 1967). inhibitory concentration = IC,0) of these 43 strains The relationships7 between the zone diameters was tested against penicillin, streptomycin, tetra- obtained with cefaloridine and cefalotin and the cycline and spiramycin, using the plate dilution corresponding IC50 values have not yet been method (Reyn, Bentzon & Ericsson, 1963). In established. Discs containing 50 ug were used in both addition, they were tested against sulfathiazole, cases, and for both substances the sizes of the zones chloramphenicol, erythromycin, nalidixic acid, kana- were correlated with the IC50 values observed for mycin, cefalotin and cefaloridine using a diffusion penicillin, i.e., increasing zone diameters with method (Thomsen, 1962). Discs for diffusion tests decreasing IC50 values. The order of magnitude of with pristinamycin and spectinomycin were not the IC50 values observed was estimated as about 4 jug available. In all, 44 of the 65 strains received in 1961 per ml to about 16 ,ug per ml of cefaloridine and less had been lyophilized. In August 1968 they were than 3 ,tg-4 ,tg per ml of cefalotin. revived and tested against spiramycin (plate dilution Since penicillin was still the drug of choice (though method), sulfathiazole, chloramphenicol, erythro- impossible to use in some cases), the effect of this mycin, nalidixic acid, kanamycin, cefaloridine and antibiotic was compared with that of the other cefalotin (diffusion method). antibiotics employed. The IC50 values of penicillin Tables 1 and 2 show results of the sensitivity were positively correlated with those of streptomycin, examinations of all the strains. The majority of the tetracycline and with spiramycin.8 The degree of strains were examined twice with each antibiotic, and sensitivity to penicillin was also positively correlated mean values are given in the tables. The results are with the sensitivity to sulfathiazole, chloramphenicol, given as IC50 per ml or as 0, +, ++ and +++, erythromycin and nalidixic acid. relating to the size of zone diameters. The ranges of the IC50 values, and various technical details, are Comparison between strains isolated in 1961 and given in the footnotes to the tables. Minimum 1967-68 inhibitory concentrations would be about twice as Out of 44 strains isolated in 1961, 28 (64%) were high as the 50 % inhibitory concentrations. Complete less sensitive to penicillin; 19 of these (68%) were

Procured by Dr L. M. Ibarra. 7The comparisons described here were performed by 'Procured by Dr E. D. C. Pereira. plotting the IC,. values or zone diameters in millimetres 3 Procured by Dr Supatra Suvanamalik and Dr Brian obtained with one antibiotic against those obtained with Hill, WHO consultant. another antibiotic in a co-ordinate system. I Procured by Dr Wong Kwok-on. These results are in agreement with those of previous 'Procured by Professor Wu-tse Liu. reports (Reyn, Korner & Bentzon, 1958; Reyn & Bentzon, Procured by Dr Nguem-van-Liem. 1968). TABLE 1 SENSITIVITY TESTS ON 44 STRAINS OF GONOCOCCI ISOLATED FROM CEYLON AND THE PHILIPPINES IN 1961

IC50 for plate dilution method a Relative zone diameters for disc diffusion (2-fold or 4-fold dilution steps) method b (average of 2 determinations) Strain No. and Clr c Tetra- ~~Sulfa- Erythro- Nali- Kana- origin PenicillinStrep- e origin Penicl C Tetra-e Spiramycinfamphe dixic~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~dtiazole amphe- ycinmycipraycnnt .diiacid mycin lAin(IUMg,l)m; toycinjStrep-nli (Mg/mI) Ggm (10 MLg) (50 Mg) (23g/mgl)5 '4 I(50 Ag)

Ceylon 24 strains of gonococci from Ceylon 1 70.088 <0.053 Is s 0.26 s 0.28 s +++ ++ 0.011 2 0.007 s s 0.26 s 0.20 s +++ ++ s s 3 <0.01 1 <0.00'/ s 0.111 s 0.14 +++ 4 0.016 0.009 s 5 0.26 0.24 s +++ +++ 5 0.50 0.30 Is r 1.49 IsIs 0.72 s +++ ++ 6 1.19 0.71 Is r >1.77 2.44 Is +++ ++ 7 0.022 0.013 s s 0.37 Is 0.36 s s +++ ++ 8 0.022 0.013 s 0.26 Is 0.22 s +++ ++ 11 1.00 0.60 Is 5r 1.25 0.86 s +++ 12 0.022 0.0i3 s s 0.26 is 0.24 s +++ s +++ ++ 13 0.022 0.013 s s 0.26 s 0.18 s +++ s ++ 14 0.022 0.013 s s 0.31 s 0.18 +++ 15 0.011 0.007 s s 0.22 is 0.20 s +++ ++ 17 1.19 0.71 Is r > 1.77 isIs 2.90 Is +++ ++ 18 0.022 0.013 s s 0.31 s 0.17 s +++ ++ s s 20 0.011 0.00/ s 0.26 s 0.2t +++ ++ 22 0.011 0.007 s s 0.19 0.24 s +++ +++ 23 0.71 0.42 Is r 1.25 Is 0.72 s +++ ++ Is s 24 <0.008 <0.005 s s 0.16 s 0.24 +++ ++ 25 0.011 0.007 s s 0.19 s 0.26 s +++ ++ 26 0.125 0.075 Is s 0.26 s 0.28 s ++-F ++ 27 0.011 0.007 s s 0.26 s 0.24 s +++ 28 0.005 s s 0.22 0.24 s +++ 29 10.0081.00 0.60 Is r >1.77 Is 2.90 Is +++ 3s

16 s 18 s 18 s 21 s 24 s 24 s 24 s 24 s Total 8 Is 6 r 6 Is 3 Is 213s Range of IC50 <0.005-0.71 not done 0.16->1 .77 C.1 4-2.90 (Mg/ml) (<0.008 IU-1.19 IU) Manila 20 strains of gonococci from Manila 4 1.41 0.85 Is s 1.49 Is 1.34 Is +++ +++ +++ +++ ++ 23 >2.00 >1.20 Is r 1.49 Is 0.72 s +++ +++ +++ +++ ++ 26 0.50 0.30 Is r 1.25 Is 0.72 s +++ +++ +++ +++ ++ 28 0.125 0.075 Is s 0.31 s 0.43 s +++ +++ +++ +++ ++ 29 0.71 0.42 Is s 1.49 Is 0.51 s +++ +++ +++ +++ ++ 30 0.50 0.30 Is s 0.63 s 0.67 s +++ +++ +++ +++ ++ 32 1.41 0.85 Is 1.49 Is 0.72 s +++ +++ +++ +++ ++ 34 0.177 0.106 Is s 0.26 s 0.30 s +++ +++ +++ +++ ++ 35 >2.00 >1.20 Is r >1.77 Is 1.60 Is +++ +++ +++ +++ ++ 36 0.50 0.30 Is 1.25 Is 0.86 s +++ +++ +++ +++ ++ 37 0.50 0.30 Is nr >?1.77 Is 0.72 s +++ +++ +++ +++ ++ 38 0.125 0.075 Is r 0.26 s 0.30 s ++ +++ +++ +++ 39 2.CO >1.20 Is r >?1.77 Is 1.60 Is +++ +++ +++ +++ +++ 40 0.50 0.30 Is r 1.49 Is 0.51 s +++ +++ +++ +++ ++ 41 >2.00 >1.20 Is >1.77 Is 2.26 Is +++ +++ +++ +++ ++ 42 >2.00 >1.20 Is r 1.49 Is 1.22 Is +++ +++ +++ +++ 43 0.125 0.075 Is 0.31 s 0.33 s +++ +++ +++ +++ ++ 44 0.25 0.150 Is r 0.31 s 0.36 s +++ +++ +++ +++ +++ 49 0.50 0.30 Is r --1.77 Is 0.61 s +++ +++ +++ +++ 50 0.50 0.30 Is ?>1.77 Is 0.61 s +++ +++ +++ +++

o s 7 s 6 s 15s 19 s 20s 20 s 20 s 4 s Total a 20 Is 13 r 14 Is 5 Is I ms 16 ms _ Range of IC,0 0.075->1.20 not done 0.31->11.77 0.30-2.26 (Mg/ml) (0.125 IU->2.00 IU) g

a S, ms, Is, r = sensitive, moderately sensitive, less sensitive and resistant, respectively. b +++, ++, +, 0 = sensitive moderately sensitive, less sensitive and resistant, respectively. Corresponding IC0o values (Mg/ml) are as follows: Sulfathiazole Chloramphenicol Erythromycin Nalidixic acid Kanamycin +++ <5.0 <1.0 <0.1 <4.0 <4.0 ++ >5.0 -15.0 >1.0- 5.0 >0.1- 1.0 >4.0-10.0 >4.0-15.0 + > 15.0-1 00.0 > 5.0-50.0 > 1.0-1 0.0 > 10.0-25.0 > 15.0-50.0 0 >100.0 >50.0 >10.0 >25.0 >50.0 c Penicillin, less sensitive: IC,- value > 0.088 lU/mI (0.053 Mg/ml). d Streptomycin, resistant: IC50 value >25 Mg/ml. e Tetracycline, less sensitive: iC,0 value >1.13 Mg/ml. f Spiramycin, less sensitive: IC,0 value >0.95 Mg/mI (arbitrary value). g Highest value observed on re-testing with 2-fold dilution steps: 1.68 lU/ml. 260 A. REYN

TABLE 2 SENSITIVITY TESTS ON 43 STRAINS OF GONOCOCCI ISOLATED IN 1967-58

IC50 for plate dilution method a Relative zone diameters for disc diffusion (2-fold or 4-fold dilution steps) method b (average of 2 determinations)

Strain No. Penicillin c Tetra- pia cnf Sulfa- amheo- Erythro- Nali- Kana- (lU/ml; Mgiml) c tomycid Ste(Mg/mI) (ug/ml) thiazole(238 tg)I nscolP mycin(10 Mg) dacid mhaicann(5mycin g2yli ~~~~~~~~~~~~~~-1(50jAg)1 (50 Mg) 1 12 strains of gonococci from Thailand 3048 1.19 0.71 Is 1.60 Is 1.90 Is +++ ++ I+++ ++ 3049 2.00 1.20 Is 1.86 Is 1.60 Is +++ +++ ++ +++ ++ 3059 1.41 0.85 Is 1.31 Is 1.60 Is +++ ++ ++ +++ ++ 3108 2.00 1.20 Is 2.20 Is 1.90 Is +++ +++ ++ +++ ++ 3170 1.41 0.85 Is r 1.31 Is 1.61 Is +++ ++ +±+ ++ 3171 2.80 1.70 Is r 1.86 Is 1.13 Is ++ ++ ++ +++ +++ r +++ 3172 0.50 0.30 Is r 1.63 Is 1.13 Is +++ ++ +++ 3192 1.19 0.71 Is r 1.86 Is 1.60 Is +++ +++ ++ +++ ++ TH 373 0.11 0.063 s 0.33 s 0.33 s +++ +++ +++ ++ Kett.H.N4 0.044 0.027 s 0.40 s 0.168 s +++ +++ +++ I++ Thai N.H.N5 1.68 1.00 Is 1.60 Is 1.90 Is ++ ++ +++ ++ 2787 (1) 1.41 0.85 Is 2.60 Is 1.60 Is +++ ++ +++ +±

16 strains of gonococci from Hong Kong GC 266 1.68 1.00 Is 1.60 Is 2.90 Is +++ ++ ++ 274 0.50 0.30 Is 1.13 Is 0.80 s +++ ++ ++ 278 0.71 0.42 Is 1.33 Is 1.34 Is +++ ++ ++ 280 1.68 1.00 Is r 1.60 Is 2.26 Is +++ ++ ++ 290 2.8 1.70 Is 1.60 Is 2.06 Is +++ ++ ++ 294 1.41 0.85 Is r 1.60 Is 3.20 Is +++ ++ ++ 300 0.84 0.50 Is 1.60 Is 1.45 Is +++ ++ ++ 303 1.68 1.00 Is 1.60 Is 2.90 Is +++ ++ ++ ++ ++ 306 0.177 0.106 Is 5 0.80 s 0.95 Is +++ 307 2.4 1.40 Is r 1.60 Is 2.06 Is ++ ++ ++ 320 0.177 0.106 Is r 0.40 s 0.56 s +++ ++ 1.13 Is 0.82 s +++ +++ ++ 322 0.59 0.36 Is s 328 1.41 0.85 Is 1.60 Is 1.13 Is +++ ++ 377 !0.63' 0.0188 o 0.40 s 0.43 s +++ ++ 335 0.03 0.0188 s 0.28 s 0.40 s +++ ++ 31811 0.125 0.075 Is 0.80 s 0.61 s +++

9 strains of gonococci from Taiwan P 6 0.50 0.30 Is 1.60 Is 2.44 Is ++ ++ ++ P18 0.35 0.21 Is 1.60 Is 1.02 Is ++ ++ ++ F26 0.35 0.21 Is r 0.28 s 0.95 Is +++ +++ K32 1.68 1.00 Is s 2.26 Is 2.68 Is ++ ++ G33 0.71 0.42 Is r 2.26 Is 2.26 Is ++ ++ T56 1.19 0.71 Is 1.88 Is 2.44 Is +++ ++ ++ G57 0.59 0.36 Is r 1.60 Is 0.86 s ++ ++ 60 1.68 1.00 Is r 1.60 Is 2.06 Is ++ ++ P101 1.41 0.85 Is 2.26 Is 2.68 Is ++ 1 6 strains of gonococci from Viet-Nam 1.41 0.85 Is 1.13 Is 1.90 Is ++ 535/67 +++ 0 +++ 542/67 2.0 1.2 Is 1.60 Is 2.26 Is ++ ++ 543/67 2.4 1.4 Is 1.90 Is 1.90 Is ++ ++ 544/67 0.59 0.36 Is 0.80 s 0.95 Is ++ ++ 635/67 1.19 0.71 Is 0.80 s 1.72 Is +++ 637/67 0.84 0.50 Is 0.80 s 1.60 Is

Total a 4 s 95s 11 s 9 40 s 32s 9s 34s 4s 39 Is 34 r 32 Is 34 Is 3 ms 11 ms 33 ms 0 Is 39 ms 1 r

Range of IC,o 0.0188-1.41 not done 0.28-2.60 0.33-3.20 (Mg/ml) (0.03 IU-2.4 IU) (See notes opposite) CHANGES IN SENSITIVITY OF VARIOUS STRAINS OF GONOCOCCI TO ANTIBIOTICS 261 resistant to streptomycin, 20 (72 %) were less been used (or to only a slight extent) in the treatment sensitive to tetracycline, and 8 (28 %) were less of gonorrhoea in the South-East Asia and Western sensitive to spiramycin. Of the 43 strains isolated late Pacific regions. However, the ICs0 values of in 1967 and early in 1968, 39 (90%) were less spiramycin were also closely correlated to the zone sensitive to penicillin; 34 of these (87%) were diameters obtained with erythromycin. The latter resistant to streptomycin, and 32 (82%) were also belongs to the macrolide group of antibiotics, and so less sensitive to tetracycline. As many as 34 (87 %) of does spiramycin. Hence, it is likely that the the 39 strains less sensitive to penicillin were also less correlation observed between the IC50 values of sensitive to spiramycin. penicillin and spiramycin is only a reflection of the The distribution of the IC,0 values of penicillin, close chemical relationship between spiramycin and tetracycline, streptomvcin and spiramycin was erythromycin, the latter possibly having been used to similar in the strains isolated in the Philippines in a higher degree than spiramycin. A forthcoming 1961 and in those from the other areas in 1967-68, paper will deal with the relationship between the characteristic being that strains with " normal penicillin and several other antibiotics including sensitivity" were lacking. spiramycin. All the strains from 1961 were fully sensitive The present results indicate that the incidence of to chloramphenicol and erythromycin, but this was gonococcal strains with decreased susceptibility to not the case with those from 1967-68. Altogether, 11 penicillin, and to others of the more generally used of the 43 strains from 1967-68 were only moderately antibiotics, is increasing in the two regions. This is a sensitive to chloramphenicol; 33 were moderately feature common to many other regions of the world. sensitive to erythromycin and 1 was resistant to that However, in some areas the opposite effect has been drug. observed. For instance, a series of recent reports from northern Europe contain information concern- DISCUSSION AND CONCLUSION ing an increasing number of gonococcal strains with " normal " susceptibility to, for instance, penicillin The finding that the in vitro effect of cefalotin was (Kallings & Gastrin, 1966; Odegaard & Gjessing, greater than that of cefaloridine is in agreement with 1967; Olsen & Lomholt, 1968). the observation by Martin et al. (1965) that, as The decreased susceptibility of the gonococcal measured by the plate dilution method, the strains to penicillin can be overcome by using higher inhibitory in vitro effect of cefalotin was greater doses and by using antibiotics other than penicillin. than that of cefaloridine. However, Lucas et al. It is noteworthy that very few (10%) of the South- (1965) reported that cefaloridine had a better in vivo East Asia and Western Pacific strains isolated in effect than cefalotin. Also, Barber & Waterworth 1967-68 were sensitive to all the antibiotics employed, (1964) found that cefalotin had a greater in vitro ef- and that an over-all decrease in susceptibility seems fect (8-16-fold) than cefaloridine. The clear-cut posi- to have occurred between 1961 and 1967-68. tive correlation observed between the cefalosporins The explanation for the reversion of the and penicillin is in accordance with the fact that the gonococcal strains from certain areas towards cefalosporins are chemically related to the penicillins "normal sensitivity " to penicillin and other (Gonella, Olexy & Jackson, 1967). antibiotics is not known; in itself, it is a consoling The positive correlation observed between the fact. It is possible that treatment with adequate doses penicillin and the spiramycin values is interesting of penicillin and other antibiotics in these areas has because, as far as it is known, spiramycin has not influenced the distribution of strains according to

a s, ms, Is, r = sensitive, moderately sensitive, less sensitive and resistant, respectively. b+++, ++, +, 0 = sensitive, moderately sensitive, less sensitive and resistant, respectively. Corresponding IC,. values (pg/ml) are as follows: Sulfathiazole Chloramphenicol Erythromycin Nalidixic acid Kanamycin +++ <5.0 <1.0 <0.1 <4.0 <4.0 ++ >5.0 -15.0 >1.0- 5.0 >0.1- 1.0 24.0-10.0 24.0-15.0 + > 15.0-100.0 > 5.0-50.0 > 1.0-10.0 > 10.0-25.0 > 15.0-50.0 0 >100.0 >50.0 >10.0 >-25.0 > 50.0 c Penicillin, less sensitive: IC60 value 2 0.088 IU/ml (0.053 pg/ml). d Streptomycin, resistant: IC.0 value >25 Pg/ml. rTetracycline, less sensitive: IC.. value .1.13 pg/ml. f Spiramycin, less sensitive: ICso value >0.95 Ag/ml (arbitrary value). 2 262 A. REYN sensitivity. Presumably, adequate treatment would instance, the less susceptible strains were more lead only to the maintenance of the present virulent that the susceptible ones. The sensitivity conditions and obviously not to an altered patterns of the strains imported at various times and distribution according to sensitivity unless, for from various places may also play a role.

RESUME SENSIBILITE AUX ANTIBIOTIQUES DE SOUCHES DE GONOCOQUES ISOLtES EN ASIE DU SUD-EST ET DANS LE PACIFIQUE OCCIDENTAL EN 1961 ET EN 1967-1968

On a constate dans la plupart des r6gions du monde des concentrations inhibitrices 50% de la penicilline, de une diminution de la sensibilit6 des gonocoques 'a la la tetracycline, de la streptomycine et de la spiramycine penicilline et it d'autres antibiotiques. Le phenomene a pour les souches isolees aux Philippines en 1961 et pour notamment ete observ6 dans les Regions OMS de l'Asie les souches isolees dans les autres regions en 1967-1968, le du Sud-Est et du Pacifique occidental. Une centaine de trait le plus remarquable etant I'absence de souches i souches de gonocoques en provenance de ces territoires sensibilite normale. La plupart des souches collectees en a ete examinee sous ce rapport au Service des Neisseria 1961 faisaient preuve d'une sensibilit6 parfaite au chlo- du Statens Seruminstitut de Copenhague (Danemark), ramphenicol et a l'erythromycine. En revanche, parmi qui est le Centre international OMS de r6ference pour les les souches isolees en 1967-1968, 25 % environ n'etaient gonocoques. La collecte des souches a eu lieu a deux que legerement sensibles au chloramphenicol, 75 % envi- epoques distinctes. En 1961, 65 souches ont ete reques de ron legerement sensibles a l'6rythromycine (une souche Ceylan et des Philippines. En 1967-1968, ce sont des etait resistante at cet antibiotique) et 10% seulement souches de Thailande, de Taiwan, du Viet-Nam et de sensibles a tous les antibiotiques utilises lors des epreuves. Hong Kong qui ont ete adress6es au Service des Neisseria. Il convient de remarquer que certains auteurs ont Les epreuves de sensibilite ont montre que les souches signale une augmentation du nombre des souches de de gonocoques isolees dans ces regions presentaient de gonocoques a sensibilite accrue aux antibiotiques en plus en plus fr6quemment une sensibilite diminuee a Europe septentrionale. Les raisons de ce retour a la l'egard de la penicilline et des antibiotiques les plus sensibilite normale ne sont pas connues. Quelques couramment utilises. On notait une repartition similaire explications possibles sont brievement envisagees.

REFERENCES

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