Antibiotic sensitivity of gonococcal strains isolated in the South-East Asia and Western Pacific regions in 1961-68*

Bull. Org. mond. Sante 1969, 40, 257-262Bull. Wid Hith Org. 19,4025-6 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 and for 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 relating to studies on the sensitivity of various strain of gonococci in the WHO South-East Asia and Western Pacific regions to antibiotics; the amount of published work on this topic is, however, limited. Using a commercial brand of impregnated antibiotic discs, Suvanamalik & Arnau (1964--66) tested a series of gonococcal cultures isolated in Bangkok, Thailand. They concluded that " some strains exist which have or develop a relative resistance to penicillin and other antibiotics ". Barile, van Zee & Yaguchi (1959) and Tawes (1966) reported on gonococcal strains, isolated from American soldiers operating in Japan and Korea, that were less susceptible to penicillin. In Madras, India, Chacko & * This study was supported by grants from the World Health Organization. 1 WHO International Reference Centre for Gonococci, Neisseria Department, Statens Seruminstitut, Copenhagen, Denmark. Yogeswari (1966) found that 45.6 % of 150 gonococcal strains isolated at random showed decreased in vitro sensitivity to penicillin. In a limited group of 25 strains they observed " a trend towards positive correlationship in the in vitro parallel sensitivities of penicillin, streptomycin and chloro- mycetin ". In 1967, Ho & Chang found that about 30% of the gonococcal strains from Taiwan had a minimal inhibitory concentration (MIC) greater than 0.2 International Unit (IU) of penicillin per ml, and that about 7% of the total isolates showed an MIC of 2 IU per ml. They compared their results with those of Tai & Han (1960) who found that 5% of the strains examined showed relatively low susceptibility to penicillin. Ho & Chang (1967) concluded that the incidence of gonococcal strains relatively resistant to antibiotics was likely to increase in Taiwan. In Australia, Smith & Levey (1967) observed that 44% of 104 gonococcal strains isolated in Sydney and Newcastle in 1966 showed a decreased susceptibility 2296 257 7 258 A. REYN to penicillin as compared with strains isolated before 1954. It may also be relevant to mention that Warren (1968) found that the percentage of gonococcal strains partially resistant to penicillin was signifi- cantly higher in an overseas infection group than in the local infection group and infection " elsewhere " in the United Kingdom. Warren's material was from Southampton during the years 1958 to 1965. MATERIAL AND METHODS Altogether, 108 gonococcal strains from the South-East Asia and Western Pacific regions have been examined in the Neisseria Department. In 1961, 65 strains from the Philippines' and Ceylon 2 were tested against sodium benzylpenicillin, dihydro- streptomycin and tetracycline (Reyn, 1963). Recent- ly, another series of strains was received from these regions, namely, 12 strains from Bangkok, Thai- land,3 16 from Hong Kong,4 9 from Taipei, Taiwan,5 and 6 from Saigon, Viet-Nam.6 The sensitivity (50% inhibitory concentration = IC,0) of these 43 strains was tested against penicillin, streptomycin, tetra- cycline and spiramycin, using the plate dilution method (Reyn, Bentzon & Ericsson, 1963). In addition, they were tested against sulfathiazole, chloramphenicol, erythromycin, nalidixic acid, kana- mycin, cefalotin and cefaloridine using a diffusion method (Thomsen, 1962). Discs for diffusion tests with pristinamycin and spectinomycin were not available. In all, 44 of the 65 strains received in 1961 had been lyophilized. In August 1968 they were revived and tested against spiramycin (plate dilution method), sulfathiazole, chloramphenicol, erythro- mycin, nalidixic acid, kanamycin, cefaloridine and cefalotin (diffusion method). Tables 1 and 2 show results of the sensitivity examinations of all the strains. The majority of the strains were examined twice with each antibiotic, and mean values are given in the tables. The results are given as IC50 per ml or as 0, +, ++ and +++, relating to the size of zone diameters. The ranges of the IC50 values, and various technical details, are given in the footnotes to the tables. Minimum inhibitory concentrations would be about twice as high as the 50% inhibitory concentrations. Complete Procured by Dr L. M. Ibarra. 'Procured by Dr E. D. C. Pereira. 3 Procured by Dr Supatra Suvanamalik and Dr Brian Hill, WHO consultant. I Procured by Dr Wong Kwok-on. 'Procured by Professor Wu-tse Liu. Procured by Dr Nguem-van-Liem. clinical information concerning the origin of the strains is not yet available, but most of the strains were said to have been picked out at random. RESULTS General features All except I of the 87 strains were fully sensitive or moderately sensitive to sulfathiazole, chlorampheni- col, erythromycin, nalidixic acid and kanamycin. Only 20 strains (23 %) were sensitive to penicillin, and these were also sensitive to streptomycin and tetracycline. Of these multisensitive strains, 16 were isolated in 1961 in Ceylon, and the remaining 4 were isolated in 1967, 2 in Hong Kong and 2 in Thailand. However, it must be remembered that the strains designated as less sensitive to penicillin are, in fact, sensitive provided that a sufficiently high dosage of a suitable penicillin is used. The strain most resistant to penicillin had IC50 = 2.4 IU (1.4 ,ug) per ml, with a corresponding MIC of 4.0 IU (2.4 ,ug) per ml (strain 307 from Hong Kong, 1967). The relationships7 between the zone diameters obtained with cefaloridine and cefalotin and the corresponding IC50 values have not yet been established. Discs containing 50 ug were used in both cases, and for both substances the sizes of the zones were correlated with the IC50 values observed for penicillin, i.e., increasing zone diameters with decreasing IC50 values. The order of magnitude of the IC50 values observed was estimated as about 4 jug per ml to about 16 ,ug per ml of cefaloridine and less than 3 ,tg-4 ,tg per ml of cefalotin. Since penicillin was still the drug of choice (though impossible to use in some cases), the effect of this antibiotic was compared with that of the other antibiotics employed. The IC50 values of penicillin were positively correlated with those of streptomycin, tetracycline and with spiramycin.8 The degree of sensitivity to penicillin was also positively correlated with the sensitivity to sulfathiazole, chloramphenicol, erythromycin and nalidixic acid. Comparison between strains isolated in 1961 and 1967-68 Out of 44 strains isolated in 1961, 28 (64%) were less sensitive to penicillin; 19 of these (68%) were 7The comparisons described here were performed by plotting the IC,. values or zone diameters in millimetres obtained with one antibiotic against those obtained with another antibiotic in a co-ordinate system. These results are in agreement with those of previous reports (Reyn, Korner & Bentzon, 1958; Reyn & Bentzon, 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 ClrTetra- ~~Sulfa- Erythro- Nali- Kana-origin PenicillincStrep- e Spiramycinfamphe dixic~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~dycin praycn t .diiorigin Penicl lAin C Strep-nli Tetra-e Ggm tiazole amphe- myci acid mycin(IU m;Mg,l) toycinj (Mg/mI) (23g/mgl)5 '4 (10 MLg) I(50 Ag) (50 Mg) 24 strains of gonococci from Ceylon 70.088 0.011 <0.01 1 0.016 0.50 1.19 0.022 0.022 1.00 0.022 0.022 0.022 0.011 1.19 0.022 0.011 0.011 0.71 <0.008 0.011 0.125 0.011 10.0081.00 <0.053 Is 0.007 s <0.00'/ s 0.009 s 0.30 Is 0.71 Is 0.013 s 0.013 s 0.60 Is 0.0i3 s 0.013 s 0.013 s 0.007 s 0.71 Is 0.013 s 0.00/ s 0.007 s 0.42 Is <0.005 s 0.007 s 0.075 Is 0.007 s 0.005 s 0.60 Is 16 s 8 Is <0.005-0.71 (<0.008 IU-1.19 IU) 1.41 0.85 Is >2.00 >1.20 Is 0.50 0.30 Is 0.125 0.075 Is 0.71 0.42 Is 0.50 0.30 Is 1.41 0.85 Is 0.177 0.106 Is >2.00 >1.20 Is 0.50 0.30 Is 0.50 0.30 Is 0.125 0.075 Is 2.CO >1.20 Is 0.50 0.30 Is >2.00 >1.20 Is >2.00 >1.20 Is 0.125 0.075 Is 0.25 0.150 Is 0.50 0.30 Is 0.50 0.30 Is o s Total a 20 Is Range of IC,0 0.075->1.20(Mg/ml) (0.125 IU->2.00 IU) g s s s 5 r r s 5r s s s s r s s s r s s s s s r 18 s 6 r not done s r r s s s r s r n r r r r r r 7 s 13 r not done 0.26 0.26 0.111 0.26 1.49 >1.77 0.37 0.26 1.25 0.26 0.26 0.31 0.22 > 1.77 0.31 0.26 0.19 1.25 0.16 0.19 0.26 0.26 0.22 >1.77 s s s IsIs Is s Isis s s s Isis s s IsIs s s s s Is is 18 s 6 Is 0.16->1 .77 0.28 0.20 0.14 0.24 0.72 2.44 0.36 0.22 0.86 0.24 0.18 0.18 0.20 2.90 0.17 0.2t 0.24 0.72 0.24 0.26 0.28 0.24 0.24 2.90 s s s s s Is s s s s s s s Is s s s s s s s s s Is 21 s 3 Is C.1 4-2.90 +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ ++-F +++ +++ +++ 24 s 20 strains of gonococci from Manila 1.49 Is 1.34 Is +++ 1.49 Is 0.72 s +++ 1.25 Is 0.72 s +++ 0.31 s 0.43 s +++ 1.49 Is 0.51 s +++ 0.63 s 0.67 s +++ 1.49 Is 0.72 s +++ 0.26 s 0.30 s +++ >1.77 Is 1.60 Is +++ 1.25 Is 0.86 s +++ >?1.77 Is 0.72 s +++ 0.26 s 0.30 s ++ >?1.77 Is 1.60 Is +++ 1.49 Is 0.51 s +++ >1.77 Is 2.26 Is +++ 1.49 Is 1.22 Is +++ 0.31 s 0.33 s +++ 0.31 s 0.36 s +++ --1.77 Is 0.61 s +++ ?>1.77 Is 0.61 s +++ 6 s 15s 19 s 14 Is 5 Is I ms 0.31->11.77 0.30-2.26 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. Ceylon 1 2 3 4 5 6 7 8 11 12 13 14 15 17 18 20 22 23 24 25 26 27 28 29 Total Range of IC50 (Mg/ml) Manila 4 23 26 28 29 30 32 34 35 36 37 38 39 40 41 42 43 44 49 50 24 s 24 s ++ ++ +++ ++ ++ ++ ++ +++ ++ ++ ++ ++ ++ ++ +++ ++ ++ ++ ++ 3s 213s ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ +++ ++ ++ ++ +++ 4 s 16 ms 24 s +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ 20s _ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ +++ 20 s 20 s A. REYN TABLE 2 SENSITIVITY TESTS ON 43 STRAINS OF GONOCOCCI ISOLATED IN 1967-58 IC50 for plate dilution method a (2-fold or 4-fold dilution steps) Relative zone diameters for disc diffusion method b (average of 2 determinations) Tetra- pia cnf Sulfa- amheo- Erythro- Nali- Kana- tomycid (Mg/mI)c thiazole P mycin d (5mycinSte g2yli (ug/ml) (238 tg)I nscol (10 Mg) acid mhaicann 1 (50jAg)1 (50 Mg) 12 strains of gonococci from Thailand 1.60 Is 1.90 Is 1.86 Is 1.60 Is 1.31 Is 1.60 Is 2.20 Is 1.90 Is 1.31 Is 1.61 Is 1.86 Is 1.13 Is 1.63 Is 1.13 Is 1.86 Is 1.60 Is 0.33 s 0.33 s 0.40 s 0.168 s 1.60 Is 1.90 Is 2.60 Is 1.60 Is +++ +++ +++ +++ +++ ++ +++ +++ +++ +++ ++ +++ +++ ++ +++ ++ +++ ++ I+++ ++ ++ +++ ++ ++ +++ ++ ++ +++ ++ ++ +±+ ++ ++ +++ +++ ++ +++ +++ ++ +++ ++ +++ +++ ++ +++ +++ I++ ++ +++ ++ ++ +++ +± 16 strains of gonococci from Hong Kong r r r 5 r r s 1.60 Is 2.90 Is +++ 1.13 Is 0.80 s +++ 1.33 Is 1.34 Is +++ 1.60 Is 2.26 Is +++ 1.60 Is 2.06 Is +++ 1.60 Is 3.20 Is +++ 1.60 Is 1.45 Is +++ 1.60 Is 2.90 Is +++ 0.80 s 0.95 Is +++ 1.60 Is 2.06 Is ++ 0.40 s 0.56 s +++ 1.13 Is 0.82 s +++ 1.60 Is 1.13 Is +++ 0.40 s 0.43 s +++ 0.28 s 0.40 s +++ 0.80 s 0.61 s +++ 9 strains of gonococci from Taiwan P 6 0.50 0.30 P18 0.35 0.21 F26 0.35 0.21 K32 1.68 1.00 G33 0.71 0.42 T56 1.19 0.71 G57 0.59 0.36 60 1.68 1.00 P101 1.41 0.85 r s r r r 1.60 Is 1.60 Is 0.28 s 2.26 Is 2.26 Is 1.88 Is 1.60 Is 1.60 Is 2.26 Is 2.44 Is 1.02 Is 0.95 Is 2.68 Is 2.26 Is 2.44 Is 0.86 s 2.06 Is 2.68 Is 6 strains of gonococci from Viet-Nam 1.41 0.85 2.0 1.2 2.4 1.4 0.59 0.36 1.19 0.71 0.84 0.50 Is Is Is Is Is Is 4 s 39 Is 0.0188-1.41 (0.03 IU-2.4 IU) 95s 34 r not done 1.13 Is 1.60 Is 1.90 Is 0.80 s 0.80 s 0.80 s 11 s 32 Is 0.28-2.60 1.90 Is 2.26 Is 1.90 Is 0.95 Is 1.72 Is 1.60 Is 9 34 Is 0.33-3.20 40 s 3 ms +++ ++ ++ 0 ++ ++ +++ +++ ++ ++ ++ 32s 9s 34s 4s 11 ms 33 ms 0 Is 39 ms 1 r (See notes opposite) Strain No. Penicillin c (lU/ml; Mgiml) 3048 3049 3059 3108 3170 3171 3172 3192 TH 373 Kett.H.N4 Thai N.H.N5 2787 (1) 1.19 2.00 1.41 2.00 1.41 2.80 0.50 1.19 0.11 0.044 1.68 1.41 0.71 1.20 0.85 1.20 0.85 1.70 0.30 0.71 0.063 0.027 1.00 0.85 Is Is Is Is Is Is Is Is s s Is Is r r r r r GC 266 274 278 280 290 294 300 303 306 307 320 322 328 377 335 31811 1.68 0.50 0.71 1.68 2.8 1.41 0.84 1.68 0.177 2.4 0.177 0.59 1.41 !0.63' 0.03 0.125 1.00 Is 0.30 Is 0.42 Is 1.00 Is 1.70 Is 0.85 Is 0.50 Is 1.00 Is 0.106 Is 1.40 Is 0.106 Is 0.36 Is 0.85 Is 0.0188 o 0.0188 s 0.075 Is ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ +++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ Is Is Is Is Is Is Is Is Is ++ +++ +++ ++ ++ +++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ 535/67 542/67 543/67 544/67 635/67 637/67 Total a Range of IC,o(Mg/ml) ~~~~~~~~~~~~~~-1 1 260 CHANGES IN SENSITIVITY OF VARIOUS STRAINS OF GONOCOCCI TO ANTIBIOTICS 261 resistant to streptomycin, 20 (72 %) were less sensitive to tetracycline, and 8 (28 %) were less sensitive to spiramycin. Of the 43 strains isolated late in 1967 and early in 1968, 39 (90%) were less sensitive to penicillin; 34 of these (87%) were resistant to streptomycin, and 32 (82%) were also less sensitive to tetracycline. As many as 34 (87 %) of the 39 strains less sensitive to penicillin were also less sensitive to spiramycin. The distribution of the IC,0 values of penicillin, tetracycline, streptomvcin and spiramycin was similar in the strains isolated in the Philippines in 1961 and in those from the other areas in 1967-68, the characteristic being that strains with " normal sensitivity" were lacking. All the strains from 1961 were fully sensitive to chloramphenicol and erythromycin, but this was not the case with those from 1967-68. Altogether, 11 of the 43 strains from 1967-68 were only moderately sensitive to chloramphenicol; 33 were moderately sensitive to erythromycin and 1 was resistant to that drug. DISCUSSION AND CONCLUSION The finding that the in vitro effect of cefalotin was greater than that of cefaloridine is in agreement with the observation by Martin et al. (1965) that, as measured by the plate dilution method, the inhibitory in vitro effect of cefalotin was greater than that of cefaloridine. However, Lucas et al. (1965) reported that cefaloridine had a better in vivo effect than cefalotin. Also, Barber & Waterworth (1964) found that cefalotin had a greater in vitro ef- fect (8-16-fold) than cefaloridine. The clear-cut posi- tive correlation observed between the cefalosporins and penicillin is in accordance with the fact that the cefalosporins are chemically related to the penicillins (Gonella, Olexy & Jackson, 1967). The positive correlation observed between the penicillin and the spiramycin values is interesting because, as far as it is known, spiramycin has not been used (or to only a slight extent) in the treatment of gonorrhoea in the South-East Asia and Western Pacific regions. However, the ICs0 values of spiramycin were also closely correlated to the zone diameters obtained with erythromycin. The latter belongs to the macrolide group of antibiotics, and so does spiramycin. Hence, it is likely that the correlation observed between the IC50 values of penicillin and spiramycin is only a reflection of the close chemical relationship between spiramycin and erythromycin, the latter possibly having been used to a higher degree than spiramycin. A forthcoming paper will deal with the relationship between penicillin and several other antibiotics including spiramycin. The present results indicate that the incidence of gonococcal strains with decreased susceptibility to penicillin, and to others of the more generally used antibiotics, is increasing in the two regions. This is a feature common to many other regions of the world. However, in some areas the opposite effect has been observed. For instance, a series of recent reports from northern Europe contain information concern- ing an increasing number of gonococcal strains with " normal " susceptibility to, for instance, penicillin (Kallings & Gastrin, 1966; Odegaard & Gjessing, 1967; Olsen & Lomholt, 1968). The decreased susceptibility of the gonococcal strains to penicillin can be overcome by using higher doses and by using antibiotics other than penicillin. It is noteworthy that very few (10%) of the South- East Asia and Western Pacific strains isolated in 1967-68 were sensitive to all the antibiotics employed, and that an over-all decrease in susceptibility seems to have occurred between 1961 and 1967-68. The explanation for the reversion of the gonococcal strains from certain areas towards "normal sensitivity " to penicillin and other antibiotics is not known; in itself, it is a consoling fact. It is possible that treatment with adequate doses of penicillin and other antibiotics in these areas has 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 lead only to the maintenance of the present conditions and obviously not to an altered distribution according to sensitivity unless, for instance, the less susceptible strains were more virulent that the susceptible ones. The sensitivity patterns of the strains imported at various times and 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 une diminution de la sensibilit6 des gonocoques 'a la penicilline et it d'autres antibiotiques. Le phenomene a notamment ete observ6 dans les Regions OMS de l'Asie du Sud-Est et du Pacifique occidental. Une centaine de souches de gonocoques en provenance de ces territoires a ete examinee sous ce rapport au Service des Neisseria du Statens Seruminstitut de Copenhague (Danemark), qui est le Centre international OMS de r6ference pour les gonocoques. La collecte des souches a eu lieu a deux epoques distinctes. En 1961, 65 souches ont ete reques de Ceylan et des Philippines. En 1967-1968, ce sont des souches de Thailande, de Taiwan, du Viet-Nam et de Hong Kong qui ont ete adress6es au Service des Neisseria. Les epreuves de sensibilite ont montre que les souches de gonocoques isolees dans ces regions presentaient de plus en plus fr6quemment une sensibilite diminuee a l'egard de la penicilline et des antibiotiques les plus couramment utilises. On notait une repartition similaire des concentrations inhibitrices 50% de la penicilline, de la tetracycline, de la streptomycine et de la spiramycine pour les souches isolees aux Philippines en 1961 et pour les souches isolees dans les autres regions en 1967-1968, le trait le plus remarquable etant I'absence de souches i sensibilite normale. La plupart des souches collectees en 1961 faisaient preuve d'une sensibilit6 parfaite au chlo- ramphenicol et a l'erythromycine. En revanche, parmi les souches isolees en 1967-1968, 25 % environ n'etaient que legerement sensibles au chloramphenicol, 75 % envi- ron legerement sensibles a l'6rythromycine (une souche etait resistante at cet antibiotique) et 10% seulement sensibles a tous les antibiotiques utilises lors des epreuves. Il convient de remarquer que certains auteurs ont signale une augmentation du nombre des souches de gonocoques a sensibilite accrue aux antibiotiques en Europe septentrionale. Les raisons de ce retour a la sensibilite normale ne sont pas connues. Quelques explications possibles sont brievement envisagees. REFERENCES Barber, M. & Waterworth, P. M. (1964) Brit. med. J., 2, 344 Barile, M. F., Zee, G. K. van & Yaguchi, R. (1959) Antibiot. Med., 6, 470 Chacko, C. W. & Yogeswari, L. (1966) Indian J. med. Res., 54, 823 Gonella, J. S., Olexy, V. M. & Jackson, G. G. (1967) Amer. J. med. Sci., 254, 71 Ho, T. J. & Chang, S. S. (1967) Far East med. J., 3, 320 Kallings, L. 0. & Gastrin, B. 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