Plasmodium falciparum sensitivity to erythromycin and 4-aminoquinoline combinations in vitro.

Although erythromycin has been reported to be active against Plasmodium falciparum in vitro and P. berghei in vivo and in vitro when given alone or with chloroquine, it has been difficult to demonstrate a beneficial effect for the combination of erythromycin and chloroquine when used for the treatment of P. falciparum infections in humans. We developed a seven-day test of parasite sensitivity to a 4-aminoquinoline and erythromycin combination in vitro. Eight isolates of P. falciparum from the Kenyan coast were culture-adapted and exposed to erythromycin with chloroquine or with amodiaquine. The interaction of the drugs was evaluated by plotting the concentration of each drug needed to inhibit parasite growth. In seven isolates the combination of chloroquine and erythromycin was antagonistic; one isolate showed slight synergy The combination of amodiaquine and erythromycin was synergistic in three isolates but antagonistic in five. An antagonistic interaction may explain why erythromycin does not enhance chloroquine treatment of malaria in vivo in Kenya.     

Activity of azithromycin or erythromycin in combination with antimalarial drugs against multidrug-resistant Plasmodium falciparum in vitro

Azithromycin, an azalide analog of erythromycin was assayed for its in vitro activity against multidrug-resistant Plasmodium falciparum K1 strain by measuring the ³H-hypoxanthine incorporation. Azithromycin caused inhibitory effects on the parasite growth with IC₅₀ and IC₉₀ values of 8.4 ± 1.2 μM and 26.0 ± 0.9 μM, respectively. Erythromycin inhibited growth of P. falciparum with IC₅₀ and IC₉₀ values of 58.2 ± 7.7 μM and 104.0 ± 10.8 μM, respectively. The activity of antimalarial drugs in combination with azithromycin or erythromycin against P. falciparum K1 were compared. Combinations of chloroquine with azithromycin or erythromycin showed synergistic effects against parasite growth in vitro. Combinations of quinine–azithromycin and quinine–erythromycin showed potentiation. Additive effects were observed in mefloquine–azithromycin and mefloquine–erythromycin combinations. Similar results were also produced by pyronaridine in combination with azithromycin or erythromycin. However, artesunate–azithromycin and artesunate–erythromycin combinations had antagonistic effects. The in vitro data suggest that azithromycin and erythromycin will have clinical utility in combination with chloroquine and quinine. The worldwide spread of chloroquine-resistant P. falciparum might inhibit the ability to treat malaria patients with chloroquine–azithromycin and chloroquine–erythromycin in areas of drug-resistant. The best drug combinations against multidrug-resistant P. falciparum are quinine–azithromycin and quinine–erythromycin.     

Comparison of the relative in vitro activity of chloroquine and amodiaquine against chloroquine-sensitive strains of P. falciparum

The activities of chloroquine and amodiaquine against a sensitive strain of Plasmodium falciparum found in children in Ibadan were compared using an in vitro technique. The criterion for drug activity was the inhibition of maturation of the parasites. Three sets of experiments were performed with each of the two drugs. The minimum concentration of chloroquine causing 90% inhibition of maturation was 25 nmol as compared with 12 nmol for amodiaquine. This suggests a two-fold increase in activity of amodiaquine when compared with chloroquine against sensitive strains of P. falciparum. The implication is that amodiaquine is a much more potent tool in malaria chemotherapy than the erstwhile overused chloroquine.     

Epidemiological survey of group A hemolytic streptococci isolated in Osaka during the 21-year period between 1967 and 1987. Part II. Antibiotic susceptibility

During the 21-year period between 1967 and 1987, a total of 4678 strains of group A hemolytic streptococci isolated in Osaka were examined for drug sensitivity. The results were summarized as follows. 1. All strains were sensitive to the beta-lactam group of antibiotics (benzylpenicillin and cephaloridine). Resistant strains (M.I.C. greater than or equal to 25 micrograms/ml) to tetracycline (TC), chloramphenicol (CP) and erythromycin (EM) were isolated in this study period. The incidence of TC-resistant strains in the whole isolates has not much varied through the whole period, in spite of the variation among several T-type. But those of CP- and EM-resistant strains varied greatly by year. 2. Before 1971, a small number of resistant strain was found in 1969 and 1970. Since 1972, increase of such strains had been seen and the incidence of CP-resistant strains reached the highest peak (32.5%). It showed a gradual decrease since 1976 and was 1.1% in 1987. 3. None of EM-resistant strains was isolated before 1972. The incidence of EM-resistant strains exhibited a steep rise in percent since 1973 and reached the highest value showing a two-peak-pattern in 1975 (36.1%) and in 1980 (36.0%). After reaching its peak it decreased gradually and was 2.9% in 1987. 4. Remarkable increase of the multiple drug resistant strains began to be observed since 1972 to 1973, and mainly T-12 and T-4 showed EM. TC. CP- and TC. CP-resistance, respectively. The phenomenon of multiple drug-resistance culminated during 1975-1977, followed by gradual decrease thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative evaluation of blood schizontocidal activity of quinine and quinidine against drug resistant rodent malaria.

Blood schizontocidal activity of quinine and quinidine has been compared against sensitive as well as chloroquine/mefloquine/quinine resistant strains of Plasmodium berghei and a multiple resistant strain of P. yoelii nigeriensis in Swiss mice. Evaluation of results on ED50/ED90 basis has shown distinct superiority of quinidine over quinine against sensitive as well as drug resistant strain of rodent malaria.     

广州市香港海鸥型菌红霉素耐药性与基因分析

目的 了解广州地区香港海鸥型菌分离株对红霉素的耐药性及红霉素耐药基因的分布情况。方法 从青蛙和草鱼肠道中分离的菌株共122株,使用K-B法对香港海鸥型菌分离株进行红霉素抗生素的耐药性测定,用PCR方法检测红霉素耐药株中红霉素抗性基因ereA,ereB,ermA,ermB,ernC,MefA/E,mphA,SAT4的携带情况,并将检测阳性结果的PCR产物进行测序分析。结果 香港海鸥型菌对红霉素耐药率为28.7%,其中蛙源株耐药率为35.1%,鱼源株耐药率为25.9%。对红霉素耐药的35株菌中,蛙源株ereA基因检出率为30.8%,鱼源株没有检出ereA基因。结论 广州地区香港海鸥型菌对红霉素的耐药率较高,蛙源株对红霉素的耐药率比鱼源株高,海鸥型菌蛙源株对红霉素产生的耐药性与ereA基因相关。     

Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes

Substance P (SP) is a potent modulator of neuroimmunoregulation. We recently reported that human immune cells express SP and its receptor. We have now investigated the possible role that SP and its receptor plays in HIV infection of human mononuclear phagocytes. SP enhanced HIV replication in human blood-isolated mononuclear phagocytes, whereas the nonpeptide SP antagonist (CP-96,345) potently inhibited HIV infectivity of these cells in a concentration-dependent fashion. CP-96,345 prevented the formation of typical giant syncytia induced by HIV Bal strain replication in these cells. This inhibitory effect of CP-96,345 was because of the antagonism of neurokinin-1 receptor, a primary SP receptor. Both CP-96,345 and anti-SP antibody inhibited SP-enhanced HIV replication in monocyte-derived macrophages (MDM). Among HIV strains tested (both prototype and primary isolates), only the R5 strains (Bal, ADA, BL-6, and CSF-6) that use the CCR5 coreceptor for entry into MDM were significantly inhibited by CP-96,345; in contrast, the X4 strain (UG024), which uses CXCR4 as its coreceptor, was not inhibited. In addition, the M-tropic ADA (CCR5-dependent)-pseudotyped HIV infection of MDM was markedly inhibited by CP-96,345, whereas murine leukemia virus-pseudotyped HIV was not affected, indicating that the major effect of CP-96,345 is regulated by Env-determined early events in HIV infection of MDM. CP-96,345 significantly down-regulated CCR5 expression in MDM at both protein and mRNA levels. Thus, SP-neurokinin-1 receptor interaction may play an important role in the regulation of CCR5 expression in MDM, affecting the R5 HIV strain infection of MDM.     

Culture of Plasmodium berghei with the short life span in mouse erythrocytes: evaluation of chloroquine resistance in three strains of the malaria parasite

This comparative study was made to examine chroloquine inhibition of C14-hypoxanthine incorporation (preferably nucleic acid precursor for plasmodium) in the short-living red blood cell cultures in mice infected with P. berghei strains differently sensitive to the agent 24 hours after incubation. These included 1) chloroquine-sensitive H strain; 2) LNK-65 strain having a spontaneously 2-3-fold decreased sensitivity to the agent; 3) strain LNK-65 ChR selected for high resistance to chloroquine. IC50 (chloroquine concentrations that ensure 50% inhibition of the incorporation of nucleic acid precursor into the cells of the parasite) was estimated for 3 P. berghei strains that were differently sensitive to chloroquine. These in vitro values adequately reflect the sensitivity of these strains to the agent in vivo.     

Comparison of in vivo and in vitro activities of antibiotics with different modes of action against a tolerant and a non-tolerant Staphylococcus aureus strain

The antibacterial efficacies of 4 antibiotics with different modes of action against a penicillin-tolerant and a non-tolerant strain of Staphylococcus aureus were investigated. For the in vitro studies the minimum inhibitory concentration (MIC) and the minimum bacterial concentration (MBC) were determined and short-term growth experiments at different antibiotic concentrations were performed. For the in vivo studies, antibacterial efficacy in an experimental infection in normal and granulocytopenic mice was evaluated. For erythromycin, rifampicin and ciprofloxacin, there was no difference in the MIC and MBC values for the 2 strains. Benzylpenicillin had an MBC value for the tolerant strains which was 256 times higher than the MIC; with the non-tolerant strain there was no difference. EC50 values, calculated from the in vitro short-term growth curves, gave similar results. Only benzylpenicillin exhibited a difference in activity against the tolerant strain, as reflected by the EC50 that was 290 times the EC50 for the non-tolerant strain. Studies in normal and granulocytopenic mice gave similar results: benzylpenicillin was 268 times less active against the tolerant strain than against the non-tolerant strain. Erythromycin, rifampicin and ciprofloxacin were 2-3 times less active against the tolerant strain than against the non-tolerant strain. The presence of granulocytes is important for the antibacterial effect of all antibiotics studied, since in the absence of granulocytes higher doses of the antibiotics are needed in order to obtain the same antibacterial effect as when granulocytes are present.     

The effect of artemisinin combined with standard antimalarials against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum in vitro

The activity of artemisinin (qinghaosu) in combination with some commonly-used antimalarial drugs was tested in vitro against a chloroquine-sensitive (NF54) and a chloroquine-resistant (K1) strain of Plasmodium falciparum. Both mefloquine and tetracycline showed marked potentiative synergism with artemisinin against both strains, whilst primaquine showed potentiation against K1. Combinations of artemisinin with pyrimethamine and with chloroquine were antagonistic. The results confirm observations on rodent malaria in vivo and indicate that the drug interactions seen were direct, through actions on the parasite, and not merely effects on drug distribution and metabolism in the mouse host.     

Analogues of N-benzyloxydihydrotriazines: in vitro antimalarial activity against Plasmodium falciparum

The antimalarial activities of a series of chlorophenyloxyalkoxy and chlorophenalkoxy N-substituted diamino-dihydrotriazines were determined in vitro against three strains of Plasmodium falciparum (Malayan Camp, Vietnam Smith, FCB) with diverse levels of resistance to chloroquine, pyrimethamine, and cycloguanil. Parasite viability was assayed by the inhibition of the uptake of radiolabelled hypoxanthine. Most of the ID-50S of these compounds were less than 1.0 ng ml-1. Consistent differences in sensitivities to these compounds were observed and appeared to be strain related. The Malayan Camp was the most sensitive and Vietnam Smith was the least sensitive. These differences appeared to be related primarily to an inherent sensitivity of a particular strain to the series of analogues examined rather than to a pattern of cross-resistance to chloroquine, pyrimethamine, or cycloguanil.     

A 23-year longitudinal study on the antibiotic sensitivities of group A streptococci from the scarlet fever patients--1956-1978

Among the group A streptococci isolated during the period 1956 to 1978 from the pharynx and the nostril of the scarlet fever patients quarantined in the Tokyo Metropolitan Toshima Hospital within 1 week of hospitalization, 1,586 strains of types 4, 6 and 12, the most prevalent serotypes, were estimated for their sensitivities to various antibiotics. Among the sensitivities, those to tetracycline (TC), chloramphenicol (CP) and erythromycin (EM), these being in close relation to prevalent serotypes, are to be reported. The first appearance of TC-resistant strain was seen in one strain (type 6) isolated in 1959, and, in 1964, the resistant strain increased in proportion in accordance with the prevalence of type 4. The resistant strain decreased a little in 1968 and in 1969, increased again from 1970, exceeded over 90% from 1973, and reached 100% in 1978. The first appearance of CP-resistant strain was seen in one strain (type 4) isolated in 1969, and then the resistant strain increased year by year along with the prevalence of type 12. The first appearance of EM-resistant strain was seen in 30 strains (type 12) isolated in 1972, and then, similarly to the case of CP-resistance, the resistant strain increased year by year together with the prevalence of type 12. Meanwhile, among the 1,586 strains isolated at the time of hospitalization and estimated of their minimum inhibitory concentrations (MIC), 932 strains (58.8%), 452 strains (28.5%), and 574 strains (36.2%) showed resistance to TC, CP, and EM, respectively. Variations of drug-resistance by serotypes were as follows: TC-resistant strains increased in accordance with the prevalence of type 4 in 1964; CP- and EM-resistant strains increased in accordance with the prevalence of type 12 in 1972; and type 6 strains were low in the rate of resistant strain to any of the three drugs. So far, prevalence of a serotype of group A streptococci has been considered to be caused by the accumulation of the subjects non-immune to the serotype. In the present study, a phenomenon was observed that prevalence of a serotype was effected by the state of resistance-acquisition to commonly used drugs. It would be clear that the resistance-acquisition plays, in addition to the immune state, a great role in evoking prevalence of a serotype.     

In vitro antimicrobial activity of rokitamycin, a macrolide antibacterial agent, against clinically isolated strains of Campylobacter and other enteritis-causing bacteria]

We determined the minimum inhibitory concentrations (MICs) of rokitamycin (TMS-19-Q, RKM), a macrolide antimicrobial agent, against strains of various bacterial species isolated from enteritis patients, and compared them with those of josamycin (JM), erythromycin (EM) and ofloxacin (OFLX). MIC90 of RKM against 147 strains of Campylobacter jejuni, and each 25 strains of Shigella spp., Salmonella spp. and diarrheagenic Escherichia coli were 1.56, 200, 800 and 200 micrograms/ml, respectively. There was only one RKM resistant (MIC greater than 100 micrograms/ml) C. jejuni strain, while most of the strains of the other species were resistant to RKM. MIC values of the other drugs were all similar to those of RKM. MIC90 of OFLX against 147 strains of C. jejuni was 0.78 micrograms/ml, lower than other drugs.     

伯氏疟原虫氯喹抗性株感染小鼠的氯喹代谢动力学研究

[目的 ]比较氯喹在正常小鼠、感染伯氏疟原虫药物敏感 (N)株和氯喹抗药性 (RC)株小鼠体内的药物动力学差异。 [方法 ]应用反相高效液相色谱法分别测定正常小鼠、感染伯氏疟原虫N株和RC株小鼠血浆中的氯喹浓度 ,采用 3P87药物动力学分析软件对数据进行分析 ,从而获得有关药物动力学参数。 [结果 ]感染RC鼠的t1/2 β与其他两组间有显著的统计学差异 (P <0 .0 5 ) ,而感染N株鼠与正常鼠间无显著差异。 [结论 ]氯喹在感染了伯氏疟原虫RC株鼠体内的消除速度显著快于正常鼠及感染N株鼠。     

小鼠疟原虫感染经氯喹治疗痊愈后再感染免疫特征分析

目的　探讨疟原虫感染小鼠在原虫血症高峰期经氯喹治愈后,再感染同/异种疟原虫的疾病进程和免疫保护特征。方法　用非致死型约氏疟原虫17XNL株（P. y 17XNL株）感染C57BL/6小鼠,感染率达高峰时（第9天）半数小鼠以氯喹治疗,其余小鼠自然痊愈。痊愈后小鼠于初次感染90 d后分别采用等量致死型约氏疟原虫17XL株（P. y 17XL株）或伯氏疟原虫ANKA株（P. b ANKA株）再次感染,采用吉姆萨薄血膜染色法观察原虫血症水平变化,并应用酶联免疫吸附试验和流式细胞术分别检测再感染前后小鼠血清中IgG抗体水平和脾细胞中记忆性T细胞亚群比例。结果　初次感染P. y 17XNL株后,自愈与氯喹治愈组小鼠血清IgG抗体水平分别为（5.047 ± 0.924）、（4.429 ± 0.624） pg/mL,差异无统计学意义（t = 0.437,P > 0.05）;但均显著高于无感染正常组小鼠的（1.624 ± 0.280） pg/mL（F = 22.522,P < 0.01）。自愈和氯喹治愈组小鼠再感染P. y 17XL株或P. b ANKA株并痊愈后,各组小鼠血清IgG抗体水平分别为（15.487 ± 1.173）、（14.644 ± 1.523）、（15.965 ± 1.150） pg/mL和（15.185 ± 1.333） pg/mL,差异无统计学意义（F = 0.542,P > 0.05）;但均高于初次感染组,差异有统计学意义（F = 67.383,P < 0.01）。感染P. y 17XNL株后自愈及氯喹治愈组小鼠再感染P. y 17XL株或P. b ANKA株并痊愈后,各组小鼠CD4+记忆性 T细胞比例分别为（34.023 ± 2.289）%、（35.608 ± 1.779）%、（34.208 ± 2.106）%和（32.820 ± 1.930）%, CD8+记忆性T细胞比例分别为（17.103 ± 1.627）%、（17.873 ± 1.425）%、（17.935 ± 2.092）%和（18.918 ± 2.823）%,组间差异均无统计学意义（F = 0.944、0.390,P均> 0.05）;但均高于初次感染后小鼠,且差异有统计学意义（CD4+记忆性T细胞,F = 50.532,P < 0.01;CD8+记忆性T细胞,F = 21.751,P < 0.01）。结论　小鼠疟疾经氯喹治疗痊愈不影响宿主在再感染时产生有效免疫保护力。初次感染后,小鼠对同种和异种疟原虫再感染均具有一定保护性且对同种疟原虫再感染的抵抗力强于异种疟原虫。     

肺炎链球菌对红霉素的耐药表型及耐药基因

目的　研究肺炎链球菌对红霉素的耐药表型及耐药基因。方法　根据美国临床实验室标准化委员会标准使用微量肉汤稀释法 ,检测 192株肺炎链球菌对红霉素、克林霉素、青霉素、喹诺酮类抗菌药物的最低抑菌浓度 (MIC)。应用红霉素、克林霉素、螺旋霉素纸片行三纸片扩散法 ,检测 14 8株红霉素耐药肺炎链球菌的耐药表型。应用PCR检测 14 8株红霉素耐药肺炎链球菌携带的耐药基因。结果　肺炎链球菌对青霉素的耐药率 (中介率 耐药率 )为 4 2 7% ,对红霉素、克林霉素的耐药率分别为 77 6 %、6 6 7%。 14 8株红霉素耐药株中 ,耐药基因以ermB基因 (79 1% )为主 ,耐药表型以内在型耐药 (cMLS) (85 1% )为主。携带ermB基因的肺炎链球菌 ,74 4 %的菌株对红霉素的MIC值 >16 0 μg/ml;而携带mefA基因的肺炎链球菌对红霉素的MIC值在 0 5～ 4 0 μg/ml之间。 结论肺炎链球菌对红霉素的耐药率较高 ;耐药表型以cMLS为主 ,耐药基因以ermB介导的靶位改变多见。     

Continuous in vitro culture of Plasmodium falciparum using microaerophilic gas generators and portable incubator

AnaeroPack Malaria Culture System (SUGIYAMA-GEN Co., Ltd.) using AnaeroPack.plas (5% O2, 5% CO2) and AnaeroPack.CO2 (15% O2, 6% CO2) was evaluated by comparing with the standard laboratory in vitro continuous culture technique. Two culture-adapted strains of Plasmodium falciparum, SGE-1 (chloroquine sensitive strain) and K1 (chloroquine resistant strain), were continuously cultured for 26 days in vitro under the 3 systems. The parasite proliferation curves under the different set systems were paralleled in both strains, which demonstrate that this AnaeroPack Malaria Culture System is useful for the culture-adapted strains of P. falciparum. Although further test using isolates from falciparum malaria patients should be carried out, the AnaeroPack Malaria Culture System seems promising for the culture in the field studies.     

Selected Derivatives of Erythromycin B-In Silico and Anti-Malarial Studies

Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their in silico molecular docking into segments of the exit tunnel of the apicoplast ribosome from Plasmodium falciparum. This is believed to be the target of the erythromycin A derivative, azithromycin, which has mild anti-malarial activity. The erythromycin B derivatives were evaluated on the multi-drug (chloroquine, pyrimethamine, and sulfadoxine)-resistant strain K1 of P. falciparum for asexual growth inhibition on asynchronous culture. The erythromycin B derivatives were identified as active in vitro inhibitors of asexual growth of P. falciparum with low micro-molar IC₅₀ values after a 72 h cycle. 5-Desosaminyl erythronolide B ethyl succinate showed low IC₅₀ of 68.6 µM, d-erythromycin B 86.8 µM, and erythromycin B 9-oxime 146.0 µM on the multi-drug-resistant K1 of P. falciparum. Based on the molecular docking, it seems that a small number of favourable interactions or the presence of unfavourable interactions of investigated derivatives of erythromycin B with in silico constructed segment from the exit tunnel from the apicoplast of P. falciparum is the reason for their weak in vitro anti-malarial activities.     

Antibacterial activity and kill kinetics of ampicillin/sulbactam (CP-45899) combinations against escherichia coli and Klebsiella aerogenes

Summary Combinations of ampicillin and sulbactam (CP-45899) were tested against 11 strains ofEscherichia coli and five strains ofKlebsiella aerogenes. With the exception of oneE. coli, strain, the strains were all highly resistant to ampicillin. Synergy was demonstrated by agar dilution in six of the ten resistantE. coli strains and in three of the fiveK. aerogenes strains. At simulatedin vivo conditions with constantly decreasing concentrations mimickingin vivo pharmacokinetics, synergy was detected against the beta-lactamase-producing strains tested, although the activity against the more resistantK. aerogenes strains was low. The correlation between antibacterial activity as determined by minimum inhibitory concentrations and the bacterial kill kinetics exhibited in thein vivo simulation model was acceptable forE. coli. The relationship was less predictable forK. aerogenes, however.

---

Antibakterielle Aktivität und Bakterizidiekinetik von Ampicillin-Sulbactam (CP-45899)-Kombinationen gegen Escherichia coli und Klebsiella aerogenes

Zusammenfassung Kombinationen von Ampicillin und Sulbactam (CP-45899) wurden in ihrer Wirksamkeit geqen 11 Stämme vonEscherichia coli und fünf vonKlebsiella aerogenes geprüft. Mit Ausnahme einesE. coli Stammes waren alle Stämme hochresistent gegenüber Ampicillin. Synergismus wurde mit Agarverdünnungsverfahren in sechs von den zehn resistentenE. coli Stämmen und in drei von den fünfK. aerogenes Stämmen nachgewiesen. Unter simuliertenin vivo Bedingungen mit die Pharmakokinetikin vivo nachahmenden, ständig abnehmenden Konzentrationen war Synergismus gegen die getesteten -Laktamase bildenden Stämme nachzuweisen. Die Aktivität gegen dieK. aerogenes Stämme mit erhöhter Resistenz war aber niedrig. Zwischen der mit minimalen Hemmkonzentrationen bestimmten antibakteriellen Aktivität und der Bakteriezidiekinetik imin vivo Simulationsmodell bestand beiE. coli Stämmen eine brauchbare Korrelation. Hingegen war diese Beziehung fürK. aerogenes weniger gut vorherzusagen.

     

Antibiotic susceptibility and T-serotypes of group A hemolytic streptococci, clinically isolated in 1986 and 1987

Determination of T-serotype for a total 245 strains (157 strains in 1986, 88 strains in 1987) of Streptococcus pyogenes (Group A hemolytic streptococci) isolated from clinical specimens (throat swab) of pediatric patients in Fukuoka Prefecture from 1986 until 1987 were performed. The susceptibilities of 9 antibiotics against 241 strains were studied. The most dominant strain was T-12 (57 strains, 36.3%) and followed by T-4 (32 strains, 20.4%) and T-28 (30 strains, 19.1%) in 1986. The total of these three strains was 75.8% of all strains. In 1987, T-4 (41 strains, 46.6%) was the dominant strain instead of T-12 (14 strains, 15.9%). T-28 was isolated only 4 strains (4.5%) in 1987, although it was isolated in 30 stains (19.1%) in 1986. In susceptibility-tests, no strains of 1986 and 1987 was resistant to beta-lactams. Resistant strains (MIC greater than or equal to 25 micrograms/ml) to erythromycin (EM), tetracycline (TC) and chloramphenicol (CP) were 4 (2.6%), 51 (33.3%) and 1 (0.7%), respectively in 1986. In 1987, resistant strains to EM and CP were not detected, to TC were 52 strains (59.1%), so there was an increase of susceptibility to EM and CP. As for relationship between T-serotype and antibiotic resistance, only one strain (T-12) showed multiple resistance in 1986, however in 1987, multiple resistant strain was not detected. In 1986 and 1987, 31 of 49 only TC resistant strains (63.3%) and 41 of 52 only TC resistant strains (78.8%) were T-4, respectively.