“Celbenin” - resistant Staphylococci
“Celbenin” - resistant Staphylococci
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DOI：
10.1136/bmj.1.5219.125
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发表时间：
1961-01
影响因子：
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通讯作者：
G. Rolinson
中科院分区：
文献类型：
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作者：
G. Rolinson
先生，1960年10月，我们从杰文斯医生那里收到两株单菌落葡萄球菌，每株都是她发现对"赛贝宁"有抗药性的。“这些是她在上面的信中提到的培养物，并命名为13136a和13136c以及13137a和13137c。随后，我们还从Jevons博士处收到了原始培养物13136和13137，这些培养物已被送往Colindale进行噬菌体分型。这些文化的起源是在她的信中描述的。我们通过在琼脂和营养肉汤中连续稀释来测试这些培养物对celbenin的敏感性。肉汤稀释液用一滴过夜肉汤培养物接种，琼脂稀释液用一环过夜肉汤培养物划线接种。试验在370 ℃下孵育.观24小时£ ¬这两种类型的测试给出了相同的结果。用培养物13136以及来自13136的分离物，最小抑制浓度（M. 1. C.）的的浓度为5.0 pg/ml。ml.正常的M。1. C.在这些试验中，青霉素耐药葡萄球菌的最低抑菌浓度为2.0 μ g。ml.文化13137 13137的分离物之一M. 1. C.是25/Ag。ml.在每种情况下，终点都是尖锐的。在肉汤培养物中，生长严重至MIC值，但超过此浓度时无可见生长。然而，在进一步的培养中，得到了非常不同的结果。培养48小时后，所有培养物在肉汤培养物中显示出大量生长，浓度高达并包括250 μ g/ml。ml.在250 pg/ml的培养基中从该生长物中分离菌株。ml.其在随后的测试中显示MIC值为250 - 500 pg/ml。ml.因此，培养物13136和13137似乎主要是一种在对苯青霉素的敏感性方面与其他青霉素抗性葡萄球菌没有明显不同的类型，但另外似乎有非常小比例的高度抗性。将大量的13136和13137细胞接种在含有琼脂的双倍稀释的celbenin上，显示在370 ℃孵育过夜后。大约每107人中只有一人的年龄在12.5岁左右。ml.浓度为250 μ g/ml时，约100 μ g/ml中只有1个生长。ml.从含有250 pg/ml的肉汤培养物中分离的抗性型。ml.在7.5%盐琼脂上生长良好，甘露醇产酸，明胶液化，凝固酶阳性。该培养物也是青霉素酶产生的，青霉素耐药的，并且对链霉素和四环素也耐药，就像培养物的其余部分一样。杰文斯博士好心地进行了噬菌体分型，结果表明这种耐药菌株与其他培养物的噬菌体类型相同。耐药菌株的纯培养物在浓度高达250 pg/ml的Celbenin肉汤中容易生长过夜。ml.这些肉汤中的氯苯甲醚含量测定为1.0 - 250 μ g/ml。ml.与以相同方式孵育的未接种的肉汤相比，孵育24小时后，未显示出可检测到的celbenin破坏。因此，该培养物的抗性不是由于"celbeninase"对celbenin的破坏。"当然，在体外，在化合物存在下，通过反复传代培养，可以很容易地获得对葡萄球菌素具有耐药性的葡萄球菌。然而，从临床的角度来看，这是否有任何意义，则是另一回事。这种类型的耐药性也很容易对青霉素G产生耐药性，但临床上从未遇到过这种类型的培养物，而且迄今为止，还没有从用这种抗生素治疗的患者中分离出对celbenin具有耐药性的菌株。1960年9月，当头孢菌素上市时，还没有发现对头孢菌素耐药的耐青霉素金黄色葡萄球菌菌株。从那以后
SIR,-In October, 1960, we received from Dr. MP Jevons two single-colony isolates each of two strains of staphylococci which she had found to be resistant to" celbenin." These are the cultures referred to in her letter above and designated 13136a and c and 13137a and c. Subsequently, we also received from Dr. Jevons the original cultures 13136 and 13137 which had been sent to Colindale for phage-typing. The origin of these cultures is described in her letter. We tested the sensitivity of these cultures to celbenin by serial dilution in agar and in nutrient broth. The broth dilutions were inoculated with one drop of an overnight broth-culture and the agar dilutions by streaking with a loopful from an overnight broth culture. The tests were incubated at 370 C. for 24 hours. Both types of tests gave the same results. With culture 13136, and also the isolates from 13136, the minimum inhibitory concentration (M. 1. C.) of celbenin was 5.0 pg./ml. The normal M. 1. C. for penicillin-resistant staphylococci in these tests is 2.0 MUg./ml. With culture 13137. and one of the isolates from 13137, the M. 1. C. was 25/Ag./ml. In every case the end-point was sharp. In the broth-cultures growth was heavy up to the MIC value, but with no visible growth beyond this con-centration. On further incubation, however, a very different result was obtained. After 48 hours' incubation all the cultures showed heavy growth in broth culture up to and including a concentration of 250 jug./ml. Strainswere isolated from this growth in 250 pg./ml. which, on subsequent testing, showed MIC values of 250-500 pg./ml. after overnight incubation.The cultures 13136 and 13137 thus appeared to be predominantly of a type not appreciably different in sensitivity to celbenin from other penicillin-resistant staphylococci, but in addition there appeared to be a very small proportion which were highly resistant. Plating out large numbers of cells of 13136 and 13137 on agar-containing doubling dilutions of celbenin showed that after incubation overnight at 370 C. only one in approximately 107 of the population grewat 12.5 Ag./ml. and only one in approxi-mately 10'grew at a concentration of 250, ug./ml. The resistant type isolated from broth cultures containing 250 pg./ml. of celbenin grew well on 7.5% salt agar, gave acid production with mannitol and liquefaction of gelatin, and was coagulase-positive. The culture was also penicillinase-producing, penicillin-resistant, and resistant also to streptomycin and tetracycline, as was the rest of the culture. Phage-typing, which was kindly carried out by Dr. Jevons, showed this resistant strain to be of the same phage-type as the rest of the culture. A pure culture of the resistant strain grew up readily overnight in broth in concentrations of celbenin up to250 pg./ml. Assay of the celbenin-content of these broths from 1.0-250, ug./ml. after 24 hours' incubation showed no detectable destruction of celbenin compared with uninoculated broths incubated in the same way. The resistance of this culture is therefore not due to celbenin-destruction by a" celbeninase." Staphylococci resistant to celbenin can, of course, be obtained quite readily in vitro by repeated subculture in the presence of the compound. Whether this is of any significance from the clinical point of view, however, is another matter. Resistance of this type also develops very readily to penicillin G, but cultures of this type are never encountered clinically, and, so far, strains resistant to celbenin have not been isolated from patients following treatment with this antibiotic. When celbenin was marketed in September, 1960, no strains of penicillin-resistant Staphylococcus aureus had been found which were resistant to celbenin. Since that …