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A bacterium cannot be clinically categorized as susceptible to an antibiotic in one hospital or country and resistant in another. The need for standardization of in vitro antibiotic susceptibility tests (the antibiogramme) appeared very soon, in the early 1950s. The World Health Organization convened in Geneva a first Expert Committee on Antibiotics in 1959 and a second in 1961 (WHO Technical Report Series 1959 No. 710 and 1961 No. 210). It immediately appeared that the Committee had to work in two fields: the methods and the interpretation of the data. However, it was also clear that the need for reference methods was a priority. In fact, the efforts devoted to define all the details of a reference method at WHO meetings and later were continuous until 1970. The problem of the clinical interpretation (determination of the breakpoints) seemed too controversial at the international level, and the second WHO Committee suggested that this area should be the concern of a ‘National Authority’. Consequently, the role of a National Committee is mainly in the field of interpretation. Nevertheless, in the past 20 years an important number of new techniques, devices and machines (more or less automated) have been proposed to simplify and accelerate the work of clinical laboratories. All these approaches cannot be accepted without a control. A national network of medical microbiology laboratories specializing in antibiotic evaluation has to play a role in this control under the supervision of a National Reference Center for Antibiotics. Evaluation of a new technique is not always easy. Some methods provide values that can be directly compared with the MIC determined by the reference methods defined at the international level. However, many others, automated or not, are intended to directly characterize clinically the strains studied. In certain instances, it is possible, using the basic principle of the proposed new technique, to perform a quantitative study in an attempt to correlate its results with those of the reference method. When this is not possible, the study of reference strains from the National Reference Center may provide a good approximation to decide if the technique is valuable or not, or has to be adjusted. Many of these evaluations can be performed in agreement with the manufacturer, who provides supplementary information and materials. The results are often confidential or not sufficient to justify a scientific publication. Since the clinical laboratories of a country need to be informed of the exact value of a new technique, the role of the National Committee is important in discussion and in informing all the medical microbiology laboratories. Such a Committee is even worthwhile for the adequate use of the new methods nationwide. As already pointed out, the major role of a National Committee is to decide on values of the breakpoints that delineate the clinical categories. The subject is controversial, as pointed out by Garrod at the first W H O meeting, because of the two definitions of resistance. The first is related to the pharmacologic data on the antibiotic concentrations achieved at the site of infection. The second is related to genetic alterations of the bacteria which, consequently, allow growth in the presence of an antibiotic concentration higher than that inhibiting the so-called susceptible bacteria. This latter notion has been exemplified since 1947 by the p-lactamase-producing strains of staphylococci. Depending on the relative importance attributed to one or the other factor, the value of the breakpoint relies heavily on judgment and experience. It is important to specify the various factors that have to be taken into account at a national level to adopt a particular breakpoint. All antibiotics are not widely used at the same time in all countries, in particular the recent molecules. The need for breakpoints is especially urgent when a new drug appears on the market. The breakpoints cannot be selected irrespective of those already chosen for the other members of the antibiotic family. A National Committee has to balance the intrinsic activity and the pharmacology of the new drug comparatively with the other members of the same family. Under certain circumstances, a particular

Three pairs of latamoxef (moxalactam)-resistant and -sensitive strains of Serratia marcescens were isolated either in vivo or in vitro. Multiple mechanisms of resistance were found, and these mechanisms involved: a decrease in permeability in each case, associated with modification of the protein composition of the outer membrane in two cases; a variable increase (two-to-six-fold) in the amount of beta-lactamase; and in one case only, some modification of the penicillin binding proteins. Thus, it may be necessary for multiple mechanisms to be present to give resistance to latamoxef in this species.

This review of spiramycin activity in vitro is based mainly on early studies. The MICs of spiramycin for common pathogenic bacteria such as staphylococci, streptococci and pneumococci are higher than those of erythromycin. Conversely, in experimental models, the activity of spiramycin is equal to or greater than that of erythromycin. In addition, the activity of spiramycin on Neisseria, Legionella, Mycoplasma, Chlamydia, and Toxoplasma spp. completes its antimicrobial spectrum and shows that spiramycin covers the majority of agents responsible for respiratory tract infections. The 'spiramycin paradox'-the discrepancy between the relatively modest activity of spiramycin in vitro and its excellent activity in vivo will be explained by other papers. Its high tissue and intracellular concentrations, and the slow recovery of bacteria submitted to spiramycin are of great importance to account for its activity in vivo.

Two plasmids determining resistance to tetracycline (RIP500) and to chloramphenicol, erythromycin, lincomycin, and pristinamycin I (RIP501) were isolated from a strain of Streptococcus agalactiae . The frequency-of-resistance loss is very low for RIP500 (4 ) but higher for RIP501 (the efficiency was dependent upon the curing agents and incubation temperature and varied between 0.5 and 96%). Derivatives susceptible to all drugs were also obtained. RIP500 and RIP501 have similar molecular weights (17.9 × 10 6 and 20 × 10 6 , respectively) and represent different percentages of total deoxyribonucleic acid (0.4 and 4%, respectively). The number of copies of RIP500 and RIP501 per cell is different, and these plasmids are likely replicated under different kinds of control (stringent and/or relaxed). No plasmid deoxyribonucleic acid was found in a derivative of strain B96 susceptible to all drugs.

Two plasmid-linked tetracycline resistance characters, tet A and tet B, were distinguishable in part, according to the level of resistance they conferred to minocycline (tet A; >6 μg/ml for tet B). Escherichia coli K-12 strains that harbored the tet B character were also resistant to tetracycline but susceptible to chelocardin. In such tet B strains, subinhibitory concentrations of tetracycline could induce resistance to chelocardin as well as to otherwise inhibitory concentrations of tetracyclines. Chelocardin itself was ineffective as an inducer and therefore could be used to select constitutively resistant mutants. E. coli K-12 strains harboring the tet A character were also resistant to tetracycline and susceptible to chelocardin; tetracycline did not induce resistance to chelocardin in these strains.

SUMMARY: Phylogenetic and epidemiological relatedness among transferable plasmids belonging to the IncC, IncM and IncH incompatibility groups has been studied by DNA-DNA filter hybridization. Hybridization was carried out on nitrocellulose microfilters, at low temperature, in formamide and under paraffin oil. The degree of hybridization among plasmids belonging to the IncC and IncM groups supported the conclusions drawn from genetic classification. Studies on relatedness among plasmids belonging to the IncH group allowed their classification into three phylogenetic sub-groups. Comparison of DNA sequences of three plasmids sharing the same genetic properties and isolated from different bacterial species suggested an epidemiological spread of the same plasmid.

Resistance plasmids isolated from Streptococcus agalactiae (group B) and S. faecalis (group D) have been compared in regard to resistance markers, molecular weight, and DNA-DNA homology. Three of them (pIP501, pIP612, and pIP613) have been found to confer identical (or very similar) resistance patterns (erythromycin, lincomycin, and streptogramin B, respectively) and to have similar molecular weights (19.8 × 10 6 , 22.7 × 10 6 , and 17.6 × 10 6 , respectively) and a high level of DNA-DNA homology in hybridization experiments (90 to 100%). These results are compatible with the view that these plasmids may derive from one common ancestor, and/or that they can be transferred between unrelated Streptococcus strains belonging to the same or different groups.

HR 756, the syn derivative of 7-[(2-(2-amino-4-thiazolyl)-2-methoxyimino)acetamido]cephalosporanic acid, is a new semisynthetic cephalosporin. It was 80 times more active than the anti derivative against β-lactamase-producing strains of gram-negative bacteria. The range of inhibitory concentrations of HR 756 against gram-negative bacteria, including Haemophilus influenzae , susceptible or resistant to penicillins and cephalosporins was from 0.01 to 0.1 μg/ml. This activity was consistently higher than those observed with cephalothin, cephaloridine, cephalexin, and cefazolin. Nevertheless, some strains of Enterobacter cloacae were resistant. HR 756 showed very similar activity to that of ampicillin against group A streptococci and Streptococcus pneumoniae .

Twenty-one drug-resistant clinical isolates of group B streptococci were investigated for drug-resistance transfer by conjugation. Six strains were resistant to tetracycline, two to chloramphenicol, one to both drugs, and twelve to macrolide antibiotics (erythromycin, oleandomycin and spiramycin), lincomycin, pristinamycin I, and/or chloramphenicol and tetracycline. Ten strains carried R plasmids which were transferable to group B and/or group D recipients by a conjugation-like phenomenon. Six plasmids were transferred at a high frequency (9 × 10−2 to 4 × 10−4) and four, at low frequency (5 × 10−6 to 7 × 10−8). The molecular weight of one plasmid (pIP501) was investigated after transfer into the new hosts and was found to be similar to that carried by the wild strain (19.8 × 106).

“METHICILLIN resistance” has been found in a number of strains of staphylococcus isolated in French hospitals. Chabbert and Baudens1 found in 1961 that ten of eighty-two strains investigated (12 per cent) were resistant to methicillin. In 1962 they found twenty-one resistant strains out of 127 (17 per cent), and in 1963 twenty-six out of 134 (19 per cent)2,3. Courtieu et al.4 found a similar picture in their investigation of hospitals in other parts of France. In 1964 they found thirty-one resistant strains out of 216 (14 per cent). The frequency found in France seems to be different from that found among strains isolated in England and the United States5–8.