Early studies on in-vitro and experimental activity of spiramycin: a review.

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.

[A study by the National Reference Center for Antibiotics on inocula for antibiotic sensitivity testing]. / Etude du Centre National de Référence des Antibiotiques sur l'inoculum de l'antibiogramme.

We compared the diameters of inhibition zones obtained during antibiotic sensitivity testing using two different techniques for preparing and seeding the inoculum, i.e. photometric adjustment followed by flooding, and turbidity adjustment followed by swab streaking. There was no significant difference between the results recorded following photometry-flooding of a light inoculum (2 to 3 X 10(6) CFU/ml) and following swab seeding of a bacterial suspension with a turbidity equal to 0.5 Mac Farland unit. These results indicate that both methods tested answer the NCCLS performance standards for disc antibiotic sensitivity testing and the critical values of the S.F.M. Antibiotic Sensitivity Testing Committee.

[Effect of ceftazidime on enterobacteria and Pseudomonas producers of beta-lactamases]. / Activité de la ceftazidime sur des entérobactéries et des Pseudomonas producteurs de beta-lactamases.

The activity of cephalotin, cefoxitin, cefamandole, cefoperazone, cefotaxime, latamoxef, thienamycin, azthreonam, cefsulodine and ceftazidime against beta-lactamase producing strains of Enterobacteriaceae and Pseudomonas was compared by determination of 99% inhibitory concentrations. The isogenic strains studied differed by a single genetic event: mutation, gene amplification, acquisition of a high or low copy-number plasmid or of a transposon and were representative of the major known mechanisms of resistance toward beta-lactams. The results obtained indicate an overall excellent activity of ceftazidime, in particular against Pseudomonas.

Different mechanisms of resistance to latamoxef (moxalactam) in Serratia marcescens.

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.

[In vitro action of moxalactam on hospital bacteria. Results of a multicenter survey]. / Activité in vitro de moxalactam sur les bactéries hospitalières. Résultats d'une enquête multicentrique.

The high potency of Moxalactam on three major groups of bacteria, i.e. Enterobacteriae, Haemophilus and Bacteroïdes, predicted by previous studies, has been confirmed by the study of hospital strains in this multicenter investigation. Among these groups, the proportion of resistant strains is very low. However, Moxalactam is not superior to older agents on staphylococci, Streptococci and Listeria, and is less active than certain new agents on Pseudomonas. Moxalactam is one of the best "third generation" cephalosporins. It is remarkable by its potency against Bacteroides fragilis and its weak activity on Streptococci and Pneumococci. The unanswered question concerns the future of resistant strains: will they remain exceptional or will they multiply?

Selection and characterization of beta-lactam-resistant Escherichia coli K-12 mutants.

beta-Lactam-resistant mutants of Escherichia coli K-12 were selected by using 12 different beta-lactam derivatives. The mutants fell into three categories showing (i) altered permeation through reduction or loss of outer membrane porin proteins (including ompF, ompR, and envZ alleles); (ii) increase in the rate of synthesis of chromosomally mediated beta-lactamase; or (iii) defective synthesis or action of cyclic adenosine 3',5'-phosphate (cya and crp alleles).

Comparative activity of cefotetan on Escherichia coli K12 possessing plasmid-mediated beta-lactamases.

The antibacterial activity of cefotetan, a new cephamycin, was compared with that of cephalothin, cefoxitin, cefamandole, cefoperazone and cefotaxime on 12 substrains of Escherichia coli K12 BM13 harbouring single and multi-copy plasmids coding for plasmid-mediated beta-lactamases TEM, SHVI, OXA-I and OXA-III. The 99% inhibitory concentrations (IC99) for the recipient strain were increased in proportion to the enzyme activity in the case of cefamandole and cefoperazone. In contrast, the activity of cefoxitin, cefotaxime and cefotetan was not significantly modified. Since these enzymes are responsible for the resistance of Enterobacteriaceae in the great majority of clinical isolates, cefotetan can be expected to be fully active against strains producing them. Cefotetan was not hydrolysed by chromosomal cephalosporinase and it was active against Enterobacter, Citrobacter and Morganella strains producing a low level of enzyme but hyperproducing variants were highly resistant to cefotetan.

Role of porin proteins OmpF and OmpC in the permeation of beta-lactams.

Mutants of Escherichia coli K-12 lacking major outer membrane proteins were obtained by selecting for resistance to the beta-lactam cefoxitin. Three classes of resistant strains were found: mutants in ompB, a regulatory locus for proteins OmpF and OmpC; mutants in ompF; and one mutant in tpo. The OmpF and OmpC proteins facilitate penetration of beta-lactams through the outer membrane.

Plasmid DNA content of multiresistant Staphylococcus aureus strains.

Multiresistant S. aureus strains (also called methicillin-resistant in clinical laboratories) share many common properties. In addition to the commonly used epidemiological markers (pattern of resistance to antibiotics and metal ions, serotype and lysotype), we considered using the molecular and genetical properties of the plasmid DNA harboured by these strains. In this paper we report an epidemiological study of two groups of S. aureus strains sampled since 1975 and carrying new resistance characters which appeared with increasing frequency in France. The Tm-SgR strains (5 strains) carry, in addition to 13 resistance characters commonly observed, two new characters: the resistance to gramin components A and B (Sg). The two new characters were shown to be encoded by a single plasmid. Amongst the 5 strains studied, two harbour a similar plasmid DNA content while the three others were clearly distinct. Because of the variability of the plasmid DNA content observed in these strains, the similarity of this content observed between two of them suggest a close phylogenic relationship. These two strains are probably derivatives from a single clone. The spread of the two new characters amongst the distinct strains might be related to the spread of ancestrally related Tm-Sg plasmids. The Tob-GenR strains (16 strains) carry, in addition to 12 wide-spread resistance markers, the newly observed resistance to many aminoglycosides, mainly the resistance to tobramycin (Tob) and gentamicin (Gen). They all harbour a 22-kb plasmid DNA generating similar restriction cleavage patterns and conferring the resistance to penicillin G, arsenate, arsenite and cadmium. Some of them harbour one or two extra small plasmids (3.4 and 2.3 kb); the presence of these two plasmids was not associated with a modification of the resistance pattern of the strains. Most of the resistance characters--including the new ones--are probably encoded by chromosomal genes. In this epidemiological situation, the spread of the new aminoglycoside resistance characters carried by the 16 strains having the same phenotype and harbouring the same 22-kb plasmid is attributed to the spread of derivatives from a single clone.

[Cefotaxime, syn isomer of a new methoxyimino cephalosporin with unusual activity (author's transl)]. / Le céfotaxime, isomère "syn" d'une nouvelle méthoxyimino-céphalosporine d'activité inhabituelle.

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

Reversible translocation of antibiotic resistance determinants in Salmonella ordonez.

Salmonella ordonez (BM 2000) codes for kanamycin (Km, aphA), ampicillin (Ap), streptomycin (SmSp:aadA and Sm:aphC), chloramphenicol (Cm), tetracycline (Tc) and sulfonamide (Su) resistances and for production of colicin Ib (Cib). Genetical analysis by incompatibility testing, conjugation, transformation and physical studies using electron microscopy, agarose gel electrophoresis, led us to associate the Km and Cib characters to a 98.7 kilobase (kb) IncI1 plasmid (pIP565), and the Sm (aphC) and Su determinants to a 8.3 kb plasmid (pIP605). The ApCmSmSp(aadA)SuTc determinants were not associated in BM2000 S. ordonez with a plasmid structure. Following conjugation of S. ordonez to E. coli, the ApCmSmSpSuTc determinants were found stably associated with a single plasmid structure (pIP173, 127.5 kb) belonging to IncI1 group. Agarose gel electrophoresis of plasmid DNA restriction endonuclease digests and electron microscopy heteroduplex analysis showed that the acquisition of the ApCmSmSpSuTc determinants resulted from the insertion into pIP565 of a 28.8 kb DNA sequence. This sequence coding for ApCmSmSpSuTu resistances in S. ordonez could be translocated either to pIP565 plasmid or to several IncI1 plasmids but never to plasmids belonging to IncW, IncP or IncFII, suggesting the existence of specific sequences on the IncI1 receptor plasmids. Moreover, R-determinants were translocated back "en bloc" from pIP173 to the chromosome of a susceptible S. ordanez. The results were consistent with the presence in BM2000 S. ordonez chromosomal DNA of an integrated translocatable sequence encoding ApCmSmSpSuTc resistances. Such a structural association could account for the stability of these resistances in the Salmonella ordonez serotype.

Determination of the ID50 values of antibacterial agents in agar.

Microorganisms were plated on agar plates containing various concentrations of an antimicrobial drug and inhibition of growth was determined at each drug concentration. The ID50 value and the gradient of the line were calculated by the least square method. When 200 approximately 800 bacterial cells were inoculated on an agar plate, growth inhibition corresponded linearly with the log concentration of a drug within range of 5 approximately 95% inhibition. The ID50 value and the gradient obtained were reproducible and reliable using microorganisms at stationary phase of growth with all tested bacterial species and all tested antimicrobial agents. It was found that the ID50 values of drugs were more reproducible and may be more reliable than the MIC (minimum inhibitory concentration) values of the drugs.

HR 756, the syn isomer of a new methoxyimino cephalosporin with unusual antibacterial activity.

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 beta-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 mug/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.