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PubMed1981

Physiological properties of penicillin-binding proteins in group A streptococci.

We detected five major penicillin-binding proteins (PBPs) in group A streptococci by labeling either cell membrane preparations or live bacteria with tritiated penicillin. All PBPs appeared to be equally accessible to penicillin in vitro and in vivo. Individual PBPs differed in their rates of deacylation, and four of the five PBPs underwent rapid inactivation both in vivo and in vitro. At least two processes seemed to contribute to in vivo inactivation; these were (i) a penicillin-induced release of all five PBPs into the growth medium and (ii) degradation, as evidenced by the appearance of penicillin-labeled protein band of lower molecular weight and also by a gradual increase in material migrating with the same electrophoretic mobility as PBP 3. Inactivation of the PBPs was stimulated greatly by pretreatment of bacteria with gentamicin, cerulenin, or Triton X-100, whereas chloramphenicol, tetracycline, and lincomycin treatments had no such effect.

Anti-Bacterial Agents↗
PubMed1972

Antibiotic susceptibility testing of Bacteroides.

Seventy Bacteroides strains isolated from clinical materials were tested in vitro against nine antibiotics by means of modified disc diffusion and agar dilution tests. Correlating the agar dilution susceptibility with the concentrations achievable in serum for each drug tested, we found that at least 90% of the strains were susceptible to clindamycin, chloramphenicol, carbenicillin, and lincomycin. Only 40% were susceptible to tetracycline. Except for tetracycline and chloramphenicol, the disc diffusion technique exhibited inadequate predictive value in terms of "susceptibility" and "resistance" for the Bacteroides strains tested.

Agar↗
PubMed1972

Binding of antibiotics to bovine and ovine serum.

The degree of binding of 37 antibiotics to bovine and ovine serum, after treatment at therapeutic doses, was determined by equilibrium dialysis and ultrafiltration methods. In general, binding values obtained by the two methods were comparable. The extent of binding varied from 0% for cephaloridine and kanamycin to >95% for novobiocin and fusidic acid. Of the 37 drugs studied, one-fourth were less than 25% bound, one-fourth were more than 75% bound, and the percentage binding of about half of the antibiotics ranged from 25 to 75%. Animal to animal variations in the extent of binding of a particular antibiotic were very small. The capacity of bovine or ovine serum to bind antibiotics was, with a few exceptions, similar to the reported capacity of human serum. At drug concentration ranges usually achieved during therapy, variations in drug levels in serum did not influence the degree of binding except with cephalexin, lincomycin, clindamycin, and chloramphenicol. With these antibiotics, the extent of binding increased two- to sevenfold with the decrease in drug concentration in serum.

Animals↗
PubMed1972

Standardized antimicrobial disc susceptibility testing of anaerobic bacteria: in vitro susceptibility of Clostridium perfringens to nine antibiotics.

The in vitro susceptibility of 43 strains of Clostridium perfringens to nine antibiotics was determined by a standardized test for rapid-growing anaerobes. Good correlation was established between the agar dilution susceptibility and the disc diffusion susceptibility results. The inhibition zone diameters around the antibiotic discs, however, were generally much smaller than those of gram-negative anaerobes previously studied. All of the strains tested were susceptible in vitro to chloramphenicol, clindamycin, doxycycline, minocycline, penicillin, and vancomycin. Erythromycin showed poor in vitro activity against this organism, with only 7% of the strains susceptible, 72% intermediate in susceptibility, and 21% resistant. In tests of the 43 strains against lincomycin, 58% were susceptible, 32.5% were intermediate in susceptibility, and 9.5% were resistant. Against tetracycline, 37% of the strains were intermediate in susceptibility and the rest were susceptible.

Anaerobiosis↗
PubMed1982

Antibiotic entry into human polymorphonuclear leukocytes.

Since bacteria which survive within phagocytes may produce serious infection, antibiotics which inactivate these intracellular organisms are needed. To establish those factors which mediate entry of antimicrobial agents into human phagocytes, we studied the uptake of 13 radiolabeled antibiotics by peripheral blood polymorphonuclear leukocytes (PMN). At intervals during a 2-h incubation period, antibiotic uptake by PMN was determined by means of velocity gradient centrifugation, which separates the cell-associated antibiotic from the extracellular antibiotic. Penicillin G and three cephalosporin antibiotics penetrated PMN poorly. The ratio of cellular concentration to extracellular concentration (C/E) of these drugs was less than 0.01 to 0.5. For gentamicin and isoniazid, the C/E values were approximately 0.8 to 1.0. Chloramphenicol, rifampin, and lincomycin, antibiotics with good lipid solubility, were concentrated twofold (C/E = 2) in PMN. Ethambutol (C/E = 5), clindamycin (C/E = 11), and two erythromycin preparations (C/E = 10 to 13) were markedly concentrated within PMN. Clindamycin uptake was rapid: greater than 70% of the total drug entry occurred within the first minute. Accumulation of clindamycin and erythromycin was an active, energy-requiring process, dependent at least in part upon glycolysis. Clindamycin entered PMN by means of an active membrane transport system which was saturable and had a high binding affinity (Km = 2 mM) and maximum velocity of uptake (Vmax = 5 nmol/45 s per 10(6) cells). These observations, together with studies of the biological consequences of intracellular antibiotics, should lead to more effective therapy for infection due to intracellular pathogens..

Anti-Bacterial Agents↗
PubMed1982

Transferable resistance to cefoxitin in Bacteroides thetaiotaomicron.

Cefoxitin resistance, but not resistance to clindamycin, erythromycin, lincomycin, or tetracycline, was transferred by a conjugation-like process from Bacteroides thetaiotaomicron UN101, a clinical isolate haboring four kinds of plasmids, to other Bacteroides species. Of a sample of 20 cefoxitin-resistant transconjugants, 8 contained all 4 plasmids, 10 contained 1 to 3 plasmids, and 2 contained no plasmids.

Bacteroides↗
PubMed1982

Activity of pirlimycin (U57930E) against strains of the Bacteroides fragilis group.

The activities of pirlimycin (U57930E), lincomycin, clindamycin, erythromycin, josamycin, oleandomycin, and spiramycin were compared against strains of the Bacteroides fragilis group. Pirlimycin was the most active; the 90% minimal inhibitory concentration was 1 microgram/ml, and the activity range was 0.125 to 4 micrograms/ml. This drug was fourfold more active than any of the other drugs, including clindamycin. The minimal bactericidal concentration (range, 0.5 to 16 micrograms/ml) shows that pirlimycin behaves as a bacteriostatic antibiotic.

Anti-Bacterial Agents↗
PubMed1983

Antimycoplasmal activity of ofloxacin (DL-8280).

Ofloxacin (DL-8280; (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- pipera-zinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid) showed a broader spectrum and a greater potency of antimycoplasmal activity than did pipemidic acid, norfloxacin, tetracyclines, and lincomycin, but was inferior to erythromycin. Its mycoplasmacidal potency against clinical isolates of Mycoplasma pneumoniae was also greater than that of other quinolones and tetracyclines.

Anti-Bacterial Agents↗
PubMed1985

Antibiotic uptake by alveolar macrophages of smokers.

Cigarette smoking, particularly when associated with chronic pulmonary disease, increases the risk of respiratory tract infection. Thus, we elevated the uptake of antibiotics by alveolar macrophages (AM) obtained by bronchoalveolar lavage from persons who smoke and have associated pulmonary abnormalities, circumstances which adversely affect certain macrophage functions. The entry of radiolabeled drugs into AM was determined by a velocity-gradient centrifugation technique, and uptake was expressed as the ratio of cellular to extracellular antibiotic concentration (C/E). Cefamandole and penicillin G were taken up poorly by the AM obtained from smokers (C/E less than or equal to 1). Cellular levels of isoniazid, gentamicin, and tetracycline were similar to their extracellular concentrations. The lipid-soluble drugs lincomycin, chloramphenicol, and rifampin were concentrated severalfold by the AM from smokers (C/E = 3 to 11). Ethambutol also entered macrophages readily (C/E = 11). Erythromycin and clindamycin were massively concentrated by the AM from smokers (C/E = 23 to 56). The AM of smokers accumulated a lipid-soluble antibiotic (rifampin) and actively transported agents (erythromycin propionate, clindamycin) more avidly than did the AM of nonsmokers. Augmented uptake of these antibiotics by the AM of smokers may be related to structural and functional alterations induced by smoking.

Adult↗
PubMed1985

Evidence for a disseminated erythromycin resistance determinant mediated by Tn917-like sequences among group D streptococci isolated from pigs, chickens, and humans.

A total of 199 streptococci isolated from feces of healthy chickens, pigs, and beef cattle and 26 human clinical isolates were tested for resistance to kanamycin, streptomycin, tetracycline, erythromycin, and lincomycin. Of 66 isolates resistant to these antibiotics, 12 transferred one or more resistance traits by conjugation in broth. Erythromycin resistance (Emr) was transferred from 10 of the 12 successful donors. AvaI digests of plasmids isolated from Emr transconjugants derived from two human, two chicken, and one pig isolate contained three fragments similar in size to those produced from Tn3871, an Emr transposon. The three fragments from each of the five digests on Southern blots hybridized to radiolabeled Tn3871. Plasmid DNA from a transconjugant derived from a second pig isolate contained two of the three Tn3871-associated AvaI fragments. One of the AvaI fragments from each of the six plasmids hybridized with a radiolabeled probe containing a cloned AvaI fragment from Tn3871 that contained the Emr determinant. Transposition of the Emr trait was demonstrated for the plasmids derived from one human and one pig isolate. We concluded that extensive DNA homology existed between plasmids from streptococcal strains obtained from two human patients, two chickens, and two pigs and the Emr transposon Tn3871, which is very similar or identical to the well-characterized Emr transposon Tn917. The detection of Tn3871-like sequences in streptococcal isolates from Arkansas, Illinois, North Carolina, and Washington, D.C. indicates wide dissemination of Emr mediated by the same or closely related transposons.

Animals↗
PubMed1987

High-performance liquid chromatography measurement of antimicrobial concentrations in polymorphonuclear leukocytes.

High-performance liquid chromatography was used to determine the penetration of 19 antimicrobial agents into human polymorphonuclear leukocytes. The ratios of the intracellular concentration to the extracellular concentration of ampicillin, piperacillin, cefazolin, ceftizoxime, cefpimizole, and ceftazidime were all less than 0.6. Lincomycin showed a high intracellular-to-extracellular ratio (3.0), while clindamycin achieved a ratio of 15.5, which was the highest ratio of all of the 19 tested antibiotics. Ratios for rifampin, isoniazid, chloramphenicol, and trimethoprim were 8.2, 1.1, 9.6, and 6.1, respectively. Six quinolone-class antimicrobial agents had ratios from 2.2 to 8.2. Flucytosine showed a penetration ratio of 4.6. Clindamycin uptake was temperature dependent and occurred best with live polymorphonuclear leukocytes; sodium fluoride, adenosine, and puromycin were inhibitory. The results obtained in this study correlate well with the results of other studies involving radioisotopic methods. This indicates that high-performance liquid chromatography is a useful method for determining the intracellular penetration of antimicrobial agents.

Adenosine↗
PubMed1987

In vitro antimicrobial activity against reference strains and field isolates of Treponema hyodysenteriae.

The in vitro susceptibilities of eight isolates of Treponema hyodysenteriae from pigs naturally infected with swine dysentery between 1976 and 1983 were determined by an agar dilution technique. Carbadox, olaquindox, tiamulin, metronidazole, furazolidone, and monensin were the most active against these field isolates regardless of the year of recovery. The influence of inoculum size on the MICs against four reference strains of T. hyodysenteriae was studied. Various degrees of activities of ampicillin and lincomycin were found, depending on the inoculum size. The effect of successive in vitro subcultures on the susceptibility of a reference strain of T. hyodysenteriae was examined. The strain resistant to tylosin became susceptible to the drug.

Anaerobiosis↗
PubMed1991

Comparison of methods for in vitro testing of susceptibility of porcine Mycoplasma species to antimicrobial agents.

The MICs of 18 antimicrobial agents used against strains of three porcine Mycoplasma species were determined by a serial broth dilution method. Twenty field strains of M. hyorhinis, ten field strains of M. hyopneumoniae, six field strains of M. flocculare, and the type strains of these species were tested. Twelve field strains and the type strain of M. hyorhinis were also tested by an agar dilution method. Tests were read at various time points. When the broth dilution method was used, the final MIC had to be read 2 days after color changes had stopped. MICs of tetracycline, oxytetracycline, doxycycline, and minocycline were low for the three Mycoplasma species tested. MICs of chlortetracycline were 8 to 16 times higher than MICs of the other tetracyclines. Spiramycin, tylosin, kitasamycin, spectinomycin, tiamulin, lincomycin, and clindamycin were effective against all strains of M. hyorhinis and M. hyopneumoniae. The quinolones were highly effective against M. hyopneumoniae but less effective against M. hyorhinis. The susceptibility patterns for M. hyopneumoniae and M. flocculare were similar.

Animals↗
PubMed1991

In vitro activities of aminoglycosides, lincosamides, and rifamycins against Mycobacterium leprae.

The in vitro activities of a variety of aminoglycosides, lincosamides, and rifamycins against Mycobacterium leprae were evaluated with the BACTEC 460 system. At 20 micrograms/ml, gentamicin, kanamycin, tobramycin, streptomycin, and amikacin were inactive. Lincomycin was active at 20 micrograms/ml, and clindamycin was active at 0.31 micrograms/ml. Rifamycin SV, rifabutin, and rifampin were active at 3.1, 3.1 to 12.5, and 200 ng/ml, respectively. The in vitro assay correlates well with the in vivo response of M. leprae to antimicrobial agents, with the exception of the aminoglycosides.

Aminoglycosides↗
PubMed1991

Role of intestinal excretion in the effect of subcutaneously administered sedecamycin on cecal infection caused by Treponema hyodysenteriae in mice.

The therapeutic effects of subcutaneously administered sedecamycin on experimental Treponema hyodysenteriae infection in mice were evaluated. Sedecamycin was more active than tiamulin and lincomycin. The efficacy of sedecamycin upon subcutaneous administration was similar to that upon oral administration. Sedecamycin given subcutaneously provided similar degrees of protection in bile duct-ligated and intact mice. Pharmacokinetic studies utilizing a liquid chromatographic technique were carried out to determine the concentration of sedecamycin in the cecum, the site of T. hyodysenteriae infection in mice. Little sedecamycin was found; however, lankacidinol, a major metabolite of sedecamycin, was found in the cecal contents of intact mice after subcutaneous or oral administration of sedecamycin. Lankacidinol was also found in the cecal contents of bile duct-ligated mice, although the concentration found after subcutaneous administration of sedecamycin was much lower than that found after subcutaneous or oral administration to intact mice. These results indicate that sedecamycin is excreted directly into the intestinal tract as an active metabolite by a route other than the bile duct. It is suggested that this intestinal excretion plays an important role in the efficacy of subcutaneously administered sedecamycin against cecal infection of mice by T. hyodysenteriae.

Animals↗
PubMed1993

In vitro antibiotic susceptibility testing of different strains of Mycoplasma fermentans isolated from a variety of sources.

The in vitro susceptibilities to antibiotics of 24 strains of Mycoplasma fermentans (isolated from human immunodeficiency virus type 1-infected AIDS patients, non-AIDS patients with acute respiratory disease, and tissue culture) were determined. MICs for 90% of the strains tested (micrograms per milliliter) were obtained for chloramphenicol (1.25), ciprofloxacin (0.078), clindamycin (0.078), doxycycline (0.625), erythromycin (> 10), gentamicin (> 10), levofloxacin (0.078), lincomycin (0.156), streptomycin (> 10), and tetracycline (0.625).

Acquired Immunodeficiency Syndrome↗
PubMed1993

Susceptibilities of Mycoplasma bovis, Mycoplasma dispar, and Ureaplasma diversum strains to antimicrobial agents in vitro.

The purpose of this study was to determine the susceptibility of various strains of Mycoplasma bovis, Mycoplasma dispar, and Ureaplasma diversum, which are prevalent causes of pneumonia in calves, to 16 antimicrobial agents in vitro. The MICs of the antimicrobial agents were determined by a serial broth dilution method for 16 field strains and the type strain of M. bovis, for 19 field strains and the type strain of M. dispar, and for 17 field strains of U. diversum. Final MICs for M. bovis and M. dispar were read after 7 days and final MICs for U. diversum after 1 to 2 days. All strains tested were susceptible to tylosin, kitasamycin, and tiamulin but were resistant to nifuroquine and streptomycin. Most strains of U. diversum were intermediately susceptible to oxytetracycline but fully susceptible to chlortetracycline; most strains of M. bovis and M. dispar, however, were resistant to both agents. Strains of M. dispar and U. diversum were susceptible to doxycycline and minocycline, but strains of M. bovis were only intermediately susceptible. Susceptibility or resistance to chloramphenicol, spiramycin, spectinomycin, lincomycin, or enrofloxacin depended on the species but was not equal for the three species. The type strains of M. bovis and M. dispar were more susceptible to various antimicrobial agents, including tetracyclines, than the field strains. This finding might indicate that M. bovis and M. dispar strains are becoming resistant to these agents. Antimicrobial agents that are effective in vitro against all three mycoplasma species can be considered for treating mycoplasma infections in pneumonic calves. Therefore, tylosin, kitasamycin, and tiamulin may be preferred over oxytetracycline and chlortetracycline.

Animals↗
PubMed1995

In vitro antibiotic susceptibility testing of clinical isolates of Mycoplasma penetrans from patients with AIDS.

In vitro susceptibilities of Mycoplasma penetrans were determined. MICs and MBCs were determined. The MICs at which 50% of the isolates are inhibited (micrograms per milliliter) for broth dilution testing were as follows: azithromycin, 0.039; chloramphenicol, 0.625; ciprofloxacin, 0.156; clindamycin, 0.078; doxycycline, 0.312; erythromycin, 0.312; gentamicin. > 10; levofloxacin, 0.078; lincomycin, 0.625; streptomycin, > 10; and tetracycline, 1.25. Bactericidal activity was significant only for ciprofloxacin (MBC at which 50% of the isolates are killed, 0.312 microgram/ml) and levofloxacin (MBC at which 50% of the isolates are killed, 0.312 microgram/ml).

AIDS-Related Opportunistic Infections↗