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PubMed1997

[Isolation and biological characterization of Legionella pneumophila mutants resistant to aminoglycoside antibotics and their protective action].

Preliminary estimation of virulence in some antibiotic resistant mutants of Legionella pneumophila, Philadelphia 1 in various models of infection revealed its decrease in the mutants resistant to azlocillin, cefotaxime, fluoroquinolone LIB-80, neamine and streptomycin. Detailed investigation of the neamine resistant mutants showed that in relation to streptomycin susceptibility such mutants could be divided into 3 classes: susceptible to streptomycin, resistant to high concentrations of streptomycin and resistant to moderate concentrations of streptomycin. Part of mutants Nea(r)Strr and Nea(r)Strr500 and all mutants Nea(r)Strr100 proved to be less virulent with respect to guinea pigs and chick embryos. The study of the spectinomycin resistant mutants of Legionella spp. did not reveal any changes in the virulence which made it possible to suggest that the influence of the mutations in the ribosomal protein genes determining resistance to streptomycin and neamine on virulence of L. pneumophila was based on the interdependence of the mutant effect on the suppression and the influence on the virulence detected by us in S. flexneri, Y. pseudotuberculosis, L. monocytogenes and F. tularensis. The Legionella mutants Nea(r)Strr100 were characterized by significant protective activity and protected immunized guinea pigs when tested in a model of their aerogenic infection.

Animals↗
PubMed1997

Antibiotic susceptibility of Neisseria gonorrhoeae in Trinidad and Tobago.

Treatment failures with standard doses of penicillin have been observed in the Sexually Transmitted Diseases (STD) clinics in Trinidad and Tobago. In the absence of an ongoing surveillance system, the antimicrobial susceptibility of 518 Neisseria gonorrhoeae strains was determined in order to guide treatment. 39 (7.6%) strains were resistant to penicillin, including 27 (5.2%) positive for beta-lactamase; that is penicillinase-producing Neisseria gonorrhoeae (PPNG). 51 (10%) strains were resistant to tetracycline, with 26 (5.0%) of these exhibiting high levels of resistance compatible with tetracycline resistant Neisseria gonorrhoeae (TRNG). Six strains showed evidence of having both PPNG and TRNG plasmids, and five strains showed chromosomally-mediated resistance to both penicillin and tetracycline. The overall resistance rate to penicillin and tetracycline was 17.7%. There was no resistance to spectinomycin, cefuroxime, ceftriaxone and norfloxacin. The resistance rates demonstrated in this study are sufficiently significant to preclude the use of penicillin and tetracycline in the STD clinics and to justify the use of newer antimicrobials. It is essential that resistance patterns be monitored by continued surveillance.

Female↗
PubMed1998

[Pharmacologic interactions of antibiotics and psychotropic drugs].

By and large, pharmacokinetic interactions are described: macrolide antibiotics, isoniazid, ciprofloxacin and ampicillin can lead to toxic concentrations of psychotropic drugs, while rifampicin causes subtherapeutic levels. Vice versa, carbamazepine might induce subtherapeutic plasma concentrations of doxycycline. These interactions are caused by inhibition or induction of the hepatic cytochrome P450 enzyme system. Case reports suggest lithium intoxication through concomitant use of tetracycline, metronidazol and spectinomycin, which is contradicted by animal studies. Clinical symptoms depend on the therapeutic index of a given drug, e.g. toxic and subtherapeutic levels are described for clozapine but not for haloperidol. No relevant pharmacodynamic drug-drug interactions are described, although, the author emphasises psychiatric side effects of macrolide antibiotics, isoniazid, beta-lactam antibiotics and fluoroquinolones. On the whole, drug-drug interactions of antibiotics and psychotropics seem rare and usually benign, though more subtle interactions might be overlooked.

Anti-Bacterial Agents↗
PubMed1994

Susceptibility of avian mycoplasmas isolated in Taiwan to 21 antimicrobial agents.

Twenty-one antimicrobial agents were incorporated individually into Frey's agar to evaluate their inhibitory activities against 86 isolates of avian mycoplasmas recently detected in Taiwan. Among them, 45 and 37 isolates were found positive with Mycoplasma gallisepticum and Mycoplasma synoviae fluorescent antibody conjugate, respectively. Twenty-one other isolates were unable to be identified by the above 2 conjugates. All of the field isolates were highly sensitive (with MIC50 < 1 microgram/ml) to enrofloxacin, gentamicin, myplabin, tiamutin and tylosin. However, those field isolates were highly resistant (with MIC50 > 32 micrograms/ml) to apramycin, chlortetracycline (CTC), erythromycin (ER), flumequine (FI), nalidixic acid (NA), oxolinic acid (OA), oxytetracycline (OTC) and spiramycin (SP). The inhibitory activities of the antibiotics which possessed an MIC90 of 50 micrograms/ml or less against local isolates were, in decreasing order, enrofloxacin (< 0.004 microgram/ml), gentamicin (1.53 micrograms/ml), tiamutin (1.81 micrograms/ml), tylosin (3.2 micrograms/ml), streptomycin (SM; 12.0 micrograms/ml), colistin (13.1 micrograms/ml), chloramphenicol (14.0 micrograms/ml), spectinomycin (15.0 micrograms/ml), myplabin (16.0 micrograms/ml), spiramycin (30.0 micrograms/ml), minocycline (32.0 micrograms/ml). The MIC90 of OA, CTC, SM, FI, SP, OTC, ER or NA was greater than 50 micrograms/ml; which work poorly in the control of mycoplasmoses. Since the antibiotic control policy is quite loose in Taiwan, many antimicrobial agents are often freely used in clinics, with a resulting gradual decrease in the inhibitory activity to the avian mycoplasmas.

Animals↗
PubMedDate not supplied

Effect of gentamicin on early mortality and later performance of broiler and Leghorn chickens.

Field and floor-pen trials demonstrated that subcutaneous injection of 0.2 mg gentamicin at one day old reduced bacteria-caused deaths in White Leghorn and broiler-type chicks. Growth, feed efficiency, and condemnation data from broiler trials suggested an advantage for treated chickens over unmedicated controls. Ninety-nine percent of clinical isolates were susceptible to gentamicin (10 mug) when tested by the modified Kirby-Bauer method. In vitro susceptibilities of these isolates to neomycin, nitrofurazone, chloramphenicol, and kanamycin varied from 90 to 94%. About half of the isolates were susceptible to dihydrostreptomycin or tetracycline in vitro, while less than 10% were susceptible to penicillin or clindamycin. In vitro tests to determine the lowest concentration of antibiotics required to inhibit the growth of 31 bacterial isolates demonstrated that less gentamicin is required than neomycin, spectinomycin, or oxytetracycline.

Animals↗
PubMed1976

CSTRIP, a fortran IV computer program for obtaining initial polyexponential parameter estimates.

A new exponential stripping program, CSTRIP, has been developed. This program overcomes the problems associated with the use of previously published techniques and enables the rapid economical calculation of initial polyexponential parameter estimates. Values for the coefficients and exponents of the exponential terms are calculated as well as estimates of lag times. An exhaustive search procedure ensures that the results are comparable to, or better than, those obtained by manual residual methods.

Computers↗
PubMed1980

Particle-size analysis of pharmaceutical powders.

An automated electrolytic sensing zone (electrozone) method was developed to determine the particle-size distribution of milled and micronized pharmaceutical powders. The powdered drugs obeyed log-normal statistics, and the distributions were well defined by thier geometric volume mean diameter and the geometric standard deviation. The results show that accurate data can be obtained between 2 and 80 micron with a precision of approximately 0.5 micron. Pulse-width analyses were performed to determine the feasibility of using a pulse-width discrimination program. However, in this case, the program discriminates against real particles and, therefore, its usefulness is limited. Milled and micronized materials are described adequately by a spherical diameter, and the automated electrozone system described is an excellent method for quality control purposes.

Chemistry, Pharmaceutical↗
PubMed1985

INTRAV and ORAL: BASIC interactive computer programs for estimating pharmacokinetic parameters.

Two interactive computer programs, INTRAV and ORAL, were written to permit pharmacokinetic modeling of experimental data and to obtain pertinent values based on derived estimates. Both programs utilize BASIC language and were developed on a microcomputer with graphics capability. Drug concentration in blood, plasma, or serum with time following either nonabsorptive (intravenous) or absorptive (oral or intramuscular) administration is input, and a semilogarithmic display of data appears on a cathode-ray tube (CRT). The user selects limits for various linear segments using a movable cursor. On command, coefficients and exponents for the differential equation which describes those limits is computed and a nonlinear curve is fitted through the data set. Results from statistical tests are available in output formats permitting the user to determine the goodness of the selected limits. Commonly used pharmacokinetic parameters are also computed and appear on the output. Numerous graphic output options are also available to permit comparisons between data sets and/or estimates derived from other computer programs. INTRAV and ORAL were compared with the widely used programs CSTRIP, ESTRIP, and NONLIN. Both INTRAV and ORAL gave estimates which were almost identical with CSTRIP and ESTRIP, whereas those obtained with NONLIN were very similar, although not identical.

Computers↗
PubMed1988

A new criterion for selection of pharmacokinetic multiexponential equations.

In linear pharmacokinetics, the time course of the plasma concentration of a drug, Ct, is expressed by the sum of exponential terms, (formula; see text) This article proposes a new statistical criterion for discriminating between alternate polyexponential models. According to this new criterion, the model that best interprets a set of experimental data points is that which minimizes the area between the approximate confidence limits of Ct.

Doxorubicin↗
PubMed1996

The dynamic structure of EF-G studied by fusidic acid resistance and internal revertants.

We have previously identified 20 different fusidic acid-resistant alleles of fusA, encoding mutant forms of the ribosomal translocase EF-G. One of these, P413L, is used here as the starting point in selections for internal revertants, identifying 20 different pseudo-wild-type forms of EF-G. We have also identified two alleles of fusA previously isolated as suppressors of 4.5 S RNA deficiency. All of these mutants are analysed in terms of their effects on the structural dynamics of EF-G. Most mutation conferring fusidic acid-resistance interfere with conformational changes of EF-G, but some may be located at a possible fusidic acid binding site. Revertants of the P413L mutations restore the function of EF-G with or without affecting the level of resistance to fusidic acid. The revertant mutations probably restore the balance between the GDP and GTP conformations of EF-G off the ribosome, and most of them are located close to the interface between the G domain and domain II. The procedure for the isolation of pseudo-wild-type forms of EF-G can be used to direct evolution progressively away from the wild-type while still maintaining the essential functions of EF-G.

Anti-Bacterial Agents↗
PubMed1996

Structural and segregational stability of various replicons in Actinobacillus actinomycetemcomitans.

Few vectors suitable for cloning in Actinobacillus actinomycetemcomitans, a periodontal pathogen, have been described. These plasmids were based either on the native A. actinomycetemcomitans replicon, pVT736-1, or derivatives of the IncP and IncQ family of plasmids. Their usefulness as cloning vectors is limited because of instability or size. Therefore, the ability of additional replicons to function in A. actinomycetemcomitans was evaluated. Derivatives of p15A, ColE1/f1, and pWV01 transformed A. actinomycetemcomitans efficiently and exhibited no structural instability in the new host. The stable maintenance of A. actinomycetemcomitans-specific DNA fragments inserted into the p15A derivative, pDMG4, demonstrated the ability of this plasmid to function as a cloning vector. In addition, pVT736-1 was used to clone selectable markers directly into A. actinomycetemcomitans. These constructs were structurally and segregationally stable.

Aggregatibacter actinomycetemcomitans↗
PubMed1978

Mapping of the resistance genes of the R plasmid NR1.

The drug resistance genes on the r-determinants component of the composite R plasmid NR1 were mapped on the EcoRI restriction endonuclease fragments of the R plasmid by cloning the fragments using the plasmid RSF2124 as a vector. The sulfonamide (Su) and streptomycin/spectinomycin (Sm/Sp) resistance genes are located on EcoRI fragment G of NR1. The expression of resistance to mercuric ions (Mer) requires both EcoRI fragment H and I of NR1. The expression of chloramphenicol (Cm) and fusidic acid (Fus) resistance requires EcoRI fragments A and J of NR1. The kan fragment of the related R plasmid R6-5 can substitute for Eco RI fragment J of NR1 in the expression of Cm and Fus resistance. The structural genes for Cm and Fus resistance appear to be a part of an operon whose expression is controlled by the same promoter.

Chloramphenicol↗
PubMed1979

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.

Ampicillin↗