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PubMed1984

[Influence of the inoculum effect on the MIC and MBC of 5 beta-lactams against Pseudomonas aeruginosa].

MICs and MBCs of five beta-lactams , i.e. ticarcillin, azlocillin, piperacillin, cefsulodin and ceftazidime for 20 strains of Pseudomonas aeruginosa were studied with inocula ranging from 10(3) to 10(9) CFU/ml. Each antibiotic exhibited an inoculum effect at 10(5)-10(7) CFU/ml. However, ticarcillin had smaller MIC and MBC increments than the four other drugs, making it more suitable in certain cases.

Anti-Bacterial Agents↗
PubMed1981

[Pharmacokinetic of antibiotics in patients with mucoviscidosis (author's transl)].

Inadequate therapeutic results in the treatment of bacterial infections in patients with Cystic Fibrosis prompted a reevaluation of pharmacokinetic parameters of orally and parenterally administered drugs in these patients. Gentamicin, Azlocillin and Ticarcillin are eliminated faster in patients with Cystic Fibrosis. Serum concentrations show a rapid decrease over 60 to 90 minutes and surpass MIC values of Pseudomonas isolates for a maximum of only 60 minutes. 70% to 90% of the administered amount of drug is eliminated within two hours in the urine. Concomitantly determined clearance rates for creatinine didn't show abnormalities, however they pointed towards an additional tubular secretion of Gentamicin which is not seen in healthy controls. Cephalexin, Epicillin and both components of Cotrimoxazol show a delay in oral absorption. The renal elimination of Cephalexin and Trimethoprim is unaltered, but the excretion of Epicillin and Sulfametrol is enhanced again. This is seen by a delay and decrease in the maximal serum concentration (Cmax), but increased urine recovery. Doubling of the dose of gentamicin administered as i. v. infusion over 45 to 60 minutes results in smooth serum curve, the MIC values of most encountered organisms are surpassed for 3 hours and more. The clinical applicability of this recommendation however awaits further investigations concerning efficacy and safety.

Adolescent↗
PubMed1993

Effects of different antibiotics on the endothelium of the porcine aortic valve.

Homograft heart valves are usually sterilized by exposure to multiple-antibiotic solutions at 4 degrees C for 24 hours. Several combinations of antibiotics have been proposed and discussed in the literature, but their toxicity to cusp endothelium has not been investigated yet. We studied the endothelial cell viability of porcine aortic valves by measuring their in vitro prostacyclin (PGI2) production after being exposed to different antibiotics solutions. Porcine aortic valves were immersed for 24 hours at 4 degrees C in RPMI medium to which antibiotics (Gentamycin 80 micrograms/ml, Azlocillin 500 micrograms/ml, Cloxacillin 25 micrograms/ml, Metronidazole 100 micrograms/ml, Amphotericin B 50 micrograms/ml, GACMA) were added separately or in combination. The basal and bradykinin (10 microM) stimulated PGI2 release of these valves in the medium were measured during consecutive incubation lasting 15 minutes at 37 degrees C, using a radioimmunoassay for 6-oxo-PGF1 alpha. Valves treated with the combination of all five antibiotics produced significantly less PGI2 in basal and stimulated conditions (1.64 +/- 0.63--7.25 +/- 1.73 ng/ml x cm2, p < 0.05) than the controls (4.66 +/- 0.66--30.55 +/- 3.84 ng/ml x cm2, p < 0.001). Although all antibiotics, when studied separately at the above mentioned concentrations, tended to reduce the biosynthesis of PGI2, amphotericin B was responsible for the most pronounced decrease in its production. The toxic effect of amphotericin B was dose dependent; at a low concentration (5 micrograms/ml), which is usually enough for antifungal action, toxicity was undetectable. At 50 micrograms/ml PGI2 production was half of that found at 5 micrograms/ml, although concentrations as high as 100 micrograms/ml have been used clinically to disinfect homografts. Scanning electron microscopy (SEM) also confirmed the extensive loss of endothelium after exposure to high concentrations of amphotericin B. Our study suggests that the other four antibiotics used in the concentrations described above do not damage endothelial function; amphotericin B is also harmless if used at a concentration of 5 micrograms/ml.

Amphotericin B↗
PubMed1994

[A method of sequential administration of antibiotics in preventive treatment of experimental plague in albino mice].

Combination of a betalactam antibiotic (ampicillin or azlocillin) or polymyxin B with rifampicin were studied with their administration in succession at various intervals in an experimental model of plague infection of albino mice. It was shown that when the administration of the betalactams or polymyxin B preceded the administration of rifampicin, the efficacy of the preventive therapy considerably increased. The time of the intervals was noted to be of importance and should be predetermined for every subsequent administration.

Ampicillin↗
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↗
PubMed1982

Cefsulodin pharmacokinetics and otitis media.

The pharmacokinetics of cefsulodin in the fluids of the ear and eye as well as in serum were studied after intramuscular administration of 200 and 400 mg/kg to eight groups of six guinea pigs. A retention of cefsulodin in the inner ear-similar to that of the aminoglycoside antibiotics - was observed. As the measured perilymph concentrations of cefsulodin and gentamicin are comparable on a weight for weight basis and as the clinical dosage of cefsulodin is much higher than that of gentamicin, the perilymph concentrations of cefsulodin reached in man are probably much higher than those of gentamicin. The results obtained are compared to those of mezlocillin, azlocillin and fosfomycin, Finally, the importance of the cefsulodin perilymph concentrations in the treatment and prophylaxis of infectious inner ear complications due to the most common pathogens of chronic otitis media as well as in the treatment of certain eye infections is discussed.

Animals↗
PubMed1988

Therapy of experimental listeriosis--an evaluation of different antibiotics.

The therapeutic activities of various antibiotics were evaluated in two murine models, i.e. the infection of normal mice as well as of nude mice. Coumermycin and rifampicin were the most active drugs, since not only inhibition of multiplication but also rapid elimination of Listeria monocytogenes could be achieved in normal and immunocompromised animals. Ampicillin was the most active beta-lactam antibiotic followed by azlocillin. The other beta-lactam antibiotics were definitely less active. The combination of ampicillin with gentamicin expressed no synergistic effect in vivo. Co-trimoxazole as well as ciprofloxacin were of moderate therapeutic value. The bacteriostatic drugs such as tetracycline and erythromycin were able to inhibit the bacterial multiplication in the normal mouse but not in the immunocompromised host. Thus an optimal drug for therapy of listeriosis does not yet exist.

Aminocoumarins↗
PubMed1982

Empiric antibiotic treatment of infections in myelosuppressed cancer patients. Preliminary results.

A prospective, randomized study was performed to compare the efficacy and safety of mezlocillin plus sisomicin (Regimen A) and cefamandole plus tobramycin (Regimen B). Sixty-one episodes of documented infections were treated in 49 adult myelosuppressed cancer patients. About two-thirds of the patients treated with either regimen responded to this antibacterial therapy. The patients failing to respond to the initial therapy were treated with additional antibiotics, either with the empiric Regimen C (cefotaxime plus amikacin plus azlocillin) or with antibiotics selected on the basis of bacteriological results (Regimen D). With these schedules, the over-all response rate was increased to about 90%. The data suggest that febrile granulocytopenic cancer patients may profit from this empiric and sequential antibiotic treatment.

Adult↗
PubMed1979

Antibacterial active components in human urine after administration of penicillins.

Four-hourly urine from volunteers and patients who had received penicillins orally or intravenously was investigated by means of thin layer chromatography and bioautography. Antibacterially active metabolites were not detected with only two of 12 penicillins, namely amoxicillin and mezlocillin. In the case of the other penicillins the metabolites possessed variable antibacterial activity as could be demonstrated using different test microorganisms. After administration of carbenicillin esters three antibacterially active spots were detected, one of which corresponded to penicillin G; the other two were active against Pseudomonas aeruginosa. The bioautogram after treatment with azlocillin showed two components which were active against Bacillus subtilis, Staphylococcus aureus and Escherichia coli; only the rapid moving component was active against P. aeruginosa, however. The formation and chemical nature of these additional active components is still to a large extent not understood. It is quite possible, however, that they affect the bio-availability of an antibiotic.

Administration, Oral↗
PubMed1983

The in vitro activity of ceftazidime against a multi-resistant serotype 12 Pseudomonas aeruginosa.

Highly resistant isolates of Pseudomonas aeruginosa serotype 12 accounted for 42.2% of the pseudomonads isolated from patients in a 600-bed hospital over a period of 18 months. In vitro studies showed that this organism was resistant to tobramycin, gentamicin, apalcillin, piperacillin, azlocillin, ticarcillin, cefotaxime and cefsulodin. All serotype 12 isolates were completely sensitive to ceftazidime. Its geometric mean MIC was 3.4 mg/l. This new cephalosporin seems promising for the treatment of patients infected with pseudomonas, especially when a resistant strain such as serotype 12 is involved.

Anti-Bacterial Agents↗
PubMed1991

Effect of various antibiotics on Listeria monocytogenes multiplying in L 929 cells.

Various antibiotics were evaluated as to their effect on Listeria monocytogenes SLCC 4013 multiplying within L 929 mouse fibroblast cells. Antibiotics were employed in concentrations above the MIC value. However, there was no measurable effect of some drugs on intracellular listeriae (azlocillin, mezlocillin, cephalothin, ciprofloxacin, chloramphenicol). With other drugs an inhibition of intracellular growth was observed (penicillin, ampicillin, rifampicin, rifapentine, erythromycin, doxycycline, co-trimoxazole, coumermycin). Notably, with none of the antibiotics a complete eradication of the listeriae was achieved. There is a good correlation of these results with animal experiments. Therefore, the cell culture system might be useful for the screening of new antibiotics.

Animals↗
PubMed1985

Gram-positive superinfections following beta-lactam chemotherapy: the significance of the enterococcus.

The recent literature was reviewed with regard to the risks of superinfection following beta-lactam chemotherapy. The summary publications for the pseudomonas-active penicillins (azlocillin, carbenicillin, mezlocillin, piperacillin and ticarcillin), cefoperazone, cefotaxime, ceftazidime, imipenem and moxalactam show marked variations. Moxalactam was most likely to produce both gram-negative (5-38%) and enterococcal (2.2-12%) superinfections. Ceftazidime or moxalactam therapy was more often associated with anaerobic superinfections, usually by Clostridium spp., than the other beta-lactams. Comparable and lower incidences of superinfections were cited for cefoperazone, ceftazidime, mezlocillin and imipenem. The most common pathogens for the above drugs were the fungi (Candida spp.), Pseudomonas spp. and some beta-lactamase-producing Enterobacteriaceae. Staphylococcal, Escherichia coli and Klebsiella spp. secondary infections were more common in patients receiving the newer penicillins. Cefotaxime had a very low incidence of superinfections (1.1%), especially caused by gram-positive organisms such as enterococci. The reasons for this favorable feature seem to be: excellent inhibitory activity and beta-lactamase stability against a wide variety of bacterial pathogens, synergistic interactions of cefotaxime and its desacetyl metabolite, enhanced anti-enterococcal activity of cefotaxime in the presence of a human serum factor and interactions of cefotaxime and desacetyl cefotaxime to suppress the development of antimicrobial resistance. The most common superinfections following cefotaxime treatment were with Pseudomonas spp., Enterobacter spp. and fungi. Cefotaxime appears to possess physical-chemical characteristics that react favorably with bacteria and the host to minimize gram-positive superinfections, especially with most enteric Streptococcus spp. (Streptococcus faecalis and Streptococcus faecium).

Anti-Bacterial Agents↗
PubMed1979

[The antibacterial efficacy of cefaclor in routine testing of clinical material from two Berlin hospitals (author's transl)].

The agar diffusion method was used to test the antibacterial efficacy of cefaclor against bacterial strains isolated routinely from patients in two hospitals in Berlin. A comparison was made with the efficacy of oxacillin, azlocillin, amikacin, gentamicin, ampicillin, co-trimoxazole, tetracycline, penicillin, cefazolin, nalidixic acid and nitrofurantoin. A total of 1235 strains of Staphylococcus aureus, enterococci, Escherichia coli, Klebsiella, Enterobacter, Proteus species, Citrobacter and Pseudomonas aeruginosa were tested. Cefaclor was superior to the other substances in its activity against E. coli, Klebsiellae, and Proteus mirabilis. Co-trimoxazole and tetracycline, on the other hand, proved more effective against indole-positive Proteus species and Citrobacter. Tetracycline was also more effective against Enterobacter. Ampicillin was the most effective agent against enterococci, and oxacillin the most effective against S. aureus. Cefaclor showed good antibacterial activity against strains which were resistant to the orally administrable agents ampicillin, tetracycline and co-trimoxazole.

Bacteria↗
PubMed1996

Epidemiology of community-acquired Pseudomonas aeruginosa infections in children.

The epidemiology of community-acquired Pseudomonas aeruginosa infections in children during a one-year period (January through December 1993) was evaluated. A total of 6,859 clinical samples, each one representing a separate individual with suspected infection, were cultured. Pseudomonas aeruginosa was isolated from 218 children with various infections occurring in the following order of frequency: chronic suppurative otitis media, 76.3%; appendicitis/peritonitis, 10.3%; osteomyelitis, 8.9%; skin or soft tissue infection, 6.3%; acute conjunctivitis, 3.0%; and urinary tract infection, 0.1%. A variety of O serogroups were identified: O1 (15.2%), O6 (14.7%), O11 (12.4%), O10 (11.5%), O3 (10.6%), O5 (5.1%), and O9 (4.6%). Other serogroups and nontypable strains were recovered at a frequency of 11.2% and 14.7%, respectively. Nontypable strains predominated in chronic otitis media (18.9%), while serogroups O1 (18.3%), O6 (17.5%), and O11 (17.5%) were recovered most frequently among the typable isolates. Susceptibility of Pseudomonas aeruginosa to antipseudomonadal agents was extremely high. The rate of susceptibility to ceftazidime was 99.6%, to azlocillin 98.6%, to piperacillin 98.2%, to aztreonam 97.3%, to gentamicin and netilmicin 97.7%, and to ciprofloxacin 99.1%. All isolates were susceptible to tobramycin, imipenem, and amikacin. The results might suggest that community-acquired Pseudomonas aeruginosa infections in children can be treated successfully with any antipseudomonadal antibiotic.

Age Factors↗
PubMed1984

Influence of subinhibitory concentrations of antibiotics on opsonization and phagocytosis of Pseudomonas aeruginosa by human polymorphonuclear leukocytes.

To determine whether pretreating Pseudomonas aeruginosa with antibiotics had an effect on phagocytosis, a serum-resistant clinical isolate was incubated with one-third of the minimum inhibitory concentrations of azlocillin, carbenicillin, cefoperazone, fosfomycin, netilmicin and piperacillin respectively prior to exposure to human polymorphonuclear leukocytes. The phagocytic process was measured by assaying radiolabeled bacteria. The uptake rates of untreated and antibiotic treated bacteria did not differ when normal human serum was used for opsonization. However, when the serum was heated to inactivate the complement system, its opsonic activity for untreated as well as for fosfomycin and netilmicin treated pseudomonas was removed and phagocytosis did not take place. In contrast, bacteria pretreated with the betalactam antibiotics still underwent phagocytosis, as also confirmed by electron microscopy. Even in the presence of rabbit immune serum untreated bacteria still required the participation of the complement system for optimal opsonization, whereas bacteria treated with beta-lactam antibiotics did not.

Anti-Bacterial Agents↗
PubMed1990

Susceptibility of Alcaligenes denitrificans subspecies xylosoxydans to beta-lactam antibiotics.

The susceptibility of 56 clinical isolates and two reference strains of Alcaligenes denitrificans subsp. xylosoxydans to beta-lactam agents was tested and related to beta-lactamase activity of the strains. The MICs of 12 beta-lactams determined by an agar dilution method showed that all the strains were sensitive to imipenem and moxalactam. Forty-one cloxacillin-sensitive beta-lactamase producing strains were highly susceptible to azlocillin, piperacillin and ticarcillin, and less susceptible to several cephalosporins (cefamandole, cefoperazone, ceftazidime). The 17 remaining beta-lactamase-producing strains, which were sensitive to clavulanic acid and to a lesser extent cloxacillin, had variable resistance to the penicillins tested and synergy was obtained when these penicillins were combined with clavulanic acid or tazobactam. The choice of agents for treatment of infections with this organism must take into account the susceptibility phenotype of clinical isolates.

Alcaligenes↗
PubMed1990

In vitro antimicrobial susceptibility of Listeria monocytogenes isolated in the UK and other Listeria species.

The MICs and MBCs of 21 antimicrobial agents were determined for 103 strains of Listeria monocytogenes isolated in the UK and 27 strains of other Listeria species. Ampicillin, penicillin, azlocillin, imipenem, gentamicin, netilmicin, amikacin, erythromycin, rifampicin, trimethoprim, clindamycin and vancomycin had good activity, while cephalothin, chloramphenicol, ciprofloxacin and ofloxacin were less active, and cefuroxime, enoxacin, norfloxacin and fosfomycin were the least active. Tetracycline had good activity against many strains, but the MIC was high for some. Unlike the other Listeria species tested, Listeria ivanovii was susceptible to fosfomycin. Inoculum size and media employed were shown to affect the MBC, tryptose phosphate broth yielding higher MBCs than Mueller-Hinton or Isosensitest broths.

4-Quinolones↗
PubMed1987

Identification of an inducible penicillinase of the lithoautotrophic hydrogen-oxidizing bacterium Alcaligenes eutrophus.

The growth of Alcaligenes eutrophus in the presence of benzylpenicillin under heterotrophic and autotrophic conditions was studied. The drug induced a penicillinase in the cells, which can be readily released and extracted from the cells after a lysozyme and EDTA treatment in the course of spheroplast formation. The isoelectric point of the enzyme is 8.1 and the molar mass was estimated to be nearly 25 kg/mol. Phenoxypenicillin is hydrolyzed in the presence of the enzyme at a higher relative rate than benzylpenicillin, ampicillin, amoxycillin and azlocillin. The cephalosporins tested, i.e. cephalosporin C, cefalexin, cefotaxime and 7-aminocephalosporanic acid, were hydrolyzed at a substantially lower relative rate than the penicillins, indicating that the enzyme is a penicillinase.

Alcaligenes↗