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PubMed1986

[Choice of a rapidly bactericidal beta-lactamin-aminoglycoside combination in the treatment of Pseudomonas aeruginosa infections at a child intensive care unit].

Morbidity and mortality among children with Pseudomonas aeruginosa infection in Pediatric Intensive Care Unit remains high. Delays in bacterial killing may be responsible for the poor outcome. Antimicrobial sensitivity and timed-killing assays were determined for ticarcillin, azlocillin, piperacillin, cefsulodin, ceftazidime, gentamicin, tobramycin and amikacin alone and in combination against 40 strains of Pseudomonas aeruginosa isolated from blood cultures and tracheal aspirate. Antibiotic concentrations used were at clinically achievable level. None bactericidal effect was observed with each beta-lactamin alone. However with the combinations azlocillin or piperacillin or cefsulodin or ceftazidime plus amikacin a bactericidal effect was observed at 4.5 hours.

Aminoglycosides↗
PubMed1986

Antimicrobial induced alterations of the human oropharyngeal and intestinal microflora.

Although the role of the normal oropharyngeal and intestinal microflora is not fully understood, there are evidences that alterations in the flora may have serious consequences. The most common and significant cause of disturbances in the normal microflora is the administration of antimicrobial agents. The microflora can be influenced by antimicrobial agents because of incomplete absorption of any orally administered antimicrobial agent, secretion of an antimicrobial agent by the salivary glands or in the bile, or secretion from the intestinal mucosa. In most cases the influence is not beneficial to the patient because suppression of the indigenous microorganisms often permits potential pathogens to overgrow and cause septic conditions, stomatitis, diarrhoea, or colitis. Antimicrobial agents that influence the normal microflora also promote the emergence of antimicrobial-resistant strains. During the recent years, the impact of different antimicrobial agents on the human microflora has been investigated by our research group. Thus the effects on the oropharyngeal and intestinal microflora by peroral administration of penicillin, bacampicillin, erythromycin, clindamycin, doxycycline, nitroimidazole, norfloxacin and ciprofloxacin have been studied. The impact on the microflora by parenteral administration of ampicillin + sulbactam, azlocillin, aztreonam, piperacillin, cefoperazone, cefoxitin, ceftriaxone, moxalactam, imipenem, nitroimidazole and clindamycin has also been investigated. Pronounced changes were observed in the microflora in patients receiving clindamycin, erythromycin, cefoperazone, ceftriaxone and moxalactam, whereas moderate changes were seen in those patients receiving doxycycline, cefoxitin, aztreonam, ampicillin + sulbactam, azlocillin and piperacillin. Penicillin, bacampicillin, imipenem, nitroimidazole, ciprofloxacin and norfloxacin produced only minor changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1986

Synergy of fosfomycin with beta-lactam antibiotics against staphylococci and aerobic gram-negative bacilli.

Fosfomycin inhibits bacterial cell wall synthesis at the initial stage. It can act synergistically with beta-lactams. The effect of the combination of fosfomycin and selected penicillins and cephalosporins against staphylococci, Pseudomonas aeruginosa, Pseudomonas cepacia and selected Gram-negative bacteria was determined. Synergy was determined by agar dilution and checkerboard titration methods; synergy was defined as an FIC index less than or equal to 0.5 and partial synergy greater than 0.5 to 0.75. Concentrations of drugs used were those that would be reached in man by intravenous and oral routes. Fosfomycin combined with nafcillin and with cefotaxime against staphylococci showed synergy for most isolates. For methicillin-resistant Staphylococcus aureus, synergy or partial synergy was found for 90% of isolates. Synergy was less frequently found with Staphylococcus epidermidis. The MICs for S. aureus were reduced from greater than or equal to 32 micrograms/ml to less than or equal to 1 microgram/ml. Fosfomycin was synergistic with ticarcillin, piperacillin, azlocillin, ceftazidime, aztreonam and imipenem against 31 to 61% of P. aeruginosa. MICs were reduced from greater than or equal to 128 micrograms/ml to 8-32 micrograms/ml, depending upon the agent. Although fosfomycin acted synergistically with azlocillin, piperacillin and ceftazidime against some P. cepacia, most often there was an indifferent interaction and MICs were in the resistant range, greater than or equal to 128 micrograms/ml. The interaction of fosfomycin and ampicillin was synergistic against a number of strains of Enterobacteriaceae, Proteus vulgaris and Providencia rettgeri, yielding MICs in an achievable range. The combination of fosfomycin with beta-lactams may be clinically useful in selected situations, particularly for methicillin-resistant staphylococci and beta-lactam-resistant P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1986

[Conditions for the mercurimetric determination of the drug content of penicillins].

Mercurimetric determination of penicillins includes direct titration with a solution of mercury (II) perchlorate in the medium of pyridine solvent or acetate buffer, which determines the content of decomposition products, and titration after alkaline hydrolysis, which indicates the total amount of penicillin. The determination which is indicated potentiometrically with continuous addition of the titrant, provides real and reproducible results in the titration rate of 0.6 ml/min with the initial concentration of penicillin 170 mg/30 ml and temperature 25 degrees C. Benzathine and procaine salts of benzylpenicillin and benzathine salt of phenoxymethylpenicillin were dissolved in dimethylformamide (DMF) before the titration in acetate buffer. Titrations of ampicillin, amoxycillin and azlocillin were performed in the mixture of acetate buffer and formamide which ensured real results. Hydrolysis of the lactam ring of azlocillin, mezlocillin, ticarcillin and piperacillin is quantitative in 10 min of action of NaOH (1 mol/l) which was confirmed by comparing with the enzymatic cleavage. Relative standard deviation for all penicillins was less than 1%. The accuracy of the method for the determination of penicillins was proved by comparing with the microbiological and iodometric determination. The mercurimetric determination of penicillins and their decomposition products in acetate buffer was applied to injections, tablets, capsules and dry sirup.

Mercury↗
PubMed1985

[Susceptibility of Pseudomonas aeruginosa to aztreonam in comparison to other pseudomonas-active beta-lactam antibiotics and gentamicin].

The in vitro activity of aztreonam, a synthetic monobactam, was evaluated against 245 strains of Pseudomonas aeruginosa, 130 of them being recent clinical isolates from patients and 115 from hospital environment. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and bactericidal kinetics were determined. The possibility of resistance development in vitro was studied. Gentamicin, cefsulodin, piperacillin and azlocillin were used as comparative agents with known antipseudomonal activity. At a concentration of 8 mg/l 83.3%, at 16 mg/l 92% of the tested strains were susceptible to aztreonam. Thus, the activity of aztreonam against Pseudomonas aeruginosa is equivalent to that of gentamicin and cefsulodin and better than that of piperacillin and azlocillin in terms of resistance. Bactericidal kinetics with fourfold MIC, which is equivalent to MBC, are nearly identical for aztreonam, piperacillin and cefsulodin. In vitro induced resistance additionally causes increased resistance against the other beta-lactam antibiotics.

Anti-Bacterial Agents↗
PubMed1979

[Pediatric pharmacology of azlocilin (author's transl)].

Pharmacokinetic investigations of acylureido-penicillins azlocillin in newborns, infants and school shildren showed age dependend results. The differences were especially evident in a prolongation of the serum half-life to 2,56 hours in newborns compared to 0.94 hours in school children. On the basis of our pharmacokinetic results and of the dosages resulting from the data the antibiotic was used clinically in twenty eight patients with Pseudomonas aeruginosa infections and one patient with a Proteus mirabilis infection. The results were much better in infections of the urinary tract than in infections of the respiratory tract. This might be due to an observe bacterial presistence in spite of highly effective levels of azlocillin in bronchial secretion. The tolerance to the antibiotic was good.

Child↗
PubMed1983

[Effect of storage time at -20 degrees C on the determination of serum concentrations of tobramycin in the presence of 6 beta-lactams].

We assessed the role of six beta-lactam antibiotics and of storage time at - 20 degrees C, in inactivation of tobramycin in patients' sera. Several ranges of concentrations were used for the combined antibiotics. The tobramycin concentrations were measured both by microbiological assay (plate diffusion) and an enzyme mediated immunoassay technique (EMIT). Using the bioassay method, the results after 8 days of frozen storage were as follows: carbenicillin and ticarcillin (256 mg/l) induced a 40-50% reduction of tobramycin activity, whereas mezlocillin (256 mg/l) had less effect: a 15-20% reduction. After 15 days at -20 degrees C the results were nearly the same except for azlocillin (256 mg/l), increasing its percentage reduction to 20%. The results obtained by EMIT procedure were significantly better after 8 days of frozen storage: only mezlocillin (5% reduction) and azlocillin (10%) were effective. Nevertheless after 15 days at -20 degrees C, the inactivating action of the pre-cited antibiotics were similar to those obtained at the same time with the bioassay method. Piperacillin and cefsulodin never induced any reduction of tobramycin levels, whatever the time of storage or quantification procedure used. So, our opinion is that patients' sera containing a beta-lactam antibiotic in combination with tobramycin should be assayed immediately upon receipt. Keeping it at -20 degrees C is not sufficient to prevent in vitro tobramycin inactivation.

Anti-Bacterial Agents↗
PubMed1983

[Sensitivity of Pseudomonas aeruginosa to beta-lactam antibiotics and effects of beta-lactamases].

The activities of carbenicillin, ticarcillin, piperacillin, cefsulodin, ceftriaxone, azlocillin, ceftazidime and apalcillin were evaluated against 128 hospital isolates of Pseudomonas aeruginosa. Against the 85 isolates that were susceptible to carbenicillin, apalcillin had the best minimal inhibitory concentrations, the median MIC being 1, 1 microgram/ml. Against the 43 isolates resistant to carbenicillin, ceftazidime inhibited 90% of organisms at a concentration of 16 micrograms/ml. A constitutive beta-lactamase, was found in 27 of the 43 resistant isolates. All the 128 isolates, but one, were producers of an inducers of an inducible beta-lactamase. Ceftriaxone, piperacillin and azlocillin were highly antagonized by cefoxitin. The extent of antagonism was lower with ticarcillin and carbenicillin.

Anti-Bacterial Agents↗
PubMed1983

[Pseudomonas aeruginosa: acquired in vitro resistance to beta-lactams].

The development of resistance acquired in vitro to 5 semi-synthetic penicillins: carbenicillin, ticarcillin, azlocillin, mezlocillin, piperacillin and to 5 cephalosporins: cefotaxime, cefoperazone, moxalactam, cefsulodin and ceftazidime, was compared in 6 strains of Pseudomonas aeruginosa. The strains were selected on the basis of their phenotypic resistance: 3 were susceptible to all the betalactam antibiotics tested, 1 was resistant to carbenicillin and ticarcillin but remained susceptible to the others, 2 were susceptible to cefsulodin and ceftazidime but resistant to the others. The development of resistance was investigated by subsequent passages in liquid medium: up to 15 passages or up to an MIC of 4 096 mg/l for a penicillin or 512 mg/l for the cephalosporins. Irrespectively of the phenotypic resistance, for all cephalosorins the MIC became greater than or equal to 64 mg/l and very often greater than or equal to 512 mg/l after 1 to 3 passages. For the penicillin susceptible strains very high MICs were obtained more rapidly with azlocillin and piperacillin (1-2 passages) than with carbenicillin or ticarcillin (5-9 passages). These results are not in favour of a monotherapy with betalactam antibiotics, especially cephalosporins, in the treatment of Pseudomonas aeruginosa infections, but suggest the preferential use of carbenicillin and especially ticarcillin for sensitive isolates.

Anti-Bacterial Agents↗
PubMed1984

Comparative in vitro activity of aztreonam, other beta-lactam antibiotics and aminoglycosides against Pseudomonas aeruginosa.

Aztreonam, ceftriaxone, moxalactam, cefotaxime, cefsulodin, cefoperazone, piperacillin, azlocillin, carbenicillin, amikacin, gentamicin, tobramycin, sisomicin and dibekacin were tested by broth dilution against 161 isolates of Pseudomonas aeruginosa. Seventy-one of these strains were selected for their resistance to carbenicillin and aminoglycosides and classified as "multiply resistant" strains. Over all, aztreonam showed the greatest antipseudomonal activity by far, followed by ceftriaxone, moxalactam, cefotaxime and amikacin. Piperacillin, azlocillin, cefsulodin, and cefoperazone were highly active against carbenicillin and/or aminoglycoside-susceptible P. aeruginosa strains, but were also poorly inhibitory against multiply resistant isolates.

Aminoglycosides↗
PubMed1994

[Combined use of quinolones with other antibiotics in treatment of experimental plague infection].

The efficacy of combinations of fluoroquinolones (ciprofloxacin and pefloxacin) with betalactams (ampicillin, azlocillin and cefotaxime), aminoglycosides (amikacin) and rifampicin was studied on albino mice infected subcutaneously with plague. The drugs were used in deliberately ineffective or insufficiently effective doses. Synergism was observes with the use of ciprofloxacin and pefloxacin in combinations with amikacin, cefotaxime or rifampicin. The combinations of ciprofloxacin with ampicillin or azlocillin had no synergistic action though the therapeutic effect was not lower. With using the specifically determined doses the efficacy of the combinations could be increased by comparison with that of the drugs used alone.

Aminoglycosides↗
PubMed1993

Single daily ceftriaxone and tobramycin in the empirical management of febrile neutropenic patients: a randomised trial.

A single-institution, randomised pilot trial was conducted to compare the clinical efficacy, microbiological efficacy and possible toxicity of empirical single daily antibiotic administration in febrile neutropenic patients with haematologic disorders (absolute neutrophil count < 1 x 10(9)/l). Upon the development of signs of sepsis, patients received either single daily dose tobramycin (5 mg/kg per day) plus ceftriaxone (2 g/day) (C + T, n = 47) or tobramycin (1.5 mg/kg, every 8 h) plus azlocillin (4 g, every 6 h) (A + T, n = 45). In addition, flucloxacillin (1-2 g, every 4 h) could be added if there was clinical suspicion of staphylococcal infection (17 in each arm). Analysis was performed for the whole group and for the subset which did not receive flucloxacillin. When evaluated at 96 h, 62% of patients randomised to C + T and 67% randomised to A + T had responded (95% confidence interval (CI) for the difference in rates, -25% to +15%). Ninety-six hour response rates for those who did not receive flucloxacillin were 73% and 78%, respectively (95% CI, -17% to +27%). Overall, 42 (89%) and 41 (91%) patients, respectively, eventually became afebrile (95% CI, -14 to 10%) and there was no evidence of altered renal function or electrolyte imbalance in patients randomised to single daily antibiotic therapy compared with the conventional (multi-daily dose) arm. Within 10 days of antibiotic commencement there was 1 death in the C + T arm and 4 deaths in the A + T arm, although overall there were 4 deaths in each arm. Our results suggest that single daily empirical antibiotic therapy with tobramycin and ceftriaxone is efficacious and is not associated with an increased incidence of renal dysfunction or electrolyte imbalance compared with conventional administration schedules of azlocillin plus tobramycin. Single daily therapy has the potential to lead to savings in nursing-staff time and materials and may well contribute to an improved quality of life for febrile neutropenic patients.

Adolescent↗
PubMed1995

[The sensitivity to antibacterial preparations of enterococcal strains isolated from gynecological patients, pregnant women, puerperae and newborn infants].

The sensitivity to a given number of antibiotics of 205 strains of enterococci, isolated for a period of one year was studied. The enterococci were isolated from materials, sent for microbiological examination in different clinical settings 55 strains of enterococci from the lower genital tract were tested (vaginal and cervical secretions), 36 strains from the upper genital tract (lochia, peritoneal aspirates, IUD), 8 strains from wounds (perineal and abdominal), 37 strains from urine and 69 strains from the newborns. There was a high sensitivity towards carbenicillin--92.7% towards azlocillin 91.2% and towards ampicillin--83.9% The strains, isolated from gynecologic patients showed increased resistance towards aminoglucosides--49.5% towards gentamycin and 46.5% towards amicacin. The resistance towards gentamicin in the newborns was 68.1%. The strains from urine were resistant to cyprofloxacine in 29.7%. All the enterococci tested were practically resistant to cefamandole and oxacilline. The author suggests that for initial therapy in proven or suspected enterococcal infection carbenicilline, azlocillin and ampicillin. They are suitable both for gynecologic patients and newborns. The aminoglucosides have to be administrated after testing because of the significant resistance found for the different strains. The same is true for erythromycin and cyprofloxacine

Anti-Bacterial Agents↗
PubMed1982

Acylureido penicillins in neonatal intensive care. Preliminary communication.

The antimicrobial sensitivity of 232 bacteria isolated from patients in a newborn intensive care unit was tested. Practically all organisms were sensitive to a combination of mezlocillin-aminoglycoside; a few were resistant to azlocillin-aminoglycoside. Eighteen patients, all severely ill, were treated with the combination acylureidopenicillin-aminoglycoside. Nine patients died, eight due to non-infectious diseases and one very small premature baby due to Serratia marcescens meningitis. The other patients showed good clinical improvement. The only side-effect observed was a macular rash in one patient.

Azlocillin↗
PubMed1982

[Clinical experience with non-specific broad-spectrum antibacterial chemotherapy (author's transl)].

49 patients were given cefoxitin in combination with azlocillin, and 15 were given an aminoglycoside as well when severe bacterial infection was suspected. In 39 cases a prompt amelioration of the clinical signs of infection was observed. Of the 17 patients who died, a post-mortem was performed in seven; only in four were signs of bacterial infection present; one had tuberculosis and one had a cytomegalovirus infection. The combination therapy was well tolerated and side-effects were rare; no bleeding complications were seen. Clinical signs of possible antagonism between the two beta-lactam antibiotics were not observed.

Adult↗
PubMed1992

Molecular epidemiological analysis of Pseudomonas aeruginosa strains causing failure of antibiotic therapy in cystic fibrosis patients.

A combination of esterase electrophoretic typing and analysis of the restriction fragment length polymorphism of ribosomal DNA regions (ribotyping) was used to compare 27 Pseudomonas aeruginosa strains isolated before and after two-week courses of anti-pseudomonal treatment in seven cystic fibrosis patients. A total of 12 courses of therapy were studied in which ciprofloxacin, ceftazidime, azlocillin or imipenem were used alone or in combination with tobramycin. Isolates at a count of greater than or equal to 10(6) cfu/ml of sputum were collected when there was evidence of therapeutic failure on the basis of persistence of isolates whether or not they were resistant to the antibiotic used for therapy. Emergence of resistance was observed in ten cases and failure to eradicate sensitive strains in five cases. Among the 27 isolates, eight zymotypes and five ribotypes were identified. With this typing approach, resistant post-therapy isolates were found to be identical to pre-therapy isolates in all cases but one. However, in one case an additional resistant strain was isolated after therapy besides that initially present. In all five cases in which susceptibility was still observed after treatment, pre-therapy and post-therapy isolates were indistinguishable. Using this molecular typing approach, all the strains were typable. Thus combination of esterase typing and ribotyping should improve the analysis of therapeutic failure in cystic fibrosis patients.

Azlocillin↗