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PubMed1987

[In vitro sensitivity at 18 antibiotics of 192 strains of Pseudomonas aeruginosa isolated at Garches Hospital].

The in vitro activity of 18 antibiotic (beta-lactam agents, quinolones and aminoglycoside has been evaluated against 192 clinical isolates of Pseudomonas aeruginosa. Minimal inhibitor concentrations (MICs) were determined by the agar dilution technique. The 50% and 90% MICs were respectively: ticarcillin (32/greater than 1 024), azlocillin (16/512), piperacillin (8/512), cefsulodin (4/128), ceftazidime (2/8), aztreonam (4/16), imipenem (2/4), nalidixic acid (128/256), pefloxacin (1/8), norfloxacin (1/8), ofloxacin (2/8), ciprofloxacin (0.25/2), gentamicin (8/256), sisomicin (4/256), tobramycin (2/128) dibekacin (4/256), netilmicin (16/256), amikacin (8/16). The sensitivity to beta-lactam agents and to quinolones was usual. Resistance to aminoglycosides was frequently observed (59%): 35.7% of the resistant isolates were resistant to gentamicin-sisomicin-tobramycin-dibekacin-netilmicin, 30% to netilmicin alone, 17.8% to gentamicin-sisomicin-tobramycin-dibekacin-netilmicin-amikacin, 7% to gentamicin-netilmicin, 5.3% to gentamicin-sisomicin-tobramycin-dibekacin; we did not find any P. aeruginosa resistant only to gentamicin or gentamicin-sisomicin.

Aminoglycosides↗
PubMed1987

[Epidemiology of Pseudomonas aeruginosa in Mauritania: study of 239 strains of various origins].

239 strains (173 from hospital infections, 20 from carriers, 46 from animal infections and environment) were studied with regard to their serogroups, biovars, phage-types and drug-resistance. 82.2% of all strains were typable by specific immune sera and distributed in 15 serogroups (0:1, 0:2, 0:3, 0:4, 0:5, 0:6, 0:7, 0:8, 0:9, 0:10, 0:11, 0:12, 0:13, 0:15, 0:16). Among them, 8 were ubiquitous (0:1, 0:3, 0:4, 0:5, 0:8, 0:9, 0:11 and 0:16) and found in hospital patients, carriers, animals and environment. Thirty-five 0:11 strains and four no agglutinable strains produced an orthonitrophenyl beta-d-galactopyranoside hydrolase (ONPG +). Among 183 strains typable by phages of the Lindberg phage-typing system, 96 different phage-types were recognized. The proportions of the strains untypable by phages were 8.6% for animal strains, 23.6% for hospital strains and 55% for strains from carriers. The frequency of the resistance to each of eleven tested antibiotics was as follows: carbenicillin: 48%, ticarcillin: 12.2%, azlocillin: 9.1%, cefotaxime: 22.8%, cefsulodin: 27.4%, ceftazidime: 0.5%, latamoxef: 6.2%, gentamycin: 12.2%, amikacin: 15.4%, tobramycin: 12.5%, norfloxacin: 0%. However, 18.7% of hospital strains, 65% from carriers and 92.5% of animal or environmental strains were susceptible to all of these antibiotics. These results are compared with those from a previous report on epidemiology of P. aeruginosa hospital infection in Ivory-Coast (Dosso, Vieu et al., Bull. Soc. Path. exot., 1987, 80, 19-27) and with the data of the scientific literature.

Animals↗
PubMed1988

In vitro antibacterial activities of eleven antibiotics against S. faecalis.

The in vitro antibacterial activities of penicillin, ampicillin, piperacillin, azlocillin, vancomycin, erythromycin, clindamycin, gentamicin, streptomycin, cefotaxime, and ceftriaxone against 198 S. faecalis strains were investigated, employing an agar dilution technique. Results were generally in accord with those of other studies. Ampicillin and penicillin showed equal activities. Twenty percent of the strains were resistant to erythromycin, which correlated with resistance to clindamycin. The activity of cefotaxime was fairly good, but the clinical importance of this observation warrants further investigation. Twenty percent showed high-level resistance to streptomycin. High-grade resistance to gentamicin was noted for one isolate only, making gentamicin the first-choice aminoglycoside for combination treatment at present.

Aminoglycosides↗
PubMed1988

Empiric antimicrobial therapy for febrile granulocytopenic cancer patients: lessons from four EORTC trials.

The results of the four EORTC trials conducted over the past 15 years suggest: (1) early empiric therapy with broad spectrum antibiotics directed against gram-negative bacterial bacteremia (GNBB) is a reasonable approach in febrile granulocytopenic patients (GCP); (2) the level and dynamics of the granulocyte count are extremely important in determining the outcome of bacteremia; severely and/or persistently neutropenic patients are the true tests of antibiotic efficacy and they benefit from antimicrobial synergism; (3) mortality from GNBB in GCP is not related directly to a given empiric antimicrobial regimen which may 'buy time' and allow appropriate therapeutic alterations; (4) only microbiologically documented infections and especially bacteremias are useful to compare responses to antimicrobial regimens; (5) the response rate of GNBB is clearly influenced by the susceptibility of the causative pathogen to the beta-lactam component of the empiric regimen and emergence of resistance to some antibiotics (cephalothin, carbenicillin, ticarcillin, azlocillin) has rendered some combinations less effective. The combination of an anti-Pseudomonas beta-lactam plus an aminoglycoside is recommended as the 'standard' for empiric therapy in febrile GCP; (6) gram-positive pathogens have become a common cause of bacteremia in GCP and although the response rate to empiric regimens may be marginal, the associated mortality is low. A general conclusion from these trials is that studies of the management of infection in GCP should include sufficient numbers of eligible patients to allow for evaluation of bacteremic patients at highest risk of death. The need for large collaborative studies stems directly from these considerations.

Agranulocytosis↗
PubMed1988

Compatibility of verapamil hydrochloride with penicillin admixtures during simulated Y-site injection.

The compatibility of verapamil hydrochloride during simulated Y-site injection with i.v. admixtures containing 11 different penicillins was studied. Admixtures of penicillin G potassium (62.5 mg/mL), nafcillin sodium (40 mg/mL), oxacillin sodium (40 mg/mL), ampicillin sodium (40 mg/mL), carbenicillin disodium (40 mg/mL), methicillin sodium (40 mg/mL), ticarcillin sodium (40 mg/mL), azlocillin sodium (40 mg/mL), mezlocillin sodium (40 mg/mL), piperacillin sodium (40 mg/mL), and amdinocillin (20 mg/mL) were prepared in both 5% dextrose injection and 0.9% sodium chloride injection in minibags. Verapamil hydrochloride injection 4 mL (10 mg) was then added to each admixture, and the admixtures were examined macroscopically and microscopically for precipitate immediately and at 15 minutes and 24 hours after mixing. To simulate Y-site injection of verapamil, verapamil hydrochloride injection 1 mL (2.5 mg) was added to 1 mL of each penicillin admixture in a test tube. For admixtures in which precipitates formed, the pH was recorded before and after verapamil was added to the admixtures. Loss of verapamil hydrochloride when mixed with the penicillin admixtures was determined using reverse-phase high-performance liquid chromatography. Addition of verapamil hydrochloride to admixtures containing nafcillin sodium, oxacillin sodium, ampicillin sodium, and mezlocillin sodium resulted in substantial loss of verapamil hydrochloride. The results for the Y-site injection study showed visible precipitation with the same penicillin admixtures. Because a precipitate formed when verapamil hydrochloride was added to nafcillin sodium, oxacillin sodium, ampicillin sodium, or mezlocillin sodium in the diluents studied, we recommended that verapamil hydrochloride be administered separately or that the i.v. tubing be flushed thoroughly before and after this drug is administered through a Y-injection site with these penicillin admixtures.

Drug Combinations↗
PubMed1988

[Determination of iodine-containing admixtures in semisynthetic penicillins].

Dependence of the values defining the content of iodine sorbing admixtures in semisynthetic penicillins on pH, reaction time and drug aliquots was studied. On the basis of this study a general approach to development of procedures for determining iodine sorbing admixtures in semisynthetic penicillins was suggested. Procedures for determination of iodine sorbing admixtures in carbenicillin, carfecillin, ampicillin, oxacillin, azlocillin and ampiox were developed.

Adsorption↗
PubMed1988

[Antibiotic therapy of angiogenic sepsis].

Introduction to medical practice of new penicillins, cephalosporins and aminoglycosides is one of the chief reserves for increasing efficacy of antibacterial therapy. The main schemes of antibiotic use in treatment of sepsis and individual regimens controlled by laboratory findings are discussed. Optimization of antibiotic therapy schemes is based on pharmacokinetic studies, quantitative assay of antibiotic sensitivity and determination of antibacterial activity of serum and other biosubstrates at definite periods after antibiotic administration. In vitro time course investigation of the bactericidal effect of gentamicin, azlocillin and cefotaxime on pathogens of purulent infections at various sizes of the inoculum provided prediction of the antibiotic therapy efficacy in various purulent septic infections. It is indicated that rational use of antibiotics markedly increases efficacy of sepsis therapy and improves social and economic indices of the treatment.

Adult↗
PubMed1988

[Prospective considerations on the dose-effect relationship in antibiotic therapy].

Even though antibiotic in vivo and in vitro modes of action are not superposable, laboratory studies allow a logical approach to the treatment of infections. The answer to the question "What dose and for how long?" frequently asked during the treatment of a severe infection is not necessarily "The maximum dose for a long duration". The following points among many others, should be taken into consideration. The rate of bacterial action of beta-lactams on Gram negative bacilli is concentration dependent for ampicillin and amoxicillin for instance. This rate is hardly concentration dependent for ureidopenicillins (azlocillin, mezlocillin and piperacillin) and azthreonam which bind principally on PBP3. With third generation cephalosporins, in relation to concentrations, two steps in bactericidal rate may be observed. The post-antibiotic effect is often short (1 hour). The rate of bactericidal action of beta-lactams on Staphylococcus aureus is hardly concentration dependent. The post-antibiotic effect may be long (4 to 6 hours). A paradoxical effect may be observed namely with Streptococcus faecalis. The killing rate of beta-lactams is inoculum dependent. The aminoglycosides have a very high bactericidal activity rate on Gram positive and Gram negative bacteria. The post-antibiotic effect is long (4 to 6 hours). The antibacterial effect is little inoculum dependent. These conclusions are driven from experiences performed on cultures in growth phase. One of the controversial point related to the in vitro in vivo relationship is the ignorance of the multiplication rate of the bacteria in the infected site.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglycosides↗
PubMed1986

Therapeutic considerations in using combinations of newer beta-lactam antibiotics.

The in vitro activity, pharmacokinetic interactions, and clinical efficacy of newer beta-lactam antibiotic combinations are reviewed. Combinations of beta-lactam antibiotics offer an antimicrobial spectrum similar to that of aminoglycoside-beta-lactam combinations without the renal or eighth cranial nerve toxicity of aminoglycosides. Synergistic activity with beta-lactam combinations is demonstrable in vitro against a wide variety of aerobic gram-negative bacilli, but the frequency, with which it is found is substantially less than for aminoglycoside-beta-lactam combinations. Also, in vitro antagonism can be demonstrated, particularly with combinations containing an agent capable of inducing beta lactamase. Substantial alterations in the pharmacokinetics of cefotaxime and desacetylcefotaxime have been demonstrated by the concomitant administration of mezlocillin or azlocillin. In addition, the clearance of moxalactam has been shown to be reduced by concomitant administration of piperacillin, and the clearance of oxacillin is reduced by concomitant mezlocillin therapy. Dosage reductions of these drugs may be appropriate in certain situations. Several clinical trials comparing therapy with beta-lactam combinations versus aminoglycoside-containing regimens in neutropenic patients have shown no difference in overall efficacy between the two regimens, with the possible exception of infections in persistently granulocytopenic patients and perhaps in patients with Pseudomonas aeruginosa infections. beta-lactam combinations are generally less nephrotoxic, but potentially more costly when newer compounds are included, than amino-glycoside-containing regimens. These beta-lactam combinations should be reserved for use in patients at high risk for aminoglycoside toxicity.

Amdinocillin↗
PubMed1986

[Evaluation of the antibiotic sensitivity of Pseudomonas sp. using the API-ATB-PSE system. Comparison with diffusion and the reference agar dilution method].

In vitro activity of twelve antibiotics (ticarcillin, mezlocillin, azlocillin, piperacillin, cefoperazone, cefsulodin, ceftazidime, gentamicin, netilmicin, pefloxacin and ciprofloxacin) was determined by measuring minimum inhibitory concentrations (MICs) using agar dilution according to WHO recommendations, agar diffusion and the API-ATB-PSE system. One-hundred and forty-two Pseudomonas strains were studied. Five species of Pseudomonas were represented, i.e. aeruginosa, maltophilia, cepacia, stutzeri and paucimobilis. Isolates came from two Paris hospitals. Percentages of total agreement, minor discrepancies and major discrepancies between the results obtained with the API-ATB-PSE method and those recorded with the reference methods were determined. After checking the discordant strains, the results are discussed in order to evaluate the reliability of the ATB method for antibiotic susceptibility testing with Pseudomonas sp.

Agar↗
PubMed1986

Antibiotic levels in the small intestine.

It is unknown if parenteral antibiotics commonly used for prophylaxis reach adequate therapeutic levels in the intestinal tissue to inhibit the growth of bacteria, such as Escherichia coli and Bacteroids fragilis, commonly associated with injury to the gastrointestinal tract. We have designed an experiment using dogs to study this problem. We considered an antibiotic to be effective if a single dose reached increased levels in the intestinal tissue to inhibit the growth of the majority of Escherichia coli and Bacteroides fragilis strains isolated from the gastrointestinal tract. Of 14 different antibiotics studied, we conclude that carbenicillin, mezlocillin, piperacillin, cefbuperazone and cefoxitin as single drugs and Timentin (ticarcillin with clavulanic acid) and clindamycin with gentamicin and co-trimoxazole (trimethoprium and sulfamethoxazole) achieved therapeutic levels. Azlocillin, cefoperazone, cefmenoxime and minocycline failed to achieve significant concentrations. This experiment using dogs was extremely useful to determine the pharmacokinetics of antibiotics in the small intestine and to predict the efficacy of antibiotics considered for prophylaxis.

Animals↗
PubMed1987

Evaluation of ciprofloxacin alone and in combination with other antibiotics in a murine model of thigh muscle infection.

The therapeutic efficacies of ciprofloxacin and some comparative drugs were evaluated in a model of thigh muscle infection in neutropenic mice. Ciprofloxacin was found to be highly effective against all gram-negative and gram-positive bacteria tested. Combinations of ciprofloxacin and either gentamicin or beta-lactam antibiotics exhibited additive or slightly synergistic effects against the Enterobacteriaceae and gram-positive isolates. Azlocillin was found to increase significantly the efficacy of ciprofloxacin against Pseudomonas aeruginosa. Antagonistic interactions with vancomycin, which impaired the bactericidal activity of ciprofloxacin against Streptococcus faecalis, were observed only in vitro but not in vivo, whereas erythromycin also slightly reduced the therapeutic efficacy of ciprofloxacin in vivo.

Animals↗
PubMed1978

[Microcalorimetric Investigations, regarding the antibacterial efficiency of chemotherapeutics (author's transl)].

An investigation method is described by which microcalorimetry and continuous density measurement are used to show the antibacterial efficiency of chemotherapeutics. Oleandomycin, erythromycin, both macrolide antibiotics, and doxycycline, a tetracycline, blockers of the protein synthesis, have the same effect on the microcalorimetric curve of a staphylococcus strain. Among the aminoglycosides tobramycin and gentamicin influenced the microcalorimetric activity of a growing E. coli strain in the same way, spectinomycin produced different curves. Penicillins interfere with the synthesis of the cell membrane by blocking the enzyme transpeptidase. Epicillin, penicillin, ampicillin, oxacillin, carbenicillin, and azlocillin influence the microcalorimetric activity of staphylococci in a typical way which is different from that of the blockers of the protein synthesis.

Aminoglycosides↗
PubMed1987

The effect of the chemical character of certain penicillins on the resistance of the beta-lactam group in their molecules. Part 5: Kinetics of thermal decomposition in solid state.

The decomposition rate at elevated temperature was studied of the following penicillins: ampicillin trihydrate (1), 6-aminopenicillanic acid (2; 6-APA), amoxicillin trihydrate (3), piperacillin (4), amoxicillin sodium (5), azlocillin sodium (6), mezlocillin sodium monohydrate (7) and azidocillin sodium (8). The pattern of decomposition was found to comply with the first-order reaction. The thermal stability of the compounds at 25 degrees C increased in accordance with the sequence 1 less than 2 less than 3 much less than 6 less than 5 less than 8 less then 7 much less than 4, which was connected with the hydrophilic and lipophilic properties of these penicillins. An isokinetic enthalpy-entrophy correlation was demonstrated. The calculated beta value was 420 K.

Amoxicillin↗
PubMed1978

[A new method for evaluation of beta-lactamase production of resistant enterobacteriaceae strains (author's transl)].

Resistant strains of Enterobacteriaceae were investigated with a chemical and microbiological test on beta-lactamase activity. The chemical method was needed as screening-test basing on the enzymatic hydrolysis of the chromogenic cephalosporin compound 87/312. The microbiological test is a modified cup plate method using Staph. aureus SG 511 as sensitive test strain for penicillins and cephalosporins. In one of the two cups of the blood agar plate 20 microliter of the beta-lactam antibiotic, in the other cup 20 microliter of the supernatant of the 24 h broth of the bacterial strain was pipettet. If the lactamase in the supernatant neutralises the antibiotic, a halfemoonlike blank is forming on the left site of the inhibition zone. An unchangeable inhibition zone demonstrates stability of the antibiotic to the enzyme. Each of 10 ampicillin- and/or cephalothin-resistant strains of E. coli, Klebsiella, Enterobacter and Serratia were investigated against 6 penicillins (penicillin G, ampicillin, ticarcillin, mezlocillin, azlocillin, bay k 4999) and 6 cephalosporins (cefoxitin, cefuroxime, cefamandol, cephalothin, cefazolin, cefradine). The microbiological method allows the statement, against which beta-lactam antibiotic the enzyme is effective. A correlation between the beta-lactamase activity and the MIC values in Enterobacteriaceae was not found.

DNA, Bacterial↗
PubMed1986

In vitro models in the study of antibiotic therapy of infections in neutropenic patients.

Most conventional methods for in vitro testing of antibiotics involve exposure of a bacterial inoculum to a constant, static concentration of drug. The in vivo concentrations of antibiotics change continually according to their pharmacokinetics. When two drugs are used, the ratios of their concentrations also change with time. The usual checkerboard tests for combined activity of two or more antibiotics do not consider the pharmacokinetic properties. An in vitro two-compartment pharmacokinetic model has been developed that presents changing concentrations of one or two antibiotics to isolated bacterial inocula. This model simulates the treatment of a bacterial infection in the absence of host defenses and thus mimics infection in a neutropenic patient. This model has been used to study the synergistic activity of beta-lactam/aminoglycoside combinations compared with conventional checkerboard and time-kill methods. Also, in this model, the addition of azlocillin or ceftazidime to netilmicin prevented the selection of resistant subpopulations of Pseudomonas aeruginosa that occurred with the aminoglycoside alone. In vitro pharmacokinetic models add kinetic parameters to conventional susceptibility testing and may prove useful in the design of trials of the optimal dosing and administration of antibiotics for infected neutropenic patients.

Agranulocytosis↗
PubMed1979

[Persistency and resistance of streptococci isolated from periodontal pockets].

Intradermal injection of cell walls or cell wall constituents (Peptidoglycane) of Streptococcus sanguis II in experimental animals caused a similarly severe inflammatory reaction as with Streptococcus A. The three "viridans" species of streptococci proved to be resistant to complement (active serum) as well as to lysozyme and were superior to Streptococcus A in their capacity for resistance to another type of muralytic enzyme isolated from Streptomyces albus. The new acylureido penicillins (Mezlocillin, Azlocillin) had an almost equally inhibitory effect on the growth of the various species of bacteria. The "viridans" and beta-haemolytic types of streptococci which induce a chemotactic reaction in vitro were about equally rapidly and effectively killed in the phagocytes (granulocytes, monocytes) isolated from a patient.

Cell Wall↗
PubMed1985

[Microbiologic and clinical significance of cefotiam].

Modern cephalosporins are of considerable importance for the therapy of severe infections by multiresistant organisms. According to in-vitro-findings on ampicillin-resistant E. coli as well as Klebsiella spp., Proteus spp., and serratia spp., altogether 159 strains, instead of cefotaxime nearly always also cefotiam can be used. The two remedies are clearly superior to cephalothin. cefotiam is ineffective to Pseudomonas aeruginosa. But in this case also cefotaxime is clearly inferior to azlocillin. In 6 of 7 casuistic instances the clinical effectiveness of cefotiam could be confirmed with good tolerability. The contemporary establishment of staph. aureus in mixed infections of serratiastaphylococci proved as as particular advantage. A primary therapeutic failure referred to a necrotizing pancreatitis, when no causative organism was proved, in which case also cefotaxime remained without any effect. Despite the improved individual medical possibilities the control of the infectious hospitalism by critical administration of antibiotics and improved hospital hygiene, particularly strict non-infection, must remain the pre-eminent task.

Adult↗