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Biomedical subjects

J Klastersky

Publications and source records attributed to J Klastersky.

At least 145 records · Page 8Linked to original sources
PubMed1988

Antimicrobial prophylaxis for major head and neck surgery in cancer patients.

A total of 113 patients were randomly allocated to receive either ticarcillin plus clavulanic acid (total dose, 20.8 g) or clindamycin (total dose, 2.4 g) plus amikacin (total dose, 1 g) as perioperative antimicrobial prophylaxis for major head and neck surgery. The two groups were similar in age, prior antineoplastic treatment (surgery, chemotherapy, and radiotherapy) or tracheostomy, and the various types of surgery including radical neck dissection. The wound infection rate was 10% in the group of patients receiving clindamycin plus amikacin and 36% in the group receiving ticarcillin plus clavulanic acid (P less than 0.05). Initiation of systemic antibiotic therapy within 15 days of surgery was necessary for 20 and 45% of these patients, respectively (P less than 0.05). The distribution of microorganisms causing wound infections was comparable in both groups, except for anaerobes, which were isolated predominantly from patients who had received ticarcillin plus clavulanic acid.

Adult↗
PubMed1988

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

The experience from four EORTC trials on antimicrobial therapy for febrile granulocytopenic cancer patients (GCP) is reviewed. 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

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↗
PubMed1987

Ceftazidime combined with a short or long course of amikacin for empirical therapy of gram-negative bacteremia in cancer patients with granulocytopenia.

To determine whether combination antibiotic therapy including a short course of an aminoglycoside was as effective and less toxic than a conventional long course of the combination for the empirical therapy of gram-negative bacteremia in patients with cancer and granulocytopenia, we conducted a randomized multicenter trial comparing ceftazidime plus a short course (three days) of amikacin, ceftazidime plus a long course (nine days) of amikacin, and azlocillin plus a long course (nine days) of amikacin. Single-organism gram-negative bacteremia occurred in 129 of 872 evaluable patients. Without a change in antibiotics, the response rates were 81 percent with ceftazidime and long-course amikacin, 48 percent with ceftazidime and short-course amikacin (P = 0.002), and 40 percent with azlocillin and long-course amikacin (P less than 0.001). Among patients with fewer than 100 granulocytes per cubic millimeter throughout therapy, the response rates were 6 percent with ceftazidime and short-course amikacin and 50 percent with ceftazidime and long-course amikacin (P = 0.03). Linear logistic-regression analysis showed that therapy with ceftazidime and long-course amikacin was the most favorable prognostic factor of the response to infection, whereas the presence of leukemia or shock was the least favorable. We conclude that ceftazidime should be given in combination with a conventional full course of an aminoglycoside (amikacin) when used for the empirical treatment of gram-negative bacteremia in cancer patients with granulocytopenia.

Adolescent↗
PubMed1987

[A comparative review of combination therapy: 2 beta-lactams versus beta-lactam plus aminoglycoside].

We have reviewed the available literature on the controlled use of combinations of beta-lactams in the treatment of fever in neutropenic patients, as compared to that of combinations of beta-lactams and aminoglycosides. We compared overall responses, responses in septicemia and various other infections, according to different pathogens and degree of neutropenia, and we evaluated toxicity. Overall, these results showed that response rates with combinations of two beta-lactams are similar to those obtained with combinations of a beta-lactam and an aminoglycoside for infections in immunocompromised patients with serious underlying diseases. They also suggest that the emergence of resistance of pathogens to beta-lactams has often been coped by the use of newer drugs in infections caused by Enterobacteriaceae, but much less effectively in the case of Pseudomonas aeruginosa infections. There are still other important theoretical reasons for preferring an aminoglycoside-containing combination for empiric therapy in febrile neutropenic patients, and our overall conclusion is that a large-scale study comparing beta-lactam combinations to the traditional beta-lactam plus aminoglycoside regimens is mandatory.

Aminoglycosides↗
PubMed1987

Dose/response study of aminohydroxypropylidene bisphosphonate in tumor-associated hypercalcemia.

Bisphosphonates (or diphosphonates) constitute a major advance in the treatment of tumor-associated hypercalcemia and also have the potential to prevent or reverse osteolysis in normocalcemic patients. Available information on adequate therapeutic doses and potential toxicity is, however, very fragmentary. This report describes a phase I study of one of the most promising bisphosphonates currently available, aminohydroxypropylidene bisphosphonate (AHPrBP or APD), in tumor-associated hypercalcemia. Only patients remaining hypercalcemic after 48 hours of rehydration were evaluated, and antineoplastic therapy was delayed at least until a normal serum calcium level was reached. AHPrBP was given as two-hour daily infusions for three days, and three different patients were treated at each of the six following dosage levels: 0.01, 0.05, 0.25, 0.75, 1.5, and 3.0 mg/kg per day. The two lowest dosages levels were insufficient to normalize serum and urinary calcium levels, but the efficacy of the four other dosages was very similar. Plasma immunoreactive parathyroid hormone levels increased as a function of calcium levels, whereas urinary hydroxyproline levels did not prove to be a very useful measure of AHPrBP's effects on bone resorption. The drug was generally very well tolerated: only six patients had transient fever and/or decreases in lymphocyte count that were not clearly related to AHPrBP dosage. The only real problem was observed at the highest dosage of 3.0 mg/kg per day in an obese woman in whom high fever and hypotension developed. Efficacy and tolerance in dehydrated patients were verified by treating seven other patients, not previously rehydrated, at 1.0 mg/kg per day for three days. In summary, the therapeutic range of AHPrBP, given for three days as a two-hour infusion daily, lies between 0.25 and 1.5 mg/kg per day. Fasting urinary calcium levels are probably the most reliable and easily measured parameter to monitor AHPrBP's inhibition of bone resorption in normocalcemic patients.

Adult↗
PubMed1987

Subrenal capsule assay for fresh human tumors in immunocompetent mice; an inappropriate technique for non-small cell lung cancer.

The subrenal capsule assay (SRA) seems to present some difficulties for the evaluation of the chemosensitivity of antineoplastic agents against fresh tumor xenografts. A study was therefore carried out to verify whether two different xenografts would behave in a similar way. Tumors such as melanoma provided adequate homogeneous material for this technique, while non-small cell lung carcinoma (NSCLC) were heterogeneous since the 1 mm3 specimen grafted under the renal capsule usually contained diffuse areas of necrosis and of infection. Furthermore, a large proportion of the grafted specimens, 257 out of 298, did not contain any tumor at all on microscopic examination even when they showed macroscopic growth. Added to these discrepancies, a random microscopic analysis of 180 adjacent fragments of NSCLC and melanomas demonstrated that the variability of heterogeneous tumors precludes any meaningful comparison between homologous tumor tissues designed to be grafted on treated and on control mice. The anti-inflammatory effect of chemotherapeutic drugs on the host's reaction to the graft is probably responsible for the differences between the macroscopic growth results observed in pieces grafted to both treated and control mice: however, it could not be simulated by hydrocortisone (HC) under our experimental conditions. This allows us to conclude that fresh tumors from NSCLC cannot be used in SRA.

Animals↗
PubMed1987

Comparative serum bactericidal activity against test anaerobes in volunteers receiving imipenem, clindamycin, latamoxef and metronidazole.

Ten healthy volunteers received on separate days the following regimens: imipenem 500 mg, clindamycin 600 mg, latamoxef 1 g, and metronidazole 500 mg. The antibiotics were given intravenously as an infusion over 15 min. Blood samples were obtained before and 30 min, 1 and 6 h after the start of the infusion. Serum bacteriostatic and bactericidal activities were measured against the following strains of strict anaerobes: two strains of Bacteroides fragilis, one strain each of B. vulgatus, B. thetaiotaomicron, B. oralis, Fusobacterium symbiosum, Eubacterium lentum, Clostridium perfringens, and Peptostreptococcus magnus. Sera from patients receiving clindamycin showed the highest inhibitory and bactericidal activities except against B. thetaiotaomicron and F. symbiosum. Imipenem had similar inhibitory and bactericidal activity to that shown by latamoxef. Metronidazole had a moderate activity against all strains although the activity persisted for 6 h. Latamoxef was the most active antibiotic against the test strain of C. perfringens.

Adult↗
PubMed1987

Pharmacokinetics of gentamicin after i.v. infusion or iv bolus.

A cross-over randomized comparative study was undertaken in ten healthy subjects to study the pharmacokinetics of 80 mg of gentamicin given as a bolus iv injection or as an infusion over 15 min using a commercially available 100 ml solution. Mean peak values at the end of the two modes of injection were respectively: 17.8 and 7.8 mg/l (P less than or equal to 0.002, Wilcoxon ranked pairs test). Mean peak values extrapolated at t = 0 for each volunteer were respectively 4.2 and 3.8 mg/l (not statistically different). Mean serum values 1 h after administration were respectively 4.2 and 3.7 mg/l (not statistically different). Mean trough values after 8 h were: 0.45 and 0.44 mg/l. Mean elimination half-lives were 139 and 142 min (P greater than 0.1).

Adult↗
PubMed1987

Bactericidal activity and killing rate of serum in volunteers receiving vancomycin or teicoplanin with and without amikacin given intravenously.

We have studied the interaction between vancomycin or teicoplanin and amikacin in two groups of five volunteers randomized to receive either (a) vacomycin, amikacin, vancomycin+amikacin, or (b) teicoplanin, amikacin, teicoplanin+amikacin. Each administration was given on separate days, in random order with a 48 hours washout period between each infusion. The serum concentrations measured microbiologically at time 0, 1 and 6 h were: 42.6, 11.4 and 4.1 mg/l respectively for teicoplanin; 27.6, 13.9, and 4.2 mg/l for vancomycin, and 44.9, 17.8, and 1.9 mg/l for amikacin. Teicoplanin was also measured using a solid-phase enzyme-receptor assay (SPERA). The serum bactericidal titres and the rate of killing in serum were measured 1 and 6 h after infusion against Staphylococcus aureus susceptible or resistant to oxacillin (5 strains each), S. epidermidis susceptible and resistant to oxacillin (5 strains each), Corynebacterium JK (5 strains), Listeria monocytogenes (5 strains), and Mycobacterium fortuitum (3 strains). The addition of amikacin to either teicoplanin or vancomycin increased the serum bactericidal titres against staphylococci with the exception of oxacillin-resistant S. epidermidis. Teicoplanin+amikacin was the most active regimen against L. monocytogenes and was equivalent to vancomycin+amikacin against M. fortuitum. Teicoplanin alone and teicoplanin+amikacin had a significantly lower killing rate against staphylococci than amikacin alone.

Amikacin↗
PubMed1987

In-vitro activity of two new carbapenems FCE 22101 and CGP 31608 in comparison with imipenem.

The minimum inhibitory concentrations (MICs) of two new penems, CGP 31608 and FCE 22101 were evaluated against 993 aerobic Gram-positive and Gram-negative bacteria and compared with imipenem. FCE 22101 was usually two to eight-fold more active than CGP 31608 except for Pseudomonas aeruginosa against which FCE 22101 was inactive. Both new penems were less active than imipenem. MBCs were equal to 1-2 X MICs. The effects of inocula, cations and serum were minimal. The MICs and MBCs were higher at pH 8 than at pH 6 or 7. Synergy between the new penems and amikacin was detected in 30% of the strains studied. Antagonism occurred with some Gram-positive bacteria.

Anti-Bacterial Agents↗
PubMed1987

In-vitro activity of LY146032 against Staphylococcus aureus, Listeria monocytogenes, Corynebacterium JK, and Bacillus spp., in comparison with various antibiotics.

The in-vitro activity of LY146032 was studied against Staphylococcus aureus, Listeria monocytogenes, Corynebacterium JK, and Bacillus spp. in comparison with several agents with action against Gram-positive bacteria. LY146032 showed an MIC90 of 0.4 mg/l for S. aureus, regardless of the resistance to penicillin or oxacillin. LY146032 was equivalent in activity to ciprofloxacin and vancomycin against S. aureus and moderately active against other species tested (MIC90, 0.8-3.2 mg/l).

Anti-Bacterial Agents↗
PubMed1987

Bactericidal activity and killing rate of serum against gram-positive cocci in volunteers receiving imipenem, oxacillin, vancomycin or ampicillin plus gentamicin.

The serum bactericidal activity and rate of killing of serum was studied in two groups of ten volunteers receiving imipenem 500 mg, oxacillin 3 g and vancomycin 1 g given iv (Group 1) or imipenem 500 mg, vancomycin 1 g, and ampicillin 3 g plus gentamicin 80 mg iv (Group 2). Serum samples collected 30 min, 1 h and 6 h after the start of a 15 min infusion were tested against Staphylococcus aureus susceptible (five strains) or resistant (five strains) to oxacillin, Staphylococcus epidermidis susceptible to (five strains) or resistant (five strains) to oxacillin (Group 1), and against Streptococcus faecalis (four strains), Streptococcus spp. (six strains). All strains of streptococci had been isolated from patients with endocarditis. Imipenem produced the highest bactericidal titres against susceptible staphylococci whereas vancomycin produced the highest titres against oxacillin-resistant staphylococci. Against "non faecalis" streptococci, imipenem was equivalent to ampicillin plus gentamicin, whereas ampicillin plus gentamicin was the most active regimen against Str. faecalis. The study of the rate of killing of serum showed that imipenem was able to kill initially 1.5 log cfu/ml of Str. faecalis but this was followed by regrowth. A similar regrowth was observed with oxacillin-resistant staphylococci. Killing curves in broth were studied with imipenem at two temperatures (30 and 37 degrees C) and two initial inocula (10(5) and 10(6) cfu/ml) for 48 h of incubation against oxacillin-resistant staphylococci; regrowth occurred more rapidly with a high initial inoculum and low temperature of incubation despite a rapid initial killing. Gentamicin was found significantly to increase the rate of killing of imipenem against Str. faecalis in killing curves in broth. In conclusion, imipenem showed excellent activity, as assessed by the measure of the bactericidal titres and rate of killing in serum, against the studied strains with the exception of oxacillin-resistant staphylococci and Str. faecalis.

Adult↗