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Biomedical subjects

H Gaya

Publications and source records attributed to H Gaya.

At least 55 records · Page 3Linked to original sources
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

Use of cephalosporins in the immunologically compromised patient.

Infection is a major threat to patients with neutropenia, particularly those with haematological malignancies who are undergoing chemotherapy. Early use of an empirical antibiotic regimen with the broadest possible spectrum of activity is recommended until culture data can guide the choice. A standard combination in many centres is an amino-glycoside and a semisynthetic penicillin with antipseudomonal activity or a cephalosporin. However, no regimen can adequately cover all potential pathogens and in these patients, who are exposed to many toxic insults, the choice of antibiotics may significantly increase the incidence of side effects, particularly nephrotoxicity. There has, therefore, been considerable interest in simpler, less toxic (and less expensive) regimens and the concept of monotherapy has been explored. Although recent studies using ceftazidime alone have supported this as an effective approach, there remain several issues to resolve; and on a more cautionary note preliminary results from the latest EORTC study, which recruited more than 1200 patients, suggest that in Gram-negative bacteraemia, conventional combination therapy remains the treatment of choice in neutropenia. While monotherapy is attractive in an environment of low drug resistance when exposure to third generation cephalosporins is infrequent, this is rarely the case. In addition, the widespread use of tunnelled catheters for venous access had led to an increase in Gram-positive infections, and the more intensive immunosuppression to the emergence of fungal infections. Although these tend not to be rapidly fatal, their presence must be considered in designing treatment strategies. The influence of the host and treatment on the type of infection and the relative merits of the differing concepts in therapy are explored in detail in this article.

Bacterial Infections↗
PubMed1986

Combination therapy and monotherapy in the treatment of severe infection in the immunocompromised host.

Profoundly granulocytopenic patients in whom fever develops are likely to have gram-negative septicemia, which may rapidly be fatal. These patients require early empiric therapy with a synergistic bactericidal combination of antibiotics that should be chosen on the basis of in vitro studies, animal models, and results of volunteer and clinical trials. From in vitro studies, it is apparent that the degree of synergy between an aminoglycoside and a beta-lactam is determined mainly by the aminoglycoside. Amikacin is the most synergistic of the aminoglycosides. A combination of an aminoglycoside such as amikacin plus a beta-lactam active against Pseudomonas is probably still the best empiric therapy available. The newer compounds and beta-lactam combinations still have to be proven effective in the clinical setting of the persistently and profoundly granulocytopenic patient with fever and bacteremia.

Agranulocytosis↗
PubMed1986

Laboratory support for choosing and monitoring antimicrobial therapy in severely ill patients.

The microbiology laboratory plays an important role both in choosing initial antimicrobial therapy and in monitoring such therapy during the course of treatment. In septicemic patients who have few, if any, clinical findings suggesting a specific etiologic diagnosis, it is useful to know the antibiotic susceptibility patterns for the given hospital or community. This type of empiric approach to therapy might require a larger variety of antibiotics than that usually considered for treatment of infected neutropenic patients. In the absence of neutropenia, there is perhaps more latitude in the initial choice, and single-drug therapy often can be considered. While patients are receiving antibiotics that should be appropriate for an identified pathogen, several laboratory procedures can be used to monitor this treatment. Antibiotic synergism studies may be useful in neutropenic patients, as well as assays of serum bactericidal activity. The serum bactericidal activity may be useful also in monitoring therapy for bacterial endocarditis or for osteomyelitis, especially when oral or home therapy is considered. Similarly, drug levels may be measured by a variety of techniques to ensure appropriate serum concentrations and to minimize drug toxicity. In addition, the preclinical evaluation of antibiotics alone and in combination can be used in guiding the design of clinical studies of these drugs in certain patient groups, such as neutropenic patients.

Agranulocytosis↗
PubMed1986

In vitro considerations in monotherapy and combination therapy for severe infections.

The introduction of the many new penicillins and cephalosporins has not radically altered the results of therapy in infected patients with impaired host defenses. Pseudomonas-active beta-lactam combinations with aminoglycosides remain the mainstay of treatment. Among the new cephalosporins, only ceftazidime shows promise in clinical trial, and the results of the fourth European Organization for Research on Treatment of Cancer (EORTC) trial, which includes the combination of amikacin plus ceftazidime, are awaited with interest. Whichever regimen is chosen, care must be taken to detect the emergence of resistant strains. This may entail changing the empiric regimen used on a cyclic basis in order to minimize the problem and maintain an acceptable level of clinical response.

Agranulocytosis↗
PubMed1986

A new enzyme-linked fluorescence assay (ELFA) for use with peroxidase-antibody conjugates: a comparison with ELISA for the quantitation of IgM antibodies to hepatitis B core antigen.

A new enzyme-linked fluorescence assay (ELFA) suitable for use with peroxidase-antibody conjugates is described. The substrate for the assay is p-hydroxyphenylacetic acid, the fluorescent product of which is stable and unaffected by light. The assay compared favourably with a standard ELISA for the quantitation of IgM antibodies to hepatitis B core antigen.

Enzyme-Linked Immunosorbent Assay↗
PubMed1986

Prospective randomized comparison of three antibiotic regimens for empirical therapy of suspected bacteremic infection in febrile granulocytopenic patients.

The standard regimen used by members of the European Organization for Research on Treatment of Cancer Antimicrobial Therapy Cooperative Group for empiric therapy of febrile neutropenic cancer patients has been treatment with ticarcillin plus amikacin. A three-arm prospective randomized controlled trial was performed to determine whether the extended-spectrum antipseudomonal penicillin azlocillin or the extended-spectrum cephalosporin cefotaxime had more or less efficacy than the beta-lactam in the ticarcillin-plus-amikacin regimen. A total of 742 patients from 22 institutions were evaluated. Single gram-negative rod bacteremias accounted for 83 episodes, and it was among these patients that the prognosis was least satisfactory, leading to a more intensive evaluation of this patient group. In these patients the azlocillin-plus-amikacin regimen resulted in a 66% response rate, compared with a 37% response rate for patients who received cefotaxime plus amikacin (P = 0.080) and a 47% response rate for patients who received ticarcillin plus amikacin (P = 0.207). The patients with gram-negative rod bacteremias and persistently profound granulocytopenia had substantially poorer response rates (37%) than the patients with rising granulocyte counts (73%; P = 0.004). A logistic regression analysis indicated that the following factors also affected infection resolution: beta-lactam utilization in the regimen (azlocillin was better than ticarcillin or cefotaxime), resolution of profound granulocytopenia (less than 100 cells per microliter) during therapy, and susceptibility to the beta-lactam antibiotic.

Adolescent↗
PubMed1986

Asymptomatic carriage of Clostridium difficile in patients with cystic fibrosis.

Faecal samples from 37 patients with cystic fibrosis and 40 control patients at the Brompton Hospital and the London Chest Hospital were examined for the presence of Clostridium difficile. The organism was isolated from 2 (17%) of control patients who were receiving antibiotics and from one (3.6%) of control patients who had no antimicrobial treatment. Thirty two per cent of the patients with cystic fibrosis excreted C difficile, though none of them had diarrhoea. Two of the three isolates from control patients and nine of the 12 isolates from patients with cystic fibrosis produced toxin B (cytotoxin) in vitro. Toxin B was present in the stools of one of the control patients and three of the patients with cystic fibrosis; toxin A (enterotoxin) was not detected in the faeces of the patients with cystic fibrosis. Two cytotoxigenic strains of C difficile isolated from patients with cystic fibrosis were examined in hamsters; both were virulent, and the animals died.

Adolescent↗
PubMed1985

A comparison of oral cefuroxime axetil and oral amoxycillin in lower respiratory tract infections.

We assessed oral cefuroxime axetil in an open study of 30 patients with lower respiratory tract infection and then compared oral cefuroxime with oral amoxycillin in a randomized double blind study in a further 40 patients. Satisfactory clinical responses were obtained in 73% of patients receiving cefuroxime axetil 500 mg tid in the open study, and in the comparative study in 71% of patients receiving cefuroxime axetil 500 mg bd, in 60% of patients receiving cefuroxime axetil 500 mg tid and in 63% of patients receiving amoxycillin 500 mg tid. There were no significant differences in response rates between the three regimens in the comparative study. There were no important adverse effects in any of the patients. Oral cefuroxime axetil is safe and effective in the therapy of lower respiratory tract infections.

Administration, Oral↗
PubMed1985

In vitro activity of temocillin against gram-negative clinical isolates.

120 consecutive clinical isolates of various species of Enterobacteriaceae and 30 consecutive clinical isolates of Haemophilus influenzae (including 5 which produced beta-lactamase) were assessed for susceptibility to temocillin using a broth microdilution technique and both 'light' (10(3) CFU/ml) and 'heavy' (10(6) CFU/ml) inocula. At the lighter inoculum, 90% of the Enterobacteriaceae were inhibited by temocillin at a concentration of 4 mg/L. 90% of the H. influenzae were similarly inhibited at a concentration of 0.5 mg/L, and no differences were observed between producers and non-producers of beta-lactamase. At the heavier inoculum, a significant inoculum effect was observed: minimum inhibitory concentrations (MICs) increased up to 128-fold for H. influenzae and somewhat less than that for the Enterobacteriaceae. Klebsiella pneumoniae was least affected by inoculum, showing only a 2- to 4-fold increase in the MIC. It is concluded that temocillin is active in vitro against the species tested and warrants further clinical trial.

Enterobacteriaceae↗
PubMed1984

Azlocillin compared with carbenicillin in the treatment of bronchopulmonary infection due to Pseudomonas aeruginosa in cystic fibrosis.

A randomised controlled open comparison of azlocillin and gentamicin versus carbenicillin and gentamicin was carried out in patients with cystic fibrosis who were chronically infected with Pseudomonas aeruginosa. The clinical response was assessed by measurements of pulmonary function and of the patients' feelings of wellbeing scored on a visual analogue scale. The sputum penetration of the antibiotics used was also studied. The two groups of 10 patients were similar in terms of age, sex, and pulmonary function at entry to the trial. Both regimens produced significant improvement in pulmonary function over 10 days. The mean FEV1 in the azlocillin group increased from 1206 to 1760 ml (p less than 0.001). In the carbenicillin group the mean FEV1 increased from 1116 to 1619 ml (p less than 0.001). Significant improvements in peak expiratory flow rate, forced vital capacity, and score on the visual analogue scale were also seen but there was no significant difference between the antibiotic regimens. Despite high serum concentrations the sputum penetration of the antibiotics was poor.

Adolescent↗
PubMed1984

Rational basis for the choice of regimens for empirical therapy of sepsis in granulocytopenic patients.

The three therapeutic trials of the EORTC International Antimicrobial Therapy Project Group are reviewed, demonstrating the efficacy of synergistic combinations of aminoglycosides with beta-lactam compounds in the initial empirical therapy of febrile episodes in granulocytopenic patients. Large numbers of patients are required in order to have sufficient evaluable cases in small but important subgroups to draw any valid and statistically significant conclusions. At present this can be achieved only by co-operative groups engaging in multicentre trials.

Administration, Oral↗
PubMed1983

Rational basis for the choice of regimens for empirical therapy of sepsis in granulocytopenic patients. A report of the EORTC International Antimicrobial Therapy Project Group.

The three therapeutic trials of the EORTC International Antimicrobial Therapy Project Group are reviewed, demonstrating the efficacy of synergistic combinations of aminoglycosides with beta-lactam compounds in the initial empirical therapy of febrile episodes in granulocytopenic patients. Large numbers of patients are required in order to have sufficient evaluable cases in small but important sub-groups to draw any valid and statistically significant conclusions. At present this can be achieved only by co-operative groups engaging in multi-centre trials.

Administration, Oral↗
PubMed1981

In vitro and in vivo studies of three antibiotic combinations against gram-negative bacteria and Staphylococcus aureus.

The activities of azlocillin, cefotaxime, and amikacin alone and in combination were evaluated in in vitro checkerboard studies, in infected neutropenic mice, and in human volunteers. The combination of cefotaxime plus amikacin was more synergistic in vitro than the others against the Enterobacteriaceae tested, and the combination of azlocillin plus amikacin was more synergistic against Pseudomonas aeruginosa and Staphylococcus aureus. Survival of neutropenic mice infected with Escherichia coli and Klebsiella pneumoniae, respectively, was greater with azlocillin plus amikacin (24 of 40 and 11 of 40) and with cefotaxime plus amikacin (21 of 40 and 17 of 40) than with azlocillin plus cefotaxime (22 of 40 and 3 of 40; P less than 0.05). Median serum bactericidal activity in volunteers receiving these antibiotics alone and in combination was greater than or equal to 1:8 with most agents and with all combinations tested against 10 strains each of E. coli, K. pneumoniae, P. aeruginosa, and S. aureus. These data suggest that clinical trials with combinations of azlocillin or cefotaxime plus amikacin deserve further study in febrile neutropenic patients.

Amikacin↗