Antibiotic resistance in Haemophilus influenzae isolated from patients with cancer.
Explore the source record for details and available documents.
Ampicillin Resistance↗
Biomedical subjects
F Meunier
Publications and source records attributed to F Meunier.
Tissue distribution and bioactivity of amphotericin B administered in liposomes to cancer patients.
Amphotericin B concentration was measured by high-pressure liquid chromatography (HPLC) and by bioassay in tissues of 11 cancer patients who died from infection and/or their underlying disease after having received amphotericin B entrapped into sonicated liposomes (ampholiposomes). These concentrations were compared to those measured in 28 patients who had only received the commercially available preparation of amphotericin B-Na deoxycholate complex (Fungizone). The fungistatic and fungicidal titres of the tissue homogenates were also evaluated using two strains of Candida spp. and one strain of Cryptococcus neoformans to determine the bioactivity of amphotericin B incorporated in our liposomes. Tissue concentrations varied with the tested tissues and were correlated with the total dose of amphotericin B administered whether given as amphotericin B-Na deoxycholate or ampholiposomes. Amphotericin B concentrations measured by bioassay in tissue methanolic extracts reached 58-81% of concentrations measured by HPLC, whereas only 15-41% was recovered from the unextracted homogenates. Fungicidal titres were seldom measured in tissues, but fungistatic titres were observed and were linearly correlated with amphotericin B concentration measured by HPLC. These results were similar for the patients who received only amphotericin B-Na deoxycholate and for those who received both preparations (amphotericin B-Na deoxycholate and ampholiposomes). Our results suggest that the tissue distribution of amphotericin B is not significantly modified by the type of preparation (deoxycholate complex or liposomes) and that most of the tissue-bound amphotericin B is not bioactive. However, higher daily doses of amphotericin B can be administered safely when incorporated in liposomes and therefore high tissue concentrations may be obtained more rapidly with ampholiposomes than with amphotericin B-Na deoxycholate.
Adult↗
Empirical antimicrobial therapy with a single daily dose of ceftriaxone plus amikacin in febrile granulocytopenic patients: a pilot study.
The optimal management of fever in granulocytopenic patients remains controversial. This pilot study investigated the potential value of single daily doses of amikacin administered empirically with ceftriaxone in febrile granulocytopenic patients. None of the patients died as a result of infection or toxicity from the prescribed regimen. Serum concentrations failed to show drug accumulation. Modifications of empirical antimicrobial therapy were made at a similar rate to other conventional regimens. Vancomycin seemed to increase the incidence of nephrotoxicity. Overall, this pilot study suggests that empirical therapy with single daily doses of amikacin plus ceftriaxone is safe and effective and should be further investigated in a larger number of patients.
Adolescent↗
Once daily dosing of aminoglycoside: one step forward.
Explore the source record for details and available documents.
Amikacin↗
Efficacy of amphotericin B encapsulated in liposomes (AmBisome) in the treatment of invasive fungal infections in immunocompromised patients.
One hundred and twenty-six patients were treated for 137 episodes of fungal infection with liposomal amphotericin B (AmBisome) at 43 investigational centres. Among the patients were 72 with malignancies, 17 organ transplant recipients, 20 patients with immunological disorders and 17 others. AmBisome treatment was instituted after toxicity from previous amphotericin B treatment in 49 cases, nephrotoxicity or renal insufficiency in 40 and failure of previous antifungal treatment in 41. One hundred and eight episodes were clinically evaluable; among these 52 were caused by Candida spp. and 34 by Aspergillus spp. Ninety-nine patients were treated for at least eight days with a maximum dose of 0.7-5 mg/kg/day. Among 64 cases with proven invasive fungal infection 58% were cured. Fungi were eradicated in 35 of 54 (65%) mycologically evaluable cases. The cumulative dose was 3.2 +/- 3.2 (mean +/- S.D.) in cases where fungi were eradicated in comparison with 3.3 +/- 2.3 g in cases where fungi persisted. The eradication rate was 83% for Candida spp. compared with 41% for Aspergillus spp. (P less than 0.01). Among 24 cases with presumptive invasive fungal infections 14 (58%) were cured. Candida spp. were eradicated in seven of ten of these cases. Among 11 cases with superficial fungal infections eight were cured and three improved. Candida spp. were eradicated in four of five patients. It is concluded that AmBisome is an effective antifungal agent in a majority of patients with invasive or superficial fungal infections.
Adolescent↗
Liposomal amphotericin B (AmBisome): safety data from a phase II/III clinical trial.
AmBisome is a commercially available preparation of amphotericin B incorporated in small unilamellar liposomes. The analysis of safety data provided in a multicentre compassionate phase II/III study evaluating 133 episodes of therapy with AmBisome in patients with severe underlying disease is very encouraging. Rapid (30-60 min) administration of a high daily dose of AmBisome is feasible without the well known side effects observed with the conventional formulation of amphotericin B (Fungizone). Although eleven of 71 patients with initially normal serum creatinine concentrations showed increased values after AmBisome therapy, 17 patients among 50 with initially high creatinine concentrations recovered normal renal function during AmBisome treatment. Hypokalaemia was observed in 24 episodes of treatment (18%). Increases in serum glutamyl oxaloacetic transaminase and alkaline phosphatase were also quite common in this selected population with severe underlying disease and the contribution of AmBisome to these changes is difficult to establish. AmBisome appears a safe alternative to conventional amphotericin B, and its efficacy should be further investigated.
Adolescent↗
Randomized study of vancomycin versus teicoplanin for the treatment of gram-positive bacterial infections in immunocompromised hosts.
Seventy-four immunocompromised patients with severe infection due to gram-positive organisms were randomized to receive either vancomycin or teicoplanin. Extensive cancer was present in 71 patients, of whom 47 died within a month. The types of infections were 46 bacteremias (39 associated with central catheters), 24 skin and soft tissue infections (3 with bacteremia), and 7 others (mainly bronchopneumonia). The most frequent pathogen was Staphylococcus epidermidis, followed by Staphylococcus aureus. Microbiological eradication was obtained in 23 of 35 evaluable patients treated with vancomycin (65.7%) and 28 of 36 patients treated with teicoplanin (77.8%) (P = 0.4). Clinical cure and improvement were obtained in 26 of 35 patients (74.3%) and 27 of 36 patients (75.0%), respectively. No significant side effects were observed with teicoplanin, in contrast to reversible increases in serum creatinine (three patients) and skin rashes (four patients) with vancomycin. Superinfection was observed in five patients treated with vancomycin and two patients treated with teicoplanin. No relation was found between peak concentration in serum (at steady state) or bactericidal titers and outcome.
Adult↗
Pharmacodynamic parameters and toxicity of netilmicin (6 milligrams/kilogram/day) given once daily or in three divided doses to cancer patients with urinary tract infection.
The pharmacologic parameters and toxicity of netilmicin (6 mg/kg/day) given once daily (qd) or thrice daily (tid) for the treatment of urinary tract infections were studied in a randomized prospective study of 60 cancer patients. The overall efficacy was 96%. Nephrotoxicity, assessed by the measure of urinary excretion of phospholipids, was lower for the patients receiving the qd regimen than for those receiving the tid regimen. Elevation of serum creatinine (20% over baseline) occurred in one patient receiving the qd regimen and in three receiving the tid regimen. Cochleotoxicity, assessed by pure-tone audiometry (250 to 18,000 Hz) occurred in one patient receiving the qd regimen and none receiving the tid regimen. Concentrations in sera were measured on days 1 and 5. No significant accumulation was observed in either group. Median serum bactericidal titers, expressed as reciprocal values (percentage of the sera with a titer greater than or equal to 8), were measured against 25 test organisms in samples collected 6 h after the administration of netilmicin and were, for the qd group, 16 (82%) against members of the family Enterobacteriaceae and less than 2 (8%) against Pseudomonas aeruginosa, and for the tid group, 4 (57%) against members of the Enterobacteriaceae and less than 2 (0%) against P. aeruginosa. The rate of killing in serum was rapid (2 to 3 log in 2 h against P. aeruginosa; 3 to 5 log in 2 h against members of the Enterobacteriaceae) and correlated with the sampling time and hence the concentration in serum of netilmicin. The duration of the postantibiotic effect in serum depended also on the strain and the sampling time of the serum.
Adult↗
Prospective randomized evaluation of ciprofloxacin versus piperacillin plus amikacin for empiric antibiotic therapy of febrile granulocytopenic cancer patients with lymphomas and solid tumors. The European Organization for Research on Treatment of Cancer International Antimicrobial Therapy Cooperative Group.
Empiric therapy for febrile granulocytopenic patients is mandatory, but whether monotherapy is a safe alternative and whether fluoroquinolones are useful agents for this indication are still controversial issues. The use of monotherapy with intravenous ciprofloxacin (200 to 300 mg every 12 h) was evaluated against combined therapy with piperacillin plus amikacin in febrile granulocytopenic patients with solid tumor or lymphoma. The study was discontinued prematurely because patients treated with ciprofloxacin had a significantly lower overall success rate than patients treated with piperacillin plus amikacin (31 of 48 patients [65%] versus 48 of 53 patients [91%], P = 0.002). Patients with gram-positive coccal bacteremia had a particularly poor outcome: therapy failed for six of eight patients (75%) treated with ciprofloxacin, while therapy failed for none of four patients treated with piperacillin plus amikacin. Death from primary infection during initially randomized protocol therapy occurred in 7 of 48 patients (14.5%) treated with ciprofloxacin and in 3 of 53 (6%) treated with piperacillin plus amikacin. This study does not support the use of this dose of intravenous ciprofloxacin as empiric monotherapy for fever in granulocytopenic patients.
Adult↗
Fungal infections in cancer patients.
Explore the source record for details and available documents.
Antifungal Agents↗
In-vitro activity of SCH39304 in comparison with amphotericin B and fluconazole.
The in-vitro activity of SCH39304, a new imidazole, was compared with that of amphotericin B using two media (Sabouraud dextrose and tissue culture (TC) medium) with or without 25% human serum. At an inoculum of 1.5 X 10(4) cfu/ml, the IC95% for amphotericin B ranged from 0.08 to 0.3 mg/l irrespective of the medium. At the same inoculum, the IC95% of the two imidazoles ranged from 0.3 to greater than 80 mg/l. The inoculum effect (from 1.5 X 10(4) to 1.5 X 10(5) cfu/ml) was less than 1 dilution for the three antifungal agents. Serum increased the inhibitory activity (IC80%) of SCH39304 and fluconazole but not of amphotericin B. The IC80%, IC95% and minimal fungicidal concentration (MFC) for amphotericin B usually ranged within two dilutions. Using kill curve methodology, the initial killing rate (0-4 h) of amphotericin B correlated with concentration (P less than 0.001), and was faster in TC medium than in Sabouraud dextrose (P less than 0.0006). SCH39304 and fluconazole did not produce any significant killing over the range of concentrations tested (0.5-20 mg/l). SCH39304 was similar to fluconazole.
Amphotericin B↗
In-vitro evaluation of the antifungal activity of amphotericin B entrapped into liposomes during storage for one year.
The stability of the antifungal activity of amphotericin B entrapped in small sonicated liposomes (ampholiposomes) was studied in vitro over a one-year period. Preparations of ampholiposomes stored at -20 degrees C or at 4 degrees C were compared monthly with freshly-prepared ampholiposomes and a commercial preparation of amphotericin B-deoxycholate (Fungizone; Squibb) by a killing curve method with Candida albicans. The bioactivity of the four preparations, each containing 1.5 or 2 mg/l of amphotericin B, was measured as the initial rate of killing and the 'relative bioactivity'. Relative bioactivity was calculated as the percentage reduction of the area under the growth curve compared with control growth. Storage of ampholiposomes for one year did not decrease their antifungal activity. Storage of ampholiposomes containing 1.5 mg/l amphotericin B for one year at -20 degrees C, but not at 4 degrees C, gave a significant increase in relative bioactivity and killing rate in comparison with freshly-prepared ampholiposomes. This was probably due to modifications in the spatial configuration of phospholipids and amphotericin B. The persisting antifungal activity of ampholiposomes stored for one year should allow the preparation of large batches to perform comparative clinical studies.
Amphotericin B↗
Prevention of infections in neutropenic patients with pefloxacin.
Bacterial infections remain a major source of morbidity and mortality in neutropenic patients. Therefore, optimal methods of prevention seem mandatory and various means have been tested, in particular specific modalities such as chemoprophylaxis, which remains controversial. Overall, non-absorbable antibiotics have been disappointing and are less commonly used because of the poor compliance of most patients. Co-trimoxazole has been shown to be effective under certain circumstances but the emergence of resistance, and the risk of prolonging the duration of neutropenia are major drawbacks despite the advantages of co-trimoxazole being well tolerated and effective in preventing Pneumocystis carinii infections. Recently, fluoroquinolones have been developed and numerous studies of prophylaxis have been performed with norfloxacin, enoxacin, ciprofloxacin, and other agents from this class, including pefloxacin. These data show a significant reduction of bacteraemia caused by Gram-negative bacilli in neutropenic patients but a high incidence of infection caused by Gram-positive cocci, mainly streptococci. The sources of those infections are many including mucositis due to chemotherapy and/or total body irradiation, as well as changes in the patient's flora due to more effective cover against Gram-negative bacilli. Future studies should further investigate regimens to achieve optimal prophylaxis for infections caused by either Gram-negative or Gram-positive pathogens during neutropenia.
Administration, Oral↗
Ceftazidime plus teicoplanin versus ceftazidime plus amikacin as empiric therapy for fever in cancer patients with granulocytopenia.
In a prospective randomized study, 100 episodes of fever (greater than 38 degrees C) and granulocytopenia (less than 1000/microliters) in cancer patients were empirically treated with ceftazidime (2 g every 8 h) plus teicoplanin (400 mg every 8 h on day 1; 400 mg every day thereafter) or ceftazidime (2 g every 8 h) plus amikacin (500 mg every 8 h). Bacteraemia, clinically documented infection and possible infection were documented in seven, 11 and 19 patients treated with ceftazidime plus teicoplanin and in 11, four and 17 patients treated with ceftazidime plus amikacin. Overall, the response rate was similar in the two groups of patients as was the need for treatment modifications and the rate of death. For documented Gram-positive bacteraemia, the response rate was 2/5 patients treated with ceftazidime plus teicoplanin and 2/7 with ceftazidime plus amikacin; for documented Gram-negative bacteraemia, the response rate was 1/2 and 3/4 patients respectively. No breakthrough bacteraemia was observed. Tolerance was excellent, although renal toxicity (elevation of serum creatinine) was observed in three patients treated with ceftazidime plus teicoplanin and in none allocated to ceftazidime plus amikacin.
Adult↗
Therapy of infections related to intraperitoneal catheters in patients with ovarian cancer.
Bacterial peritonitis is a common complication associated with catheters implanted for intraperitoneal anticancer chemotherapy in patients with extensive ovarian carcinoma. During an ongoing trial of intraperitoneal cisplatin-melphalan vs. cisplatin-gamma interferon, given via an intraperitoneal 'Port-a-cath' catheter, 6 episodes of suspected bacterial peritonitis occurred in 5 patients. Clinical symptoms were present in all episodes and 3 episodes were documented microbiologically. Teicoplanin was given intraperitoneally, 400 mg three times a day on the first day and once daily thereafter. Serum and peritoneal concentrations were measured by bioassay. Despite clinical improvement during therapy, the catheter was removed in 4 out of 5 patients after the end of intraperitoneal teicoplanin, due to the presence of infection. Additional patients are required to evaluate the efficacy of intraperitoneal teicoplanin in the treatment of catheter-related peritonitis associated with anticancer intraperitoneal chemotherapy.
Aged↗
[Systemic mycotic infections].
Invasive fungal infections are common in immunocompromised patients. Early diagnosis is still difficult and prophylactic modalities seems mandatory but are yet to be defined. Standard therapy of invasive fungal infections relies on the administration of intravenous amphotericin B. This agent is difficult to administer and toxic. Recently, new antifungal agents have been developed and are currently under investigation. Those new agents included itraconazole and fluconazole as well as new galenic preparations of amphotericin B such as liposomes. All these studies should provide optimal management of invasive fungal infections and improve the prognosis of those patients.
Amphotericin B↗
Fluconazole treatment of fungal infections in the immunocompromised host.
Immunocompromised patients are predisposed to opportunistic fungal infections. Candidiasis is reported most frequently both as a localized infection (eg, oropharyngeal candidiasis) and as life-threatening systemic candidiasis. With relatively few antifungal agents in the clinical armamentarium, the optimal management of candidiasis remains controversial. Among the agents that are available, amphotericin B is difficult to administer, 5-fluorocytosine cannot be used alone due to the frequent emergence of resistant yeasts, and ketoconazole, which is effective for esophageal and oropharyngeal candidiasis, is not recommended for systemic candidiasis, especially in granulocytopenic patients. Recently, fluconazole, a new triazole antifungal agent, has been found to be active against Candida spp and is being studied in various clinical settings. In addition to its oral formulation, it is available for intravenous (IV) administration, which is a significant advantage in treating debilitated or noncompliant patients. In a randomized, double-blind study, we compared the efficacy of 100 mg/d oral fluconazole with that of 400 mg/d ketoconazole in cancer patients with oropharyngeal candidiasis. Although clinical and microbiological outcomes were similar for both groups, relapses occurred earlier in ketoconazole- than in fluconazole-treated patients. In another study, we administered fluconazole IV 100 to 300 mg/d to 13 patients, eight of whom had fungemia. Preliminary results are encouraging. Further studies of fluconazole as prophylaxis in granulocytopenic patients and as therapy for documented systemic candidiasis are under way. These studies are expected to define specific indications for fluconazole in immunocompromised patients.
Adolescent↗
[Antibiotherapy in the patient with granulocytopenic cancer].
Granulocytopenia is the leading alteration of the natural host defense mechanisms, whether caused by an underlying disease or associated with anticancer chemotherapy and radiation therapy. Severe granulocytopenia predisposes to septicemia which is now more often due to Gram positive than to Gram negative bacteria. The empiric therapy of febrile episodes with rapidly bactericidal antibiotics has dramatically modified the prognosis of septicemia. The optimal treatment remains controversial although the usual regimen include both a cephalosporin (or a large spectrum penicillin) with an aminoglycoside. The empiric treatment with a specific anti-Gram positive antibiotic such as vancomycin does not modify prognosis, adds significant side-effects and increases the cost. Monotherapy has been associated with the need for treatment modification in 30-80% of the episodes depending on the type of infection (fever of unknown origin, clinically or microbiologically documented infection). The patients who remain febrile despite adequate antibacterial empiric treatment beneficiate of an empiric antifungal treatment. Care should be taken about the recent emergence of vancomycin-resistant Staph. haemolyticus, Corynebacterium JK and non-JK, and non-aeruginosa pseudomonas (only susceptible to cotrimoxazole). More fungal infections are observed with a significant emergence of non-albicans Candida, dermatophytes and filamentous fungi (P. boydii, Fusarium, ...) associated with disseminated infections.
Agranulocytosis↗