[Qualification of low temperature vaporized hydrogen peroxide sterilization: Towards greater harmonization of practices?] / Qualification de stérilisateurs à basse température au peroxyde d'hydrogène : vers une meilleure harmonisation des pratiques ?

OBJECTIVES: Comparing performance qualification procedures for low temperature vaporized hydrogen peroxide sterilization. Assessing conformity with draft standard ISO/DIS 22441. METHODS: Qualification reports from several providers have been compared according to specific criteria: choices of cycles, loads, sterile barrier systems, probes, biological and chemical indicators; checking of packaging integrity and exposure to sterilizing agent. RESULTS: Six out of 8 reports based on 4 distinct sterilizers have been performed by third-party providers. Routine and process challenge devices are respectively used in 6 and 3 of these reports. Sizes and masses are never mentioned whereas load configuration is always specified. All reports use at least one biological indicator and 50% of them use one chemical indicator at a minimum. Most frequent wrapping materials are Ultra® and Tyvek® bags (respectively 50% and 37.5% of reports). Each qualification monitors per process pression and temperature, and 37.5% of them also quantify hydrogen peroxide concentration. Packaging integrity and environmental exposure are checked in respectively 50% and 12.5% of all reports. All reports have received providers approval. CONCLUSION: Qualification procedure is based on steam sterilization NF EN 14937 standard, which seems unsuitable for low temperature process. The lack of autonomy, the heterogeneity of loads and measurement choices reveal a low harmonization of practices. New standard should dispel the doubts about this heterogeneity.

[ISO 9001 certification of a sterilization unit: Transition to the 2015 version]. / Certification ISO 9001 d'un service de stérilisation : passage à la version 2015.

OBJECTIVES: The sterilization unit of Pitié-Salpêtrière-Charles Foix hospital group is ISO 9001 certified on one of its sites. The purpose of this work is to describe how the unit prepared for the transition from the 2008 version to the 2015 version of the standard, as well as the conduct of the audit. METHODS: The pharmaceutical team has received prior training from French national organization for standardization (Afnor) to understand the new requirements and how to apply them to the sterilization unit. SWOT and PESTEL methods were used. A 3-month retro planning has been established. Deadlines were the annual management review and the certification audit. Audits carried out by the Quality and Risk Management Department helped to identify the priorities. RESULTS: The compliance of the quality management system (QMS) has led to the identification of internal and external challenges, relevant stakeholders and risks and opportunities. Management leadership and communication has been strengthened and control over external providers has improved. The auditor did not identify any non-compliance, but said that the system had to mature regarding the recent application of the new requirements. CONCLUSIONS: The QMS is more effective, new strengths and weaknesses have been identified and requirements of the unit and stakeholders have been better defined. The pharmaceutical investment necessary for this approach has been important. Involvement in the quality approach of all the staff of the unit lies to the success of the project.

[Study impacto: Descriptive analyzis of pharmacist's clinical practice in onco-hematology]. / Étude impacto : analyse descriptive des pratiques de pharmacie clinique en cancérologie.

Pharmaceutical analyses of chemotherapy prescriptions by hospital pharmacists are activities codified by regulation and rules (bon usage). The involvement of the pharmacists in clinical pharmacy activities in the oncology setting is not clearly identified, justifying the development of a mapping of these activities from a questionnaire addressed to the professionals. One hundred and seven centers have participated to this study at the national level (overall participation rate of 32.4%). More than 95% of them used a computerized ordering system and three quarter of them submit the introduction of new compounds to an analysis by the drug therapeutic committee. Prescription analysis allowed detecting around 2% of errors from the current prescription. Clinical pharmacist participates to tumor boards of onco-hematology (RCP) at a level of 46% for senior pharmacist and 42% for junior pharmacist. This involvement in the RCP allowed anticipating protocol's modification and temporary used authorization. Ninety-two percent of the senior pharmacists estimate that they highlight the risk of no reimbursement for prescription out of the guideline during RCP, resulting to a modification of the prescription for 40% of them. This level of intervention is lower with respectively 64% and 10% for the juniors. This study underlines the expert value of the clinical pharmacist dedicated to oncology setting in pre and post analysis prescriptions. It could be targeted by a prospective analysis of both clinical and pharmacoeconomics impact of these interventions.

[Evaluation of the impact of a training program on vitamin K antagonists (VKA) implemented by pharmacy students aiming at improving the knowledge of patients receiving vitamin K antagonists during their hospital clinical training course]. / Évaluation de l'impact d'un programme de formation aux antagonistes de la vitamine K (AVK) pour les étudiants en pharmacie sur l'amélioration des connaissances des patients traités par AVK pris en charge au cours de leur stage clinique hospitalier.

INTRODUCTION: We developed a training program for pharmacy students aiming at supporting patients receiving vitamin K antagonists (VKAs). The objective was to estimate how the program impacts VKA-treated patient knowledge acquisition and/or improvement on their anticoagulant treatment. METHOD: Using dedicated tools, pharmacy students received education on VKA treatment. Once appointed to clinical wards of Assistance publique-Hôpitaux de Paris, they were in charge of evaluating patient's knowledge on VKA treatment before and after training. Evaluation was conducted using a face-to-face standardized interview (14-item questionnaire). A global score was calculated for each patient. An univariate and multivariate analysis was performed to identify potential variables influencing score result. RESULTS: One hundred and seventy VKA-treated patients were recruited in seven hospitals for evaluation of their knowledge on VKA treatment and on clinical at risk situations. Before intervention, patients obtained an average score of 12.3±3.2 (maximum: 18). Factors significantly associated with the score were possession of a VKA information booklet, VKA treatment duration, treatment initiation and age. Fifty-two patients with a low score were further trained by the pharmacy student. After intervention, their initial score was improved significantly, from 9.9±3.3 to 13.5±2.3 (P<0.0001). DISCUSSION AND CONCLUSION: Increasing patient knowledge is a way to decrease the rate of adverse effects. This study demonstrates that patients with primary poor knowledge improved it significantly thanks to pharmacy students' intervention. This may contribute to lower the VKA-associated risk of adverse events and consequently to the improvement of patients quality of life and healthcare expenditures.

Cost-effectiveness analysis comparing epidural, patient-controlled intravenous morphine, and continuous wound infiltration for postoperative pain management after open abdominal surgery.

BACKGROUND: Continuous wound infiltration (CWI), i.v. patient-controlled analgesia (i.v.-PCA), and epidural analgesia (EDA) are analgesic techniques commonly used for pain relief after open abdominal surgery. The aim of this study was to evaluate the cost-effectiveness of these techniques. METHODS: A decision analytic model was developed, including values retrieved from clinical trials and from an observational prospective cohort of 85 patients. Efficacy criteria were based on pain at rest (VAS ≤ 30/100 mm at 24 h). Resource use and costs were evaluated from medical record measurements and published data. Probabilistic sensitivity analysis (PSA) was performed. RESULTS: When taking into account all resources consumed, the CWI arm (€ 6460) is economically dominant when compared with i.v.-PCA (€ 7273) and EDA (€ 7500). The proportion of patients successfully controlled for their postoperative pain management are 77.4%, 53.9%, and 72.9% for CWI, i.v.-PCA, and EDA, respectively, demonstrating the CWI procedure to be both economically and clinically dominant. PSA reported that CWI remains cost saving in 70.4% of cases in comparison with EDA and in 59.2% of cases when compared with PCA. CONCLUSIONS: Device-related costs of using CWI for pain management after abdominal laparotomy are partly counterbalanced by a reduction in resource consumption. The cost-effectiveness analysis suggests that CWI is the dominant treatment strategy for managing postoperative pain (i.e. more effective and less costly) in comparison with i.v.-PCA. When compared with EDA, CWI is less costly with almost equivalent efficacy. This economic evaluation may be useful for clinicians to design algorithms for pain management after major abdominal surgery.

Economic implications of using pegfilgrastim rather than conventional G-CSF to prevent neutropenia during small-cell lung cancer chemotherapy.

BACKGROUND: For the prevention of chemotherapy-induced febrile aplasia, a single injection of pegfilgrastim per cycle has the same efficacy as six to ten injections of conventional granulocyte colony-stimulating factor (G-CSF). However, there are few data on the economic impact of pegfilgrastim use, especially in the context of small-cell lung cancer. METHODS: This retrospective study involved 31 patients and 129 treatment cycles (32 with pegfilgrastim and 97 with granulocyte colony-stimulating factor (G-CSF)). We estimated the direct costs for preventing and managing febrile aplasia from the payer's perspective and also conducted a willingness-to-pay study with 100 healthy subjects, in order to estimate how highly a single-jab strategy was valued relative to multiple injections. RESULTS: The costs per cycle were respectively 1743 euros+/- 837 euros and 1466 euros +/- 836 euros for the pegfilgrastim and G-CSF strategies (p < 0.001). The excess cost of the pegfilgrastim strategy was partly compensated for by the perceived value of the single-jab strategy: 88% of interviewees would prefer the pegfilgrastim strategy; 16% would be willing to pay all the excess cost (277 euros) and 67% would be willing to pay half the excess cost. CONCLUSION: In this willingness-to-pay survey, the excess cost associated with pegfilgrastim relative to other G-CSF-based prophylactic strategies is partly offset by the perceived convenience of a single injection.

[Prescription guidebook for temozolomide usage in brain tumors]. / Guide de prescription et de bon usage du témozolomide dans les tumeurs cérébrales.

Malignant gliomas are the most frequent primary brain tumors in adults. Temozolomide is an oral alkylating cytotoxic agent of second generation, used in the treatment of high-grade gliomas. It is indicated in newly diagnosed glioblastoma multiform as well as in recurrent or progressive malignant gliomas, such as glioblastoma multiform or anaplastic astrocytoma. However, temozolomide is also used, off label, in other clinical situations and the main objective of this study was to establish recommendations and guidelines for relevant prescriptions of temozolomide in primary brain tumors and brain metastasis in adults. The literature review was analysed by experts who determined the evidence level (A to E) according to the scale of recommendations adopted by the "Haute Autorité de santé--HAS--(French National Authority for Health)". For high-grade and low-grade gliomas, based on the level of evidence from the literature, the use of temozolomide can be justified, with a B2 score attributed to these indications. In contrast, for the others indications, the use of temozolomide appeared to be more controversial or even not recommended (score C to E). Regarding the dosing schedule and administration scheme, as well as the co-administration with other anticancer drugs, a C score was attributed for the off label situations.

[Impact on renal function of an early switch from conventional to liposomal amphotericin B formulation in the empirical treatment of fungal infections]. / Impact sur la fonction rénale d'un relais précoce de la formulation conventionnelle de l'amphotéricine B par sa formulation liposomale dans le cadre d'un traitement empirique antifongique (Etude Nephemat).

OBJECTIVE: The authors had for aim to define the threshold of nephrotoxicity before switching to other antifungal treatment in hematological patients treated by conventional amphotericin B (AmB) as an empiric antifungal treatment. DESIGN: A prospective randomised multicenter study was made on 32 neutropenic hematological patients receiving conventional AmB for empirical antifungal treatment. The patients were randomised after a greater than or equal to 30% increase of serum creatinine (sCr). Patients in the early-switch group received liposomal AmB just after randomisation and patients in the late-switch group received liposomal AmB only when serum creatinine increase was greater or equal to 100% or sCr reached 170mumol/L. RESULTS: Thirty-one patients were analysed: 16 patients in the early-switch group and 15 patients in the late-switch group (seven switched to liposomal AmB and eight continued conventional AmB treatment). The mean age of patients was 48 years and 68% were men. The most frequent underlying haematological malignancy was acute leukemia (94%). In the late-switch group, the degradation of renal function continued after randomisation contrary to the early-switch group: median variations of calculated sCr clearance in early- and late-switch groups were -16.8 and -1.5%, respectively (P=0.03). Moreover, an early switch was cost-effective with a sCr lower duration of hospitalisation in comparison with a late switch. CONCLUSIONS: This randomised trial suggests that an early switch to Liposomal AmB improves and preserves renal function in comparison with a late switch.

Cost analysis applied to postoperative analgesia regimens: a comparison between parecoxib and propacetamol.

BACKGROUND: Postoperative pain management represents a significant part of perioperative costs. Non-opioid analgesics are often used in combination with opiates to improve pain relief and reduce opioid-related side effects. OBJECTIVE: To assess the costs and cost efficacy of intravenous (i.v.) parecoxib versus i.v. propacetamol in postoperative pain. METHODS: A prospective, randomised, double-blind, clinical evaluation was performed to compare the efficacy of a single bolus injection of 40 mg parecoxib and 2 g propacetamol, administered twice within 12 h following surgical repair of inguinal hernia. Resources for each arm of treatment were collected, and total costs were determined, including costs of drug acquisition, devices and labour for preparation of the two analgesic drugs. Cost-efficacy analysis was performed as the cost to achieve complete satisfaction with analgesia. Incremental cost efficacy was determined as the ratio between the differential costs and the differential patient satisfaction. The analysis was performed from an institutional perspective over a 12 h time frame. RESULTS: A total of 182 patients was evaluated. Pain at rest and morphine consumption were observed to be reduced in the parecoxib group. The percentages of patients totally satisfied with their pain management 12 h after surgery were 87% in the parecoxib-treated group and 70% in the propacetamol-treated group (P < 0.01). The average cost per patient was higher in the parecoxib group, 6.65 euros vs 5.28 euros in the propacetamol group). Cost per patient satisfied was calculated at a mean value of 7.64 euros for parecoxib and 7.54 euros for propacetamol. Incremental cost per additional patient satisfied was 8.02 euros in the parecoxib-treated group when preparation costs were included. Sensitivity analysis (+/-15%), including a bootstrap method applied to costs and efficacy, did not modify these conclusions. CONCLUSION: Parecoxib exhibits higher cost and greater patient satisfaction than does propacetamol. From a cost-efficacy approach, incremental cost per additional patient satisfied for parecoxib treatment must be analysed in light of overall perioperative pharmaceutical cost.

[A prospective study of quality of life and treatment of chemotherapy-induced anaemia in lung cancer]. / Qualité de vie et traitement de l'anémie chimio-induite dans le cancer bronchopulmonaire: étude prospective.

INTRODUCTION: The impact of chemotherapy-induced anemia on the quality of life (QOL) of patients with lung cancer has been little studied. OBJECTIVE: We evaluated the feasibility of measuring QOL among patients receiving chemotherapy for lung cancer, and the possible correlation of QOL with the haemoglobin level. METHODS: This was a prospective study of 53 patients starting chemotherapy (total 155 cycles); QOL was measured with the specific Fact-An scale. RESULTS: The mean haemoglobin level before treatment was 13.1+/-2.3 g/dl. During chemotherapy 45.3% of patients received erythrocytic growth factors and 15.1% were transfused; 26.4% of patients refused to answer or could not answer the QOL questionnaire. There was a strong correlation between the Hb level and overall QOL (r=0.343, p=0.0004), as well as the physical and functional subscales (but not the cognitive and social subscales). CONCLUSIONS: Although QOL could not be measured in one-quarter of cases, it was clearly affected by anaemia, which supports a strategy of early diagnosis and management of anaemia due to chemotherapy for lung cancer.

Cost consequences of adjuvant capecitabine, Mayo Clinic and de Gramont regimens for stage III colon cancer in the French setting.

BACKGROUND/AIMS: To compare the cost consequences of oral capecitabine and two different intravenous regimens of 5-fluorouracil/folinic acid (de Gramont and Mayo Clinic regimens) as adjuvant therapy in stage III colon cancer in France. METHODS: Clinical efficacy and safety data were taken from published clinical trials. Medical resource use was estimated from published data and expert opinion. Direct costs (drug acquisition, inpatient and home drug administration, laboratory tests, transportation, and management of adverse events) were considered over a time horizon of 46 months (3.8 years). The perspective taken was that of the French Sickness Funds. RESULTS: In patients treated with capecitabine, relapse-free survival was 1.3 months longer than with the Mayo Clinic regimen, which has been shown to be as effective as the de Gramont regimen. In the base case analysis, capecitabine was less costly (3,654 EUR/patient) than the Mayo Clinic (10,481 EUR/ patient) and de Gramont (7,204 EUR/patient) regimens. In the sensitivity analysis, capecitabine remained dominant except when the intravenous regimens were assumed to be administered at home in all patients. CONCLUSIONS: In France, capecitabine is more effective and less costly than both the Mayo Clinic and de Gramont regimens as adjuvant therapy for colon cancer.

Optimizing fluoroquinolone utilization in a public hospital: a prospective study of educational intervention.

Fluoroquinolone (FQ) utilization should be optimized, with the aim of controlling both multidrug-resistant bacteria and costs. In the present study, the appropriateness of FQ prescriptions for urinary tract infections (UTIs) before and after an educational intervention was examined prospectively. FQ-prescribing physicians received oral and written guidelines between the two phases of the study. All patients admitted to Saint-Antoine University Hospital (Paris) and treated with FQs for UTIs during the study period were included. The main outcome measures of the appropriateness of FQ prescriptions were based on the principles of Antibiotic Utilization Review. The study involved 127 patients. The main prescribing errors before the intervention were wrong routes of administration and failure to take into account antibiotic susceptibility results. The rate of erroneous prescriptions fell by 74.4% after intervention. About 71% of the improvement can be attributed to the intervention (71.4%; 95% confidence interval, 39.3-86.8). The intervention had an overall positive impact on FQ prescription quality. The decrease in inappropriate prescriptions was due mainly to the use of antibiotic susceptibility results (23% vs. 11.5%, P<0.05) and better consideration of indications (18.9% vs. 3.8%; P<0.05). Future educational interventions will cover other indications and will take into account costs and local antimicrobial susceptibility patterns.

Evaluation of the stability and efficacy of rhGM-CSF as a topical agent in a gel formulation.

OBJECTIVE: It has been reported that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), applied as a solution or an emulsion, improves wound healing. In order to confirm these data, the wound-healing efficacy of this growth factor was studied in a murine model. METHOD: In this double-blind randomised study, murine excisional wounds were treated with either sterilised rhGM-CSF gel (10 micrograms/cm2) or a sterilised placebo gel (control group). rhGM-CSF was applied at dosages of 10 micrograms/cm2/day to wounds until complete closure occurred. RESULTS: rhGM-CSF stability in gel formulation was excellent during the first week but decreased thereafter. Full wound healing occurred within 9.7 days (mean time) in the intervention group compared with 10 days in the control group. This difference was not statistically significant. Histological evaluation of the healed wounds indicated that there was a similar percentage of neutrophils in the cellular infiltrate in both groups. CONCLUSION: rhGM-CSF sterile gel had an excellent safety profile and was easy to use, but did not significantly accelerate the healing rate in this model.

The relationship between introduction of American society of clinical oncology guidelines and the use of colony-stimulating factors in clinical practice in a Paris university hospital.

BACKGROUND: Clinical practice guidelines are issued periodically by professional medical societies or committees to assist practitioners in clinical decision making. However, it is unclear whether such guidelines have any lasting impact on clinical practice. OBJECTIVE: The purpose of this study was to assess the impact of the American Society of Clinical Oncology (ASCO) guidelines regarding use of hematopoietic colony-stimulating factors (CSF) on cancer care in a university hospital in Paris. METHODS: The study was performed at Hjpital Tenon, an 830-bed university hospital in Paris, in 1996 and 1997, both before and after the ASCO guidelines were implemented. The guidelines were first disseminated as a continuing medical education program and then actively implemented using a CSF prescription order form summarizing the guidelines. This form had to be used during the patient consultation and was sent to the Hjpital Tenon pharmacy for CSF dispensation. Even if CSF use did not comply with the ASCO guidelines, the pharmacy filled the prescription. Seven other university hospitals in Paris, where the ASCO guidelines were not actively implemented, comprised the control group. The main outcome measure was the proportion of prescriptions in compliance with the 1996 update of the ASCO guidelines. Secondary outcome measures were the proportions of prescriptions in compliance with ASCO guidelines regarding primary prophylactic, secondary prophylactic, and therapeutic CSF administration. RESULTS: Before implementation of the ASCO guidelines, CSF use in compliance with the guidelines was 39% (41/105) at the study site and 31% (16/51) at the control sites (P > 0.05). Six months after dissemination and implementation of the guidelines, the proportion of CSF prescriptions complying with ASCO guidelines increased significantly versus baseline (P = 0.003) in the study group, to 61% (50/82). However, even after the guidelines were implemented, compliance with guidelines on primary prophylactic CSF administration did not change significantly versus before implementation in the study group (12% [5/41] before implementation vs 6% [2/33] after implementation; P > 0.05). CONCLUSIONS: The results suggest an association between the active implementation strategy (continuing medical education and CSF prescription reminder form) and physician compliance with the ASCO guidelines. Implementation of the ASCO guidelines appears to have had some impact on medical practice.

Multicenter study of the impact of prescription guidelines on the use of colony stimulating factors.

The aim of this work was to assess the impact of circulating guidelines for correct prescription practices of colony stimulating factors (CSF). Two hospital groups were compared, a 'guidelines' group (seven teaching hospitals) that circulated the guidelines and a control group (eight teaching hospitals) that did not. In addition, two periods were compared before and after distribution of the guidelines: from 17 February to 2 March 1996 and from 17 February to 2 March 1997. The assessment involved compliance with the guidelines for the following parameters: indications, dose regimen, time to start of CSF therapy and duration of CSF therapy between the control and guideline groups and also between the two periods. The population included 404 patients analyzed (209 in 1996 and 195 in 1997) for the indication of post-chemotherapy neutropenia. Total compliance in the first period (all four items) was 44.2% in the control group and 50.8% in the guideline group (nonsignificant), and during the second period was 31.9 and 59.6% in the two groups (p<0.001). During the first period, the differences in compliance with the guidelines for indication, dose regimen, time to start of treatment and duration between the groups were not significant. In the second period, this difference became significant and in favor of the guideline group for dose regimen (p = 0.009) and treatment duration (p = 0.02). The results of this study show the need to continuously define prescription reference systems according to available data, and to circulate them widely to improve the quality of health care and to control expenses.

An observational evaluation of the rate of awakening after isoflurane or desflurane used in daily clinical practice.

STUDY OBJECTIVE: To evaluate the rate of awakening after desflurane (D) or isoflurane (I) anesthesia when used during daily clinical practice. DESIGN: Observational prospective study. SETTING: University-affiliated metropolitan hospital. PATIENTS: 68 ASA physical status I and II patients (18-75 yrs) scheduled for abdominal surgeries. INTERVENTIONS: Patients scheduled for abdominal surgery of various duration received either D or I. No time was specified for discontinuation of the inhaled drugs at the end of the surgery. T0 for recovery parameters was stated as the end of the surgery. A p-value < 0.05 was considered as significant. Results are expressed as medians and ranges. MEASUREMENTS AND MAIN RESULTS: 68 patients (32 in D group and 36 in I group) were analyzed. Patient demographic data were similar between the two groups. Duration of surgery was 151 minutes (83-428 min) and 174 minutes (40-552 min) for I and D, respectively. Extubation occurred earlier after D (18 min [9-35 min]) as compared to I (32 min [7-77 min]). Time to reach the Aldrete score at 10 was faster after D (30 min [12-45]) as compared to I (46 min [15-110]). Unlike I, the rate of awakening after D was independent of the duration of surgery. The differences between D and I reached statistical significance in surgical procedures lasting more than 100 minutes. CONCLUSION: Used during routine conditions, D allows for faster recovery than I in surgical procedures lasting more than 100 minutes. The rate of awakening after D remained independent of the duration of the surgical procedure.

Impact of ASCO guidelines for the use of hematopoietic colony stimulating factors (CSFs): survey results of fifteen Paris university hospitals.

To assess whether physicians comply with American Society of Clinical Oncology (ASCO) guidelines for the use of CSFs, a prospective survey was performed in 15 Paris university hospitals involved in cancer treatment in 1997. If 45% of the prescriptions complied with the guidelines, primary prophylactic administration, which represented 52% of cases, did not comply with ASCO guidelines. These results suggested that primary prophylactic administration was one major clinical situation in which physicians could benefit from guidance to use a CSFs and that criteria defined by ASCO to allow primary prophylactic administration were not applied in clinical practice.

Effect of mitoxantrone liposomes on multidrug-resistant breast cancer cells.

A major obstacle in efficacy of breast cancer chemotherapy is the emergence of multidrug resistance. We investigated modulation of multidrug resistance by liposome-encapsulated mitoxantrone in a drug resistant human breast MCF7R cell line and the influence of liposome composition. Neutral high phase-transition temperature and anionic low phase-transition temperature phospholipid liposomes, reduced the resistance factor from 142 to 15 and 38, respectively. The higher cytotoxicity obtained with mitoxantrone-encapsulation was not necessarily related to higher intracellular uptake. Our data suggest that liposomes, according to their lipid composition, may alter the P-glycoprotein function by plasma membrane stabilization and modulate multidrug resistance in human cancer.

Clostridium difficile-associated diarrhea in HIV-infected patients: epidemiology and risk factors.

A retrospective analysis of all the cases of Clostridium difficile-associated diarrhea (CDAD) in hospitalized patients infected with HIV was performed over a 52-month period to assess the incidence, epidemiology, and risk factors of CDAD. A case of CDAD was defined as a patient with diarrhea and a positive stool cytotoxin B assay. Sixty-seven cases of CDAD were recorded in HIV-infected patients between January 1991 and April 1995. The annual incidence of CDAD ranged from 1.7 to 6.4 per 100 HIV-infected patients discharged from hospital. The 67 CDAD cases included 48 (72%) first episodes and 19 (28%) relapses. Serogroup C accounted for 69% of strains from initial episodes of CDAD. To identify risk factors for CDAD, 34 HIV-infected patients with a first episode were compared with 66 HIV-infected controls matched for the length of hospital stay. Three independent factors remained significantly associated with CDAD among HIV-infected patients: CD4+ cell counts <50/mm3 (OR = 5.2; 95% CI = 1.4-19.3; p = 0.01), clindamycin use (OR = 5.0; 95% CI = 1.3-18.3; p = 0.02) and penicillin use (OR = 4.6; 95% CI = 1.1-18.8; p = 0.03). C. difficile is a common enteric pathogen responsible for nosocomial diarrhea in HIV-infected patients. Clinicians should keep this pathogen in mind when searching for the cause of diarrhea in these patients, especially those who are severely immunocompromised or have received clindamycin or penicillin.

Plasma itraconazole concentrations in patients with neutropenia: advantages of a divided daily dosage regimen.

A group of 36 patients in the hematology department of Saint-Antoine Hospital, Paris, France, was on chemotherapy. The patients were also given antiacid drugs to prevent gastrointestinal toxicity and itraconazole as prophylaxis against aspergillosis. The antifungal drug was given as 100-mg capsules three times a day shortly after meals. The plasma itraconazole and hydroxyitraconazole concentrations were measured by high-performance liquid chromatography at steady state. Of 36 patients, 29 (81%) had adequate plasma itraconazole concentrations (> or = 250 ng/ml) after 8 +/- 2 days. The 7 patients with low plasma itraconazole concentrations were given 200 mg three times a day. Of the 36 patients, 34 (94%) had effective plasma concentrations within 2 weeks of the beginning of treatment. The two remaining patients were lost to follow-up. The proposed itraconazole regimen provides effective prophylaxis against aspergillosis and represents a substantial economic advantage over a single daily dose of 400 to 600 mg. The marked intrapatient and interpatient variations in plasma itraconazole indicate the need for regular therapeutic drug monitoring to ensure effective plasma itraconazole concentrations in all neutropenic patients.