Efficacy of itraconazole in the prevention of fungal infections among neutropenic patients with hematologic malignancies and intensive chemotherapy. A double blind, placebo controlled study

We studied the efficacy and safety of itraconazole for the prevention of fungal infection in neutropenic patients given cytotoxic chemotherapy for hematologic malignancies. Patients were randomly allocated to receive either itraconazole (200 mg bd) or placebo in addition to oral amphotericin B until the patient either developed fungal infection or had completed antileukemic treatment. Forty six patients (83 neutropenic episodes) treated with itraconazole and 46 placebo treated patients (84 neutropenic episodes) were evaluable. No specific toxicity was noted. Nine fungal infections developed in the itraconazole group, of which four were histologically or microbiologically proven and 15 in the patients given placebo (eight proven) (p < 0.12). All these patients received IV amphotericin B. The incidence of Candida albicans infections tended to be lower in the itraconazole group, but overall, there was no measurable improvement in the prevention of fungal infections and mortality by itraconazole.     

Development of resistance by Enterobacter cloacae during therapy of pulmonary infections in intensive care patients

The emergence of resistance during therapy and the efficacy of different antibiotic therapy regimens were studied in 38 intensive care patients suffering from pulmonary infections caused by Enterobacter cloacae. Every three days a fresh isolate was obtained from each patient and tested in vitro for susceptibility to 16 antibiotics by determination of the minimal inhibitory concentrations. During therapy with cefotaxime and tobramycin the E. cloacae strains from 47% of the patients became resistant to cefotaxime within 6 days. In all cases resistance encompassed all other broad-spectrum penicillins and cephalosporins tested, as well as aztreonam. Development of resistance regularly led to persistence of bacteria. Resistance to tobramycin, ciprofloxacin or imipenem was not observed. Treatment of 25 patients with persisting E. cloacae infections was successful in 17 out of 18 patients treated with imipenem and in 6 out of 7 patients receiving ciprofloxacin.     

Paradoxical hypertension after reversal of heart failure in patients treated with intensive vasodilator therapy

Hypertension is a major cause of heart failure, evolving from left ventricular hypertrophy to systolic and diastolic dysfunction. Although effective heart failure therapy has been associated with a lowering or no change in systemic arterial blood pressure in long-term follow-up, this study describes the symptomatic, clinical, and left ventricular functional response of a subgroup of heart failure patients with a prior history of hypertension who demonstrated a paradoxical hypertensive response despite high-dose vasodilator therapy. We prospectively identified 45 patients with a past history of hypertension who had become normotensive with symptomatic heart failure. Of these 45 heart failure patients, 12 became hypertensive while receiving therapy in follow-up, with systolic blood pressure > or = 140 mm Hg (Group A). The remaining 33 patients did not have a hypertensive response to therapy (Group B). In the 12 Group A patients, 60+/-10 years old, with symptomatic heart failure for 6.3+/-4.3 years, vasodilator therapy was intensified in the 2.0+/-0.5 years of follow-up, achieving final doses of enalapril 78+/-19 mg and isosorbide dinitrate 293 +/-106 mg per day. New York Heart Association classification improved from 2.9+/-0.8 to 1.3+/-0.5 (P < or = .0001), with a reduction in heart-failure-related hospitalizations. Left ventricular ejection fraction increased from 17+/-6% to 40+/-10% (P < .0001). Follow-up blood pressure at 1 to 3 months was unchanged. However, both systolic and diastolic blood pressure increased at final follow-up, rising from 116+/-14 to 154+/-13 mm Hg (P = .0001) and from 71+/-9 to 85+/-14 mm Hg (P = .004), respectively. Renal function remained unchanged. Although both groups had similar clinical responses, there were more blacks and women in the hypertensive Group A. Effectively, 12 of 45 (27%) heart failure patients with an antecedent history of hypertension demonstrated a paradoxical hypertensive response to vasodilator therapy. The recurrence of hypertension in a significant portion of patients successfully treated for heart failure has important clinical implications.     

T-lymphocytopaenia, opportunistic infections and pathological findings in Ghanaian AIDS patients and their sexual partners

Ninety-nine patients at Center for Disease Control (CDC) clinical stage IV were studied. Twelve (12.12%) of these patients turned out to be HIV seronegative. Ten out of the 12 HIV negative patients were immunocompetent whereas the other two had proportional decreases in both CD4+ and CD8+ T-lymphocytes. HIV-1, HIV-2, and dual infection, were detected in 51.5%, 2%, and 22.2% respectively of clinical AIDS patients. The other 12.12% of clinical AIDS patients were indeterminate for HIV antibodies. All HIV positive patients with the exception of two, were immunocompromised with respect to CD4+ and CD8+ T-lymphocyte counts. Two healthy spouses and three children of patients who died from the disease were seronegative for HIV antibodies. Herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV) antibody titres were higher in HIV infected than uninfected blood. Patients with chronic diarrhoea, lymphadenopathy, pneumonia, and tuberculosis, either alone or in combination of two or more of such symptoms, were found to be more likely to be confirmed by serology and immunology as definitive AIDS patients in Ghana. In postmortem studies on 20 patients, pneumonia due to tuberculosis constituted the major cause of death. Toxoplasmosis, cytomegaloviral eosophagitis and enteritis, and cryptococcosis were the major opportunistic infections detected. Programmed cell death (apoptosis) was found by the DNA gel electrophoresis method to be an unlikely major mechanism of accelerated culture induced death of PBMCs from CDC stage IV AIDS patients.     

Renal stones in Kelantan, Malaysia--has the pattern changed?

Records of 183 patients with renal stones managed at Hospital Universiti Sains Malaysia between 1985 and 1995 were retrospectively evaluated. The commonest symptom was lumbar pain which may be associated with either frequency, blood stained urine or dysuria. One hundred and sixty-one patients (88%) had upper tract stones while the remainder had lower tract stones. Positive urine cultures were seen in 33 patients. The commonest organism isolated was Escherichia coli followed by Klebsiella aeruginosa and Staphylococcus aureus. Almost all of our patients had renal impairment at presentation and 70% of them progressed to chronic renal failure. In contrast to previous findings, the pattern of renal stone in this region is similar to that described in Western society. Its effect on renal function is serious and hence warrant special attention.     

Value of high dosage fluconazole in therapy of candida infections in intensive care medicine

The administration of fluconazole in the ICU setting in dosages of > or = 800 mg/day or > or = 10 mg/kg/day has been reported in about 400 patients with candidiasis of different localisation including candidemia, with a rapidly increasing incidence of serious candidal infections. In Germany, fluconazole is approved for therapy of life-threatening infections caused by Candida spp. and Cryptococcus neoformans in a dosage of up to 800 mg/day. Especially in non-neutropenic patients with life-threatening infections caused by Candida spp., Cryptococcus neoformans and Coccidioides immitis, the results of a limited number of dose-finding trials show dose-dependent response rates. These findings strongly advocate the application of high-dose fluconazole; their evaluation, however, still awaits final clarification. The good safety profile even for maximum dosages of up to 2000 mg/day and the linear, predictable pharmacokinetics up to 1600 mg/day indicate the excellent tolerability of fluconazole in the clinical situation, which justifies prospective, randomized clinical trials with treatment groups as homogeneous as possible for further evaluation of the optimum dosage and duration of treatment in the various types of candidal infection.     

Incidence and pattern of liver involvement in haematological malignancies

Copper release from copper-bearing IUD's was studied in vitro and in vivo using atomic absorption spectrophotometry in deionized water, normal saline solution and normal ovulatory cervical mucus. In these media, copper release from a 375 mm2 DIU occurs without latency, showing comparable amounts for identical time intervals. Daily copper release was shown to be respectively 8 and 11 times higher in cervical mucus and normal saline solution than in deionized water. Although copper ions are detectable in ovulatory cervical mucus under physiological conditions, the copper content appears 5 to 6 times higher in women bearing a copper IUD. Obviously, the copper amount is dependent on the copper exposed surface: the daily in vitro release from a 250 mm2 IUD is 18% inferior to that observed from a 375 mm2 model. In vivo, the daily copper release in ovulatory mucus of 380 or 200 mm2 IUD users is respectively 5 and 3.5 times higher than in controls.     

NIH conference. Recent advances in the management of AIDS-related opportunistic infections

Secondary infections remain the leading cause of death in patients with the acquired immunodeficiency syndrome (AIDS). Dealing with the rapidly evolving spectrum of infectious problems seen in patients with AIDS requires knowledge of current therapeutic and prophylactic strategies. Through an extensive preclinical trials network supported by both industry and government, an increasing number of new agents are being identified and rapidly moved into clinical trials. Several agents are now available to treat diseases caused by Pneumocystis carinii, and corticosteroids have become a useful adjunct to antimicrobial agents in the treatment of P. carinii pneumonia. Although the treatment of toxoplasmosis remains a challenge, alternatives to sulfadiazine and pyrimethamine are now available. Mycobacterial infections, particularly with Mycobacterium tuberculosis, have become an increasing problem for patients with AIDS, and both old and new combination drug regimens are being used. Cytomegalovirus disease, until recently an untreatable problem, can now at least be partially managed with antiviral agents. The use of more complete prophylactic regimens may decrease the morbidity and mortality from opportunistic infections.     

Antibacterial therapy in pyo-sepsis complications of patients in intensive care units

A combined psychophysiologic study of 100 individuals living in territories contaminated by radionuclides and 60 people from ecologically clean region. There were no significant differences in the incidence of neurotic disorders between people from these regions (61.2 and 65.3%, respectively). The highest sensitivity to small radiation doses was observed at rather young age (20-40 years). It was found that a considerable role in the development of borderline psychic disorders belongs to both somatic disturbances due to low-dose radiation and psychogenic effects. A combined action of psychogenic and somatogenic factors aggravated symptoms of neurotic disorders and promoted widening of a range of psychic disturbances. Some part of the population from the contaminated territories tended to the development of cerebro-vascular psychoorganic pathology resultant from a breakdown of the reserves of the adaptation. Now the stress factor of radionuclides exposure is not so important as social and economic problems.     

Effect of prophylaxis on the clinical manifestations of AIDS-related opportunistic infections

Administration of targeted prophylaxis for AIDS-related opportunistic infections has contributed significantly to the recent decrease in mortality among patients with AIDS in the United States. Most reported prophylaxis trials have focused on determining (a) the percentage of cases prevented and (b) the effect of widespread antibiotic use on drug susceptibility. A third phenomenon that is seldom reported on is the attenuating effect of failed prophylaxis on the clinical presentation of opportunistic infections (OIs). With the increasingly widespread use of prophylaxis for OIs, more atypical "breakthrough" cases of opportunistic infections will be seen. Reports of clinical changes are reviewed below. Investigators should routinely report the clinical manifestations of breakthrough cases in all articles pertaining to prophylaxis for opportunistic infections in patients with AIDS.     

Benefit of oral zinc supplementation as an adjunct to zidovudine (AZT) therapy against opportunistic infections in AIDS

Zinc is perhaps the most important trace element for immune function. Congenital or acquired zinc deficiencies are associated with immune abnormalities and increased susceptibility to infectious diseases. AIDS subjects suffer from reduced zinc bioavailability, more severe in stage IV than in stage III. Such zinc deficiency causes, among other effects, a profound reduction in the biological activity of one of the thymic hormones, thymulin (zinc-facteur-timique-serique, ZnFTS). With these premises, zinc sulphate was administered orally at a daily dose of 200 mg for 30 days to AZT-treated stage III subjects with generalized lymphadenopathy (17 subjects) and stage IV subgroup C1 (12 subjects) AIDS patients. 18 stage III subjects with generalized lymphoadenopathy and 10 stage IV subgroup C1 subjects treated only with AZT served as controls. Zinc sulphate supplementation of stage III and in stage IV C1 patients was followed by an increase or a stabilization in the body weight and an increase of the number of CD4+ cells and the plasma level of active zinc-bound thymulin. The frequency of opportunistic infectious episodes in the 24 months following entry into the study was reduced after zinc supplementation in stage IV C1 subjects (11 infections vs 25 in controls) and delayed in stage III zinc-treated subjects (1 infection/24 months vs 13 infections/24 months in controls). The effect of zinc on opportunistic infections is restricted to infections due to Pneumocystis carinii and Candida, whereas no variations have been observed in the frequencies of cytomegalovirus and toxoplasma infections. These data may support the benefit of zinc as an adjunct to AZT therapy in AIDS pathology.     

Magnitude and prevention of nosocomial infections in the intensive care unit

Nosocomial infections among intensive care unit (ICU) patients usually are related to the use of invasive devices (e.g., mechanical ventilators, urinary catheters, or central venous catheters). This article discusses the impact of these devices and other risk factors for nosocomial infection in ICU patients. Data on etiologic pathogens and device-related infection rates from the National Nosocomial Infection Surveillance System are presented, general infection control guidelines for ICUs are reviewed, and special infection control problems encountered in ICUs are discussed.     

Physical therapy in the rehabilitation of patients with aerobic infections of the extremities

OBJECTIVE: To evaluate how infection of extremity after war wound influenced the possibilities and immediate effects of a physical therapy. METHODS: The retrospective clinical investigation comparing two groups: group A (n = 86) with infection, group B (n = 87) without infection. Main indicators for possibilities of the physical therapy were the numbers and types of physical procedures used. For the estimation of immediate effects of physical therapy the muscle power and the range of motion were used. RESULTS: The number of daily physical procedures in the group with infection, compared to the group without infection, was significantly lesser ((A: 2.87 +/- 1.73; B: 4.02 +/- 1.73; p < 0.001). The patients with infection were significantly less frequently submitted to thermotherapy, hydrotherapy, interferent current and electrostimulation. Patients with infection, compared to patients without infection, had significantly poorer improvement of amplitude of analyzed movements at the end of treatment (A: 6.66 +/- 7.28 degrees; B: 16.66 +/- 14.79 degrees; p < 0.001). CONCLUSION: The infection of the extremities limited the possibilities and reduced the immediate effects of physical therapy.     

Evolution of the nutritional support pattern in pediatric intensive care

OBJECTIVES: To evaluate patterns of usage and monitoring of nutritional support in a Pediatric ICU of a teaching hospital and the role of an education program in nutritional support given throughout the resident physician training. DESIGN: In a historical cohort study, records from children who received nutritional support during the year 1992 were analyzed. Thereafter a continuing education program in Nutritional Support was conveyed to the residents. In a second phase of the study, the same parameters were reevaluated in children who received nutritional support throughout the year 1995. SETTING: Pediatric Intensive Care Unit of Department of Pediatrics, Escola Paulista de Medicina. PATIENTS: All the children who were given nutritional support during a period of five days or more. Based on this criteria 37 children were selected for the first phase of this study, and 35 for the second one. INTERVENTION: The education program included theoretical lectures about basic themes of nutritional support and journal article reading sessions. It was given to successive groups of residents on a weekly schedule. MEASUREMENTS: Daily records of fluid, protein, caloric and micronutrient supply, nutritional assessment and metabolic monitoring. RESULTS: In the first phase of the study, an exclusively parenteral route was utilized for 80.5%, and a digestive route 19.5% of the time period. Nutritional assessment was performed on 3 children; no patient had the nutritional goals set. The nitrogen to nonprotein calories ratio and the vitamin supply were inadequate, whilst the supply of trace elements was adequate except for zinc. Nutritional monitoring was performed on almost all patients but without uniformity. In the second phase, the exclusive parenteral route was used for 69.7% and the digestive route for 30.3% of the time period; no significant increase in the use of the digestive route was detected. The nonprotein calories to nitrogen ratio and micronutrient supply were adequate. The frequency of nutritional assessment increased, but deficiency in nutritional monitoring and infrequent enteral feeding were still detected. CONCLUSION: There were deficiencies in the implementation of nutritional support, which were partially corrected in the second phase of the study by the training of the residents. Reinforcement of the education program, which should be applied to the whole medical staff, and the organization of a multidisciplinary team in charge of coordinating the provision of nutritional support are suggested.     

Coagulation system in patients with blood malignancies treated with estrogens in the course of cytostatic therapy

Hospital managers initiate a nurse orientation program modeled after critical pathways. The structure allows them to assess nurses' competency while providing experience.     

Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients

The efficacy and safety of oral fluconazole versus a polyene regimen in preventing mycoses in neutropenic patients was compared. Patients with haematological malignancy or bone marrow transplantation received as antifungal prophylaxis either fluconazole 200 mg daily or a regimen consisting of clotrimazole trouches 10 mg twice daily with mycostatin, 500,000 I.U. four times daily, benadryl and cepacol mouthwash. Ninety patients at risk for fungus infection were evaluable. Four of 42 patients (9.5%; confidence interval 2%-23%) on fluconazole and 17 of 48 patients (35.4%; confidence interval 22%-52%) (p < 0.01) on the clotrimazole regimen developed a clinically significant fungal infection, including 3 (7.1%) and 11 (22.9%) patients respectively who had severe fungal infection, mainly pulmonary aspergillosis. Death directly due to a fungal infection within 100 days of the start of prophylaxis occurred in 2 of 42 patients (4.8%) and 9 of 48 patients (18.8%) respectively (p < 0.06). Kaplan-Meier analysis showed that the chance of survival on fluconazole was statistically greater than for the clotrimazole regimen (p < 0.04). A decrease of candidal colonisation of the gastrointestinal and genitourinary tracts occurred only in patients receiving fluconazole. No significant toxicity occurred. A 200 mg daily dose of fluconazole given to these patients thus appears to be well tolerated and to provide a protective effect against the development of fungal infection and death from severe fungal disease.