[Prevention of pneumocystosis with pentamidine aerosols].
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Biomedical subjects
Publications and source records attributed to B Regnier.
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The study objective was to describe the clinical, biologic, and hemodynamic features of adult overwhelming meningococcal purpura and to examine the prognostic factors by multivariate analysis at the time of admission to the intensive care unit. Thirty-five patients (greater than or equal to 13 years of age) with meningococcal infection, circulatory shock, and generalized purpuric lesions of abrupt onset were recorded in eight intensive care units from 1977 to 1989. The patients were young (mean age, 26.6 years; range, 13 to 68 years) and had been previously healthy. The female-to-male ratio was 3:1. Mortality was 54.3%, with most deaths occurring within the first 48 hours, usually secondary to irreversible shock with multiple organ failure. Ischemic complications (eight cases), prolonged heart failure (seven cases), and secondary septicemia (five cases) were the chief complications among survivors. Initial hemodynamic study after volume loading showed low stroke volume index (mean +/- SD, 29.4 +/- 13 mL/m2) and tachycardia (mean +/- SD, 138 +/- 16 beats per minute), a profile suggesting a greater myocardial depression than usually observed in gram-negative bacillary septic shock. Univariate prognostic analysis showed that four variables at the time of admission were associated with fatal outcome: a plasma fibrinogen level of 1.5 g/L or less, a factor V concentration of 0.20 or less, a platelet count lower than 80 x 10(9)/L, and a cerebrospinal fluid leukocyte count of 20 x 10(6)/L or less. Stepwise regression analysis showed that low fibrinogen level (less than or equal to 1.5 g/L) was the sole adverse prognostic variable (odds ratio = 2, 95% confidence interval, 1.5 to 2.7). Adult overwhelming meningococcal purpura is still associated with high mortality and morbidity. Low fibrinogen level at time of admission may permit early recognition of the most severely ill patients.
Good Clinical Practice (GCP) is a quality assurance system dealing with all stages of clinical trials which is progressively being adopted by European countries. European GCP guidelines are in preparation and will be issued soon. However, implementation of the guidelines poses major and costly problems. The training of investigators, the proper functioning of research ethics committees, the practice of obtaining written informed consent, source data verification, and quality control with internal audit and official inspections are among the most difficult issues. The obvious benefits of GCP are the improved quality of clinical trials and of data generated by such trials, as well as mutual recognition of studies conducted abroad.
Cefixime is a new orally active cephalosporin. Its MICs and beta-lactamase stability are similar to those of the parenteral third generation cephalosporins. This trial was conducted to determine the effectiveness and safety of ceftriaxone as compared with a treatment where oral cefixime was given after a 4-day treatment with ceftriaxone in severe upper urinary tract infections usually requiring parenteral treatment during two weeks. In an open, controlled trial, 95 patients met the inclusion criteria; 48 received IV ceftriaxone 2 g daily during 4 days, followed by IM or IV ceftriaxone 1 g daily for 11 days; 47 patients were treated by IV ceftriaxone 2 g.o.d. during 4 days and then by oral cefixime 200 mg b.i.d. for 11 days. Clinical cure at the end of treatment was achieved in 44 patients in the cefixime group and 47 patients of the ceftriaxone group. Ten to 84 days after the end of treatment, the overall clinical cure and bacteriologic eradication rates for these patients were 74.3 per cent (29/39) for cefixime and 81 per cent (34/42) for ceftriaxone. Treatment failure occurred in two patients in the cefixime arm, one in a patient with renal atrophy and vascular stenosis and the other in an 86-year old diabetic and bed-ridden woman with an infection following the use of a urinary catheter. There were eight relapses or re-infections (about 20 per cent) in each group. Seven minor adverse events were seen in six patients treated with ceftriaxone: pain upon IM injection (3 cases), diarrhea (2 cases) associated in one case with a generalized rash for which treatment was discontinued, and nausea (one case). Laboratory changes in both groups were not noteworthy and without clinical relevance. These results suggest that it seems possible to propose new parenteral cephalosporins with conversion to the oral route on the 5th day using the same class of drugs in the treatment of severe upper urinary tract infections, excluding certain urological or vascular underlying conditions and provided that duration of treatment is adapted to the type of clinical setting. These data define more accurately the use of cefixime with respect to currently available drugs.
We studied prospectively 132 patients with acquired immunodeficiency syndrome to define the spectrum of enteric pathogens during this disease, with special reference to the correlation between the lesions, the infections, and the symptoms. Forty-four percent of the patients harbored at least one enteric pathogen: the most frequently recovered were Cryptosporidium (28), cytomegalovirus (16), Entamoeba histolytica (13), Giardia lamblia (9), and Mycobacterium avium intracellulare (7). Patients harboring pathogens were more likely to be diarrheics (69%) than patients without a pathogen (38%; P = 0.01) and more likely to have endoscopic lesions (29%) than patients without a pathogen (4%; P less than 0.001). The most common pathogen associated with diarrhea was Cryptosporidium. Cytomegalovirus, Entamoeba histolytica, and Salmonella typhimurium were each significantly associated with endoscopic lesions. Patients with cytomegalovirus infection tended to have a greater incidence of ulcer than patients without cytomegalovirus infection. Stool analysis diagnosed 61% of the infections, while endoscopy diagnosed 44%. Seven percent were recognized by stool analysis and endoscopy. When considering the 24 patients in whom accurate diagnosis warranted endoscopic biopsies, stool examination alone would have given an incomplete diagnosis in 14 patients (due to the presence of polyinfection). The frequency of inaccurate diagnosis of infection by stool determination alone, plus the development of new antiviral agents that suppress cytomegalovirus, may favor the earlier application of endoscopic evaluation in these patients.
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The penetration of ofloxacin was studied in 22 patients with purulent meningitis or ventriculitis treated with conventional antibiotics. Three successive doses of 200 mg were infused at 12-h intervals during the acute stage of the disease. Ten patients received three additional doses when the meninges were considered to be healed. Cerebrospinal fluid (CSF) was drawn 0.5, 3, 6, or 12 h after the last infusion. Serial plasma and CSF samples were also obtained from patients with ventricular drainage. Concentrations in CSF ranged from 0.96 +/- 0.15 to 1.80 +/- 0.29 microgram/ml, depending on sampling time. The percentage of penetration in ventricular fluid, expressed as the ratio of the CSF area under the curve from 0 to 12 h to the plasma area under the curve from 0 to 12 h, was 73 +/- 6. Ofloxacin readily diffuses into CSF of patients with meningitis or ventriculitis and may be useful for treatment of CSF infections caused by susceptible pathogens.
Pentamidine concentrations were determined in plasma after a single aerosolization of 4 mg/kg pentamidine base on 18 patients breathing spontaneously (Group I) and in eight patients receiving mechanical ventilation (Group II). All the patients had documented pneumocystosis. Large interindividual variations in concentrations appeared, especially in Group I. Low concentrations were observed in Group I: Cmax = 65.6 +/- 9.4 micrograms/L (mean +/- SEM), contrasting with high levels in Group II: Cmax = 215.8 +/- 49.8 micrograms/L (mean +/- SEM). Consequently, the mean area under the curve from zero to 4 h was 2.6-fold higher in Group II than in Group I. These findings underline the risk of dose-related pentamidine toxicity in ventilated patients treated with aerosolized pentamidine and the interest of plasma pentamidine monitoring.
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Two patients developed disseminated subcutaneous nodules with febrile illness. In both cases, Pseudomonas aeruginosa was isolated from the lesions; blood cultures yielded the same organism in one case, and were negative in the other. The portal of entry was thought to be a jugular hemodalysis catheter in the first case and a necrotic zoster complicating lymphoma in the second case. Both patients' condition improved with antibiotic therapy and the Pseudomonas nodules resolved without surgical drainage.
Twenty-four AIDS patients, who underwent gastrointestinal evaluation, died from their disease and were autopsied. Seven had Cytomegalovirus colitis (group I) and 17 did not (group II). Clinical manifestations, digestive lesions, and infections were compared in the two groups. Chronic watery diarrhea was present in all the patients with colitis but was also present in 65% of the patients without colitis. Hematochezia was present only in the group with colitis (one of seven patients) but appeared late in the diarrheal course, due to necrotizing colitis. No other difference were noted between the two groups (mean duration of diarrhea, frequency and nature of the other infections). As for group I specifically, colonic ulcerations due to Cytomegalovirus were present in all the patients, varying from punctate and superficial erosions to deep ulcerations, with granular and friable intervening mucosa. Severe colonic lesions appeared during the course of Cytomegalovirus colitis in two patients who developed lethal necrotizing colitis. Finally, the clinical and pathologic features of these seven cases were compared to other reports of Cytomegalovirus infection of the colon.
Thirty-five patients with the acquired immunodeficiency syndrome (AIDS) and central nervous system toxoplasmosis, seen over a 30-month period, were treated with the combination pyrimethamine/sulfadiazine. All patients had clinical and computed tomographic scan findings consistent with active neurotoxoplasmosis. Mean duration of total therapy was six months. During the first two months of therapy, four patients died of acute neurotoxoplasmosis and 31 showed improvement. Of the 24 patients evaluable for long-term therapy, 14 (58 percent) achieved complete resolution and 10 had late clinical (n = 7) and/or computed tomographic scan (n = 6) sequelae. Six patients experienced 10 relapses, which occurred within six weeks of treatment discontinuation in seven of 10. Reintroduction of the combination led to complete resolution of the relapse in eight cases. These clinical results were correlated with brain anatomic findings in the 15 autopsied cases. Side effects, noted in 25 of 35, were mainly hematologic toxicity (n = 21) and cutaneous rash (n = 12). However, the combination had to be definitively stopped in only two cases and sulfadiazine alone had to be withdrawn in eight other cases. These data suggest that pyrimethamine/sulfadiazine is highly efficacious in neurotoxoplasmosis and that life-long therapy is needed to prevent relapses in patients with AIDS.
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The pharmacokinetics of teicoplanin were studied in 15 adult patients in the acute phase of severe infections caused by gram-positive cocci. All the subjects were given a daily intravenous bolus dose of 6 mg of teicoplanin kg-1 (body weight). The pharmacokinetic study was performed over a 48-h period after injection 4. The subjects were categorized according to their mean creatinine clearances (ml.min-1.kg-1) during the study period: group 1 (n = 3), greater than 1.6; group 2 (n = 6), 0.8 to 1.6; and group 3 (n = 6), 0.15 to 0.8. Mean concentrations of teicoplanin in serum at 1, 24, and 48 h were 33 +/- 8, 9 +/- 3, and 6 +/- 2.5 micrograms.ml-1, respectively. The mean half-lives of the concentration-time curve from 12 to 48 h were 28 +/- 4, 44 +/- 24, and 48 +/- 14 h in groups 1, 2, and 3, respectively (group 3 versus group 1: P less than 0.05). The mean area under the serum concentration-time curve from time zero to 24 h was 344 +/- 92 mg.h.liter-1, and the mean hybrid volume of distribution was 1.09 +/- 0.46 liter.kg-1. These values were similar for the three groups, with a trend for larger areas under the curve in group 3. Creatinine clearance correlated directly with the total body clearance of teicoplanin (r = 0.70) and with the renal clearance of teicoplanin (r = 0.82). However, in critically ill patients, the wide interindividual variations in pharmacokinetic parameters are more relevant than those related to the variations in renal function when creatinine clearance is above 0.30 ml.min-1.kg-1. We concluded that, in such conditions, monitoring of concentrations of teicoplanin in serum is mandatory.