Dibekacin in the newborn: pharmacokinetics and evaluation of ototoxicity in neonates and premature infants.
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Biomedical subjects
Publications and source records attributed to C Safran.
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Cefotaxime levels were measured in the middle ears of 12 children, after operations for insertion of a transtympanic aerator for serous or relapsing otitis. Mean auricular cefotaxime levels were 4,3 and 5,1 mcg/ml on the right and left respectively. Mean serum level one hour after 25 mg/kg i.m. was 14,5 mcg/ml. In can be concluded that cefotaxime penetrates effectively into the middle ear. Its use should be reserved for difficult or menacing cases of otitis, but its bacteriological activity with regard to Haemophilus influenzae and certain enterobacteria is of value in cases where ampicillins may be ineffective due to resistance of strains.
A study of the pharmacokinetics of cefoperazone (CPZ), used as the sole antibiotic, was performed in 17 children and neonates. The types of infections treated were 7 UTI, 2 otitis media, 2 RTI, 4 septicemia or severe neonatal infections. Causative bacteria included 6 E. coli, 3 Pseudomonas aeruginosa, 1 C perfringens, 1 Klebsiella pneumoniae and 2 Staphylococcus aureus. Cefoperazone was administered by means of rapid IV injections (over 5 min) or IV infusions BID. The blood samples were taken by means of capillary microtubes at time 0, 0.25, 0.50, 0.75, 1, 2, 4, 6, 8 and 12 hours after the end of the first injection. After centrifugation and freezing at -80 degrees DEG method using modified Difco M2 Agar (Nall plus sodium citrate) and stock organinism Bacillus subtilis Atcc 6633. The results achieved in children and neonates were compared, in the 11 children (mean age 6.5 years). The mean single dose was 53 mg/kg. The mean maxima concentration was 145 mcg/ml and was obtained at 0.5 h. Mean serum half-life is 2.4 h. For the neonates mean age was 16 days and the dosage was 47 mg/kg, the maxima concentration was 232 micrograms/ml and was obtained at 0.6 h. The mean serum half-life was 3.4 h in the 2 groups, serum levels at 12 h were still high with a mean of 6.2 micrograms/ml for the 17 children. It appears that doses of 25-50 mg/kg given BID would be satisfactory.
Tonsillar diffusion of two antibiotics was compared in 61 children, 26 receiving 100 mg/kg/d of ampicillin, and the other 35 being treated with 50 mg/kg/d of triacetyloleandomycin during the 24 hours preceding tonsillectomy. Drug levels were measured by a microbiological method. The mean ampicillin level in the tonsil was 0,84 mcg/ml for a serum level of 4,1 mcg/ml 90 minutes before sampling, concentrations being absent in the tonsil in 12 cases (45 p. cent). Mean triacetyloleandomycin levels in the tonsil were 12,16 mcg/ml for a serum level of 2,27 mcg/ml 90 minutes before sampling, concentrations being absent in the tonsil in only 4 cases (11 p. cent). Very high concentrations of triacetyloleandomycin as against low or no levels of ampicillin were therefore detected in the tonsil. This suggest that macrolides should be employed in preference to ampicillin for the treatment of recurrent sore throats, and tonsillixis, and for preventive treatment of acute rheumatic fever.
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Using the technique of decision analysis to evaluate data on single-modality and combined-modality therapy in Hodgkin's disease, we have been able to determine which treatment gives the best chance for prolonged disease-free survival in given settings. Both the potential of combined-modality therapy for inducing secondary hematologic malignancies and the rate of salvage with MOPP following relapse after radiotherapy have been studied to observe the effect of different rates of these variables on the therapeutic decision. An analysis of patients with known pathologic stage endorsed the continued use of extended-mantle radiotherapy for Stages IA and IIA disease; under most of the conditions analyzed, combined-modality therapy appeared the best option for Stage IIIA disease. The results for Stages IB and IIB disease showed neither combined-modality therapy nor total nodal irradiation to have a conclusive advantage. We also analyzed management decisions for patients who had not had pathologic staging. For this, probabilities of each pathologic stage were derived from a large patient data base and were incorporated into the decision analysis. The results of this analysis indicated that, despite the mortality of laparotomy, treatment designated according to pathologic stage was more effective than immediate combined-modality therapy for most types of patients. For certain patients in whom the clinical features could be used to predict a high probability of advanced disease, the most effective management was immediate MOPP chemotherapy without staging laparotomy.
We used decision analysis to explore the role of lymphangiography for staging Hodgkin's disease. Factors included were status of the patient before the test, accuracy and mortality of lymphangiography, mortality of laparotomy and effectiveness of selected treatment. We analyzed hypothetical cases with varying probabilities being in Stages I+II, III and IV to determine the population in which indication for laparotomy would depend upon results of lymphangiography. Calculations made for asymptomatic patients revealed that the diagnostic usefulness of lymphangiography is restricted to patients either with a relatively low probability of Stage IV or with a very high probability of Stage IV disease. This population is further restricted as false-positive and false-negative results of lymphangiography increase.
A family of computer programs has been developed to help physicians effectively utilize available clinical information as in indicator of tumor extent for the staging of Hodgkin's disease patients. Decision analysis techniques were employed to suggest chronologic sequencing of selected, risk-associated tests, tailored to the individual patient, that minimize the risk of iatrogenic mortality. These quantitative techniques provide an objective measure of expected survival for a given plan of action. By using this information a physician and patient can balance expected survival vs morbidity of proposed staging procedures. Physicians can then focus on the interrelation between the inherent diagnostic uncertainty, therapy-induced expected survival, and morbid consequences of staging procedures. The use of these decision-making tools enables the physician to identify patient-specific presentations where the formation of an individual diagnostic plan could lead both to reduction in testing and to an increased survival rate.
Emergency readmissions among patients discharged from the medical service of an acute-care teaching hospital were analyzed. Using the multivariate technique of recursive partitioning, the authors developed and validated a model to predict readmission based on diagnoses and other clinical factors. Of the 4,769 patients in the validation series, 19% were readmitted within 90 days. Twenty-six per cent of the readmissions occurred within ten days of discharge, and 57% within 30 days. Readmitted patients were older, had longer hospitalizations, and had greater hospital charges (p less than 0.01). The discharge diagnoses of AIDS, renal disease, and cancer were associated with increased risks of readmission regardless of patients' demographics or test results. The relative risks (95% confidence interval) associated with these diagnoses were: AIDS, 3.3 (1.4-7.8); renal disease, 2.3 (1.7-3.0); cancer, 2.8 (2.4-3.4). Other patients at increased risk were those with diabetes, anemia, and elevated creatinine (2.1; 1.6-2.8) and those with heart failure and elevated anion gaps (2.2; 1.7-2.8). For patients without one of these diagnoses, a normal albumin and no prior admission within 60 days identified patients at reduced risk for readmission (0.4; 0.3-0.4). Thus, commonly available clinical data identify patients at increased risk for emergency readmission. Risk factor profiles should alert physicians to these patients, as intensive intervention may be appropriate. Future studies should test the impacts of clinical interventions designed to reduce emergency readmissions.
The authors analyzed the value of using mean corpuscular volume (MCV) as a guide for selecting tests for further evaluation of anemia in hospitalized patients. Of the 2,082 patients with anemia admitted to the medical service of a teaching hospital over one year, 655 (31%) had further diagnostic tests to evaluate the cause of the anemia. Within this group of 655 patients, 399 (61%) had normal MCVs. Over half the patients with abnormal serum vitamin B12, folate, or ferritin levels, or with low serum iron (Fe) levels with elevated total iron-binding capacity (TIBC), did not have the MCVs expected according to the classification of anemia proposed by Wintrobe. Furthermore, 5% of patients with evidence of iron deficiency had high MCVs, and about 12% of patients with decreased vitamin B12 levels had low MCVs. The MCV was quite specific in identifying patients who had low ferritin levels: specificity was 83%; however, sensitivity was only 48%. The MCV was also specific (88%) for identifying patients who had low Fe with elevated TIBC; however, sensitivity was only 43%. The MCV was poor in identifying patients with abnormalities of serum vitamin B12 and folate levels. In this study the MCV did not provide sufficient diagnostic accuracy to be a useful criterion for the selection of more definitive tests in the evaluation of anemia in hospitalized patients.
BACKGROUND: There have been numerous reports indicating a relation between psychological distress and coronary artery disease. The authors tried to determine whether psychological distress in patients hospitalized for coronary artery disease is associated with the amount of medical care required after discharge. METHODS: Using a prospective clinical cohort, 210 patients who had been admitted for myocardial infarction (n = 67), percutaneous transluminal coronary angioplasty (n = 75), or coronary artery bypass grafting (n = 68) were followed for 6 months. Index psychological status was determined from questionnaires measuring depression and anxiety. Disease severity was assessed by the index hospitalization medical record of left ventricular ejection fraction, number of stenotic vessels, and number of noncardiac comorbidities. The amount of subsequent medical care delivered was based on the number of days of rehospitalization for cardiac-related illness and for any reason within 6 months after discharge. This was determined from a combination of computer medical record and patient self-report. RESULTS: The authors first determined that both psychological depression and disease severity each predicted days of rehospitalization. (Anxiety was not predictive of rehospitalization.) Next, disease severity was controlled for using partial correlation, and depression was still predictive of rehospitalization. Finally, the authors combined the predictor variables using a regression model to predict rehospitalization. Depression was a significant main effect in all models predicting rehospitalization. CONCLUSIONS: Psychological depression appears to be an important predictor of rehospitalization among persons who have been admitted with coronary artery disease.
In March of 1997, the National Research Council (NRC) of the National Academy of Sciences issued the report, "For the Record: Protecting Electronic Health Information." Concluding that the current practices at the majority of health care facilities in the United States are insufficient, the Council delineated both technical and organizational approaches to protecting electronic health information. The Beth Israel Deaconess Medical Center recently implemented a proof-of-concept, Web-based, cross-institutional medical record, CareWeb, which incorporates the NRC security and confidentiality recommendations. We report on our WWW implementation of the NRC recommendations and an initial evaluation of the balance between ease of use and confidentiality.
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The authors analyzed two invasive procedures used to visualize the biliary tree, endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC), and also explored the utility of preinvasive workups for patients with suspected cholestasis. For this analysis they used published ranges for success, fatality, complications, diagnostic accuracies of the procedures, and prognostic information about the underlying diseases. The choice between ERCP and PTC was found to be a "close call," but ERCP was generally favored as the first-choice procedure. The results suggest that noninvasive imaging does not help decide between ERCP and PTC. Although noninvasive imaging may identify those patients with common duct dilation, the higher success rate with PTC in these patients is offset by a slightly higher mortality rate. Consequently, the choice between ERCP and PTC remains close even if ultrasound has shown that biliary ducts are dilated. Furthermore, it is shown that these noninvasive tests are most useful when they can conclusively determine the presence or absence of biliary obstruction. For many patients, noninvasive imaging will not obviate the need for invasive tests.
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