Teicoplanin Dosing Strategy for Treatment of Staphylococcus aureus in Korean Patients with Neutropenic Fever

PURPOSE: The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (Ctrough) and microorganism-specific (AUC24/MIC) targets over two weeks of teicoplanin administration according to several dose regimens for the treatment of Staphylococcus aureus in Korean patients with neutropenic fever. MATERIALS AND METHODS: One thousand virtual concentrations were obtained for each dose using the population pharmacokinetic parameters of teicoplanin adopted from a published study. Simulation of 1,000 virtual MICs was performed using the MICs of 78 clinical isolates of S. aureus collected from a hospital in Korea. Thereafter, these simulated MICs were randomly allocated to 1,000 virtual patients in whom the TARs for AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L were determined. The relationship of the maintenance dose with the steady-state TAR was predicted with respect to the AUC24/MIC >125 [or 345] using logistic analysis. RESULTS: The standard dose regimen of teicoplanin showed TARs of about 70% [or 33%] and 70% [or 20%] at steady-state in cases with AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L, respectively. CONCLUSION: The current standard dose regimen was predicted to be insufficient to adequately treat S. aureus in Korean patients with neutropenic fever. To assure at least an 80% TAR in this population, dose adjustment of teicoplanin should be considered.

Comparison of Parametric and Bootstrap Method in Bioequivalence Test

The estimation of 90% parametric confidence intervals (CIs) of mean AUC and Cmax ratios in bioequivalence (BE) tests are based upon the assumption that formulation effects in log-transformed data are normally distributed. To compare the parametric CIs with those obtained from nonparametric methods we performed repeated estimation of bootstrap-resampled datasets. The AUC and Cmax values from 3 archived datasets were used. BE tests on 1,000 resampled datasets from each archived dataset were performed using SAS (Enterprise Guide Ver.3). Bootstrap nonparametric 90% CIs of formulation effects were then compared with the parametric 90% CIs of the original datasets. The 90% CIs of formulation effects estimated from the 3 archived datasets were slightly different from nonparametric 90% CIs obtained from BE tests on resampled datasets. Histograms and density curves of formulation effects obtained from resampled datasets were similar to those of normal distribution. However, in 2 of 3 resampled log (AUC) datasets, the estimates of formulation effects did not follow the Gaussian distribution. Bias-corrected and accelerated (BCa) CIs, one of the nonparametric CIs of formulation effects, shifted outside the parametric 90% CIs of the archived datasets in these 2 non-normally distributed resampled log (AUC) datasets. Currently, the 80~125% rule based upon the parametric 90% CIs is widely accepted under the assumption of normally distributed formulation effects in log-transformed data. However, nonparametric CIs may be a better choice when data do not follow this assumption.

A Case of Acute Renal Failure due to Rhabdomyolysis Associated with Dermatomyositis in Breast Cancer / 대한신장학회잡지

Dermatomyositis is a clinical syndrome of unknown etiology characterized by a nonpurulent inflammatory myopathy involving striated skeletal muscle associated with rheumatoid arthritis, or systemic lupus erythematosus, sometimes underlying malignancy. A few cases of acute renal failure due to rhabdomyolysis in dermatomyositis has been reported. But, no case combined with breast cancer have been reported. We experienced a case of acute renal failure due to rhabdomyolysis associated with dermatomyositis. The patient was admitted to the our hospital due to breast cancer. After breast cancer operation, she complained of progressive muscle weakness. The heliotrope rash involved the eyelid, bridge of nose and forehead. And eczematoid dermatitis involved the lower abdomen and both forearm and hands. The laboratory findings revealed LDH 2,944IU/L, CPK 2,244IU/L and SGOT 214IU/L. Serum myoglobin and aldolase were increased, and antinuclear antibody was 1:40(positive, homogenous pattern). Electromyogram revealed myopathic findings compatible with dermatomyositis. Then, the patient developed acute renal failure requring hemodialysis. After acute hemodialysis, acute renal failure resolved. But, the patient died on the 113th hospital day due to sepsis. Here, we report a case of acute renal failure due to nontraumatic rhabdomyolysis associated with dermatomyositis in breast cancer.

A Case of Splenic Abscess with Multiple Fistulas Caused by Klebsiella pneumoniae / 감염

Splenic abscess is an uncommon but frequently fatal condition. Signs and symptoms are variable and do not always include left upper quadrant pain or tenderness. Unexplained thrombocytosis in a septic patient with persistent left pleural effusion is suggestive of splenic abscess. We report a case of splenic abscess with complicated multiple fistulas by Klebsiella pneumoniae which was successfully managed by antibiotic therapy, and percutaneous catheter drainage.

Effect of Erythropoietin on Dialyzer Reuse, Dialysis Efficacy and Other Clinical Parameters / 대한신장학회잡지

The use of erythropoietin for correction of anemia in maintenance hemodialysis patients affects dialyzer reuse, dialysis efficacy and other clinical parameters. This study showed the change of Kt/Vurea, nPCR, pre-dialysis BUN, body weight, ultrafiltration volume, pre-dialysis blood pressure, heparin dosage, the number of dialyzer reuse caused by the administration of erythropoietin in reuse(n=11) and first use(n=9) patients who were started erythropoietin since January, 1995. 1) In 20 all patients, hematocrit increased significantly after EPO treatment 20.7+/-0.8%, 27.8+/-0.7%, ultrafiltration volume increased from 2.0+/-0.3L to 2.5+/-0.2L(P1.0/kg/ day) and then pretreatment versus posttreatment nPCR, pre-dialysis BUN and ultrafiltration volume were compared. In low baseline protein intake group, significant increases of ultrafiltration volume, nPCR were observed. However, pre-dialysis BUN were not changed significantly. In high protein intake group, nPCR, pre-dialysis BUN, ultrafiltration volume were changed without significance. In conclusion, EPO treatment did not affect Kt/Vurea, dialyzer reuse, nPCR, predialysis blood pressure, heparin dosage. But ultrafiltration volume increased significantly after EPO treatment. Maybe increased appetite in low baseline protein intake group caused the increased posttreatment ultrafiltration volume.

24 hour circadian pattern of blood pressure and its related target organ damage in hypertensive subjects / 대한내과학회지

OBJECTIVE: Pattern with essential hypertension generally shows the same circadian pattern as the normothensive person with a night-time reduction or "DIP" in blood pressure in sleep. The definition of "Dipper" and "Non-dipper" are assigned according to arbitrary criteria e.g. a night time average blood pressure which is at least 10% less than the average daytime blood pressure. Prospective evidence that the absence of an overnight dip is a strong adverse prognostic indicator for target organ damage .Thus we investigate circardian rhythm of blood pressure, related target organ damage, its frequency & drug in hypertensive subjects. Method : 24hr ambulatory blood pressure monitoring, history taking, physical examination, fundoscopy, ECG, chest X ray, dipstick urinanlysis, serum creatinine level are performed in essential hypertensive subjects. Exclusion criteria are duration of hypertension over 5 years, DM, renovascular hypertension & heart failure. RESULTS: Total 42 patients performed study.17 subjects classify dipper group,25 subjects classify non-dipper group. Between dipper & non-dipper group shows no significantly difference at stroke history, C/T ratio over 0.5 in chest X-ray, left ventrcular hypertrophy in ECG,ST-T change in ECG, proteinuria & serum creatinine level. Non-dipper group shows significantly difference to dipper group in frequency of hypertensive retinopathy and number of combined drug used subjects. CONCLUSION: Number of hypertensive retinopathy is significantly frequency in non-dipper group. Hypertensive retinopathy is atherosclerotic complication, thus we predict other target organ damage, therefore non-dipper type circardian rhythm of blood pressure is adverse prognostic factor for target organ damage of hypertensive subjects.

A Case of Mixed Malarial Infection with Plasmodium falciparum and Plasmodium vivax / 감염

We experienced a case of mixed infection with Plasmodium falciparum and P. vivax in a 48-year old Korean man. He returned to Korea from Papua New Guinea, where he worked for 20 days. Approximately one month after return to Korea, he developed high fever and myalgia. Malaria was suspected and he was admitted to our hospital. The peripheral blood smear demonstrated ring forms of P. falciparum. He was treated with quinine and doxycycline successfully. However, fever and myalgia reappeared five months later. This time, the peripheral blood smear showed gametocytes of P. vivax, while indirect immunofluorescence antibody test revealed high titers to both P. vivax and P. falciparum. He was treated with chloroquine and primaquine. Three months later, vivax malaria recurred again; he was treated with chloroquine and higher dose of primaquine. The patient was well after 6 months of follow-up. We hereby report a case of mixed malarial infections with a review of literatures.

24 Hours Heart Rate Variability in Elderly Hypertensive Patients

BACKGROUND: Heart Rate Variability help us to diagnose the impairment of autonomic nervous system in patients with diabetes, hypertension, ischemic heart disease, chronic renal disease, and arrhythmia. Change of autonomic nervous system is related to circadian rhythm, stress, physical activity, and so on. Especially, impairment of vagal nervous system with age help us to expect sudden cardiac death, myocardial infarction, and arrhythmia. So we survey heart rate variability by using 24 hours holter monitoring to expect impairment of autonomic nervous system in elderly hypertensive patients. METHODS: In order to assess 24 hours heart rate variability, we use Del Mar Avionics 563 holter monitoring on 11 elderly hypertensive patients( > or =65 years), 12 younger hypertensive patients( <65 years), and 15 normal subjects. RESULTS: 1) Standard deviation of mean R-R interval, LF(low frequency), HF(high frequency), TPSD(total power spectral density) are more decreased in elderly hypertensive patients than in younger hypertensive patients in 24 hours health rate variability analysis(t-test p<0.05). 2) According to age, elderly control group had lower LF power spectral parameter than younger control group had, but other parameters were not decreased, and elderly hypertensive group had lower LF, HF, TPSD, SD of mean R-R interval than younger hypertensive group did(p<0.05). 3) In circardian rhythm, normal subjects had high HF power spectral parameter and low LF power spectral parameter at evening and night. On the other hand, elderly hypertensive group had constant low level of LF, HF power spectral parameter during the day and night. CONCLUSIONS: On heart rate variability analysis using by 24 hours Holter monitoring, heart rate variability was decreased, and impairment of autonomic nervous system was accelerated in elderly hypertensive patients.