Therapeutic drug monitoring for gentamicin in Hospital Universiti Sains Malaysia

We evaluated the usefulness of therapeutic drug monitoring (TDM) for gentamicin and the use of a two-point peak and trough pair concentration method to adjust its dose. Of the 194 patients included, initial concentrations were appropriate in only sixty nine. In the seventy one cases of dosage adjustments using this method, those attaining therapeutic levels increased overall from 38% to 67%. It is concluded that TDM for gentamicin with dosage adjustment using this simple pharmacokinetic approach is useful and adequate in monitoring for gentamicin therapy.     

Amikacin therapy. Use against infections caused by gentamicin- and tobramycin-resistant organisms.

Amikacin sulfate was used in 24 treatment courses for 25 serious infections caused by aerobic or facultative anaerobic Gram-negative organisms resistant to numerous drugs. Sites of infection included urinary tract (11 cases), pleuropulmonary (6 cases), primary bacteremia (5 cases), and miscellaneous (3 cases). Serratia marcescens and Pseudomonas sp accounted for 73% of the isolates. The mean minimal inhibitory concentration (MIC) of these organisms to amikacin was 3.6 microgram/ml; to gentamicin, 39 microgram/ml; and to tobramycin, 32 microgram/ml. The mean peak serum concentration of the drug was 20.8 microgram/ml. Eleven patients were critically ill at the onset of therapy, and seven patients were bacteremic. The overall favorable response rate was 80%. The most serious side effect was ototoxicity, which occurred in three of 15 patients examined by serial audiometry.     

Salivary theophylline estimation in the management of asthma in children.

Simultaneous sampling was performed to determine whether saliva could replace plasma in the monitoring of theophylline dosages. Forty-eight children with moderate to severe asthma received oral theophylline preparation (usually sustained release) on a daily basis. They provided simultaneous saliva and plasma samples at routine out-patient visits. Saliva and plasma theophylline concentrations showed a wide variation between individuals, and their ratios also differed. Saliva theophylline concentrations below 7 micrograms/ml reflect plasma concentrations below 10 micrograms/ml, i.e. sub-therapeutic, while saliva concentrations above 7 micrograms/ml are consistent with therapeutic dosage. Estimation of saliva theophylline concentration on routine visits avoids the discomfort of blood sampling. It reflects whether daily oral theophylline dosage in childhood asthma is below or within the therapeutic range. The need for changes in dosage and the degree of patient-compliance with therapy can be usefully indicated.     

慢性肾功能不全患者血清T_3T_4TSH浓度变化的临床意义

用放射免疫法对10例慢性肾功能不全患者和20例正常人进行血清T_3、T_4和TSH浓度测定,结果肾功能不全患者血清T_3浓度明显低于正常人(P<0.001),血清T_3浓度与血清BuN、Cr、24小时尿蛋白总量、尿白蛋白、尿β_2-微球蛋白浓度呈明显负相关(P<0.025～0.001),血清T_4、TSH浓度与正常人无显著性差异;尿毒症患者血清T_3、T_4浓度明显低于氮质血症患者(P分别<0.05,<0.025)。说明血清T_3、T_4浓度变化对疗效与预后判断有一定意义。     

In vitro susceptibilities to 23 antimicrobial agents of Haemophilus influenzae from pediatric patients in Japan

One hundred eighty-six clinical isolates of Haemophilus influenzae (H. influenzae) collected from January 1996 through December 1997 from 182 pediatric patients and 16 isolates from blood or cerebrospinal fluid (CSF) of 13 patients with bacteremia and purulent meningitis collected during the last ten years were examined for in vitro susceptibilities to 23 antibiotic agents, including 3 penicillins, 9 cephalosporins, 4 carbapenems and others, as well as for their encapsulated types and beta-lactamase production. Ceftriaxone (a third generation cephalosporin) had the highest activity against the strains in this study (minimal inhibitory concentration, MIC90 of 0.025 microgram/ml) and cefditoren (a new oral cephalosporin) was the most active oral antimicrobial agent (MIC90 of 0.05 microgram/ml). Meropenem had a much higher activity against H. influenzae (MIC90 of 0.2 microgram/ml) than the other carbapenems (imipenem, MIC90 of 1.56 micrograms/ml, panipenem, MIC90 of 1.56 micrograms/ml, and biapenem, MIC90 of 3.13 micrograms/ml). Regarding the serotyping of the encapsulated strains, 172 strains (85.1%) were nontypeable and 30 (14.9%) were serotyped (24 strains of type b, 4 strains of type e, one each of type a and c). Fifteen of the strains isolated from blood and CSF were type b and one was nontypeable. Sixteen of 202 strains (7.9%) produced beta-lactamase and all of them produced both penicillinase and cephalosporinase. The production of beta-lactamase in this study was lower than that reported in previous studies [1-3]. In this study, some strains were found against which the MICs of carbapenems were very high (highest MIC of imipenem was 12.5 micrograms/ml, of panipenem was 6.25 micrograms/ml and of biapenem was 25 micrograms/ml). Therefore, we assayed the binding affinities of imipenem for each of penicillin-binding proteins (PBPs) about one of these resistant strains. In resistant strains, inhibitory concentrations (IC50) of imipenem for PBP4 and 5 were much higher than those in susceptible strains. Thus, the results demonstrate the decrease of the affinity of imipenem for PBP4 and 5. It seems, therefore, that the major factor in the resistance to imipenem of H. influenzae was the low affinity of PBP4 and 5 for the drug.     

Serum aluminium concentration and aluminium deposits in bone in patients receiving haemodialysis

Serum aluminium concentrations and biopsy specimens of bone were examined in 56 patients with end stage chronic renal failure receiving maintenance haemodialysis. Deposits of aluminium in bone specimens were often associated with low bone formation with or without osteomalacia. Serum aluminium concentrations of greater than 3.7 mumol/l (10 micrograms/100 ml) indicated a high probability of deposits of aluminium in bone specimens, although high serum concentrations did not predict the type of renal bone disease. Biopsy of the bone is the best method of detecting aluminium intoxication of bone. A serum aluminium concentration of 3.7 mumol/l should be the threshold beyond which bone biopsy should be performed to confirm an overload of aluminium and identify histological bone changes induced by aluminium.     

Evaluation of three antibiotic programs in newborn infants.

Emergence of gram-negative bacteria resistnant to a number of antibiotics in intensive care nurseries for neonates emphasizes the need for alternatives in antibiotic combinations. One commonly used combination, gentamicin-ampicillin, and two newer combinations, tobramycin-cephalothin and amikacinampicillin, were evaluated prospectively in 60 newborns in such a nursery. Subjects were randomly assigned to one of the above therapy groups. Dosages in mg/kg.d were 100 for ampicillin and cephalothin, 6 for gentamicin and tobramycin and 15 for amikacin. Aminoglycoside serum concentrations, clinical tolerance and toxicity were monitored. Aminoglycoside concentrations after intravenous administration of the drugs were within the expected range (gentamicin and tobramycin 4 to 6 microgram/mL and amikacin 15 to 20 microgram/mL). There was no hematologic, renal or hepatic toxicity attributable to antibiotic therapy and the combinations were tolerated equally; no bilirubin displacement was detected in vitro or in vivo.     

高效毛细管电泳法快速测定内江猪血清头孢唑啉钠

报道用高效毛细管电泳技术快速测定内江猪血清头孢唑啉钠（ｃｅｆａｚｏｌｉｎｓｏｄｉｕｍ,ＣＥＺ）的方法,血清用乙腈去除蛋白质,经离心后上清直接进样,毛细管血径７５μｍ,在５０ｍｍｏｌ／Ｌ碳酸钠／碳酸氢钠ｐＨ１０）中,电压２０ＫＶ分离５分钟,２５４ｎｍ紫外检测,此方法操作简单,测定迅速,线性范围为５－３２０μｇ／ｍｌ,日内相对标准偏差为１．７％,日间相对标准偏差为８．０％,平均加样回收率为１０７．９％     

Renal function in patients over 40 with homozygous sickle-cell disease

Renal function was examined in 25 patients aged 40-64 with homozygous sickle-cell (SS) disease. Investigations included intravenous urography and measurement of blood urea and creatinine concentrations and creatinine and protein excretion in 24-hour collections of urine. Serum creatinine concentrations did not differ significantly from those of 25 other patients with SS disease aged 18-39 years, but serum urea concentrations were significantly higher (p less than 0.001). Intravenous urography showed loss of caliceal cupping (nine patients), irregular renal outline (five), and cystic extension from the calix (one). Six patients had creatinine clearances below the fifth percentile for age and sex. Proteinuria was more common in these patients, and haemoglobin concentrations were much lower than in the 19 patients without renal insufficiency (mean 5.6 v 8.2 g/dl; p less than 0.001). Haemoglobin concentration was strongly correlated with creatinine clearance (r=0.70), particularly with clearances below 100 ml/min/1.73 m2 (r=0.96; p less than 0.001). A possible mechanism of renal insufficiency in SS disease is cortical scarring, which is asymptomatic, not associated with hypertension, and accompanied by only minor proteinuria. A falling haemoglobin concentration is a sensitive and early indicator of renal impairment in SS disease.     

Endothelin and acute renal failure: study on their relation and possible mechanisms]

In order to investigate the role of endothelin in the pathogenesis of ARF, we determined the plasma endothelin (pET) level in different clinical ARF patients and experimental ARF rat models. It was found that pET level was significantly higher in hepatic renal syndrome (n = 9, pET 210.1 +/- 32.0 pg/ml), epidemic hemorrhagic fever (n = 18, 113.3 +/- 14.86 pg/ml), septic shock ARF (n = 8, 121.5 +/- 13.5 pg/ml), gentamicin ARF (n = 7, 55.9 +/- 6.23 pg/ml) patients, and in HgCl2 ARF (n = 8, 31.75 +/- 3.07 pg/ml), glycerine ARF (n = 8, 44.75 +/- 9.8 pg/ml) rats, compared with that of normal persons (n = 9, 33.6 +/- 3.08 pg/ml) or of normal rats (n = 10, 11.4 +/- 0.98 pg/ml). Both in the patients and animal groups, there were a linear relationship between the levels of pET and Scr (r = 0.603 4 and 0.844, P less than 0.01, respectively). Intrarenal infusion ET in dosage of 0.16 micrograms.kg-1/h produced a severe reduction of RPF and GFR in the infused kidney, without significant similar changes on the contralateral kidney. Pretreated with captopril ameliorated the renal hemodynamic changes induced by iv ET (0.67 micrograms.kg-1/h), whereas indomethacin potentiated this effect. It is concluded that both circulating or local generated ET during the ARF play an important role in the pathogenesis of ARF. RAS and PG might involve in its mechanisms.     

Gentamicin and ticarcillin serum levels.

Ticarcillin disodium and gentamicin sulfate serum levels were measured one and five hours after intravenous administration. Patients receiving ticarcillin plus gentamicin had a significantly lower mean gentamicin level one and five hours after antibiotic administration than patients receiving cephalothin sodium plus gentamicin. The serum ticarcillin levels were significantly lower five hours after administration in patients receiving ticarcillin plus gentamicin than in those receiving ticarcillin plus cephalothin. Low antibiotic serum levels in patients with serious infections treated with these antibiotic combinations are of potential clinical significance; therefore, to ensure an optimal antimicrobial therapy, it is advisable to determine the drug serum concentrations (especially aminoglycoside) even in patients with normal renal function when treating with combinations of antimicrobials.     

Treatment of typhoid carriers with amoxicillin. Correlates of successful therapy

Fifteen chronic enteric carriers of Salmonella typhi were treated with amoxicillin trihydrate, 2 g by mouth, three times per day. Nine of ten patients who were able to take the full amoxicillin regimen were cured; among five patients treated with a lower daily amoxicillin dosage because of gastrointestinal (GI) side effects, only two were cured (P less than .05). The mean serum amoxicillin concentration at termination of therapy was higher (P less than .01) in five patients who were cured (10.4 +/- 1.6 microgram/ml) than in the four who failed (3.0 +/- 0.7 microgram/ml), although the latter values were all above the minimal inhibitory concentrations for infecting organisms. This study suggests that amoxicillin treatment of chronic typhoid carriers could be enhanced by treating with doses sufficient to provide suprainhibitory serum concentrations of the antibiotic. However, GI intolerance to amoxicillin could limit this therapeutic approach.     

Correlation between manifestations of digoxin toxicity and serum digoxin, calcium, potassium, and magnesium concentrations and arterial pH

In 18 patients with gastrointestinal manifestations of digoxin toxicity the mean serum digoxin concentration (+/- SEM) was 3.16 micrograms/l (+/- 0.25), the calcium to potassium ratio 0.31 (+/- 0.01), and the mean arterial pH 7.406 (+/- 0.017). In contrast 19 patients with digoxin induced automaticity had a mean serum digoxin concentration of 1.24 micrograms/l (+/- 0.15; p less than 0.001), a calcium to potassium ratio of 0.38 (+/- 0.01; p less than 0.01), and an arterial pH of 7.498 (+/- 0.008; p less than 0.001). Eight out of 13 patients with digoxin induced cardiotoxicity had serum concentrations of the drug within the therapeutic range (0.8-2.0 micrograms/l). The calcium to potassium ratio, however, was lower than in the patients with automaticity (0.31 +/- 0.02; p less than 0.01) and the arterial pH was 7.370 (+/- 0.033; p less than 0.05). Serum magnesium concentrations were similar in all groups. In this study patients with digoxin induced gastrointestinal symptoms had high serum concentrations of the drug, whereas those with drug induced automaticity had therapeutic concentrations. This second group, however, was identified by their higher calcium to potassium ratios and higher pH values.     

Comparison of erythromycin base and estolate in gonococcal urethritis.

A randomized double-blind trial of 152 men with gonococcal urethritis compared the therapeutic efficacy of erythromycin estolate and erythromycin base. Twenty-one of 86 (24%) men treated with the estolate and 15 of 66 (23%) treated with the base had recurrent or persistent gonococcal infection when seen after a 9-g course of erythromycin. The serum erythromycin activity among estolate-treated patients (3.57 +/- 0.84 microgram/ml) was nearly twice that for base-treated patients (1.76 +/- 0.80 microgram/ml). Our findings do not support routine use of erythromycin for treatment of pregnant, penicillin-allergic patients.     

Experimental study on distribution of serotypes and antimicrobial patterns of group B streptococcus strains

OBJECTIVE: To obtain information on the distribution of serotypes and antimicrobial agent susceptibilities to group B streptococcus (GBS) strains isolated in Beijing area from 1991 to 1996. METHODS: Bacterial isolates of GBS were obtained from vaginal and cervical tract of pregnant and nonpregnant women in Beijing Tian Tan Hospital by culture. A total of 76 GBS strains were identified finally by coagglutination. Serotyping was determined by Standard Lancefield method. Susceptibility to test agents was assessed by determining the minimal inhibitory concentrations (MICs) with agar dilution method that was established by the National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: Seven serotypes were identified among 76 GBS strains isolates. Types II (33%), III (23%) and I a (16%) were the predominant serotypes in pregnant and nonpregnant women. MICs of penicillin G and ampicillin were < or = 0.06 microgram/ml. MICs of cephazolin, cefuroxime and cefoperozone were 0.003 microgram/ml-0.06 microgram/ml. MICs of erythromycin were 0.003 microgram/ml-0.03 microgram/ml. MICs of gentamycin were 1 microgram/ml-32 micrograms/ml. MICs of amikacin were 4 micrograms/ml- > or = 64 micrograms/ml, nearly 12.8% and 40.4% of the strains were resistant to gentamycin and amikacin, respectively. CONCLUSIONS: Our study provides useful epidemiologic data for preparation of GBS type-specific vaccines which can prevent GBS infections and antimicrobial agents susceptibility patterns in China. Routine reports on GBS susceptibilities by clinical laboratories and continuous surveillance for changes in the susceptibility are of considerable clinical importance.     

Rapid assessment of corticotropin reserve after pituitary surgery

Corticotropin deficiency may occur after pituitary surgery, and, if unrecognized and untreated, it can be fatal. In this study the insulin tolerance test was used to assess hypothalamic-pituitary-adrenal reserve five to seven days after pituitary surgery, and postoperative morning serum cortisol concentration was compared with the insulin tolerance test for predicting corticotropin deficiency. In 35 patients with pituitary tumors studied prospectively, 27 had normal insulin tolerance test results five to seven days after pituitary surgery; in these patients, the morning serum cortisol concentration two to three days after surgery was 250 nmol/L (9 micrograms/dL) or greater. Eight patients had subnormal insulin tolerance test results or clinical evidence of adrenal insufficiency; the morning serum cortisol concentration in these patients was 80 nmol/L (3 micrograms/dL) or less. Postoperative adrenal insufficiency was transient (one to three months) in five of these eight patients. We retrospectively identified 45 patients whose postoperative morning serum cortisol values were 200 nmol/L (7 micrograms/dL) or greater; none of these patients had clinical evidence of adrenal insufficiency. We conclude that a morning serum cortisol level obtained two to three days after surgery and 24 hours after the discontinuation of hydrocortisone accurately predicts postoperative corticotropin reserve.     

高效液相色谱法测定大鼠血清中4-壬基酚和双酚A

目的 建立高效液相色谱测定血清4-壬基酚和双酚A的方法。方法 大鼠血清样品用正己烷-乙醚混合溶剂(70：30)提取,采用C18色谱柱分离,以乙腈-乙酸铵缓冲液(pH 4．5)(80：20)为流动相,在激发波长227nm、发射波长313nm处用荧光检测器检测。结果 血清中的待测组分的质量浓度与峰面积呈良好的线性关系,4-壬基酚和双酚A线性范围分别为0．013～5．0 μg／ml,0．004～3．0 μg／ml。本方法的检测限4-壬基酚为13 ng／ml,双酚A为4 ng／ml,加标回收率4-壬基酚为83．8％～100．0％,双酚A为83．3％～100．0％;日内精密度为1．70％～2．70％,日间精密度为2．06％～9．78％。结论 该法适用于血清中双酚A和4-壬基酚质量浓度检测。     

Bioavailability of etoposide after oral administration of the solution marketed for intravenous use: therapeutic and pharmacoeconomic perspectives.

BACKGROUND: Oral etoposide administration is a suitable alternative to the intravenous route; therefore, commercial capsules have been developed. Before these capsules were available in Mexico, we studied drug bioavailability after oral administration of the intravenous etoposide solution (IVES). METHODS: Eight adult cancer patients received a 50-mg oral etoposide dose as IVES and blood samples were collected over a period of 24 h. Plasma etoposide concentration was determined by high-performance liquid chromatography, plasma concentration against time curves were constructed, and bioavailability parameters were calculated. RESULTS: Oral IVES yielded an adequate bioavailability profile because Cmax was 2.38 +/- 0.30 micrograms/mL, AUC was 12.87 +/- 2.02 micrograms/mL and half-life was 6.72 +/- 0.97 h. CONCLUSIONS: Considering that the pharmacokinetic aim is to maintain plasma concentrations between 0.5 and 1.0 microgram/mL for several hours while avoiding high concentrations, i.e., of 10 micrograms/mL or higher, oral administration of 50-mg etoposide as IVES appears to be a suitable dosing option. In addition, oral IVES is considerably less expensive than intravenous administration in terms of both drug presentation and administration.     

肝癌细胞在Ⅳ型胶原裱衬表面的粘附特性

定量描述肝癌细胞和肝细胞在Ⅳ型胶原裱衬表面的粘附特性,探讨细胞粘附力与Ⅳ型胶原裱衬浓度及Ⅳ型胶原与层粘连蛋白复裱衬时ＬＮ复合浓度的相关关系。方法采用分步裱衬的方法制作 有关裱衬表面,即依次在玻璃表面裱衬多聚赖氨酸和Ⅳ型胶原／ＬＮ,最后以牛血清白蛋白作用阻断非特异性粘附。细胞粘附力采用微管吸吮技术进行测定。