Bacteriological, pharmacokinetic and clinical studies of 5% and 10% granules of cefdinir in the pediatric field]

Bacteriological, pharmacokinetic and clinical studies on cefdinir (CFDN, FK482), a new oral cephalosporin, 5% and 10% granules, were performed in the field of pediatrics. The results are summarized below. 1. Antibacterial activities Antibacterial activities of CFDN against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, Escherichia coli and Klebsiella pneumoniae were studied in comparison with those of cefaclor (CCL), cefixime (CFIX) and amoxicillin (AMPC). MIC80's of CFDN against S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, B. catarrhalis, K. pneumoniae and E. coli were 0.78, 0.20, less than or equal to 0.025, 0.39, 0.10, 0.20 and 0.10 micrograms/ml, respectively. These results show that CFDN has high antibacterial activities against these organisms. MIC80's of CFDN against Gram-positive bacteria were similar to those of AMPC, and was lower than those of CCL and CFIX. As for antibacterial activities against Gram-negative bacteria (GNB), the MIC80 of CFIX against H. influenzae was 0.05 micrograms/ml, which was slightly lower than that of CFDN. THe MIC80's of CFDN against other GNB were similar to those of CFIX. 2. Absorption and excretion Blood concentrations and urinary excretion rates of CFDN 5% and 10% granules and 100 mg capsule were determined. The data on CFDN 10% granules were similar to those on CFDN 5% granules. At a dose of 3 mg/kg, peak blood concentrations (Cmax's) of CFDN ranged from 0.20 to 2.12 micrograms/ml with 5% granules and from 0.50 to 1.15 micrograms/ml with 10% granules at 2 to 3 hours after dosing. At a dose of 6 mg/kg, peak concentrations were 0.66-2.06 micrograms/ml and 0.70-1.52 micrograms/ml with 5% granules and with 10% granules, respectively. At 8 hours after dosing, blood concentrations were 0.04-0.54 micrograms/ml at 3 mg/kg and 0.06-0.27 micrograms/ml at 6 mg/kg. Blood half-lives were 1.33-4.36 hours at 3 mg/kg and 1.14-3.27 hours at 6 mg/kg. AUC's were 1.7-11.0 micrograms.hr/ml with 3 mg/kg and 2.4-8.7 micrograms.hr/ml with 6 mg/kg. With administration of single 100 mg capsule, Cmax's, blood concentrations after 8 hours, T1/2's and AUC's were 0.79-1.88 micrograms/ml, 0.20 micrograms/ml, 1.54-2.72 hours, and 5.2 micrograms.hr/ml, respectively. Urinary recovery rates in the first 8 hours ranged from 6.85 to 39.2% with 3 mg/kg and 6.08-25.5% with 6 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)     

Laparoscopic treatment of duodenal carcinoid tumor

A 46-year-old man with epigastralgia and slight elevation of urinary 5-hydroxyindole acetic acid (5HIAA) was found to have a well-demarcated carcinoid tumor in the duodenal bulb. The tumor measured 8 mm in size, and showed submucosal involvement but no metastasis to the liver and regional lymph nodes. After laparoscopic exposure and lifting of the duodenal wall around the tumor, wedge resection of the duodenal bulb including the tumor was performed successfully with a laparoscopic endostapler under direct endoscopic control. The postoperative course of the patient was uneventful. Laparoscopic wedge resection of the duodenum would be an appropriate minimally invasive treatment for selected duodenal neoplasms with special preoperative assessments and intraoperative considerations. Received: 27 January 1997/Accepted: 4 December 1997     

Substitute meniscus of Teflon-net for the knee joint of dogs

Investigations conducted in 20 joints of 17 dogs suggest that a Teflon-net substitute meniscus preserves knee joint functions more effectively than a regenerated or absent meniscus. Teflon-net is an ideal material for meniscal replacement because it is easily obtainable, has flexibility and histo-compatibility, and is rapidly infiltrated with cells. A comparative study should be undertaken of knee joint functions with the substitute meniscus and the remains of the meniscus after partial meniscectomy before clinical use of the Teflon-net is feasible. The adhesion between the substitute meniscus and the popliteal muscle also requires further laboratory investigation.     

Experimental and clinical studies on 6059-S (author's transl)

Experimental and clinical studies in the pediatric field on 6059-S, a newly synthesized broad spectrum parenteral antibiotics, were carried out, and the following results were obtained. Antibacterial activities of 6059-S against S. pyogenes, S. aureus, E. coli and P. aeruginosa, recently isolated from patients, 50 strains respectively was compared with that of cefazolin (CEZ), cefmetazole (CMZ), ceftizoxime (CZX), cefotiam (CTM) and ticarcillin (TIPC). 6059-S was less active than the other compound against S. aureus and S. pyogenes, but was about 1-5 times more active than other CEZ, CTM, CMZ and CZX against E. coli, and 6059-S had a activity against P. aeruginosa. It was equal or slightly more activity than that of TIPC. Serum concentrations were measured in 14 infants (3 y 3m-12 y) by one shot or intravenous drip infusion with 10 mg/kg or 20 mg/kg. By one shot intravenous infusion, the peak of serum concentrations of 6059-S with 10 mg/kg and 20 mg/kg were 40.4-44.2 mcg/ml, 79.1-90.8 mcg/ml at 30 minutes after administration respectively, and that's half life were 1.5, 1.4 hours. By intravenous drip infusion, the peak of serum concentration was 89.9 mcg/ml at the end of administration, 13.7 mcg/ml at 5 hours after administration, and half life was 1.5 hours. The urinary recovery rate of 6059-S were 97.4, 67.4% during 6 hours in 2 cases. The cerebrospinal fluid concentration of 6059-S were 2.4-3.6 mcg/ml at 90 minutes after intravenous infusion administration, and the CSF/serum ratio were about 7-8%. Clinical studies of 6059-S was performed in total of 27 cases (25 patients); 8 cases of urinary tract infection, 15 cases of respiratory tract infection, 1 case of staphylococcal scalded skin syndrome, 1 case of peritonitis, 2 cases of purulent meningitis, with the dose of 6059-S 150 mg/kg/day in purulent meningitis, 40-80 mg/kg/day in other disease. That's efficacy rate was 85.2%. Side effect observed in this therapy were 2 cases (exanthema 1, diarrhea 1), and 2 cases of rise of GOT, GPT.     

Cardiovascular Responsiveness After Isotonic Exercise in Cirrhotic Patients: Study on Sympathoadrenergic and Renin-angiotensin Systems

Objectives: The aim of this study was to evaluate cardiovascular responsiveness after isotonic exercise in cirrhotic patients. Methods: Included were 11 cirrhotic patients and 10 age-matched normal suhjects, who served as controls. Hemodynamic data were obtained on each subject before and after muscle exercise on a treadmill (7 metabolic units). Plasma noradrenaline concentration and plasma renin activity also were determined. Results: In both groups, isotonic exercise increased heart rate and systolic arterial pressure, whereas diastolic arterial pressure was not modified. The increase in heart rate and systolic arterial pressure did not differ significantly between the two groups. Plasma noradrenaline concentration and plasma renin activity also were increased. The changes in plasma noradrenaline concentration and plasma renin activity was higher in cirrbotic patients than in controls ( P < 0.05, P < 0.05), although the differences were not significant when calculated as a percentage. Conclusions: Cardiovascular responsiveness to isotonic exercise is almost intact in cirrhotic patients. However, supernormal activation of the sympathoadrenergic and renin-angiotensin systems is required to maintain cardiovascular homeostasis in these patients.     

Projections from the superior colliculus to the ventral lateral geniculate nucleus in the hereditarily microphthalmic rat

Projections from the superior colliculus (SC) to the ventral lateral geniculate nucleus (LGNv) were studied in hereditarily microphthalmic and normal rats by means of wheatgerm agglutinin conjugated with horseradish peroxidase (WGA-HRP). Unilateral injection of a tracer into the LGNv in normal rats revealed WGA-HRP positive neurons on both sides of the SC. In the ipsilateral SC, most of the labeled neurons were distributed in the upper part of the stratum opticum (SO) and the lower part of the stratum griseum superficiale (SGS). A few labeled neurons were also found in the same layers of the contralateral SC. After unilateral injections of the tracer into the LGNv of microphthalmic rats, labeled neurons appeared in similar layers of the SC on both sides. However, the number of labeled neurons in the ipsilateral SC decreased to 30% of normal, whereas on the contralateral side these neurons were apparently more numerous than those in normal rats. The soma size of the labeled SC neurons in microphthalmia was not significantly different from normal. These results indicate fundamentally that tecto-LGNv projecting neurons exist in microphthalmic rats despite the fact that they lack optic nerve afferents. Furthermore, the present results, taken together with our previous results, indicate that the diminution in the number of tecto-LGNd neurons was severest (3%), the tecto-LGNv neurons less severe (30%) and the tecto-LP neurons least severe (50% of that of normal).     

Studies on phage type, beta-lactamase activity and sensitivity of multiple drug-resistant Staphylococcus aureus isolated from clinical specimens to cefmetazole

The 868 strains of S. aureus were isolated at the Department of Pediatrics, Third Hospital and Aoto Hospital, The Jikei University, School of Medicine and the Kanagawa Prefectural Nursing and Hygienic School Hospital during 6 months from May to October in 1981. From them 66 strains not sensitive to CEZ were selected by a 3-concentration disk method. A total number of 54 strains except for 12 isolated from the same infant patient was examined for their MIC's for 6 drugs, CMZ, CEZ, CTM, CXM, MCIPC and GM. Moreover, phage typing and beta-lactamase activity determination were carried out in them. 1. Antibacterial activity Sixty-six (7.6) of 868 strains were not sensitive to CEZ. The MIC's of CMZ against these resistant strains were between 1.56 and 50 micrograms/ml with a peak between 3.13 and 6.25 micrograms/ml when the 10(5) cells/ml bacterial suspension were inoculated. CMZ was superior in antibacterial activity to CEZ and CXM by about 4 degrees and to CTM by about 3 degrees. MCIPC and GM has higher antibacterial activity against a few strains than CMZ. However, the number of strains with MIC higher than or equal to 50 micrograms/ml was 17 for MCIPC and 40 for GM, but only 2 for CMZ. Thus, the former 2 drugs were far inferior to the latter one. 2. Phage type (1) Nineteen strains (35.2%) had MIC's for CEZ greater than 50 micrograms/ml and CMZ less than 6.25 micrograms/ml. Seventeen of them belonged to the nontypable. (2) Fourteen (25.9%) had MIC's for CEZ greater than 100 micrograms/ml. Of them 9 were allocated to the group III, 3 to the mixed (I + II + III, I + III) group and 2 to the nontypable. (3) Of 20 strains (37.0%) which had MIC's for CEZ greater than 100 micrograms/ml and CMZ less than 6.25 micrograms/ml 5 belonged to the group I, 3 to the group III and 12 to the nontypable. (4) Five strains classified into the group I were all isolated at the Kanagawa Perfectural Nursing and Hygienic School Hospital. (5) Eleven of 15 strains belonging to the group III were isolated at the Third Hospital, The Jikei University, School of Medicine. (6) Seventeen of 21 strains isolated at the Aoto Hospital, The Jikei University, School of Medicine belonged to the nontypable. (7) Phage type was considered to be influenced by difference in areas, infection within hospitals, etc., 3. beta-Lactamase activity beta-Lactamase activity was demonstrated at levels between 0.07 and 3.26 mumol/min/mg in all 54 strains. There was no correlation between MIC for CEZ or CEZ and beta-lactamase activity. It was suggested that beta-lactamase might not contribute to mechanism of resistance of S. aureus to each drug examined.     

Clinical experience with CS-1170 in children (author's transl)]

CS-1170 was tried in children with various infections, and the following results were obtained. Some studies on the drug's pharmacokinetics were also made, and the results were as shown below: 1. The time course of serum concentration following one-shot intravenous injections of 30 mg/kg in 8 patients aged between 3 and 13 was studied. The results were: 53.4 microgram/ml, 23.4 microgram/ml, 6.6 microgram/ml, 1.8 microgram/ml and 0.5 microgram/ml at 30 minutes, 1 hour, 2 hours, 4 hours and 6 hours after the drug administration, respectively. Urinary recovery rate was 36% to 69.8% by 2 hours after, 10.9% to 70% by 2 to 4 hours after, 0.6% to 5.4% by 4 to 6 hours after the administration, and by 8 hours after the injection 91.3% of the drug was excreted in the urine. 2. Of 13 cases including 8 cases of bronchopneumonia, 2 cases of urinary tract infections, a case each of suppuration in the neck, lymphadenitis and pyothorax, CS-1170 was found to be effective in 10 cases (83.3%), while effectiveness of the drug was undeterminable in one case. 3. No remarkable side effect including allergic symptom such as eruption was observed, though transient elevation of GOT and GPT was noted in one case.     

Candida glabrata fungemia in a diabetic patient with neurogenic bladder: successful treatment with micafungin

A 69-year-old man was transferred to our hospital because of fever and acute renal failure. 5 weeks prior to admission, he was admitted to another hospital and treated with several antibiotics including vancomycin, but fever did not subside and renal dysfunction showed rapid progression. On admission, laboratory findings revealed pyuria, inflammatory changes, acute renal failure, and disseminated intravascular coagulation (DIC). Computed tomography showed left ureteral stone and hydronephrosis. Gallium scintigraphy showed avid uptake in the left kidney. Serum concentration of vancomycin was 57.4 micro/ml. Candida glabrata was isolated from blood, sputum and urine. Under the diagnosis of fungemia and left pyelonephritis, he was treated with micafungin (150 mg/day), gabexate mesilate and insertion of a double-ended pigtail catheter. The above treatment produced regression of systemic inflammation, DIC and acute renal failure. At the last follow-up 3 weeks after discharge, ureteroscopy showed that the ureter stone had already passed but a soft white-yellowish bezoar was detected in the ureter. In this case, neurogenic bladder, poorly controlled diabetes, and long-term antibiotic treatment probably enhanced the development of C. glabrata infection. Antifungal treatment with micafungin is useful in patients with non-albicans Candida infection.