Impact of systemic inflammatory response syndrome and surgical Apgar score on post-operative acute kidney injury.

BACKGROUND: Surgical Apgar Score (SAS) is relatively weakly associated with post-operative outcomes in emergency surgery, compared with elective surgery. A combination of systemic inflammatory response syndrome (SIRS) and SAS may be useful for prediction of poor outcomes after emergency surgery. METHODS: A retrospective study was conducted in patients who underwent emergency abdominal or cerebral surgery from January 2005 to December 2010. AKI was diagnosed using Acute Kidney Injury Network criteria for 2 days after surgery. Pre-operative SIRS was defined as SIRS score ≥ 2. Patients were divided into those with SAS ≥ 5 and < 5. Independent risk factors for post-operative AKI were identified. Ability to predict post-operative AKI was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Of 742 patients, 175 (24%) had post-operative AKI. Pre-operative SIRS (OR 1.9, 95% CI: 1.2-2.9, P < 0.01) and SAS < 5 (OR 2.6, 95% CI: 1.7-4.1, P < 0.01) were independent risk factors for post-operative AKI. Patients without SIRS and SAS < 5 had an increased risk of post-operative AKI (odds ratio (OR) 3.6, 95% confidence interval (CI) 1.9-6.7, P < 0.01) and those with SIRS and SAS < 5 had increased risks of post-operative AKI (OR 5.9, 95% CI: 3.7-9.3, P < 0.01) and hospital mortality (OR 3.5, 95% CI: 1.9-6.3, P < 0.01). In ROC analysis, the c-statistic using both SIRS and SAS < 5 was 0.81 (95% CI: 0.77-0.84, P < 0.01) and higher than without use of these factors (P < 0.01). CONCLUSION: Pre-operative SIRS and SAS are independently associated with post-operative AKI. Simultaneous use of pre-operative SIRS and SAS may improve prediction of poor post-operative outcomes.

JTK-853, a novel non-nucleoside hepatitis C virus polymerase inhibitor, demonstrates a high genetic barrier to resistance in vitro.

JTK-853 is a novel, non-nucleoside, palm site-binding hepatitis C virus (HCV) polymerase inhibitor that has demonstrated antiviral activity in HCV-infected patients during 3 days of treatment. To estimate the genetic barrier of JTK-853 to resistance in vitro, colony formation assays were conducted using HCV replicon cells (genotypes 1a and 1b). The colony formation assays revealed that the numbers of resistant colonies for JTK-853 were much lower than those for other direct-acting antivirals, including palm site- or thumb pocket-binding non-nucleoside HCV polymerase inhibitors (NNIs), an NS5A inhibitor (NS5Ai), and a protease inhibitor (PI). Furthermore, the numbers of resistant colonies for JTK-853 in combination with the NS5Ai or PI were lower than those for other combinations of NS5Ai + NNI, and NS5Ai + PI. Our findings demonstrate that JTK-853 has a high genetic barrier to resistance, and suggest that its combination therapies will be potent in suppressing the emergence of drug resistance in HCV-infected patients.

[Influence of dexamethasone on the clinical course of bacterial meningitis in children. Especially on secondary fever. Experiences in 27 institutions].

Of pediatric patients with purulent meningitis seen at the institutions listed in the title page of this paper between 1986 and 1994, 93 patients treated with antibiotics and dexamethasone (DXM) were compared with 91 patients treated with antibiotics alone. The patients receiving antibiotics with dexamethasone achieved overall improvement in inflammatory symptoms and signs and cerebrospinal fluid findings and became afebrile significantly earlier than those receiving antibiotics alone. However, some of the patients became febrile again. The secondary fever rate for the DXM group was much higher than that for the antibiotic alone group (p < 0.0001). In most of the rebounded cases, the body temperature rose above 38 degrees C and remained elevated for 2-4 days. Cerebrospinal fluid (CSF) was cultured daily in 54 and 32 patients receiving antibiotics with and without DXM, respectively. Although this study was not a controlled study in a strict sense, these patients compared. In both groups, the CSF became mostly culture-negative within 48 hours. In a few patients receiving DXM, however, it became culture-negative after 72 hours or longer. DXM caused an adverse effect in a patient with meningitis caused by Streptococcus pneumoniae. The adverse effect was mild gastrointestinal bleeding, which recovered spontaneously. From the findings described above, the use of DXM combined with antibiotic therapy was considered to accelerate the relief from fever and improvement of inflammatory symptoms and signs and CSF findings. The body temperature rose again in more than half of the patients receiving DXM, but fell to normal spontaneously without treatment. The elevation doubtlessly could not be distinguished from recurrence of the meningitis itself or complications. It seems to be likely that no treatment but careful observation is required even if the fever recurs as far as the CSF findings showed favorable progress with excelluent general conditions. When DXM is given, it is essential that CSF tests and culture are repeated during the early stages and the progress is monitored carefully.

[Clinical and bacteriological evaluation of ceftriaxone (CTRX) dosed once daily in children with community-acquired pneumonia].

Clinical and bacteriological evaluation was performed as follows on ceftriaxone (CTRX) at a dose of 50 mg/kg once daily to pediatric patients with community-acquired pneumonia. Of 48 subject patients, CTRX was markedly effective in 36 (75.0%), effective in 9 (18.7%), slightly effective in 2 (4.2%), and failure in 1 (2.1%), indicating the overall effective rate of 93.7%. In 47 (97.9%) patients with the exception of 1, it was observed during the period of administration that fever was resolved and clinical symptoms as well as radiographically abnormal shadows were found relieved or improved. Patients infected by an isolated strain accounted for 34 (70.8%), while those by multiple strains 14 (29.2%), indicating that either Streptococcus pneumoniae or Haemophilus influenzae, or both were detected in almost all patients (45 cases). Of the 48 patients, bacteriological effect was eliminated in 44 (91.7%), and replacement of the bacteria in the remaining 4 (8.3%). MIC90 of CTRX against detected bacteria was 0.2 microgram/ml with H. influenzae, < or = 0.025 microgram/ml with PSSP, 0.1 microgram/ml with PISP, and 0.39 microgram/ml with PRSP. Blood concentration of CTRX at 50 mg/kg upon completion of 1-hour drip intravenous infusion was 89.7 +/- 25.2 micrograms/ml, and 6.6 +/- 0.9 micrograms/ml at 24 hours after the completion, indicating that the concentrations had been well above the levels of MIC90 throughout the 24 hours. Abnormal symptoms, which were most likely adverse drug reactions, were not observed in any patients, and no abnormal changes were noted in patients, whose clinical lab values were taken before or after the administration. Situations may differ by region in Japan, however, infants under 3 are generally exempted from medical payment regardless of inpatients or outpatients. When hospitalized, psychological burden upon pediatric patients without guardians attended must be enormous. If they are over 3, there is a difference in medical costs between inpatients and outpatients, with greater economic burden on inpatients. Thus, it was considered worth attempting the outpatient treatment as one of new therapies for community-acquired pneumonia, though the outpatient treatment should not be encouraged without due consideration. Based on these results, CTRX dosed once daily to pediatric patients with community-acquired pneumonia is clinically and bacteriologically superior in usefulness. Further review may be necessary, however, it is considered that outpatient treatment can also serve as one of the options, if safety of once-a-day administration of CTRX can be established.

Distribution of mefE and ermB genes in macrolide-resistant strains of Streptococcus pneumoniae and their variable susceptibility to various antibiotics.

From February to October 1995, 62 erythromycin-resistant strains of Streptococcus pneumoniae isolated at Yamanashi Red Cross Hospital were tested to determine their susceptibility to various macrolides, subjected to resistance induction tests by the disc diffusion method and analysed for genes encoding resistance to macrolides (ermB and mefE). On the basis of resistance induction testing, the isolates were classified as having either inducible (59.7%) or non-inducible (40.3%) macrolide resistance. The ermB gene was always detected in resistance-inducible type isolates, either alone or in combination with mefE. The mefE gene alone was found only in non-inducible type isolates. Isolates with non-inducible resistance (those with only the mefE gene) had an intermediate level of resistance to 14-membered macrolides, and were susceptible to rokitamycin, a 16-membered macrolide. According to NCCLS guidelines, 9.6% of S. pneumoniae strains were judged to be susceptible to penicillin, 62.9% of reduced susceptibility and 27.4% penicillin resistant. No correlation was detected between the presence of particular macrolide-resistance genes (ermB, ermB + mefE, or mefE) and resistance to penicillin G.

[Pharmacokinetic and clinical evaluation of tazobactam/piperacillin in the pediatric field].

Pharmacokinetic and clinical evaluation was conducted on the combination drug, tazobactam/piperacillin (TAZ/PIPC, YP-14), of newly developed beta-lactamase inhibitor, tazobactam (TAZ), and antibiotic agent of penicillin group for injections, piperacillin (PIPC), and the following results were obtained. 1. Absorption and excretion Both serum levels of TAZ and PIPC after the intravenous drip infusion for 30 minutes at the dose of 25 mg/kg or 50 mg/kg of TAZ/PIPC showed peaks at the end of the intravenous drip infusion (in 30 minutes after the commencement of the administration) with the levels of 11.93 or 26.05 micrograms/ml for TAZ and 49.80 or 107.50 micrograms/ml for PIPC. The halflife times were 0.51 or 0.67 hours for TAZ and 0.51 or 0.54 hours for PIPC. The serum level of desethyl-piperacillin (DEt-PIPC), an active metabolite of PIPC, showed a peak one hour after the end of the intravenous drip infusion (in 90 minutes after the commencement of the administration) with the level of 0.79 or 1.47 micrograms/ml. On the other hand, cumulative recovery ratios into urine were 41.3% or 40.4% for TAZ and 38.7% or 37.8% for PIPC. The recovery ratio for DEt-PIPC, an active metabolite of PIPC, was 1.9% or 0.3%. 2. Clinical evaluation TAZ/PIPC was administered to 47 cases (pneumonia: 25 cases, bronchitis: 16 cases, cutaneous soft tissue infection: 3 cases, urinary tract infection: 2 cases and lymphadenitis: 1 case). Clinical efficacy evaluation was conducted in 45 cases, excluding one case with bronchitis complicated by measles and other one case with left cervical cellulitis complicated by mumps. Good or more efficacy was observed in the all cases (excellent efficacy: 28 cases and good efficacy: 17 cases). The eradication rate in 31 cases where the pathogenic bacteria were identified and bacteriological efficacy was revealed was 93.5% (29/31 cases). Out of them, bacterial replacement was observed in 5 cases. Decrease in bacteria (including partial eradication) was observed in the remaining 2 cases. Adverse reactions were not reported in any cases. Abnormal values of clinical laboratory examination were reported in 5 cases (increase in platelet count: 2 cases, decrease in leukocyte count: 2 cases and increase in eosinophil count: 1 case). However, there was no case requiring any treatment.

[Antimicrobial activities of cefcapene against clinical isolates from respiratory tract infections of outpatients].

In order to evaluate antimicrobial activity of cefcapene (CFPN), minimum inhibitory concentrations (MICs) of CFPN and reference drugs were determined against clinical isolates from respiratory tract infection of out patients that were obtained in our laboratory from January to June of 1997. The results are summarized as follows; 1. The MIC90 of CFPN against penicillin (PC)-susceptible Streptococcus pneumoniae (PSSP) was equal to those of benzylpenicillin (PCG), ampicillin (ABPC) and cefditoren (CDTR), and was lower than those of cefaclor (CCL), cefdinir (CFDN) and erythromycin (EM). 2. The MIC90 of CFPN against PC-intermediate S. pneumoniae (PISP)/PC-resistant S. pneumoniae (PRSP) was equal to that of CDTR, and was lower than those of PCG, ABPC, CCL, CFDN and EM. CFPN showing strong antimicrobial activities against PISP. 3. CFPN showed strong antimicrobial activities against beta-lactamase producing and non-producing Haemophilus influenzae. The MIC90 of CFPN was stronger than those of ABPC, CCL, CFDN and EM, and was approximately equal to that of CDTR. CFPN also showed strong antimicrobial activities against strains which did not produce any beta-lactamase and were resistant to CCL with MIC of > or = 25 micrograms/ml. 4. Antimicrobial activities of CFPN against Moraxella subgenus Branhamella catarrhalis was stronger than that of ABPC and CCL, though the MIC90 of CFPN was rather high, 3.13 micrograms/ml. 5. CFPN showed strong antimicrobial activities against PISP and beta-lactamase producing H. influenzae, and also against the CCL-resistant H. influenzae indicative mutations of penicillin-binding proteins (PBPs). From those results, cefcapen-pivoxil was found to be clinically effective against community acquired respiratory tract infection.

[Clinical evaluation of faropenem against infections in pediatric fields].

The recent increases in the prevalence of penicillin-resistant Streptococcus pneumoniae becomes a point at issue clinically. We carried out a clinical study in 40 cases in the pediatrics department, as faropenem (FRPM) was proved to have an excellent antimicrobial activity against penicillin-resistant Streptococcus pneumoniae. The study was planned to investigate in detail the movement of stools that had been a problem in a clinical development studies out before. In this study, an observation of the daily movement of stools was one of the principal evaluation items, hence the patients were divided into two groups. One group (S-group) were administered FRPM only, the other group (E-group) were administered FRPM in combination with a medicine for intestinal disorders (Enteronon-R). An observed frequencies of any loose bowel movements were 94.7% in S-group, and 63.2% in E-group, hence the study suggested that the combination drug was effective. The patients observed higher frequencies of development of the movement of stools, all of them were recovered from in the course of administration or within 4 days after administration, however whether or not being treated symptomatic therapy. Clinical efficacy rates of FRPM on mainly respiratory infections were 94.6%. In this study, 4 strains (patients) of penicillin-resistant Streptococcus pneumoniae were isolated. Against penicillin-resistant Streptococcus pneumoniae, FRPM demonstrated more potent antibacterial activity than the oral penicillins and cephems tested here except cefditoren. Clinical efficacies was deemed effective in all of the 4 cases, and bacteriologically, 3 organisms were eradicated. As for side effects including diarrhea and loose stool, no serious side effects were observed. Based on the above results, FRPM is effective against most infections in the pediatric field which Streptococcus pneumoniae are isolated at high frequencies highly, and is considered to cases in be useful an attention will have to be paid to stool movement, however.

[Trend of bacterial meningitis in children over a 14 year period (1981 through 1994) in Japan--an analysis based on studies in 27 institutions].

We observed 266 children with purulent meningitis in 27 institutions in Japan during the 14 years from 1981 on dividing these years into 3 periods, 1981-1985, 1986-1990 and 1991-1994, and studied the trend of causative organisms identified in 254 among the 266 patients. Their ages were less than 3 months after birth in 50 children and 3 months or older in 216: there were 141 boys and 125 girls. The causative organisms were H. influenzae in 134 patients and S. pneumoniae in 50, most of them being aged 3 months or older. Next to the above bacteria ranked S. agalactiae in 29 and E. coli in 12, many of the patients were aged less than 3 months. Staphylococcus spp. was found in 7 patients and about 70% of them were aged 3 months or older. L. monocytogenes was found in 4 patients and N. meningitidis in 3 and they were aged 3 months or older in both patient groups. S. pyogenes, Enterococcus spp., Peptostreptococcus spp., P. Mirabilis and Enterobacter spp. were detected each in 1 patient. The causative organism was unknown in 21 patients and there was no double infection. H. influenzae were detected in 18 patients in 1981-1985 period (36.7%), in 56 in 1986-1990 (54.9%) and in 60 in 1991-1994 (63.8%) showing an increasing tendency, but S. pneumoniae exhibited neither an increasing nor decreasing tendency. There was a decreasing tendency with S. agalactiae and E. coli, but the details were not clear because there were few patients aged less than 3 months. Although the period of coexistence of 4 main bacterial species was not made clear in this study. Listeria is considered to develop mainly in the early childhood, and we believe that the conventional way of using a cephem preparation and ampicillin combined for patients under 6 years need not be altered. However, panipenem (phonetic) is likely to be effective for insensible S. pneumoniae for the time being.

[Pharmacokinetic and clinical studies with cefluprenam in the pediatric field. Pediatric Study Group of Gefluprenam].

Evaluation of efficacy and safety of cefluprenam (code number: E1077, abbreviation: CFLP), a newly developed injectable cephem antibiotics was conducted on adult patients with various infections, and followed by the study group organized from 39 institutions in pediatric field, as the drug showed no toxicity problems in suckling animals. Informed consents from legal representatives were obtained prior to the study. 1. Clinical efficacy. Two-hundred eighty one cases were included for analysis of clinical efficacy after 40 cases of exclusion or drop-out were subtracted from a total of 321 cases. However, the cumulative number of cases evaluable for analysis was considered to be 289, because 8 cases that had 2 different diseases at the same time were counted in each category of disease. In the cases in which causative organisms were identified (group A), 148 of 154 cases were rated as good or excellent, with an efficacy rate of 96.1%. As for clinical efficacies by disease, efficacy rates were 6/6 for purulent meningitis, 4/5 for sepsis, 95.7% (62/65) for pneumonia, 100.0% (29/29) for urinary tract infections, and 94.1% (16/17) for skin and soft tissue infections. The rate of excellent responses among excellent and good responses was 73.6% (109/148), showing a higher value than any of recent injectable beta-lactams. On 32 cases with S. pneumoniae infection, the efficacy rate of CFLP was 100.0%. In the cases where causative organisms were not identified (group B), 128 of 135 cases were rated as good or excellent, with an efficacy rate of 94.8%. In the all cases including both the group A and the group B, the efficacy rate was 95.2% (276/289) and the rate of excellent responses among excellent and good response was 70.7% (195/276). Against severe infections, CFLP exhibited excellent clinical efficacy, showing an efficacy rate of 8/8 for meningitis, 3/5 for sepsis and 100.0% (22/22) for severe pneumonia. As for bacteriological responses, eradication rates were 95.2% (177/186) in total. Against Gram-positive cocci, the eradication rate was 92.7% (76/82), with eradication rates of 94.3% (33/35) for Staphylococcus aureus, and 93.3% (28/30) for Streptococcus pneumoniae. Against Gram-negative rods, the eradication rate was 97.1% (101/104), and eradication rates were 100.0% (22/22) for Escherichia coli, 97.5% (39/40) for Haemophilus influenzae and 100.0% (19/19) for Molaxella catarrhalis. In cases in which more than 3 days of treatment with previous chemotherapy resulted in no response, the efficacy rate of CFLP was 94.2% (98/104), rated excellent in 68 cases and good in 30 cases. In these cases, the eradication rate was 98.1% (52/53). 2. Pharmacokinetics. CFLP was intravenously administerrd to 12 subjects at doses of 20 to 40 mg (potency)/kg. In 9 subjects aged more than 12 months, maximum serum levels (Cmax), T 1/2 beta and AUC of CFLP were 155.3 +/- 9.8 micrograms/ml, 1.43 +/- 0.18 hours and 111.7 +/- 15.0 micrograms.hr/ml, respectively, when a dose of 20 mg (potency)/kg was used. In 2 subjects aged not more than 12 months, the mean Cmax, T 1/2 beta and AUC were 153 micrograms/ml, 1.6 hour and 81 micrograms.hr/ml, respectively, at a dose of 20 mg(potency)/kg. The mean Cmax, T 1/2 beta and AUC were 332 micrograms/ml, 0.93 hours and 157.3 micrograms.hr/ml, respectively, in 1 subject at a dose of 40 mg (potency)/kg. In 10 subjects dosed 20 mg (potency)/kg, urinary levels were 2413 +/- 512, 1471 +/- 524, and 470 +/- 115 micrograms/ml in 0-2, 2-4, and 4-6 hours after dosing, respectively, showing a cumulative urinary excretion rate of 61.4 +/- 6.3%. In 1 subject dosed 40 mg (potency)/kg, urinary levels were 5700 and 4770 micrograms/ml in 0-2 p3d 2-4 hours after dosing, respectively, showing a cumulative urinary excretion rate of 42.1%. Cerebrospinal fluid concentrations of CFLP, on 10 subjects with purulent meningitis dosed 40-103 mg (potency)/kg were 3.2-32.9 micrograms/ml at 0.5-2 hours after administration within 4 days after the onset of

Pharmacokinetics of antibiotics in children.

In designing the dosage regimen of antibiotics including beta-lactams in the field of pediatrics, the choice of adequate drugs, as well as the dosage and the number of administrations have not been performed exactly. This is possibly because of the extended spectrum of antibacterial activity in recent drugs. Even the timing of discontinuation has not been seriously considered. The present report mainly concentrates on several cephalosporins and demonstrates the pharmacokinetic characteristics of the drugs, and further, describes the difference in pharmacokinetic parameters between age groups. On the other hand, it has been suggested that based on the minimum inhibitory concentration for 80% (MIC80) of antibiotics against subject micro-organisms, the effective area under the concentration-time curve, time above MIC80 and Cmax/MIC80 should be considered and the suitability of drug choice, the dosage of suitable drugs, and the number of administrations should be decided. The dosage regimen in the present study was not designed to take into account the effects of sub-MIC and post-antibiotic effect. However, for monotherapy, the dosage regimen was designed to maintain the concentration of at least MIC, which is sufficient from the viewpoint of saving life.

[Pharmacokinetic and clinical evaluation of azithromycin using fine granules or capsules in the pediatric patients].

Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluations. 1. Antibacterial activities. MIC profile of AZM was as follows: 0.78 approximately 1.56 micrograms/ml against Staphylococcus aureus, < or = 0.025 approximately 0.10 microgram/ml against Streptococcus pyogenes, 0.10 approximately 0.39 and 6.25 micrograms/ml against Streptococcus pneumoniae, < or = 0.025 approximately 0.39 microgram/ml against Moraxella(Branhamella) catarrhalis, 0.39 approximately 3.13 micrograms/ml against Haemophilus influenzae, and 0.20 approximately 6.25 micrograms/ml against Haemophilus parainfluenzae. 2. Absorption and excretion. The elimination half-life of AZM after its administration at 10 mg/kg/day for three days was 28.1 approximately 46.1 hours. The cumulative urinary excretion rate in the first 120 hours after start of treatment was 4.01 approximately 8.47%. 3. Clinical evaluation. AZM was given to 76 pediatric patients to treat following infections: pharyngitis in seven, tonsillitis in 11, bronchitis in 11, pneumonia in 19, Mycoplasma pneumonia in eight, scarlet fever in 13, infective enteritis in one, SSTI in four, and otitis media in two. Effectiveness of AZM was assessed in 75 patients and the drug was rated "excellent" or "good" in 71 resulting in an efficacy rate of 94.7%, 87.0% of the 46 cases indicated that AZM had eradicated bacteria identified before the treatment. One patient complained of moderate diarrhea which disappeared after treatment of anti-diarrheic. Abnormal laboratory changes were reported in 12 patients in the following: decreased leukocytes in eight, increased eosinophils in two, increased platelet count in one, and increased GPT in one. All cases of abnormality was deemed mild in severity and clinically insignificant.

[Optimum dose study of cefozopran in the pediatric field].

Cefozopran (SCE-2787, CZOP) was administered to patients with pediatric infections three to four times daily by intravenous injection or 30-minute intravenous drip infusion, and investigations were made in individual cases, on relationships among doses, pharmacokinetics, effects on pathogenic bacteria and MIC against them, and clinical effects. The following results on optimal doses of CZOP were obtained. 1. Clinical cases in which CZOP was administered at a dose of 10 mg (potency)/kg The subjects were 7 patients including 4 patients with pneumonia. Severities of the diseases were severe in one of the patients with pneumonia, and moderate in the other patients. The MIC against pathogenic bacteria (4 strains) isolated from these cases ranged from 0.2 to 1.56 micrograms/ml. The serum concentrations were in a range between 1.4 and 7.6 micrograms/ml at 4 hours after administration. In some cases, the serum concentrations were lower than the MICs, though slightly. In the clinical evaluation, CZOP was excellent in 3 cases, good in 2 cases and fair in 1 case. The evaluation was impossible in 1 case. The efficacy rate was 83.3% (5/6). In bacteriological evaluation, 3 out of the 4 strains disappeared. Adverse reactions and abnormal laboratory test values were not observed. 2. Cases in which CZOP was administered at a dose of 20 mg (potency)/kg The subjects were 5 patients including 2 with pneumonia, and severities were severe in one of the patients with pneumonia, and moderate in the other patients. The MICs against the pathogenic bacteria (3 strains) isolated from these cases ranged from 0.1 to 1.56 micrograms/ml. While, serum concentrations at 4 hours after administration were in a range between 3.0 and 7.7 micrograms/ml sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 1 case and good in four cases, with an efficacy rate of 100% (5/5). In the bacteriological evaluation, all the 3 strains disappeared. No adverse reactions were observed, but an abnormal laboratory test value showing eosinophilia was noted in one case. 3. Cases in which CZOP was administered at a dose of 40 mg (potency)/kg The subjects were 5 patients including 3 with pneumonia. The severity was moderate in 2 of the pneumonia patients, and severe in the other three cases. The MICs against the pathogenic bacteria (4 strains) isolated from these cases were in a range between 0.1 and 0.78 micrograms/ml. The serum concentrations at 4 hours after administration ranged from 6.5 to 21.9 micrograms/ml, sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 4 cases and good in 1 case, with an efficacy rate of 100% (5/5). The efficacy rate in the bacteriological evaluation was also 100%. As adverse reaction, red urine was observed in one case. Eosinophlia was noted in one case in the laboratory tests. When CZOP was administered to patients with pediatric infections at a dose of 10 mg (potency)/kg, the clinical effect of the drug was insufficient in a case in which serum concentration of CZOP at 4 hours after administration was lower than the MICs against the pathogenic bacteria. When CZOP was administered at a dose of 20 mg (potency)/kg, sufficient concentrations were obtained, and the drug efficacies were found to be excellent or good in all cases. Therefore, the effective dose normally used is considered to be 20 mg (potency)/kg. When CZOP was administered at a dose of 40 mg (potency)/kg, the drug was found to be excellent or good in all of the cases although the severities were high in more than half of the cases tested. In addition, the rate of excellent efficacies was 80% (4/5). Furthermore, no severe adverse reactions were observed. It was, therefore, confirmed that CZOP should be administered at a dose of 40 mg (potency)/kg in severe or intractable cases.

[Bacteriological, pharmacokinetic and clinical studies of SY5555 dry syrup in the pediatric field].

Bacteriological, pharmacokinetic and clinical studies on SY5555 dry syrup (powder which is dissolved before use), a new penem antibiotic for oral use, were performed. The following results were obtained. 1. Antibacterial activities. MICs of SY5555, clavulanic acid/amoxicillin (CVA/AMPC), cefotiam (CTM), cefpodoxime (CPDX), cefaclor (CCL) and cefdinir (CFDN) were determined against clinically isolated Staphylococcus aureus, coagulase negative staphylococci, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli and Enterobacter cloacae at a dose of 10(6) CFU/ml. MICs of SY5555 against S. aureus, CNS, S. pneumoniae, S. pyogenes, H. influenzae, M. catarrhalis, E. coli and E. cloacae were 0.2, 0.2, 0.2, < or = 0.025, 0.78, 0.2, 0.78 and 3.13 micrograms/ml, respectively, showing excellent antibacterial effects on these pathogens. Although the effects of SY 5555 against H. influenzae and E. coli were slightly inferior to those of CPDX and CFDN, the drug showed the most excellent antibacterial effect on other strains as compared with the control drugs. 2. Absorption and excretion In this study, plasma concentrations and urinary recovery rates were examined after administration of SY5555 at doses of 5 and 10 mg/kg (potency) after meals. With both 5 and 10 mg/kg doses, peak plasma concentrations were reached 1 hour after administration, at 0.25-2.61 micrograms/ml (mean 1.47 micrograms/ml) and 1.08-2.17 micrograms/ml (mean 1.74 micrograms/ml), respectively. The plasma levels rapidly decreased to 0.06-0.19 micrograms/ml (0.12 micrograms/ml) and 0.0503-0.0637 micrograms/ml) after 6 hours. The half-lives 1.12 hours in the 5 mg/kg group and 1.0 hour in the 10 mg/kg group. The urinary recovery rates were determined in the first 8 hours after administration in the 5 mg/kg and 6 hours in the 10 mg/kg group, and the values were as low as 1.05-12.3% and 1.6-4.33%, respectively. 3. Clinical results The clinical responses were examined in a total of 73 cases including 4 acute pneumonia, 13 acute bronchitis, 11 tonsillitis, 3 pharyngitis, 12 scarlet fever, 2 pertussis, 6 urinary tract infection, 6 otitis media, 7 lymphadenitis, 2 staphylococcal scalded skin syndrome, 2 phlegmon, 4 impetigo and 1 purulent parotitis. The treatment was effective or better in 66 of 70 cases with an efficacy rate of 94.3% (3 undeterminable cases were excluded). Bacteriological effects were examined during the clinical course for detected or suspected pathogens found before administration of SY5555. The effects were determined in 50 cases including 7 cases of polymicrobacterial infections, 57 strains in total. Eight strains, however, persisted, hence the overall eradication rate was 86.0%.(ABSTRACT TRUNCATED AT 400 WORDS)

[Pharmacokinetic and clinical evaluation of cefozopran in the pediatric field].

We conducted pharmacokinetic and clinical studies on cefozopran (CZOP, SCE-2787), an aminothiadiazolmethoxyiminoacetamido cephalosporin, and obtained the following results. 1. Concentrations in serum/excretion in urine We studied pharmacokinetic in children upon intravenous bolus injection and 30-minute intravenous drip infusion in single doses of 10 and 20 mg/kg. Upon intravenous bolus injection, mean serum concentrations 30 minutes after administration of 10 and 20 mg/kg were 27.8 and 52.3 micrograms/ml, respectively, and half-lives were 2.01 and 2.02 hours, respectively. Upon 30-minute intravenous drip infusion, mean serum concentrations on completion of the drip infusions of 10 and 20 mg/kg were 36.8 and 70.3 micrograms/ml, respectively, and half-lives were 1.74 and 4.11 hours, respectively. Their urinary recovery rates in the first 8 hours after administration were higher than 67.0% in the former regimen and between 23.2 to 98.0% in the latter. 2. Clinical results 54 patients were treated with CZOP for 32 cases of pneumonia, 11 cases of bronchitis, 3 cases of cervical lymphadenitis, 1 case of purulent tonsillitis, 2 cases of phlegmon, 2 cases of enterogastritis and 3 cases of urinary tract infections. CZOP gave "excellent" or "good" responses in 53 cases. 1 case of urinary tract infection showed fair response. Diarrhea was observed in 1 case. Abnormal laboratory test results were noted in 9 patients including elevations of eosinophils, GOT and GPT. In no cases the treatment had to be discontinued.

[Pharmacokinetic and clinical studies of SY5555 in the pediatric field. Pediatric Study Group of SY5555].

SY5555, a new oral penem, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained: 1. Pharmacokinetics Pharmacokinetics of SY5555 dry syrup (powder which is dissolved before use) was investigated in 64 children. At a dose level of 3 mg (potency)/kg, Cmax and T1/2 were 0.33 micrograms/ml and 0.95 hours (n = 1), respectively, in the non-fasting state. At a dose level of 5 mg/kg Cmax and T1/2 were 2.09 +/- 1.25 micrograms/ml and 1.20 +/- 1.07 hours, respectively, in the fasting state, and were 1.21 +/- 0.70 micrograms/ml and 1.33 +/- 0.90 hours, respectively, in the non-fasting state. At a dose level of 10 mg/kg, Cmax and T1/2 were 2.96 +/- 1.89 micrograms/ml and 0.89 +/- 0.43 hours, respectively, in the fasting state, and were 2.45 +/- 1.37 micrograms/ml and 1.17 +/- 0.53 hours, respectively, in the non-fasting state. At a dose level of 15 mg/kg, Cmax and T1/2 were 4.30 +/- 2.15 micrograms/ml and 0.82 +/- 0.09 hours, respectively, in the non-fasting state. Data of Cmax and AUC showed that plasma concentration of the drug depended on dose levels. Urinary recovery rates in the first 6 hours were 1.71% (n = 1) in the non-fasting state at a dose level of 3 mg/kg, 4.13 +/- 1.40% in the fasting state and 4.17 +/- 3.29% in the fasting and the non-fasting state, respectively at a dose level of 5 mg/kg, and 6.02% (n = 1) and 4.64 +/- 2.81%, respectively, at a dose level of 10 mg/kg. At a dose level of 15 mg/kg, urinary recovery rate in the first 6 hours was 7.97% (n = 2) in the non-fasting state. 2. Clinical results 1) Dry syrup The clinical efficacy of the SY5555 dry syrup was evaluated in 506 cases. SY5555 was administered at daily doses of 15-30 mg/kg divided into 3 equal doses to most patients. Daily doses of 12- < 18 mg/kg were given to 46.6% of the patients. The overall clinical efficacy rate was 92.9%, and this drug was effective in 93.0% of the 301 patients for whom the causative pathogens were identified, and in 92.7% of the 205 patients with infections for whom the causative pathogens were unknown. The efficacy rate at daily doses of 12 - < 18 mg/kg was 94.5% similar to those obtained at daily doses of 18- < 27 mg/kg (91.7%) or 27- < 33 mg/kg (91.3%). The bacteriological eradication rate was 82.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

[Pharmacokinetic and clinical studies of S-1108 in the pediatric field].

Pharmacokinetic and clinical studies on S-1108, a new oral cephem antibiotic, were performed in the field pediatrics. The following results were obtained. 1) Antibacterial activities Antibacterial activities of S-1006, the active form of S-1108, were studied against clinically isolated strains of (Staphylococcus aureus (n = 5), Streptococcus pneumoniae (n = 6), Streptococcus pyogenes (n = 3), Haemophilus influenzae (n = 8), Branhamella catarrhalis (n = 5) and Haemophilus parainfluenzae (n = 2). MIC values ranged < or = 0.025-1.56 for GPC and < or = 0.025-0.78 microgram/ml for GNR. 2) Absorption and excretion Blood concentrations and urinary excretion rates of S-1108 were measured upon administration of S-1108 after meal at dose of 3 mg/kg (n = 4), 4 mg/kg (n = 1) and 6 mg/kg (n = 1). The peak blood concentrations of S-1006 at a dose of 3 mg/kg (n = 4), ranged from 0.57 to 1.82 micrograms/ml at 1, 2 and 4 hours after dosing. Mean pharmacokinetic parameters T1/2 and AUC were 1.29 +/- 0.69 hours and 4.47 +/- 2.25 micrograms.hr/ml, respectively. At a dose of 4 mg/kg and 6 mg/kg, peak concentrations were 1.79 and 1.27 micrograms/ml at 2 and 3 hours after treatment. T1/2 and AUC were 1.34 and 1.11 hours, and 8.19 and 5.65 micrograms.hr/ml, respectively. Urinary recovery rates ranged from 13.0 to 37.2% for the first 8 hours after administration. 3) Clinical studies Clinical efficacies were examined in 32 cases of various pediatric infections including 5 cases of acute pneumonia, 11 cases of bronchitis, 2 cases of scarlet fever, 8 cases of tonsillitis, 1 case of pharyngitis, 2 cases of otitis media and 3 cases of UTI. Clinical efficacy rate was 96.9% (31/32) and bacteriological eradication rate was 87.1% (27/31). There were no side effects and abnormal laboratory test values except 1 case (Eosino. 2-->10%) in the 32 cases.

[Effect of cefditoren pivoxil on carnitine metabolism in pediatric patients].

Carnitine metabolism was studied in 16 pediatric patients with various infections under the treatment with cefditoren pivoxil (CDTR-PI) in granular form. Pivalic acid released from pivaloyloxymethyl ester of the drug was metabolized to pivaloylcarnitine. As results, an increase in urinary carnitine excretion (predominantly as pivaloylcarnitine) and, a decrease in free carnitine concentration and a high acyl/free carnitine ratio in serum (plasma) were observed during the treatment. When the dosing was terminated, pivaloylcarnitine in plasma and then in urine disappeared, and the concentration of free carnitine, acyl/free carnitine ratio returned to the normal range. No carnitine-related side effects were observed throughout the study.

[Criteria for clinical evaluation of antibiotics in pediatrics. The purpose and process for establishing the criteria].

This paper describes the purpose and process for establishing "Criteria for Clinical Evaluation of Antibiotics in the Pediatric Field", which was reported in the Japanese Journal of Antibiotics Vol. 46, May, 1993. The Criteria Committee was organized in November 1991. Four meetings were held to establish the draft criteria. The criteria were applied to the evaluation of oral cephem S-1108 and parenteral cephem SCE-2787. When the criteria were compared with the conventional criteria, the results indicated that no difference was obtained in the efficacy rate as a whole, the sum of "Good" and "Excellent" cases, but there was a difference in the cases judged to be "Excellent". Partial alteration was made to the draft criteria and the Committee produced the final version of the criteria. However, the criteria are far from complete, so it will be subjected to further revision it accordance with future advance in chemotherapy.