Administration of teriparatide improves the symptoms of advanced bisphosphonate-related osteonecrosis of the jaw: preliminary findings.

Teriparatide is a synthetic polypeptide hormone that contains the 1-34 amino acid fragment of the recombinant human parathyroid hormone that stimulates bone formation. Currently, it is approved only for the treatment of osteoporosis. The outcomes of daily teriparatide injections for the treatment of bisphosphonate-related osteonecrosis of the jaw in 10 patients are reported here. Two of the 10 cases dropped out due to adverse events. Of the remaining eight cases, seven exhibited clinical improvement of the jaw-related symptoms of osteonecrosis and progression of the sequestration, while one case did not show improvement of the symptoms. Administration of teriparatide in patients with osteonecrosis of the jaw promotes bone formation and subsequent sequestration over a short period of time. These results suggest that adjunctive teriparatide therapy is a viable and effective option for treating osteonecrosis of the jaw.

Identification of the female-determining region of the W chromosome in Bombyx mori.

The W chromosome of the silkworm Bombyx mori is devoid of functional genes, except for the putative female-determining gene (Fem). To localize Fem, we investigated the presence of W-specific DNA markers on strains in which an autosomal fragment containing dominant marker genes was attached to the W chromosome. We produced new W-chromosomal fragments from the existing Zebra-W strain (T(W;3)Ze chromosome) by X-irradiation, and then carried out deletion mapping of these and sex-limited yellow cocoon strains (T(W;2)Y-Chu, -Abe and -Ban types) from different Japanese stock centers. Of 12 RAPD markers identified in the normal W chromosomes of most silkworm strains in Japan, the newly irradiated W(B-YL-YS)Ze chromosome contained three, the T(W;2)Y-Chu chromosome contained six, and the T(W;2)Y-Abe and -Ban chromosomes contained only one (W-Rikishi). To investigate the ability of the reduced W-chromosome translocation fragments to form heterochromatin bodies, which are found in nuclei of normal adult female sucking stomachs, we examined cells of the normal type p50 strain and the T(W;2)Y-Chu and -Abe strains. A single sex heterochromatin body was found in nuclei of p50 females, whereas we detected only small sex heterochromatin bodies in the T(W;2)Y-Chu strain and no sex heterochromatin body in the T(W;2)Y-Abe strain. Since adult females of all strains were normal and fertile, we conclude that only extremely limited region, containing the W-Rikishi RAPD sequence of the W chromosome, is required to determine femaleness. Based on a comparison of the normal W-chromosome and 7 translocation and W-deletion strains we present a map of Fem relative to the 12 W-specific RAPD markers.

Antibodies labeled with fluorescence-agent excitable by infrared rays.

Endoscopy is not significantly better than fiberoscopy for the diagnosis of minute cancers of the digestive tract. However, labeling of these lesions with an agent that can be detected videoendoscopically, with subsequent computer processing of the electronic signals, should facilitate endoscopic diagnosis of microlesions. We developed an antibody labeled with an indocyanine green(ICG) derivative that has a specific fluorescence emission at 807 nm upon excitation at 768 nm. The physiochemical characteristics of this labeled antibody resemble those of ICG. The activity of the antibody is suitable for immunohistochemical staining, and the antibody fluoresces under infrared ray excitation. This antibody should prove useful for performing vital immunostaining for infrared endoscopy.

Acquisition of nonmaternal Enterobacteriaceae by infants delivered in hospitals.

To determine whether Escherichia coli strains that colonize the intestinal tract of newborn infants in hospitals are of maternal origin or come from the environment, plasmid profiles of E. coli strains isolated from the stools of infants were compared with those from the stools of their mothers. Twenty-nine mother-infant pairs were studied in three different hospitals. In only 4 of 29 pairs, plasmid profiles of E. coli or other Enterobacteriaceae were shared by infant and mother; vertical transmission seemed to be uncommon, unlike findings in previous reports. In one hospital, 8 of 10 infant fecal E. coli strains shared a single plasmid profile, strongly suggesting nosocomial acquisition. In another, 7 of 9 neonate strains also shared a unique profile, and additionally carried K1 capsular antigen, a known virulence factor. Two other infants from the latter nursery acquired a urinary tract infection with E. coli K1 carrying the same plasmid profile. This study indicates that nosocomial acquisition of hospital strains of E. coli by neonates may be common in some hospitals and that the clinical implications are potentially serious.

Mixed invasive aspergillosis and candidiasis in a fatal case of leukemia.

A fatal case of leukemia complicated by mixed invasive aspergillosis and candidiasis is presented. Mixed fungal infections may occur in any immunocompromised patients. We should be careful to look for different morphologies of fungi in diagnostic examinations of lesions in these patients.

K1 antigen, serotype and antibiotic susceptibility of Escherichia coli isolated from cerebrospinal fluid, blood and other specimens from Japanese infants.

K1 antigens, serotypes and antibiotic susceptibilities of Escherichia coli isolates from neonates and infants were investigated. The presence of K1 antigen was tested by the K1-specific phage method. The number of K1 positive strains was 27 (84%) of 32 isolates from cerebrospinal fluid, 11 (25%) of 44 from blood and 4 (22%) of 18 from other specimens. Fourteen (33%) of the K1 positive strains were serotyped as O16:H6, and 8, 7 and 5 were serotyped as O18ac:H7, O1:H7 and O7:H-, respectively. One of 5 of the K1 negative strains were distributed into 30 different combinations of O and H antigens. The ampicillin resistance rates were 19% in K1 positive strains and 45% in K1 negative ones. The incidence of chloramphenicol resistance was the same in K1 positive and negative strains (21%). Ampicillin resistance was not noted in O16:H6 strains, but the incidence of antibiotic resistance was high (65% to ampicillin and 53% to chloramphenicol) in the rough-type strains.

Septicemia in immunocompromised children and their intestinal flora.

Quantitative fecal bacteriology was performed in eight immunocompromised children with septicemia. The most marked change observed was suppression of the anaerobic bacteria. In seven patients, the predominant organisms were aerobic gram-negative bacilli (GNB), and in six of these were the same as the causative organism of the septicemia. Thus, overgrowth of GNB in the gastrointestinal tract may result in invasion of the blood stream and septicemia in immunocompromised patients. To prevent this complication it is necessary to allow the normal intestinal flora to be maintained in these patients as long as possible. Antibiotics should therefore be prescribed with caution. For the same reason, use of immunosuppressive drugs should be kept to a minimum. Bacteriological examination of the stool and pharynx is useful in the management of immunocompromised patients.

[Clinical and pharmacokinetic evaluation of cefdinir in children].

Thirty children were treated with cefdinir (CFDN) for the evaluation of its clinical efficacy and side effects. Their ages ranged from 1 to 9 years. The dosage of CFDN ranged from 8.1 to 15.9 mg/kg/day with the treatment continued for 2 to 10 days. Twenty-eight of the 30 patients were evaluated for clinical efficacy; 10 patients with tonsillitis, 3 with scarlet fever, 4 with lower respiratory infections, 2 with otitis media, 2 with cervical lymphadenitis, 3 with urinary tract infections and 4 with skin and soft tissue infections. The remaining 2 patients who had viral diseases were included in the evaluation for side effects. Clinical responses were excellent in 14 patients, good in 12, fair in 1 and poor in 1 with an efficacy rate of 92.9%. Diarrhea was noted in one of the 30 patients. A pharmacokinetic study on CFDN was performed in 8 fasting patients whose ages ranged from 3 to 7 years. Serum concentrations of CFDN peaked at 0.59 to 1.76 micrograms/ml (mean 1.13 microgram/ml) at 2 hours after dosing of 3 mg/kg in 4 patients, and 0.89 to 2.49 micrograms/ml (mean 1.49 micrograms/ml) 2 or 3 hours after dosing of 6 mg/kg in the other 4 patients. The 8-hour urinary excretion rates were 16.0% to 21.3% (mean 17.4%) in 4 patients given a dose of 3 mg/kg and 10.9 to 21.1% (mean 15.5%) in 4 patients given a dose of 6 mg/kg.

Effects of aztreonam on fecal flora and on vitamin K metabolism.

The effects of aztreonam on fecal flora and on descarboxy prothrombin (PIVKA-II) in plasma and gamma-carboxyglutamic acid (Gla) in urine as an index of vitamin K metabolism were studied in seven children (age range, 2 months to 2 years) with urinary tract infections. Daily doses of aztreonam were 60 to 80 mg/kg. Stool specimens were obtained before the treatment, on days 3 to 5 of aztreonam use, and from 3 to 5 days after the cessation of treatment. The counts of enterobacteria decreased (P less than 0.01) and those of streptococci increased (P less than 0.05) during aztreonam treatment. The anaerobic organisms, especially bifidobacteria and bacteroides, showed no marked change. PIVKA-II and Gla were investigated before and during the treatment with aztreonam. PIVKA-II was not detected in seven patients before or during aztreonam use. There were no significant differences in the levels of Gla in urine before or during the treatment.

Antibiotic susceptibility of type b Haemophilus influenzae and Streptococcus pneumoniae, and antibiotic concentration in cerebrospinal fluid.

Antibiotic susceptibilities of 38 type b Haemophilus influenzae and 28 Streptococcus pneumoniae strains isolated from cerebrospinal fluid, blood and other specimens between 1973 and 1988 were studied. Minimal inhibitory concentrations (MICs) of ampicillin against 10 beta-lactamase positive and 28 negative H. influenzae isolates were 32-64 and 0.25 micrograms/ml, respectively. The MIC of chloramphenicol against one of the beta-lactamase positive H. influenzae strains was 8 but MICs against the rest of the organisms were 0.5-1 micrograms/ml. MICs of cefotaxime, ceftriaxone and cefuroxime against all H. influenzae strains were 0.016, 0.008 and 0.5 micrograms/ml, respectively. No S. pneumoniae isolates were resistant to penicillin G and MICs of this drug were 0.016-0.032 micrograms/ml. MICs of cefotaxime, cefriaxone and cefuroxime against all S. pneumoniae strains were 0.016-0.032, 0.016-0.032 and 0.032-0.063 micrograms/ml, respectively. MICs of chloramphenicol against 15, 4 and 9 of S. pneumoniae isolates were 2, 8 and 16 micrograms/ml, respectively. Antibiotic concentrations in the cerebrospinal fluid of patients with bacterial meningitis after intravenous administration of ampicillin (50-70 mg/kg x 4/day), penicillin G (31-63 mg/kg x 4/day), cefotaxime (50 mg/kg x 4/day) and chloramphenicol (25 mg/kg x 4/day) were 4.70 +/- 1.83 (n = 11), 0.57 +/- 0.32 (n = 7), 4.97 +/- 2.60 (n = 9) and 8.52 +/- 3.54 micrograms/ml (n = 3), respectively. The initial choice of antibiotics in older children with bacterial meningitis is a combination of ampicillin (75 mg/kg x 4/day) and cefotaxime (50 mg/kg x 4/day) to cover ampicillin-resistant H. influenzae, S. pneumoniae, and Listeria monocytogenes in Japan. These antibiotics should be changed according to the causative organisms and their antibiotic susceptibilities.

[Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the first report). Study on effectiveness and safety in mono-therapy with aztreonam. A study of aztreonam in the Perinatal Co-research Group].

Pharmacokinetics and clinical study of aztreonam (AZT) in neonates and premature infants were conducted with the following results: 1. Pharmacokinetics (1) Serum concentrations of AZT at 30 minutes after one-shot intravenous injection of 10 mg/kg and 20 mg/kg to neonates including premature infants were 20.6-26.6 micrograms/ml and 38.5-46.4 micrograms/ml, respectively, and decreased thereafter. A dose response was observed in the serum concentrations with administration of AZT 10 mg/kg and 20 mg/kg. (2) Serum half-lives (T1/2) tended to be shorter in both mature and premature infants as their day-ages increased and T1/2 tended to be prolonged in premature infants compared with mature infants. (3) Changes in serum concentration upon one-hour intravenous drip infusion of AZT 20 mg/kg were very similar to those upon one-shot intravenous injection. (4) Urinary excretions in the first 6 hours after one-shot intravenous injection of AZT 10 mg/kg or 20 mg/kg tended to increase in mature infants as they grew and showed excretion rate of 26.2-54.3% but those in premature infants did not show any specific tendency with rate of 17.5-45.1%. Urinary excretions upon intravenous drip-infusion showed a tendency very similar to those upon intravenous injection. 2. Clinical studies (1) Clinically evaluable cases of AZT treatment were 88 cases (91 diseases), in which pathogenic organisms were identified in 56 cases (Group A), i.e., sepsis 9, purulent meningitis 2, pneumonia 8, urinary tract infection (UTI) 33 and others. Total efficacy rate was 98.2% including "excellent" (39), "good" (16) and "fair" (1). Number of cases in which pathogenic organisms were unknown (Group B) was 11, i.e., suspected sepsis (4), pneumonia (3) and intrauterine infection (4) and the efficacy rate was 100% with "excellent" (4) and "good" (7). Thus, both group A and B showed excellent results. AZT was also given to 24 cases for prophylaxis and all the cases showed prophylactic effect of AZT.4+ Bacteriologically AZT was deemed effective in 53 cases out of 56 (Group A) with identified pathogens "eradicated" and "unchanged" (2), thus the bacterial eradication rate was 96.2%. (3) A minor degree of loose feces was observed in 1 (1.3%) of 80 cases as a side effect. Abnormal laboratory test values found were eosinophilia (3 cases), elevation of GOT and GPT (2), platelet-increase (1), elevation of GOT (1), and thrombocytopenia.elevation of GOT.GPT.LDH (1). Every one of these was of a minor degree and transient. From the above pharmacokinetics and clinical results, standard dosage of AZT to neonates and premature infants should be in a unit dose of 20 mg/kg, twice daily to those with ages between 0 and 3 days, and 2 to 3 times daily to those with ages 4 days and above, by intravenous injection or intravenous drip infusion.

[Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the second report). Study on effectiveness and safety in combination therapy using aztreonam and ampicillin. A study of aztreonam in the Perinatal Co-research Group].

Pharmacokinetics and clinical effects were studied in a combination therapy with aztreonam (AZT) and ampicillin (ABPC) in neonates and premature infants. The results obtained are summarized as follows. 1. Pharmacokinetics (1) Average serum concentrations at 30 minutes after one-shot intravenous injection of AZT 20 mg/kg and ABPC 25 mg/kg to a 4-7 days age-group of neonates were 41.3 (AZT) and 30.5 (ABPC) micrograms/ml, respectively. They gradually decreased to 14.7 and 2.7 micrograms/ml at 6 hours after the administration, but the concentration of AZT was always higher than that of ABPC. (2) Serum half-lives (T1/2) in the 4-7 days age-group were 3.61 hours for AZT and 1.42 hours for ABPC, thus T1/2 of AZT was longer. However, T1/2 of AZT was scarcely affected in the concomitant administration of ABPC. (3) Urinary excretion of AZT in the concomitant administration to the 4-7 days age-group was 52.7%, which was the same or a little higher comparing to that in AZT alone administration. 2. Clinical studies (1) AZT and ABPC were concomitantly administered to 160 cases and 133 cases were evaluated for efficacy. Pathogenic organisms were identified in 29 cases (Group A) and the efficacy rate was 86.2% (25/29). The number of cases in which pathogenic organisms were not identified (Group B) was 50 and in this group, the efficacy rate was excellent, 94.0% (47/50). AZT and ABPC were concomitantly administered to 54 cases for prophylaxis and in all the cases the administrations showed prophylactic effect. (2) Bacterial changes were confirmed in 21 of the 29 cases in which pathogenic organisms were identified initially and all of these 21 cases showed bacterial eradication, i.e., the bacterial eradication rate in the treatment was 100%. (3) There were 2 cases in which side-effects were observed among the analyzed 152 cases (1.3%). The side effects found were 1 case each of diarrhea and eruption. Abnormal laboratory values were found in 23 cases (15.9%), i.e., eosinophilia (9 cases), platelet-increase (4), elevation of GOT (4), elevation of GOT and GPT (3) and others (3). From the above pharmacokinetics and clinical results, the combination therapy of AZT and ABPC is considered to be one of the useful empiric antibiotic-therapies when pathogenic organisms are unknown in the infections of neonates and premature infants.

[Clinical and pharmacokinetic evaluation of aztreonam in neonates].

Nine neonates were treated with aztreonam (AZT) and its clinical efficacy and side effects were evaluated. Six of the patients were treated with a combination of AZT and ampicillin. Ages of the patients ranged from 0 to 24 days, and their body weights ranged from 2,290 to 4,260 g. Doses of AZT ranged 18.8 to 23.7 mg/kg every 8 to 12 hours for 3 to 7 days. Three patients with infections including urinary tract infection, cervical abscess, and suspicion of sepsis, appeared to respond to the treatment of AZT alone. Among them, clinical results were excellent in 1, good in 2 patients. Those patients subjected to the combination therapy showed excellent response in 1 and good in 5. The drug was well tolerated, but 1 had diarrhea. The pharmacokinetics of AZT was studied in 9 patients. Their ages ranged from 0 to 30 days, and body weights ranged from 2,000 to 4,000 g. Serum concentrations of AZT were 27.2 to 48.3 micrograms/ml at 1 hour after single 20 mg/kg intravenous bolus injection, and the levels were 3.4 to 15.5 micrograms/ml at 6 hours in 5 infants heavier than 2,500 g. Elimination half-lives of AZT ranged from 1.57 to 3.72 hours (mean 2.72 hours). Serum concentrations of AZT were 21.6 to 41.8 micrograms/ml at 1 hour after single 20 mg/kg intravenous bolus injection, and the levels were 10.2 to 17.0 micrograms/ml at 6 hours in 3 infants lighter than 2,500 g. The elimination half-lives of AZT were 3.63 to 4.86 hours (mean 4.31 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical and pharmacokinetic evaluation of cefmenoxime in neonates and young infants].

Twenty-three newborn and young infants, including 13 low-birth-weight infants, were treated with cefmenoxime (CMX) and the clinical efficacy and side effects were evaluated. The ages of the patients ranged from 1 to 102 days, and their weights ranged from 0.83 to 4.19 kg. Doses given were 18-42 mg/kg every 6 to 12 hours for 2 to 16 days. Among 12 infants with bacterial meningitis and sepsis, the results were excellent in 2, good in 7 and fair in 3 patients. The drug was well tolerated and no adverse effects were observed in the 23 patients. Pharmacokinetic studies of CMX were done in 5 infants whose mean body weight was 3.03 kg (range 2.4 to 4.2 kg). Serum concentrations at 15 minutes after 10 mg/kg intravenous bolus injections were 35.6 and 55.7 micrograms/ml in two 12- and 18-day-old patients. In 3 patients with ages of 7, 7 and 24 days, serum concentrations were 54.6, 102 and 100 micrograms/ml, respectively, at 15 minutes after 20 mg/kg doses. Elimination half-lives of the drug were 1.3 to 1.5 (mean 1.4) hours in these patients. Excretion rates into urine in the first 8 hours were 30.3, 74.2, 77.6 and 85.6% in four patients given 10 or 20 mg/kg doses. The cerebrospinal fluid level at 3 hours after the dose was 0.4 micrograms/ml on 15th day of treatment in 1 patient with bacterial meningitis given 20 mg/kg every 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

[Selective decontamination of intestinal flora with oral aztreonam in compromised children].

Effects of oral aztreonam on fecal flora were studied in 6 compromised children. Their ages ranged from 4 to 14 years. Daily doses of aztreonam were 10 to 30 mg/kg. The stool specimens were obtained before the treatment, on day 5 to 7 of aztreonam use and 2 to 5 days after the cessation of treatment. The counts of enterobacteria decreased from 10(7.7) to 10(4.4) per gram of wet feces (p less than 0.01), and bifidobacteria also decreased from 10(10.2) to 10(8.4) per gram of wet feces (p less than 0.01) during aztreonam administration. Those of streptococci increased from 10(2.9) to 10(9.4) per gram of wet feces (p less than 0.001). The other anaerobic organisms showed no marked change. Based upon the above results, we conclude that oral administration of aztreonam may be useful for selective decontamination of intestinal flora in compromised hosts.

[Clinical and pharmacokinetic evaluation of cefteram pivoxil in children].

Twenty-six children were treated with cefteram pivoxil (CFTM-PI) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 8 months to 9 years. Doses of CFTM-PI ranged 7.5-20.1 mg/kg/day for 4 to 19 days. The twenty-six patients including 10 patients with tonsillitis, 1 pharyngitis, 3 otitis media, 2 scarlet fever, 1 bronchopneumonia, 1 lymphadenitis, 6 urinary tract infections, 1 vaginitis and 1 staphylococcal scalded skin syndrome were evaluated for clinical efficacy. Results were excellent in 11, good in 13, and fair in 2 patients. Out of the 26 patients, one case showed elevated GOT and GPT, and another case showed elevated GOT. The pharmacokinetic study of CFTM-PI was performed in 9 fasting patients whose ages ranged from 2 to 11 years. Serum peak concentrations of CFTM were 0.92 to 1.05 micrograms/ml (mean 0.99 microgram/ml) at 1 to 2 hours after a dose of 1.5 mg/kg each to 3 patients, 1.12 to 1.38 micrograms/ml (mean 1.25 micrograms/ml) after a dose of 3 mg/kg each to 3 patients and 0.66 to 2.1 micrograms/ml (mean 1.17 micrograms/ml) after a dose of 6 mg/kg each to 3 patients. The portions of the drug excreted into urine within 8 hours were 8.9% and 14.7% in 2 patients, each given a dose of 1.5 mg/kg, from 13.0 to 23.1% (mean 18.4%) in 3 patients, each given a dose of 3 mg/kg, and 6.3% and 8.7% in 2 patients, each given a dose of 6 mg/kg.

Acinetobacter calcoaceticus biovar anitratus septicaemia in a neonatal intensive care unit: epidemiology and control.

Nineteen neonates with septicaemia caused by Acinetobacter calcoaceticus biovar anitratus were treated in a neonatal intensive care unit between October, 1983 and March, 1986. The ages of the patients at the onset of septicaemia ranged from 4 to 22 days (mean 9.7 days). Their birth weights ranged from 1000 g to 3350 g (mean 1790 g) and were less than 2000 g in 14 patients. Antibiotics had been administered to 17 of the 19 neonates before the onset of septicaemia, and all mature infants had received prior antibiotic therapy, intubation or had suffered from a convulsion. Acinetobacter anitratus strains were isolated from pharyngeal swabs and/or faeces from 35 (79.5%) out of 44 infants of less than 2000 g. These strains were also isolated from the hands of staff members, and from equipment such as sinks and baths in the unit. It was likely that nosocomial infection via the hands of the staff occurred. Encouraging frequent hand-washing, strict antibiotic use, and cohorting of colonized infants resulted in a reduction of colonization and no further cases of septicaemia were reported.

[Clinical and pharmacokinetic evaluation of cefpodoxime proxetil in children].

Twenty nine children were treated with cefpodoxime proxetil (CPDX-PR, CS-807) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 2 months to 10 years. Dose levels of CPDX-PR ranged from 7.5 to 12.0 mg/kg/day for 5 to 12.7 days. The 29 patients included 9 tonsillitis, 2 otitis media, 5 scarlet fever, 3 bronchopneumonia, 1 lymphadenitis, 8 urinary tract infections and 1 staphylococcal scalded skin syndrome, and they were evaluated for the clinical efficacy of CPDX-PR. Results were excellent in 21 and good in 8 patients. Out of the 29 patients, 3 cases showed diarrhea and 2 cases showed elevated GOT and GPT. The pharmacokinetics of CPDX-PR was studied in 9 patients whose ages ranged from 1 to 9 years. The serum peak concentrations of CPDX in 5 patients were between 1.37 and 4.10 micrograms/ml (mean: 2.53 micrograms/ml) at 1 to 6 hours after dosing 3 mg/kg before meals. Those of 4 patients ranged 3.29 to 4.88 micrograms/ml (mean: 4.36 micrograms/ml) at 2 hours after administering 6 mg/kg before meals. Portions of CPDX excreted into urine within 6 hours ranged from 20.3 to 34.3% (mean 27.1%) in 5 patients who were given 3 mg/kg, and ranged from 24.1 to 65.7% (mean 41.1%) in 4 patients given 6 mg/kg.

[Clinical and pharmacokinetic evaluation of imipenem/cilastatin sodium in neonates and young infants].

Twenty three neonates and young infants were treated with imipenem/cilastatin sodium (IPM/CS) and its clinical efficacy and side effects were evaluated. Ages of the patients ranged from 0 to 83 days, and their body weights ranged from 750 to 4,760 g. Doses of IPM/CS ranged from 17.4 to 21.5 mg/kg as IPM every 6 to 12 hours for 3 to 12 days. Sixteen patients with infections including sepsis, meningitis and pneumonia, appeared to have responded to the IPM/CS treatment. Among them, clinical results were excellent in 2, good in 12 and fair in 2 patients. The drug was well tolerated, but 1 patient had diarrhea, 1 had redness of body during infusion, 1 had elevated GOT and GPT, and 2 patients showed only elevated values of GOT only among the 23 patients. The pharmacokinetics of IPM/CS were studied in 7 patients. Their ages ranged from 0 to 9 days, and body weights ranged from 2.5 to 4.0 kg. Serum concentrations of IPM were between 18.0 and 96.9 micrograms/ml and those of CS ranged 31.7 and 144.5 micrograms/ml in 6 patients at the end of intravenous drip infusion 20 mg/20 mg/kg during 30 or 60 minutes. Elimination half-lives of IPM ranged from 1.2 to 2.0 hours, and those of CS ranged from 1.4 to 2.7 hours. Serum concentrations of IPM was 14.7 micrograms/ml and that of CS was 32.4 micrograms/ml in 1 patient at the end of 30 minute-drip infusion 10 mg/10 mg/kg. The elimination half-lives of IPM was 1.5 hours, and that of CS was 2.9 hours.(ABSTRACT TRUNCATED AT 250 WORDS)