Clinical and pharmacokinetic evaluation of imipenem/cilastatin sodium in children

Nineteen episodes of infection in 17 children (one had 3 episodes) were treated with imipenem/cilastatin sodium (MK-0787/MK-0791), and the clinical efficacy and side effects were evaluated. The ages of patients ranged from 1 month to 8 years 1 month and their body weights ranged from 3.9 to 25.2 kg. The MK-0787/MK-0791 was administered intravenously by a 30-60 minutes infusion, in doses ranging from 8-42 mg/8-42 mg/kg every 6 to 12 hours for 3 to 40.5 days. Among 18 episodes in 16 patients (one patient proved to have rubella meningoencephalitis and was excluded from evaluation of the clinical efficacy) with bacterial infections including sepsis, pneumonia, acute suppurative thyroiditis and urinary tract infections, the results were excellent in 10, good in 5, fair in 2, and poor in 1 episode. Some side effects were noted; among all 19 episodes in the 17 patients diarrhea was noted in 3, rash in 1, slightly elevated serum transaminases in 1 and thrombocytosis in 1 episode. Pharmacokinetic studies were done in 7 patients whose ages ranged from 3 years 2 months to 13 years 1 month. Plasma concentrations of MK-0787 in 2 children were 19.6 and 20.0 micrograms/ml at 15 minutes and 5.6 and 2.1 micrograms/ml at 2 hours after a 10 mg/10 mg/kg intravenous 30-minute drip infusion of MK-0787/MK-0791. Plasma half-lives of MK-0787 were 1.52 and 0.74 hour, and total urinary recoveries were 54.6 and 71.4% during 0-6 hours. After a 20 mg/20 mg/kg intravenous 30-minute drip infusion into 2 other children, plasma concentrations of MK-0787 were 46.8 and 44.0 micrograms/ml at 15 minutes and 7.8 and 7.4 micrograms/ml at 2 hours. Plasma half-lives were 0.82 and 0.83 hour, and total urinary recoveries were 110.2 and 80.5% during 0-6 hours. Plasma concentrations of MK-0787 were less than 0.2, 0.2 and 1.2 micrograms/ml just before the next doses in 3 patients given 11-20 mg/11-20 mg/kg of MK-0787/MK-0791 every 6-8 hours. The time course of the plasma levels and urinary excretion in these patients were similar to those noted in the previous 4 patients following a single dose. Plasma concentrations of MK-0787 in a girl were 0.3 micrograms/ml just before the next dose and 8.2 micrograms/ml at 2 hours after multiple doses of 14 mg/14 mg/kg every 6 hours for 3 days and then 28 mg/28 mg/kg every 6 hours for 35 days.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical evaluation of imipenem/cilastatin sodium in gynecological infection

The MK-0787/MK-0791 is a combination of imipenem (a carbapenem antibiotic) and cilastatin sodium (a dehydro peptidase-I inhibitor) in a 1 to 1 ratio, which produces a higher urinary recovery of imipenem than imipenem alone. The MK-0787/MK-0791 was used in 8 female patients with intrapelvic infections. Clinical efficacies were very good in all the patients. There were neither subjective nor objective side effects nor abnormal laboratory findings.     

Clinical evaluation of imipenem/cilastatin sodium in the internal medicine

Fifty-two patients with moderate or severe infections associated with internal medicine were treated with imipenem/cilastatin sodium (IPM/CS) and the efficacy and the safety of this drug were evaluated. There were 20 patients with pneumonia, 10 with acute exacerbation of chronic respiratory tract infections, 9 with sepsis, 2 with pyothorax, 3 with intraabdominal infection, 2 with urinary tract infection, 1 with pulmonary abscess, 1 with infective endocarditis, 4 with fever of unknown origin. Forty-four patients were evaluable for the efficacy. Clinical efficacies were excellent in 12 patients, good in 26, fair in 3 and poor in 3. The overall clinical efficacy was 86.4%. The efficacy rate was 63.6% in patients previously treated and 93.9% in patients previously untreated with other antibiotics. Bacteriologically, Staphylococcus aureus (8 strains), Streptococcus pneumoniae (5), Streptococcus pyogenes (1), other Gram-positive coccus (1), Klebsiella pneumoniae (8), Haemophilus influenzae (4), Pseudomonas aeruginosa (3), Serratia marcescens (3), Escherichia coli (3), Branhamella catarrhalis (1), Citrobacter freundii (1), Klebsiella oxytoca (1), Enterobacter sp. (1), and Peptostreptococcus sp. (1) were eradicated. P. aeruginosa (3) and Acinetobacter sp. (1) decreased. S. aureus (1), S. epidermidis (1), P. aeruginosa (5), and S. marcescens (1) persisted or appeared. The eradication rate was 83.7%. Six patients showed adverse reactions including general fatigue 1, epigastralgia 1, eruption 1, eosinophilia 1 and elevation of S-GOT 2. But all of the adverse reactions were mild or slight, and transient. These findings indicate that IPM/CS is a useful and safe drug against bacterial infections in internal medicine.     

Clinical evaluation of imipenem/cilastatin sodium in the pediatric field

Imipenem/cilastatin sodium (MK-0787/MK-0791) was evaluated for its safety and efficacy in 7 pediatric patients with infections. The clinical efficacy ratio was 100 percent. No side effect was observed except for elevations of S-GOT and S-GPT and eosinophilia in 1 patient. It may be considered that MK-0787/MK-0791 is a safe and useful antibiotic for the treatment of pediatric infections.     

Clinical evaluation of intramuscular imipenem/cilastatin sodium in surgical infections]

A multi-center clinical study was carried out at the first Department of Surgery, Okayama University Medical School and its affiliated institutions to evaluate the efficacy and safety profiles of intramuscular imipenem/cilastatin sodium (IPM/CS) in surgical infections, which were mainly biliary tract infections and peritonitis. The following results were obtained: 1. The efficacy rate was 72.0% in a total of 25 evaluable patients and 81.8% in patients with cholecystitis. 2. The efficacy rates in patients with and without underlying diseases were 70.0% and 73.3%, respectively, and they were 71.4% in patients with mild or moderate infections and 75.0% in patients with severe infections. 3. Bacteriologically, the eradication rate was 100% for Gram-positive bacteria and 62.5% for Gram-negative bacteria, with an overall eradication rate of 78.6%. The eradication rate for monomicrobial infections was 71.4% and that for polymicrobial infections was 100%. 4. Out of 25 patients, one developed diarrhea as a drug-related adverse reaction, and laboratory abnormalities attributable to the treatment were observed in 5 patients. None of them was serious, however. 5. The overall usefulness rate was 60.0%, and the usefulness for cholecystitis (72.7%) was superior to that for cholangitis (33.3%).     

Clinical study of imipenem/cilastatin sodium in children with severe infections

Clinical studies of imipenem/cilastatin sodium (IPM/CS) were conducted in 40 pediatric patients. 29 out of the 40 patients were treated for infections and 11 for prophylaxis. The following results were obtained. 1. The response rate in 29 patients with infections was 79.3%. Among the 29 patients, 16 patients who presented with malignant diseases showed the response rate of 68.8%. The response rate was lower in patients with severe infections than in those with mild or moderate infections, and a lower response rate was associated with severe neutropenia. However, there were no differences in the response rates between patients who had previously been treated and those who had been untreated with other antibiotics. The response rate in 6 patients from whom causative organisms were isolated was 83.3% and that in the remaining 23 patients was 78.3%. 2. The response rate in 11 patients to whom IPM/CS was administered prophylactically was 63.6%. 3. As for side effects, a rash was observed in 1 patient and hematuria in another, and the abnormal laboratory test results observed were elevations of GOT and GPT in 1 patient. However, they were not clinically significant. From the above results, it appears that IPM/CS may be used as a drug of the first choice for the treatment of patients with severe infections in which the causative organisms are unknown, and for the prophylaxis of infection in patients with neutropenia.     

Clinical evaluation of therapy for aspiration pneumonia with imipenem/cilastatin sodium

In an open, prospective, multicenter trial the clinical efficacy of imipenem/cilastatin sodium (IPM/CS) for the treatment of 14 cases with aspiration pneumonia was investigated. The mean age was 75.4 years old. Diseases of central nervous system were present in 11 cases, cardiovascular diseases, pulmonary diseases and diabetes mellitus in 2 cases each respectively. Seven cases were community-acquired and another seven were hospital-acquired. Six cases were moderate and 8 cases were severe. Causative organisms were determined in 9 cases (64.3%), multiple causative organisms were isolated in 3 cases. Isolated organisms were Staphylococcus aureus (4), Pseudomonas aeruginosa (3), Klebsiella pneumoniae (3), Escherichia coli (1), Acinetobacter calcoaceticus (1). Detection of anaerobes was not attempted. Clinical effects of IPM/CS were excellent in 3, good in 8, fair in 2, poor in 1, the efficacy rate was thus 78.6%. P. aeruginosa was isolated from 2 out of 3 cases in which therapy with IPM/CS failed. Monotherapy with IPM/CS appears to be highly effective for cases of aspiration pneumonia, but the disease due to IPM-resistant P. aeruginosa is an exception.     

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)     

Pharmacokinetics of imipenem/cilastatin sodium in children with peritonitis.

Fifteen children (3-12 years) with peritonitis were given imipenem/cilastatin intravenously (15 or 25 mg/kg) every six hours for 3-14 days. One day during treatment days 2-8, multiple blood and urine samples were collected from each individual over a six hour dosing interval. Twelve children completed the study. The urinary recovery of imipenem and cilastatin averaged 50-70% of the administered dose. The plasma t1/2 for imipenem averaged 55 min. while that for cilastatin was even more rapid (approximately 38 min.). Little or no accumulation of either imipenem or cilastatin was observed for this regimen in this age group of paediatric patients. Steady state conditions prevailed within 2 days of initiation of therapy. The pharmacokinetics of imipenem and cilastatin in paediatric patients 3-12 years of age appear similar to those observed for adults.     

Clinical studies on imipenem/cilastatin sodium in pediatric field

Clinical studies on imipenem/cilastatin sodium (MK-0787/MK-0791) was carried out in 12 patients in pediatric field. The overall efficacy rate was 83.3%. As for adverse reaction, soft stool was observed in 1 patient. In clinical laboratory findings, there was 1 patient with granulocytopenia.     

Clinical studies on imipenem/cilastatin sodium in perinatal use

The clinical efficacy and the safety of imipenem/cilastatin sodium (IPM/CS) in perinatal infections were studied. The results are summarized below. 1. Clinical efficacy was evaluated in 12 patients with intrauterine infections (endometritis), 3 patients with amniotic fluid infections, 2 patients with puerperal fever and 3 patients with other infections. The drug was administered by intravenous drip infusion at a 0.5g to 1.0g dose as IPM and the total doses during an entire course of treatment were 1.5g to 15g. 2. Clinical efficacies were excellent in 4 (20%) and good in 16 patients (80%) and the efficacy rate was 100%. Ten patients had not improved upon treatments with other previous antibiotics. 3. Infective bacteria were eradicated in 4, decreased in 1, and replaced in 6 patients. 4. No side effects or abnormal clinical laboratory test values were observed in any patient.     

Clinical study of imipenem/cilastatin sodium in the perinatal period

A clinical study was carried out on imipenem/cilastatin sodium (IPM/CS) in the perinatal period, and the results obtained are summarized as follows. IPM/CS was given to 5 cases with puerperal intrauterine infection and 2 with puerperal fever. The clinical efficacies were evaluated as good in 6 cases and poor in 1. The clinical efficacy rate was 85.7%. In a bacteriological examination, 9 strains were isolated from 6 cases, and 7 strains were eradicated with an eradication rate of 77.8%. No side effects were observed in any of the cases treated with IPM/CS.     

Clinical evaluation of imipenem/cilastatin sodium against severe infections in patients with hematopoietic disorders

Sixty-eight patients with severe infections associated with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) and the efficacy and safety of this drug were evaluated. 1. Fifty-nine patients were evaluable for the efficacy. Clinical efficacies were excellent in 10 patients, good in 24, fair in 11 and poor in 14, and the overall efficacy rate was 57.6%. 2. The clinical efficacy rates were 62% against septicemia and suspected septicemia, 40% against pneumonia and 100% against urinary tract infection (1 case). 3. The clinical efficacy rates when these patients were grouped according to numbers of neutrophils after treatment were: less than 100/mm3; 44.4%, 101-500/mm3; 58.3% and over 501/mm3; 60.5%. The efficacy rate was particularly excellent, 60.0%, for patients with neutrophil counts were less than 100/mm3 both before and after treatment. 4. Sixty-eight patients were evaluable for the safety. Side effects were observed in 5 patients and abnormal laboratory test values were observed in 5 patients.     

Clinical studies on imipenem/cilastatin sodium in the perinatal period

Clinical studies were carried out on imipenem/cilastatin sodium (IPM/CS) in the perinatal period, and the results are summarized below. 1. IPM/CS was administered to a total of 10 patients including 7 with puerperal intrauterine infections and 3 with pyelonephritis at a dose of 0.5 g/0.5 g twice daily through intravenous drip infusion. IPM/CS showed satisfactory results. Clinical efficacies were excellent in 1 patient, good in 9 with an efficacy rate of 100%. 2. As for bacteriological evaluation, 12 strains out of 14 detected in 8 patients before the treatment were eradicated upon IPM/CS administration, with an eradication rate of 85.7%. The remaining 2 strains persisted. 3. Neither subjective and objective side effects nor abnormal laboratory test values were observed in any of the patients or their babies.     

Pharmacokinetics and clinical evaluation of imipenem/cilastatin sodium in pediatric surgery

Pharmacokinetic and clinical studies on imipenem/cilastatin sodium (IPM/CS) in pediatric surgery were performed and the results obtained are summarized below. 1. Plasma and urinary levels of IPM/CS were measured in 9 neonate patients following drip-infusion for 1 hour of IPM/CS (dose of IPM 10 mg/kg for 5 patients, 20 mg/kg for 4 patients). In the 10 mg/kg group, peak plasma levels were observed at the end of infusion or after 1 hour of it. IPM 9.95-14.2 micrograms/ml, CS 7.7-30.1 micrograms/ml. In the 20 mg/kg group, peak levels were found at the end of the infusion, IPM 39.2-41.7 micrograms/ml, CS 48.1-58.8 micrograms/ml. In both groups, plasma levels of IPM/CS decreased rapidly, and plasma half-lives (T 1/2) in the 20 mg/kg group were 0.9-1.2 hours (IPM) and 0.8-1.1 hours (CS). Urinary recovery rates were 17.7-28.7% (10 mg/kg), 21.1-36.9% (20 mg/kg) for IPM and 27.1-43.8% (10 mg/kg) and 21.5-76.5% (20 mg/kg) for CS. 2. Bile levels of IPM/CS were measured in 3 patients with congenital biliary atresia and 1 patient with neonatal hepatitis. Peak levels of IPM/CS in bile were noted 1 hour after the end of infusion, and they were 3.01-12.3 micrograms/ml for IPM, and 2.5-13.1 micrograms/ml for CS. Recovery rates in bile in 7 hours after the end of infusion were 0.03-0.12% (IPM), 0.01-0.12% (CS). 3. IPM/CS was administered to 9 patients as prophylaxis against postoperative infections and to 2 patients with postoperative cholangitis. No infectious complications were observed in patients after the prophylactic use. In 1 patient with cholangitis, clinical effect was good and organisms were eradicated. No clinical or laboratory adverse reactions due to the administration of IPM/CS were noted. It is concluded that IPM/CS is an effective and safe antibiotic in pediatric surgery.     

Clinical study on imipenem/cilastatin sodium in the field of pediatrics

Imipenem/cilastatin sodium (MK-0787/MK-0791) was administered to pediatric patients with infections, and the following results were obtained. Pharmacokinetic study Two children, 11 years of age (38 kg body weight) and 3 years of age (15.5 kg body weight), were administered by 30 minutes intravenous drip infusion a single dose of 500 mg/500 mg (13.2 mg/13.2 mg per kg) and 250 mg/250 mg (16.1 mg/16.1 mg per kg) of MK-0787/MK-0791, respectively. Serum concentrations of MK-0787 reached their peaks at the end of drip infusion at a value of 56.33 micrograms/ml and 55.98 micrograms/ml, respectively. Concentrations of the drug decreased as the time after the administration increased, and they reached 0.14 microgram/ml and 0.12 microgram/ml, respectively in the older and the younger children at 6 hours after the administration. Half-lives (T 1/2) of the drug in serum were calculated to be 1.21 hours and 1.04 hours, respectively. The concentration of the drug in cerebrospinal fluid for the 11 years old was 0.52 microgram/ml 2 hours after the drip infusion and the serum concentration at the time was 4.02 micrograms/ml. Peak serum concentrations of MK-0791 in the 2 children were 53.73 micrograms/ml and 22.99 micrograms/ml, respectively, at the end of drip infusion. After 1 hour, the serum concentration of the drug decreased to 10.54 micrograms/ml in 1 case and not detectable in the other case. Urinary recovery rates of MK-0787 in 6 hours after the drip infusion was 82.9% and 63.6% in the 2 children and those of MK-0791 were 57.9% and 74.6%. Clinical study Clinical studies on MK-0787/MK-0791 were carried out in 6 pediatric patients; 1 each with femoral cellulitis, sepsis suspected, salmonellosis, acute tonsillitis, bronchopneumonia and streptococcosis. Lengths of treatment were 2 2/3-4 days for 5 cases and 6 days for 1 case. The patients were treated by 30-60 minutes intravenous drip infusions twice a day for 1 case, and 3 times a day for 5 cases at daily doses of 54.5-66.7 mg/kg. The treatment was effective in all cases, with 3 cases judged excellent and 3 cases good. The safety of the drug was studied in 7 patients. No side effects nor clinically abnormal values were observed in any cases.     

Fundamental and clinical evaluation of imipenem/cilastatin sodium in the perinatal period

To evaluate the efficacy of imipenem/cilastatin sodium (IPM/CS) in the field of obstetrics and gynecology, fundamental (measurement of IPM/CS concentrations in mothers' milk) and clinical studies were performed. Concentrations of IPM/CS in mothers' milk were measured every 1 hour up to 6 hours after a 30-minute drip infusion of 500 mg/500 mg of IPM/CS. IPM/CS was distributed similarly to other cephalosporins. In the clinical study, a 500 mg/500 mg dose of IPM/CS was administered to 5 patients with puerperal intrauterine infections and to 3 patients with urinary tract infections by a 30-minute drip infusion b.i.d. or t.i.d. Good responses were observed in all 8 patients, though the infections were mild or moderate. From these results, IPM/CS appeared to be a useful drug for the treatment of perinatal infections.     

Pharmacokinetic and clinical evaluation of imipenem/cilastatin sodium in neonates and premature infants. A study of imipenem/cilastatin sodium by a perinatal co-research group

Pharmacokinetics and clinical studies of imipenem/cilastatin sodium (IPM/CS), a combined preparation of a new carbapenem antibiotic and a dehydropeptidase-I inhibitor, respectively, were carried out in neonates and premature infants in a joint study by a co-research group. 1. Peak blood levels of IPM/CS when administered at 10 mg/10 mg/kg or 20 mg/20 mg/kg by 30- or 60-minute intravenous drip infusion were achieved at the end of infusion. A dose response was clearly observed between the doses and the peak levels achieved. 2. The areas under the blood concentration time curve (AUC) of CS were greater than those of IPM in most patients. Blood half-lives of IPM and CS tended to be longer in younger neonates and premature infants than in older subjects. The blood half-life of CS tended to be longer than that of IPM. 3. Cumulative urinary recovery rates of CS were greater than those of IPM, cumulative urinary recovery rates tended to be greater in older neonates and premature infants than younger subjects. 4. One hundred and thirteen patients were treated for bacterial infections with IPM/CS and 32 patients were treated prophylactically. Daily doses of IPM/CS ranged from 9 mg/9 mg/kg to 150 mg/150 mg/kg. 5. Clinical efficacies of IPM/CS were evaluated in a total of 56 patients with identified etiologic pathogens. The efficacy rate was 98.2% with 33 patients rated as excellent, 22 patients as good and 1 patient as fairly good. (Diagnoses were sepsis in 10 patients and meningitis in 2 patients, etc.) Fifty-seven patients with no identified etiologic pathogens were rated as excellent for 22 patients, good for 34 patients and fairly good for 1. The efficacy rate in these patients was 98.2%. Thirty-two patients were treated prophylactically and the results obtained were satisfactory. 6. Bacteriologically, the eradication rate was 94.5% in 56 patients; i.e., 52 were eradicated, 2 were decreased, 1 persisted and 1 was unknown. 7. Adverse effects were observed in 7 (4.4%) of 160 patients, i.e., 2 patients had diarrhea and 2 patients had rash, etc. Abnormal laboratory data considered related to the therapy occurred in 28 (17.6%) of 159 patients, with 10 patients with eosinophilia (6.3%) and elevation of GOT and/or GPT, etc. All these were non serious, and all values returned to normal after discontinuance of therapy. An abnormal prothrombin (PIVKA II) was observed in 1 of 10 patients tested.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical evaluation of imipenem/cilastatin sodium against severe infections complicating hematological disorders and solid tumors

Imipenem/cilastatin sodium (IPM/CS) was administered to a total of 67 patients with severe infections complicating hematological disorders and solid tumors. Fifty patients are included in the present analysis of efficacy and 64 in that of safety. 1. Out of 31 patients with hematological disorders, responses were excellent in 10 patients, good in 10 patients, and the efficacy rate was 64.5%. Out of 19 patients with solid tumors, responses were excellent in 8 patients, good in 8 patients and the efficacy rate was 84.2%. 2. For patients whose responses to other antibiotics had been poor, the efficacy rate was 59.3% in the group with hematological disorders and 62.5% in the group with solid tumors. 3. The relationship between the neutrophil count and efficacy was studied in the patients with hematological disorders. The efficacy rate for 8 patients whose neutrophil counts were 500/mm3 or less was 75.0%. 4. For the patients with hematological disorders, the efficacy rate for patients from whom causative organisms were isolated was 70.0% and that for patients for whom they were unknown was 61.9%. 5. Adverse reactions were observed in 3 patients and abnormal laboratory test results in 2 patients. However, they were mild and disappeared after discontinuation of this drug. From these results, IPM/CS is considered to be a useful antibiotic for the treatment of severe infections complicating hematological disorders and solid tumors.     

Clinical evaluation of imipenem/cilastatin sodium against infections in compromised children (malignancy, hematological disease, collagen disease)]

Eighteen immuno-compromised children (malignancies, hematological diseases, collagen diseases) with neutropenia and infections were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and the safety of the drug were evaluated. 1. Responses to IPM/CS were excellent in 13 patients, good in 1, and fair in 4. None of the patients displayed a poor response to the treatment thus the efficacy rate was 77.8%. 2. Of 5 patients with sepsis, 4 had excellent or good responses. IPM/CS was effective against sepsis caused by Enterococcus faecalis and Pseudomonas aeruginosa. 3. In patients with severe neutropenia (WBC less than 100/mm3), the efficacy rate was 70%. 4. As for side effects, elevations of GOT and GPT were observed in 1 patient with liver cirrhosis. These results indicate that IPM/CS is safe and effective in immuno-compromised children with neutropenia and infections.