Abstract: Dipylidium caninum, the dog tapeworm, is a common intestinal cestode of domestic dogs and cats, but few cases have been reported of human infection by this parasite in Japan. We repot a case of D. caninum infection in a 17 month-old girl, who sometimes had symptoms of abdominal pain, diarrhea, and dysphoria at night. Her mother noted the appearance of small white worms in her stool, and she was seen by a local pediatrician. Despite antiparasitic therapy wiht pyrantel pamoate, the problem persisted and was eventually referred for further workup to Kurume University Hospital. The diagnosis was made by microscopic examination of the excreted proglottids, which contained characteristic egg capsules. She was successfully treated with a singledose of praziquantel and four adult parasites were recovered. The longest intact worm was 32cm. Her family had household pets (a dog and a cat). The pets were seen by the local veterinary and both were evidenced D. caninum. Humans, primarily children, become infected when they accidentally ingest fleas. Parents usually find proglottids as multiple white objects, often described as cucumber, melon, or pumpkin seeds, in stool, diapers, or on the perineum. Most general practitioners and pediatricians may treat children with enterobiasis (pinworm) infection, and in case the treatment fails, other parasite infection should be considered such as this worm. A history of dog or cat pets, fleas, and flea bites may be important clues to diagnosis. Pets found to be infected should also be treated.

Abstract: Clinical isolates of Haemophilus influenzae from Japan (n = 296) and the United States (n = 100) were tested by the microdilution method for susceptibility in vitro to 10 beta-lactam antibiotics and molecular mechanisms of beta-lactam resistance. For all isolates, PCR was used to identify six elements, including beta-lactamase-producing ampicillin (AMP)-resistance (BLPAR) and beta-lactamase-nonproducing AMP-resistance (BLNAR) genes as follows: (1) TEM-1 type beta-lactamase gene, (2) ROB-1 type beta-lactamase gene, (3) part of normal ftsI gene encoding PBP3, which is involved in septal peptidoglycan synthesis, (4) a portion of the ftsI gene possessing some amino acid substitutions commonly detected in BLNAR strains, (5) p6 gene encoding P6 membrane proteins specific to H. influenzae, and (6) serotype b capsule gene. In Japanese and U.S. isolates, respective prevalences of each resistance class in Japan and the United States were 55.1% and 46% for beta-lactamase-nonproducing, AMP-susceptible (BLNAS); 3.0% and 26% for the TEM-1 type beta-lactamase gene; 0% and 10% for the ROB-1 type; 26.4% and 13% for low-BLNAR with a low degree of AMP resistance; and 13.2% and 0% for BLNAR strains. A few remaining isolates were beta-lactamase-producing strains with a mutation in the ftsI gene. MICs of all beta-lactam agents against low-BLNAR strains were 2-8 times higher than against BLNAS. MICs of cephalosporin antibiotics against BLNAR strains were 16-32 times higher than against BLNAS. The rank order of beta-lactam MIC90 values against BLNAR strains was piperacillin = ceftriaxone = cefditoren (0.25 microg/ml), meropenem (0.5), cefotaxime (1), AMP = cefpodoxime (8), cefdinir (16), amoxicillin (16), and cefaclor (64). Serotype b isolates were few in both countries (2.4% in Japan, 3% in the United States). Differences in proportions of respective AMP-resistant genes in H. influenzae isolates between the two countries might reflect differences in antibiotic agents ordinarily given to outpatients with community-acquired bacterial infections.

Abstract: Among 1,011 recently isolated Streptococcus pyogenes isolates from 10 Central and Eastern European centers, the MICs at which 50% of isolates are inhibited (MIC(50)s) and the MIC(90)s were as follows: for telithromycin, 0.03 and 0.06 microg/ml, respectively; for erythromycin, azithromycin, and clarithromycin, 0.06 to 0.125 and 1 to 8 microg/ml, respectively; and for clindamycin, 0.125 and 0.125 microg/ml, respectively. Erythromycin resistance occurred in 12.3% of strains. Erm(A) [subclass erm(TR)] was most commonly encountered (60.5%), followed by mef(A) (23.4%) and erm(B) (14.5%). At <0.5 microg/ml, telithromycin was active against 98.5% of the strains tested.

Abstract: The macrolide and levofloxacin susceptibilities of 992 isolates of Streptococcus pneumoniae from clinical specimens collected in 1999 and 2000 were determined in 10 centers in Central and Eastern European countries. The prevalences of penicillin G-intermediate (MICs, 0.125 to 1 microg/ml) and penicillin-resistant (MICs, < or =2 microg/ml) Streptococcus pneumoniae isolates were 14.3 and 16.6%, respectively. The MICs at which 50% of isolates are inhibited (MIC(50)s) and the MIC(90)s of telithromycin were 0.016 and 0.06 microg/ml, respectively; those of erythromycin were 0.06 and >64 microg/ml, respectively; those of azithromycin were 0.125 and >64 microg/ml, respectively; those of clarithromycin were 0.03 and >64 microg/ml, respectively; and those of clindamycin were 0.06 and >64 microg/ml, respectively. Erythromycin resistance was found in 180 S. pneumoniae isolates (18.1%); the highest prevalence of erythromycin-resistant S. pneumoniae was observed in Hungary (35.5%). Among erythromycin-resistant S. pneumoniae isolates, strains harboring erm(B) genes (125 strains [69.4%]) were found to be predominant over strains with mef(E) genes (25 strains [13.4%]), L4 protein mutations (28 strains [15.6%]), and erm(A) genes (2 strains [1.1%]). Similar pulsed-field gel electrophoresis patterns suggested that some strains containing L4 mutations from the Slovak Republic, Bulgaria, and Latvia were clonally related. Of nine strains highly resistant to levofloxacin (MICs, >8 microg/ml) six were isolated from Zagreb, Croatia. Telithromycin at < or =0.5 microg/ml was active against 99.8% of S. pneumoniae isolates tested and may be useful for the treatment of respiratory tract infections caused by macrolide-resistant S. pneumoniae isolates.

Abstract: Antipneumococcal activity of BMS 284756 was compared to those of six agents by MIC and time-kill methodologies. BMS 284756 had the lowest MICs compared to those of ciprofloxacin, levofloxacin, and moxifloxacin against quinolone-susceptible (< or =0.016 to 0.06 microg/ml) and quinolone-resistant (0.03 to 1 microg/ml) pneumococci. BMS 284756 was bactericidal against 11 of 12 strains at two times the MIC after 24 h.

Abstract: Among 585 Streptococcus pneumoniae strains isolated in 22 Croatian hospitals 21 strains (3.6%) were quinolone nonsusceptible. MICs of all quinolones were high for seven strains tested with the same serotype (23F) and mutations in gyrA, parC, and parE. The remaining 14 strains were more heterogeneous and had mutations only in parC and/or parE, and the MICs of quinolones were lower for these strains.

Abstract: Amino acid alterations in or flanking conserved motifs making up the active binding sites of penicillin-binding proteins (PBPs) 1a, 2b, and 2x of pneumococci were correlated with changes in affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor for these PBPs. Four penicillin-susceptible (PSSP), eight penicillin-intermediate (PISP), and six penicillin-resistant (PRSP) pneumococci were studied by DNA sequencing of the penicillin-binding sites of the pbp1a, -2x, and -2b genes of strains and by determining 50% inhibitory concentrations of the seven agents for PBP1a, -2x, and -2b. Two PSSP strains had alterations in PBP2x (L(546)-->V) (one strain) or PBP2b (T(445)-->A) (one strain). All eight PISP strains had at least two alterations--T(338)-->P or A or H(394)-->Y in PBP2X and T(445)-->A in BPB2b. All PRSP strains had the same changes seen in PISP strains, as well as T(371)-->A or S substitutions in PBP1a. The two most resistant PRSP strains had a second change in PBP2x (M(339)-->F) in a conserved motif. The affinities of penicillin and ampicillin for all three PBPs were decreased for PRSP and most PISP strains. The affinity of amoxicillin for PBP1a and -2x was decreased only for PRSP. Cefaclor and cefprozil showed decreased affinity of PRSP but not PISP for all three PBPs. Cefuroxime showed decreased affinity of PISP and PRSP for PBP1a and -2x but no change for PBP2b. Cefditoren showed no difference in PBP affinity based on penicillin or cefditoren MICs, indicating a different PBP target for this agent. Overall, the MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.

Abstract: The activity of cefditoren and six other cephalosporins was tested against 250 pneumococci, including strains resistant to macrolides and quinolones. Cefditoren gave the lowest MICs, with MIC(50) and MIC(90) values of < or =0.016/0.03, 0.125/0.5 and 0.5/2.0 mg/L for penicillin-susceptible, -intermediate and -resistant pneumococci, respectively. A time-kill study of 12 pneumococcal strains with varying drug susceptibilities showed that cefditoren, at 2 x MIC, gave 99% killing of all strains after 12 h, with 99.9% killing after 24 h. Other cephalosporins gave similar kill kinetics but at higher concentrations. Against 160 Haemophilus influenzae, cefditoren had the lowest MICs (MIC(50) and MIC(90) both < or =0.016 mg/L), irrespective of beta-lactamase production. Time-kill studies of cefditoren compared with five other oral cephalosporins showed that cefditoren, at 8 x MIC, was bactericidal against 8/9 strains and gave 90% killing of all strains at the MIC after 12 h. Activity was bactericidal (99.9% killing) after 24 h with all drugs tested. Multistep studies of four penicillin-susceptible, four penicillin-intermediate and four penicillin-resistant strains showed that cefditoren, co-amoxiclav and cefprozil did not select for resistant mutants after 50 subcultures, compared with cefuroxime and azithromycin, where resistant mutants were selected in two and nine strains, respectively. Single-step mutation studies showed that cefditoren, at the MIC, had the lowest frequency of spontaneous mutants compared with other drugs.

Abstract: Single- and Multi-step selection studies were used to test the ability of BMS-284756, ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin to yield resistant clones from 12 quinolone-susceptible and -resistant Streptococcus pneumoniae strains. Although all quinolones selected, to a greater or lesser degree, for resistant clones with mutations usually in parC or gyrA, BMS-284756 tended to select for resistant clones at a lower rate than other quinolones studied.

Abstract: OBJECTIVE: Two clinical strains of Streptococcus pyogenes, 237 and 544, one isolated in Slovakia and the other in Croatia, that were resistant to azithromycin (MIC 8 and 2 mg/L, respectively) but susceptible to erythromycin (MIC 0.5 and 0.12 mg/L, respectively) did not contain any gene known to confer macrolide resistance by ribosomal modification (erm gene) or efflux [mef(A) and msr(A) genes]. The aim of the study was to determine the mechanisms of macrolide resistance in both strains. METHODS: Portions of genes encoding ribosomal proteins L22 and L4, and 23S rRNA (domains II and V) in the two macrolide-resistant strains and in control strains susceptible to macrolides, were analysed by PCR and single-strand conformational polymorphism, to screen for mutations. The DNA sequences of amplicons from resistant strains that differed from those of susceptible strains, in terms of their electrophoretic migration profiles, were determined. RESULTS: S. pyogenes 237 displayed a KG insertion after position 69 in ribosomal protein L4. S. pyogenes 544 contained a C2611U mutation in domain V of 23S rRNA. CONCLUSION: Mutations at a similar position in ribosomal protein L4 and 23S rRNA have been reported previously in macrolide-resistant pneumococci. This report shows that similar mutations can be found in macrolide-resistant S. pyogenes.

Abstract: NCCLS agar dilution was used to test activity of telithromycin compared to clarithromycin, penicillin G, ciprofloxacin, levofloxacin, sparfloxacin and moxifloxacin against 26 pneumococci with defined quinolone resistance (type II topoisomerase and efflux) mechanisms. Thirteen strains were penicillin susceptible, six intermediate and seven resistant. Clarithromycin resistance (mef and/or erm) was seen in eight strains. Ciprofloxacin MICs (mg/L) were 8-64 compared to 1-32 (levofloxacin), 0.5 . or = 32 (sparfloxacin) and 0.125-4 (moxifloxacin). Telithromycin MIC50 and MIC90 values (mg/L) were 0.016 and 0.25, with only one strain having an MIC of 2 mg/L.

Abstract: MICs of penicillin G and other drugs and serotypes were determined for 218 strains of Streptococcus pneumoniae isolated from children in southwestern Japan. Twenty-one (9.6%) and 81 (37.2%) isolates were penicillin-resistant (MIC >/=2.0 microg/ml) and intermediate (MIC 0.13-1.0 microg/ml), respectively. Panipenem was most active parenteral agent against penicillin-intermediate (MIC(90) 0.125 microg/ml) and -resistant strains (MIC(90) 0.25 microg/ml). Among oral beta-lactam agents, cefditoren had good activity against penicillin-intermediate and resistant strains (MIC(90) 0.5/1.0 microg/ml). Serogroup 6 was the most prevalent (65/218) among all strains and 19F (44 strains) was the most prevalent among penicillin-intermediate and -resistant strains. Both pbp2b resistant and susceptible genes were found in penicillin-intermediate strains. Pbp2x resistant genes were found in 33 of 80 (41.3%) cefotaxime-susceptible strains. These results suggest that possible resistance mechanisms may occur even in drug susceptible strains and that drug susceptibility survey should be updated carefully in Japan.

Abstract: BACKGROUND: Sepsis remains lethal to children. At our institution, we have noted that approximately 2% of all hospitalized patients have had sepsis. In the present study, we analyzed episodes of sepsis that occurred in our ward. METHODS: Sepsis that occurred in our institution between January 1984 and December 1998 was reviewed and analyzed. RESULTS: Three hundred and sixty-six episodes of sepsis in 244 admitted patients were analyzed. Sepsis occurred in approximately 2% of all hospitalized patients. Forty-three of 244 patients were under 1 year of age. Eighty-seven percent (212/244) of cases had underlying diseases. Hematologic disorders or neoplasms were the most common underlying disease, comprising 55% of all patients (133/244). Two-hundred and fifty-one of 366 episodes of sepsis were acquired during hospitalization. We identified 409 causative agents. There were 25 polymicrobial infections (25/366; 7%). Gram-positive bacteria comprised 68% of all organisms (280/409). Staphylococcus aureus was the most common organism, comprising 18% of causing agents (75/409). Sixty-six organisms came from the insertion of a central venous catheter. Eighty-one patients experienced recurrent episodes of sepsis. In terms of complications, respiratory distress was the most common complication (36 episodes) and there were 15 episodes of shock. Thirty-seven patients died of sepsis. Sepsis caused by Gram-negative bacteria showed significantly higher mortality than Gram-positive bacteria (11/43 (26%) vs 15/146 (10%); P= 0.053). CONCLUSIONS: In our institution, approximately 20% of septic patients were under 1 year of age and 90% had underlying diseases. The causative agents of sepsis affected the outcome.

Abstract: A 8-year old Japanese boy who returned from Tanzania was admitted to our hospital because of fever, vomiting, and headache. He was diagnosed as a Plasmodium falciparum infection verified by a blood smear. He was treated with quinine and halofantrine, and recovered completely. Malaria infection should be considered when patients return from Malaria endemic areas.

Abstract: A drug susceptibility test of the combination drug TAZ/PIPC, which consists of a newly developed beta-lactamase inhibitor, tazobactam (TAZ), and one of penicillin antibiotics, piperacillin (PIPC), with combination ratio of 1:4 in potency, was conducted with stock strains and clinical isolates. The clinical efficacy and safety of its injection was also evaluated in children with a variety of infectious diseases. The results were as follows: 1. In susceptibility test, 114 strains from 4 species of stock strains were treated with 8 drugs, that is, TAZ/PIPC, PIPC, penicillin G (PCG), ampicillin (ABPC), cefotiam (CTM), cefotaxime (CTX), ceftazidime (CAZ), and sulbactam/cefoperazone (SBT/CPZ). Of three clinically isolated species from patients, Staphylococcus aureus (S. aureus) was treated with TAZ/PIPC, PIPC, methicillin (DMPPC), CTM, CTX, and SBT/CPZ, and the others were treated with the same drugs except for DMPPC. The MICs were measured for these bacterial strains inoculated at the concentration of 10(6) CFU/ml. The MIC90 values of TAZ/PIPC against 45 strains of Streptococcus pyogenes (S. pyogenes), one of the stock cultures of Gram-positive cocci, were 0.05 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. The MICs of TAZ/PIPC for 28 strains of Streptococcus agalactiae (S. agalactiae) were 0.39 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. As for Gram-negative bacilli, the MIC90 of TAZ/PIPC against 10 strains of Bordetella pertussis (B. pertussis) were 0.10 microgram/ml and similar to those of PIPC. The MIC90 of TAZ/PIPC against 31 strains of Haemophilus influenzae (H. influenzae) were 0.05 microgram/ml and similar to those of PIPC, CTX, and SBT/CPZ. Regarding Gram-positive cocci isolated from patients received this combination drug, the MIC90 of TAZ/PIPC against 2 strains of S. aureus, a non beta-lactamase producing strain and a low-beta-lactamase producing strain, were 0.78 microgram/ml and 3.1 micrograms/ml, respectively; the former value was similar to those of PIPC, DMPPC, CTM, and CTX, and the latter was similar to those of PIPC, DMPPC, CTX, and SBT/CPZ. Of 4 strains of Streptococcus pneumoniae, 2 strains were inhibited at 0.05 microgram/ml, and the others at 1.56 micrograms/ml; both values were similar to those of PIPC, SBT/CPZ. As for Gram-negative bacilli, 6 of 7 strains of H. influenzae did not produce beta-lactamase and 1 strain was a high producer. The MICs of TAZ/PIPC against beta-lactamase nonproducing strains were < or = 0.025 microgram/ml in 5 strains and 0.39 microgram/ml in 1 strain, and the values were similar to those of PIPC and SBT/CPZ. While the MIC of TAZ/PIPC against the high beta-lactamase producing strain was 0.78 microgram/ml; similar to that of SBT/CPZ and smaller than that of PIPC. 2. The results of clinical effects on 7 diseases in 33 cases were as follows: TAZ/PIPC was clinically judged "excellent" in 17 (51.5%); good in 14 (42.4%); fair in 2 (6.1%). No case with no response was seen in this study, and the total efficacy rate of "excellent" and "good" was 93.9%. 3. Bacteriological effects were evaluated in 17 strains of 4 species, and all of them were eradicated. 4. Adverse reactions were judged in 35, which consisted of 33 in which the clinical effects were evaluated and 2 dropped from this study. Of these cases, diarrhea was observed in 4 (11.4%). 5. Laboratory tests revealed an increase in platelets in 1 of 32 cases (3.1%), and eosinophilia in 2 of 29 cases (6.9%). Biochemical profile showed an increase in GPT alone and abnormal increases in both GOT and GPT in 1 each out of 21 cases.

Abstract: A retrospective clinical study of 64 cases with bacterial meningitis beyond the neonatal period in the department of pediatrics of St. Mary's Hospital (1985-1995) was conducted. Haemophilus influenzae (H. influenzae) (28 cases, 43.8%) and Streptococcus pneumoniae (S. pneumoniae) (23 cases, 35.9%) were common pathogens. The prognosis was classified into three groups; normal (42 cases, 65.6%), neurological sequelae (17 cases, 26.6%) and death (5 cases, 7.8%). We analyzed the risk factors associated with their outcome. The body temperature at admission, platelet count, CSF examination (WBC, glucose, GOT, GPT) were prognostic factors. The prognosis of bacterial meningitis caused by S. pneumoniae was worse than those due to H. influenzae (p = 0.0347).

Abstract: Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC than AZM against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections. AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was evaluated in 23 patients with five different infections. AZM was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different bacteria. 6. As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7. As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and GPT, one with increased GPT. They were all on fine granular form of AZM. As far as abnormalities found in patients administered with AZM in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.

Abstract:

Abstract: During August and September, 1992, we experienced 4 cases of Hansenula anomala (H. anomala, synonym Pichia anomala) fungemia in immunocompromised patients. Two patients had been suffering from a malignant disease, 3 of them had received broad-spectrum antibiotics and a central venous catheter (CVC) had been inserted in all of them. H. anomala was isolated as the sole pathogen from all 4 patients. Three of them responded favorably to fluconazole after withdrawal of the catheter, but one failed. H. anomala should be considered as a possible cause of catheter-related infections.

Abstract: It is not exaggeration to say that infectious meningitis is most often seen among infections of the nervous system caused by various microorganisms, in which viruses are main causative pathogens. Infectious meningitis due to bacteria includes purulent one with acute progress, tuberculous and fungal ones which are representative for subacute meningitis. They can not be easily treated. As brain abscess is similar to them, diagnosis and chemotherapy on these four diseases are briefly summarized here. It is needless to say that the prognosis is influenced by early diagnosis and how fast appropriate chemotherapy is started in all four diseases. Dexamethasone therapy should be tried in purulent meningitis in order to decrease hearing disturbance which is unable to be prevented by chemotherapy.

Abstract: A case of uncommon iritis due to Chlamydia pneumoniae (C. pneumoniae) is reported. The patient was a 9-year-old boy who had suffered from cough, pharyngeal pain, and low grade fever. The symptoms persisted for more than 1 month in spite of an oral cephem antibiotic. Ophthalmalgia, congestion around the iris and cough had lasted with alleviation and exacerbation. A diagnosis of C. pneumoniae infection was made by specific polymerase chain reaction (PCR) method and microimmunofluorescence test (MIF). The symptoms subsided with administration of clarithromycin (CAM: 300 mg/day) for 2 weeks. Because of the simultaneous alleviation of iritis, C. pneumoniae infection was considered to introduce the iritis. Much remains to be clarified about this pathogenesis of iritis and more detailed evaluations are required.

Abstract: Flomoxef (FMOX), an oxacephem antibiotic of beta-lactam antibiotic family, was administered to 16 infants including 6 neonates and 10 premature infants at a dose of 20 or 40 mg/kg via intravenous injection, and plasma and urinary concentrations and the urinary recovery were determined. In addition, FMOX was administered via intravenous injection at daily doses averaging 85.5 mg/kg divided into 2 to 4 times for durations averaging 9 days to 96 infants from 0- to 90-day old (mainly neonates and premature infants). In 44 of the 96 infants with bacterial infections, clinical and bacteriological efficacies were evaluated, and prophylactic effects of FMOX were determined in the remaining 52 infants. Adverse reaction and laboratory tests abnormalities were evaluated also. The obtained results are summarized as follows. 1. Upon administration of FMOX at 20 or 40 mg/kg to neonates and premature infants via intravenous injection, plasma concentrations, half-lives and AUC were determined. In 3 neonates of 5, 7 and 16 days of ages administered with 20 mg/kg of FMOX, peak plasma concentrations of 62.5 to 99.7 micrograms/ml were achieved in 5 or 15 minutes after injection. Half-lives of FMOX in these neonates were 1.48 to 1.78 hours and AUC's were 112 to 161 micrograms.hr/ml. The same dose (20 mg/kg) of FMOX was administered to 3 premature infants of 5- 16- and 19-day of ages and initial blood samples were obtained at 5 minutes after injection from the 5-day old subject and at 15 minutes after injection from the 16-and 19-day old subjects. Peak plasma concentrations of 63.6 to 79.9 micrograms/ml were observed in the samples. Half-lives were 1.69 to 2.20 hours and AUC's were 174 to 201 micrograms.hr/ml. When 3 neonates (one 17-day old and two 24-day old subjects) were administered with 40 mg/kg of FMOX, peak plasma concentrations obtained at 5 minutes after injection were 99.7 to 122.0 micrograms/ml. Half-lives were 1.28 to 1.92 hours and AUC's were 170 to 357 micrograms.hr/ml.(ABSTRACT TRUNCATED AT 400 WORDS)