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We compared the duration of fever in children infected with A(H1N1)pdm09, A(H3N2), or influenza B viruses following treatment with baloxavir marboxil (baloxavir) or neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, or laninamivir). This observational study was conducted at 10 outpatient clinics across 9 prefectures in Japan during the 2012-2013 and 2019-2020 influenza seasons. Patients with influenza rapid antigen test positive were treated with one of four anti-influenza drugs. The type/subtype of influenza viruses were identified from MDCK or MDCK SIAT1 cell-grown samples using two-step real-time PCR. Daily self-reported body temperature after treatment were used to evaluate the duration of fever by treatment group and various underlying factors. Among 1742 patients <19 years old analyzed, 452 (26.0%) were A(H1N1)pdm09, 827 (48.0%) A(H3N2), and 463 (26.0%) influenza B virus infections. Among fours treatment groups, baloxavir showed a shorter median duration of fever compared to oseltamivir in univariate analysis for A(H1N1)pdm09 virus infections (baloxavir, 22.0 h versus oseltamivir, 26.7 h, P < 0.05; laninamivir, 25.5 h, and zanamivir, 25.0 h). However, this difference was not significant in multivariable analyses. For A(H3N2) virus infections, there were no statistically significant differences observed (20.3, 21.0, 22.0, and 19.0 h) uni- and multivariable analyses. For influenza B, baloxavir shortened the fever duration by approximately 15 h than NAIs (20.3, 35.0, 34.3, and 34.1 h), as supported by uni- and multivariable analyses. Baloxavir seems to have comparable clinical effectiveness with NAIs on influenza A but can be more effective for treating pediatric influenza B virus infections than NAIs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronavirus family that also includes endemic human coronaviruses (HCoVs) types OC43, HKU1, 229E, and NL63. HCoVs share extensive sequence homology with SARS-CoV-2. It has been assumed that HCoV infection occur primarily in winter and spring in Japan before the coronavirus disease 2019 (COVID-19) pandemic and that its frequency is the same for all age groups., Methods: Nasopharyngeal swab samples were collected for HCoVs and SARS-CoV-2. All medical data were retrospectively analyzed. Our primary objective was to describe the epidemiology of HCoV in the Furano, Japan during the COVID-19 pandemic. Our secondary objective was to compare the prevalence of HCoV with that of SARS-CoV-2., Results: From September 2020 to August 2022, 113 (6.2 %) of 1823 cases were positive for any HCoV. The HCoV-NL63 activity peaked in January-March 2021. The HCoV-OC43 activity peaked in June-August 2021. HCoVs were mostly detected at age ≤11 years and most frequently at age ≤2 years. HCoVs showed high detection in 2021, while SARS-CoV-2 showed moderate detection in 2020-2021, but significantly increased in 2022., Conclusions: During the COVID-19 pandemic, HCoV-OC43 activity peaked in the summer. The frequency of HCoV infection varied widely by age group and was higher among those aged ≤11 years. These were different from those reported before the COVID-19 pandemic. These findings suggest that the disease dynamics of HCoVs remain unclear and that continued surveillance is essential in the post-COVID-19 pandemic., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: This study assessed the differences in daily virus reduction and the residual infectivity after the recommended home stay period in Japan in patients infected with influenza and treated with baloxavir (BA), laninamivir (LA), oseltamivir (OS), and zanamivir (ZA)., Methods: We conducted an observational study on children and adults at 13 outpatient clinics in 11 prefectures in Japan during seven influenza seasons from 2013/2014 to 2019/2020. Virus samples were collected twice from influenza rapid test-positive patients at the first and second visit 4-5 days after the start of treatment. The viral RNA shedding was quantified using quantitative RT-PCR. Neuraminidase (NA) and polymerase acidic (PA) variant viruses that reduce susceptibility to NA inhibitors and BA, respectively, were screened using RT-PCR and genetic sequencing. Daily estimated viral reduction was evaluated using univariate and multivariate analyses for the factors such as age, treatment, vaccination status, or the emergence of PA or NA variants. The potential infectivity of the viral RNA shedding at the second visit samples was determined using the Receiver Operator Curve based on the positivity of virus isolation., Results: Among 518 patients, 465 (80.0%) and 116 (20.0%) were infected with influenza A (189 with BA, 58 with LA, 181 with OS, 37 with ZA) and influenza B (39 with BA, 10 with LA, 52 with OS, 15 with ZA). The emergence of 21 PA variants in influenza A was detected after BA treatment, but NA variants were not detected after NAIs treatment. Multiple linear regression analysis showed that the daily viral RNA shedding reduction in patients was slower in the two NAIs (OS and LA) than in BA, influenza B infection, aged 0-5 years, or the emergence of PA variants. The residual viral RNA shedding potentially infectious was detected in approximately 10-30% of the patients aged 6-18 years after five days of onset., Conclusions: Viral clearance differed by age, type of influenza, choice of treatment, and susceptibility to BA. Additionally, the recommended homestay period in Japan seemed insufficient, but reduced viral spread to some extent since most school-age patients became non-infectious after 5 days of onset., (© 2023. The Author(s).)

Background: Previous reports have not clarified the difference in clinical efficacy between baloxavir and oseltamivir against influenza., Methods: A prospective observational study was performed during 2017-2018, 2018-2019, and 2019-2020 influenza seasons. The primary endpoint of this study was to compare the duration of fever between patients who received baloxavir and those who received oseltamivir., Results: A total of 235 influenza-infected patients (3-18 years of age), including 91 who received oseltamivir and 144 who received baloxavir, were enrolled. The proportions of influenza A(H3N2) virus, influenza A(H1N1)pdm09 virus, and influenza B virus-infected patients were 31.5%, 42.6%, and 26.0%, respectively. Patients who received oseltamivir were significantly younger than those who received baloxavir. Univariate analyses showed that the duration of fever was shorter with baloxavir than with oseltamivir against influenza virus overall, influenza A virus, influenza B virus, and influenza A(H1N1)pdm09 virus, but not for influenza A(H3N2) virus. In multivariate analyses, hazard ratios for influenza virus overall (0.53 [95% CI, 0.38-0.73]), influenza B virus (0.16 [95% CI, 0.07-0.41]), and influenza A(H1N1)pdm09 virus (0.55 [95% CI, 0.32-0.93]) were significantly lower in the patients who received baloxavir than those who received oseltamivir. However, the differences between influenza A virus and influenza A(H3N2) virus were not significant between the two groups., Conclusion: For influenza virus overall, influenza B virus, and influenza A(H1N1)pdm09 virus, baloxavir treatment resulted in shorter duration of fever than oseltamivir treatment, but not for influenza A virus and influenza A(H3N2) virus., (© 2022 Japan Pediatric Society.)

Background: The aim of this study was to determine the sensitivity and specificity of a novel immunochromatographic (IC) assay (APD1806) using monoclonal antibodies against the matrix (M) protein of human metapneumovirus (hMPV) for detection of hMPV from nasopharyngeal swab samples based on the results of real-time RT-PCR., Methods: Nasopharyngeal swab samples taken from 189 patients aged 0 - 5 years who were suspected of having respiratory tract infections associated with hMPV were used in this study. The samples were tested both by the IC assay and by real-time RT-PCR for detection of hMPV., Results: The sensitivity and specificity of the IC assay for detection of hMPV were 88.8% (95/107) and 92.7% (76/82), respectively., Conclusions: The IC assay using monoclonal antibodies against the M protein of hMPV is an accurate and fast assay that is suitable as a diagnostic tool for hMPV infection. The optimal timing of the IC assay is 12 hours or more after the onset of fever due to hMPV infection.

Coronavirus disease 2019 (COVID-19) is a severe infectious disease of the respiratory tract caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, and has a high mortality rate. The disease emerged from Wuhan, China, in late 2019, and spread to Japan, including Hokkaido, in January 2020. In February 2020, 3 children were diagnosed with COVID-19 in Furano, Hokkaido, Japan. During this period, influenza and human metapneumovirus infections were prevalent among children in the Furano region. Two of the 3 patients experienced co-infection with other respiratory viruses, including influenza virus A or human metapneumovirus. To the authors' knowledge, the cases described in the present report were the first pediatric patients with COVID-19 in Japan. In children with COVID-19, the possibility of co-infection with other respiratory pathogens should be considered.

Background and Objectives: The importance of Streptococcus dysgalactiae subsp. equisimilis (SDSE) in causing sporadic pharyngitis in children remains controversial. The aims of this study were (1) to report the incidence and (2) to compare the epidemiologic and clinical features of patients with SDSE to those with Streptococcus pyogenes (SP)., Methods: A prospective study was conducted on acute pharyngitis associated with SDSE in children over a 2-year period. SDSE was identified using a phenotypic method, M protein gene (emm) analysis and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Patients with positive SDSE or SP cultures received cephalosporins for 5 days and were followed up. The emm genotyping and specific virulence genes analyses were performed., Results: From 3416 throat cultures, 67 isolates (2.0%) were identified as SDSE and 515 (15.1%) were identified as SP. The mean age of patients with SDSE (8.3 years) was older than those with SP (6.6 years; P < 0.01). There was minimal seasonal variation in the isolation rates of SDSE. The febrile patients' rates, gender distribution, cervical lymph node adenopathy rates, hospitalization rates, eradication and failure rates and the nonsuppurative sequelae between patients with SDSE and SP were similar. All SDSE isolates possessed important virulence genes. The emm genotyping of SDSE showed high strain diversity., Conclusions: The incidence of acute pharyngitis associated with accurately identified SDSE was 2/15 of that with SP. Epidemiologic and clinical features of acute pharyngitis associated with SDSE are indistinguishable from those with SP, with the exception of age and seasonal variation.

The oropharyngeal swab specimen was superior to the nasopharyngeal swab specimen for the detection of Mycoplasma pneumoniae in children with lower respiratory tract infection. The oropharyngeal loop-mediated isothermal amplification had 100% sensitivity and specificity compared with polymerase chain reaction testing, whereas the oropharyngeal rapid antigen detection test using immunochromatographic assay had relatively low sensitivity (66%) and reasonable specificity (90.7%)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Little is known about the clinical effectiveness of neuraminidase inhibitors against H275Y influenza A(H1N1)pdm09 virus. A cluster of H275Y influenza A(H1N1)pdm09 virus with cross-resistance to oseltamivir and peramivir was detected among untreated community patients in Hokkaido, Japan, during the 2013-2014 influenza season., Methods: This was a retrospective observational study. Specimens from nasopharyngeal swabs underwent rapid testing and single-nucleotide polymorphism identification on real-time polymerase chain reaction. We collected clinical data from the H275Y group and a 275H wild-type comparison group. All children were given one of four neuraminidase inhibitors., Results: Twenty-eight children infected with influenza A(H1N1)pdm09 virus were analyzed. Ten viruses had the H275Y substitution, while the other 18 had wild-type 275H. Mean fever duration after treatment and after onset was 25.3 h (95%CI: 14.1-36.5) and 48.9 h (95%CI: 34.4-63.3) in the H275Y group, respectively, and 26.1 h (95%CI: 18.7-33.6) and 46.3 h (95%CI: 35.7-56.8) in the 275H group, respectively. In the H275Y group, three patients were treated with oseltamivir, one with peramivir, five with zanamivir, and one with laninamivir. All of them had mild symptoms and received only outpatient care. Fever duration was 7.5-21.0 h and 18.0-66.0 h after treatment and after onset, respectively, in the patients treated with oseltamivir and peramivir, and 20.5-42.0 h and 42.0-88.0 h, respectively, in those treated with zanamivir and laninamivir., Conclusion: Fever in the H275Y children treated with oseltamivir and peramivir resolved rapidly during the 2013-2014 influenza season., (© 2015 Japan Pediatric Society.)

Background: Mycoplasma pneumoniae (MP) is a major pathogen of lower respiratory tract infection (LRTI) in children. A rapid diagnostic method during the acute phase is required for the prescription of effective antibiotics., Methods: A prospective, single-centered study was conducted on community-acquired LRTI in children. We regarded the day of fever onset as the first day of illness. In part 1, we studied 191 patients with signs of LRTI. We compared diagnostic reliability using loop-mediated isothermal amplification (LAMP) assay and serological testing at the first visit. In part 2, we evaluated the clinical characteristics of 117 patients with positive LAMP assay., Results: In part 1, 31 patients met the definite MP infection criteria. LAMP assay had a sensitivity of 96.8% and specificity of 100%, whereas enzyme immunoassay had a sensitivity of 38.7% and specificity of 76.9%, and particle agglutination test had a sensitivity of 19.4% and specificity of 93.1%. In part 2, of 106 patients with fever, 100 patients were diagnosed by the day 7 of illness. The diagnosis was made a mean of 3.5 ± 2.1 days after the onset of fever., Conclusions: LAMP assay had excellent sensitivity and specificity for the detection of acute MP infection at the first visit. This assay can diagnose MP infection during the very acute phase. LAMP assay is appropriate for genetic point-of-care diagnosis of MP infection in hospital laboratories., (© 2014 Japan Pediatric Society.)

Background: Both B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are useful biomarkers for the assessment of congestive heart failure (CHF) in adults. The purpose of this study was to determine whether BNP and NT-proBNP levels could be used to stratify the severity of CHF in children., Methods and Results: The study comprised 181 children with CHF and 232 healthy children aged from 4 months to 14 years who were categorized into CHF grades I, II, III and IV according to the modified Ross scoring system. The plasma BNP and serum NT-proBNP levels were significantly correlated with increasing CHF grades. The NT-proBNP levels were significantly different among the 4 CHF grades. However, only 2 significant differences were observed in the BNP levels between each CHF grade. NT-proBNP testing with cut-off points of >438 pg/ml (> or =grade II), >1,678 pg/ml (> or =grade III) and >7,734 pg/ml (grade IV) in the patients below 3 years of age, and >295 pg/ml (> or =grade II), >1,545 pg/ml (> or =grade III) and >3,617 pg/ml (grade IV) in those above 3 years of age was determined to be highly sensitive and specific by receiver operating characteristic analysis., Conclusions: The blood levels of BNP and NT-proBNP therefore reflect the severity of CHF in children. In particular, NT-proBNP is a useful biomarker for evaluating CHF in children.

Background: Our data in rats suggest that an elevated amniotic fluid erythropoietin (EPO) level at birth indicates antepartum fetal hypoxia. However, the short gestation period in rats does not permit a direct comparison of our data with humans., Methods: We conducted a retrospective study of the relationship between EPO levels at birth and abnormal fetal heart rate (FHR) records in 113 infants., Results: Among the cesarean section group, the cord serum and amniotic fluid EPO levels in the infants with antepartum abnormal FHR records were significantly higher than those in the control infants. Among the vaginal delivery group, the cord serum EPO levels in the infants with intrapartum abnormal FHR records was significantly higher than that in the control infants. The EPO levels in either cord serum and amniotic fluid discriminated between infants with antepartum abnormal FHR records. The control infants had a sensitivity of 83% and a specificity of 96%. Six of the seven infants with abnormal EPO levels in both cord serum and amniotic fluid had symptoms of prolonged fetal hypoxia. Five infants with abnormal EPO levels in only cord serum had symptoms of acute fetal hypoxia before birth. Four of the 14 infants with abnormal EPO levels at birth had poor outcomes in the neonatal period., Conclusions: We concluded that EPO levels in both cord serum and amniotic fluid at birth are valuable for determining the timing of fetal hypoxia and may predict the outcome in the neonatal period.

The delivery of nitric oxide (NO) via a nasopharyngeal tube is an alternative to endotracheal intubation. A male infant with end-stage pulmonary hypertension (PH) due to a severe hypoplastic lung developed a PH crisis on day 145 and received NO inhalation via a nasopharyngeal tube. Clinical improvement was maintained for 7 days with 18-22 ppm NO inhalation. The patient remained in close physical contact with his parents without the use of sedation. Blood methemoglobin levels remained below 1%. The environmental NO levels were less than 0.06 ppm and NO2 less than 0.3 ppm throughout the treatment, well within the safety margin. On day 152, the patient succumbed to hypoxemia and heart failure. The use of a nasopharyngeal NO delivery system without sedation, as an alternative to endotracheal intubation with sedation, was a practical method in treating a patient with PH while maintaining a certain quality of life for the patient and the family.

Erythropoietin (EPO) levels in amniotic fluid and serum were measured in hypoxic (fraction of inspired oxygen, FiO2, 0.09) and posthypoxic (following a 24-hour period of hypoxia, FiO2 0.09) fetal rats on day 21 of gestation. Each of the study groups comprised 12-20 fetuses. Each of the control groups consisted of 21 or 22 fetuses. Fetal serum EPO levels at 3, 6, 9, 12, and 24 h of hypoxia were significantly higher than the control level. Amniotic fluid EPO levels at 9, 12, and 24 h of hypoxia were also significantly increased compared to the control level. Fetal serum EPO levels returned to baseline during the 12- to 48-hour period after hypoxia. During the 0- to 48-hour posthypoxic period, amniotic fluid EPO levels were significantly higher than the control level. These data demonstrate that rates of appearance and turnover of amniotic fluid EPO are different from those of fetal serum EPO.

The following results were obtained in pharmacokinetic, bacteriological and clinical investigations of a cephem antibiotic for injection, cefozopran (SCE-2787, CZOP), administered to neonates and premature infants. 1. Pharmacokinetics (1) Half-lives (T 1/2's) of CZOP in 0-day-old (less than 24 hours after birth) neonates and premature infants were longer than those in 1-day-old or older infants. When half-lives were compared between 0-day-old neonates and 0-day-old premature infants, longer half-lives were observed in premature infants. (2) When CZOP was intravenously administered to 1-day-old or older neonates and premature infants at a dose of 20 mg/kg, no differences were noted in blood concentrations between neonates and premature infants from 30 minutes to 6 hours after administration as well as T 1/2's. (3) Blood concentration of CZOP administered at doses of 10, 20 and 40 mg/kg were dose-dependent. (4) Urine excretion rates of CZOP administered to 1-day-old or older neonates and premature infants were approximately 30 to 60% in the first 6 hours after administration. Urine excretion rates in 0-day-old neonates and premature infants were low. 2. Clinical results (1) Of a total of 136 cases to which CZOP was administered, clinical efficacy evaluation was possible in 96 cases, and safety evaluation in 132 cases. (2) The clinical efficacy rates were 78.6% (22/28) in 28 cases in which causative organisms were detected (Group A), and 97.1% (66/68) in 68 cases in which no such organisms were detected (Group B), with the total efficacy rate (Groups A and B) of as high as 91.7% (88/96). (3) Bacteriological evaluations were made with 33 strains isolated from the 28 cases of Group A. Elimination rates for Gram-positive and Gram-negative bacteria were 88.2% (15/17) and 92.3% (12/13), respectively, with the total elimination rate of 90.0% (27/30). No microbial substitution was noted. (4) As an adverse reaction, diarrhea was noted in one case (0.8%). Abnormal laboratory test values were noted in 15 cases (12.3%) including eosinophilia, elevated GPT, and elevated gamma-GTP. All of these abnormalities were transitory, and none of them critical. As a result of above pharmacokinetic and clinical investigations, CZOP is considered to be highly useful in the treatment of indicated infections in neonates and premature infants. It appears that 20 mg/kg of CZOP can be administered by intravenous injection or intravenous drip infusion to neonates and premature infants aged 0-day (less than 24 hours after birth) once or twice daily, to those aged 1 (24 or more hours after birth) to 7 days twice or three times daily, and to those aged 8 or more days three to four times daily, and that the dose can be increased up to 40 mg/kg in cases of critical or intractable infections.

A 3 day old neonate with septicemia and meningitis due to Plesiomonas shigelloides is described. We could not detect the source of this infection. The patient was treated with cefotaxime and survived without sequelae. Nine previously reported cases with this infection were reviewed.

We investigated pharmacokinetics and clinical effects of flomoxef sodium (6315-S, FMOX) in neonates and premature infants. These results are summarized as follows: 1. Pharmacokinetics (1) Plasma concentration (Ct) and half-lives (T1/2) were determined upon after intravenous one-shot injection (i.v.) of FMOX to neonates of different day-age groups (0-3 (n = 25), 4-7 (n = 18), 8-28 (n = 32) days of birth). At a dose of 10 mg/kg. i.v., mean C30 (30 minutes concentration) values were 21.2, 21.8 and 21.3 micrograms/ml, respectively, in the different groups mentioned above, and the mean T1/2 values were 3.37, 1.85 and 1.63 hours. At 20 mg/kg i.v., mean C15 (15 minutes concentration) values were 54.4, 51.4 and 50.7 micrograms/ml, and mean T1/2's were 2.99, 2.32 and 1.79 hours, respectively. At a dose of 40 mg/kg i.v., mean C15 values were 104.0, 95.9 and 99.2 micrograms/ml, and the mean T1/2's were 3.40, 1.20 and 1.80 hours, respectively. (2) Plasma concentrations and T1/2 after intravenous one-shot injection of FMOX in premature infants in group (0-3 (n = 14), 4-7 (n = 10), 8-28 (n = 13) days of birth). Mean C15's at doses of 10, 20 and 40 mg/kg in the different groups of infants were 24.0, 28.6, 21.7 and 54.0, 54.6, 55.5 and 98.2, 93.0, 106.0 micrograms/ml, and T1/2's were 4.10, 2.53, 2.57 and 4.28, 2.27, 3.02 and 4.66, 2.86, 2.09 hours, respectively. Mean Cmax values were clearly dose dependent, and mean T1/2 values tended to be longer in premature infants compared to neonates. (3) Urinary recovery rate of FMOX after intravenous injection in neonates and premature infants. Mean urinary recovery rates of FMOX in the first 6 hours after i.v. (one-shot) at doses of 10, 20 and 40 mg/kg to neonates and premature infants were 38.9-62.8% in the neonates and 30.7-61.5% in the premature infants. (4) Plasma concentrations and urinary recovery rates upon 1 hour drip infusion of 20 mg/kg in the neonate groups (or the premature infant groups) as follows: Mean C50 values were 31.0, 32.7 and 23.4 micrograms/ml, and T1/2 were 2.94, 3.68 and 2.25 hours, respectively. The recovery rates were 35.2-52.9% in the first 6 hours after administration. 2. Clinical studies The number of clinically evaluable cases in the FMOX treatment of premature infants was 199, in which the causative pathogens were identified in 71 cases (A group) and not identified in 128 cases (B group).(ABSTRACT TRUNCATED AT 400 WORDS)

Forty-three newborn and young infants including 13 low-birth-weight (LBW) infants were treated with flomoxef (FMOX) and the clinical efficacy and side effect were evaluated. The ages of the patients ranged from 0 to 99 days, and their body weights from 797 to 9,000 g. Dose levels were 10.5 to 48.5 mg/kg every 6 to 8 hours for 3 to 12 days. Those patients who responded to the FMOX treatment included 8 infants with sepsis, 14 with suspected sepsis, 6 with intrauterine infection, 2 with meningitis, 7 with pneumonia, 1 with staphylococcal scalded skin syndrome, 1 with epididymitis and 4 with urinary tract infections. The results were excellent in 17 and good in 22 patients. The drug was well tolerated, although diarrhea occurred in 2, slightly elevated serum concentrations of transaminases in 2, and eosinophilia and thrombocytosis in 1 patient each. Pharmacokinetic studies on FMOX with 20 mg/kg dose were done in 19 patients including 8 LBW infants. Serum concentrations at 15 minutes after intravenous bolus injection in five 1- to 6-day-old LBW, five 1- to 6-day-old and four 8- to 19-day-old mature infants were 52.6, 52.7 and 58.0 micrograms/ml, respectively, and those at 4 hours were 22.1, 13.3 and 5.2 micrograms/ml, respectively. Serum half-lives of the drug were 3.93, 2.29 and 1.62 hours, respectively, and excretion rates of this drug into urine in the first 6 hours after administration were 30.4, 45.1 and 58.7%, respectively. Mean serum concentrations just after intravenous 1-hour drip infusion in three 8- to 54-day-old LBW and two 8- and 10-day-old mature infants, were 31.5 and 18.9 micrograms/ml, respectively, and those at 4 hours were 15.3 and 4.3 micrograms/ml, respectively. Serum half-lives of the drug were 2.88 and 1.75 hours, respectively, and excretion rates of the drug into urine in the first 6 hours were 22.6 and 47.5%, respectively. The cerebrospinal fluid level at 3 hours after a dose was 7.09 micrograms/ml on the second day of treatment in a patient with Staphylococcus aureus meningitis receiving 50 mg/kg of the drug every 6 hours per day. Its level at 1 hour after a dose was 3.52 micrograms/ml on the 8th day of treatment in the same patient. The influence of FMOX on the fecal flora was studied in 7 patients. The characteristic pattern observed during the drug administration was the disappearance of Bifidobacterium, the decrease or disappearance of Enterobacteriaceae and the preservation of Streptococcus.(ABSTRACT TRUNCATED AT 250 WORDS)