Correlation between antibiotic use and antibiotic resistance: A multicenter study using the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system in Hokkaido, Japan.

BACKGROUND: The Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system aggregates information related to antimicrobial resistance (AMR) measures in participating medical institutions nationwide and is intended to be used for promotion of AMR measures in participating facilities and their communities. This multicenter study aimed to determine the usefulness of the J-SIPHE system for evaluating the correlation between antibiotic use and antibiotic resistance in Hokkaido, Japan. METHODS: Data on antibiotic use and detection rate of major resistant Gram-negative bacteria at 19 hospitals in 2020 were collected from the J-SIPHE system, and data correlations were analyzed using JMP Pro. RESULTS: The detection rate of carbapenem-resistant Pseudomonas aeruginosa was significantly positively correlated with carbapenem use (Spearman's ρ = 0.551; P = .015). There were significant positive correlations between the detection rate of fluoroquinolone-resistant Escherichia coli and the use of piperacillin/tazobactam, carbapenems, and quinolones [ρ = 0.518 (P = .023), ρ = 0.76 (P < .001), and ρ = 0.502 (P = .029), respectively]. CONCLUSIONS: This is the first multicenter study to investigate the correlation between antibiotic use and antibiotic resistance using the J-SIPHE system. The results suggest that using this system may be beneficial for promoting AMR measures.

Multicenter study for brain/body hypothermia for hypoxic-ischemic encephalopathy: Changes in HMGB-1.

BACKGROUND: We measured changes in the blood level of high-mobility group box-1 (HMGB-1) at 24 h intervals in neonates treated with brain/body hypothermia (body hypothermia therapy: BHT) for hypoxic-ischemic encephalopathy (HIE), to evaluate the usefulness of HMGB-1 level for determining outcomes. METHODS: We studied 15 neonates with HIE who underwent BHT (BHT (+) group) and six neonates with HIE who did not (BHT (-) group). We recorded HMGB-1 changes at 24 h intervals, creatinine phosphokinase, and the resistance index of the anterior cerebral artery. Magnetic resonance imaging (MRI) was used to determine short-term outcome. RESULT: Baseline HMGB-1 was significantly higher in the BHT (+) group than in the BHT (-) group. Thereafter, HMGB-1 in the BHT (+) group significantly decreased at 24 h intervals, reaching the reference range by 2 days of age. In the BHT (+) group, when patients were classified into clinically significant neurological disorder due to HIE (+) and (-) according to MRI, the neurological disorder (+) group had higher mean HMGB-1. CONCLUSIONS: In HIE, HMGB-1 differs according to the presence of BHT, suggesting that HMGB-1 measurement soon after birth might be useful for determining BHT necessity and short-term outcome.

Dried umbilical cords in the retrospective diagnosis of congenital cytomegalovirus infection as a cause of developmental delays.

To clarify the impact of congenital cytomegalovirus (CMV) infection on developmental disabilities, 20 children with disabilities of unknown cause were analyzed. Five children were CMV positive and had no clinical manifestations at birth. Intracranial calcification was observed in 4 cases. Thus, congenital CMV infection is a significant cause of developmental disabilities.

Frequency of human cytomegalovirus-specific T cells during pregnancy determined by intracellular cytokine staining.

The characteristics of cytomegalovirus (CMV)-specific T-cell immunity was investigated in pregnant women with primary, latent, or reactivated CMV infection, and in a comparative group of non-pregnant women. Forty-six pregnant and 8 non-pregnant women were examined based on the presence of serum antibody activity against CMV and viral excretion in urine. The frequency of CMV-specific CD4(+) T cells in peripheral blood lymphocytes was determined by staining for intracellular cytokines, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha. There was no change in the frequencies of CMV-specific CD4(+) T cells in CMV-seropositive normal non-pregnant and pregnant women at any gestation. However, the frequency of CMV-specific CD4(+) T cells in pregnant women associated with CMV reactivation or reinfection was significantly higher than in CMV-seropositive normal pregnant and non-pregnant women. There were no CMV transmissions to the infants of all these women. These CMV-specific T cells responses in pregnant women may contribute some to block the intrauterine CMV infection in their infants.

Human cytomegalovirus infection during pregnancy and detection of specific T cells by intracellular cytokine staining.

OBJECTIVE: The flow cytometric assay was evaluated as a tool for real-time monitoring of human cytomegalovirus (HCMV)-specific cellular immunity in pregnant women. METHODS: We screened for HCMV infection in pregnant women in Sapporo, Japan, during the year 2000, by serologic assays, virus isolation from urine, and PCR to detect DNA in cervical swabs. The frequencies of HCMV-specific CD4+ T cells in pregnant women with serum anti-HCMV IgG antibody were detected by intracellular cytokine (ICC), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) staining. RESULTS: The levels of intracellular cytokines in pregnant women with serum anti-HCMV IgG antibody were significantly higher than those in women without anti-HCMV IgG antibody (P = 0.011 for IFN-gamma and P = 0.023 for TNF-alpha) but lower than those in non-pregnant women with serum anti-HCMV IgG antibody. Frequencies of HCMV-specific CD4+ T cells were higher in infants with symptomatic congenital infection than in infants with asymptomatic perinatal infection. CONCLUSIONS: This ICC assay may reflect immunologic activity against HCMV infection in pregnant women with immunosuppressive conditions.

Chlamydia trachomatis infection in early neonatal period.

BACKGROUND: The clinical characteristics of Chlamydia trachomatis respiratory tract infections in Japanese neonates were investigated. METHODS: Clinical, laboratory and microbiological characteristics of five infants with pneumonia due to C. trachomatis in early neonatal period were analyzed. RESULTS: Only C. trachomatis was identified in 4 infants. Both C. trachomatis and cytomegalovirus was identified in one. Wheezing, tachypnea and cyanosis were common in infants. Mothers of five infants had negative chlamydial EIAs at 20 weeks of gestation. CONCLUSIONS: We identified five cases of C. trachomatis respiratory tract infections in early neonatal period with the possibility of intrauterine infection. Targeted screening, early diagnosis, and effective treatment of perinatal and neonatal chlamydial infections seems to be necessary.

Immunological evaluation and clinical aspects of children with congenital cytomegalovirus infection.

To determine the ability of immunological response to human cytomegalovirus (CMV), the flow cytometric assay was evaluated as a tool for real-time monitoring of specific cellular immunity in children with congenital CMV infection. Longitudinal cohort study of 2 children with asymptomatic and 2 with symptomatic congenital CMV infection evaluated at birth and followed up with serial age-appropriate neurodevelopmental testing. Frequencies of CMV-specific CD4 (+) T cell in these children were detected by intracellular cytokines (ICC), interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, staining. Findings detected by CT and MRI were the most sensitive predictor for neurodevelopmental prognosis. Frequencies of CMV-specific CD4(+) T cells detected by ICC, both IFN-gamma and TNF-alpha, were higher in 2 children with symptomatic congenital CMV infection than those in 2 children with asymptomatic congenital infection. Frequencies of CMV-specific CD4(+) T cells in 2 children with symptomatic congenital infection were significantly higher than those in 6 healthy children of 1 to 5-years of age with serum anti-CMV IgG antibody without serum anti-CMV IgM antibody and viral excretion in to urine (p < 0.01). The ICC assay reflects immunological activity against CMV infection in children with asymptomatic or symptomatic congenial infection. Categorizing findings obtained by the ICC assay may helps to determine the prognosis of children with congenital CMV infection.

Reactivation of varicella-zoster virus in facial palsy associated with infectious mononucleosis.

Facial palsy with infectious mononucleosis, although well-recognized, is rare in children, and its pathogenesis is uncertain. To our knowledge there has been no previous report describing varicella-zoster virus reactivation as a cause of facial palsy associated with infectious mononucleosis. We report such a patient in whom serology showed reactivation of varicella-zoster virus.

Use of an inactivated varicella vaccine in recipients of hematopoietic-cell transplants.

BACKGROUND: The reactivation of varicella-zoster virus from latency causes zoster and is common among recipients of hematopoietic-cell transplants. METHODS: We randomly assigned patients who were scheduled to undergo autologous hematopoietic-cell transplantation for non-Hodgkin's or Hodgkin's lymphoma to receive varicella vaccine or no vaccine. Heat-inactivated, live attenuated varicella vaccine was given within 30 days before transplantation and 30, 60, and 90 days after transplantation. The patients were monitored for zoster and for immunity against varicella-zoster virus for 12 months. RESULTS: Of the 119 patients enrolled, 111 received a transplant. Zoster developed in 7 of 53 vaccinated patients (13 percent) and in 19 of 58 unvaccinated patients (33 percent) (P=0.01). After two patients in whom zoster developed before transplantation were excluded, the respective rates were 13 percent and 30 percent (P=0.02). In vitro CD4 T-cell proliferation in response to varicella-zoster virus (expressed as the mean stimulation index) was greater in patients who received the vaccine than in those who did not at 90 days, after three doses (P=0.04); at 120 days, after all four doses (P<0.001); at 6 months (P=0.004); and at 12 months (P=0.02). The risk of zoster was reduced for each unit increase in the stimulation index above 1.6; a stimulation index above 5.0 correlated with greater than 93 percent protection. Induration, erythema, or local pain at the injection site was observed in association with 10 percent of the doses. CONCLUSIONS: Inactivated varicella vaccine given before hematopoietic-cell transplantation and during the first 90 days thereafter reduces the risk of zoster. The protection correlates with reconstitution of CD4 T-cell immunity against varicella-zoster virus.

[Pharmacokinetic and clinical studies on teicoplanin for sepsis by methicillin-cephem resistant Staphylococcus aureus in the pediatric and neonate field].

Pharmacokinetics, clinical efficacy and safety of teicoplanin (TEIC) were evaluated in pediatric and neonate patients with MRSA sepsis in the dosages approved in overseas. The administrated dose for pediatrics patients was 10 mg/kg once at hour 0, 12 and 24, followed by every 24 hours intervals. In neonates patients, first dose was 16 mg/kg, then 8 mg/kg every 24 hours intervals. 1. Pharmacokinetic results. All 17 patients (9 neonates and 8 pediatrics) who received TEIC were evaluated for pharmacokinetics. Trough concentrations were analyzed in 16 patients (9 neonates and 7 pediatrics) excluding one patient for lack of measurement of drug concentration at day 7. No patient with a concentration exceeding 60 micrograms/mL in peak or trough concentrations were reported. Mean concentrations in trough at day 3, 4 and 7 in neonates were 15.2, 14.7 and 17.8 micrograms/mL, and in pediatrics were 12.5, 12.2 and 13.1 micrograms/mL, respectively. These results were similar to those reported in foreign pediatrics and neonates patients. 2. Efficacy and safety results. Since no patient was excluded, all patients were evaluated for efficacy and safety. Microbiological efficacy as well as clinical cure were secondarily evaluated in 2 patients for whom MRSA was isolated from blood. Clinical efficacy rate was 76.5% (13/17) and number of cases in judgments of excellent, good, fairly improved and no change were 12, 1, 3 and 1 cases respectively. The patients for whom MRSA was isolated from blood were judged as MRSA eradicated case and cured without any additional anti-MRSA drugs. Adverse events were reported in 2 neonates and 3 pediatric patients. Possibly related adverse events to study drug (adverse drug reactions) were: 1 case of respiratory disorder, thrombocythemia, gamma-GTP increased, GOT increased and GPT increased in 3 pediatrics. These results suggest that an application of overseas dose regimen of TEIC for neonate and pediatrics is appropriate in Japan.