Panton-Valentine leukocidin-positive novel sequence type 5959 community-acquired methicillin-resistant Staphylococcus aureus meningitis complicated by cerebral infarction in a 1-month-old infant.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a pathogen of major importance in pediatric patients. CA-MRSA can cause skin and soft tissue infection in children and young active adults with no predisposing factors, and life-threatening infections such as meningitis or necrotizing pneumonia have been reported. We report here a case of CA-MRSA meningitis complicated by acute left middle cerebral artery (MCA) infarction and necrotizing pneumonia in a previously healthy 1-month-old Vietnamese boy. He was firstly treated with vancomycin, but changed to linezolid because of persistent fever and low vancomycin trough level. He recovered successfully with residual right-sided hemiparesis. The mode of transmission of CA-MRSA and the mechanism of cerebral infarction (thrombotic or embolic) were unknown. The isolate was genotyped as staphylococcal cassette chromosome (SCC) mec type V with a novel sequence type (ST) 5959 harboring the Panton-Valentine leukocidin (PVL) gene. ST 5959 is a double locus variant of ST 59, which is a major PVL-positive CA-MRSA strain isolated in invasive disease in Asian countries. This case report may serve as a warning about the dissemination of PVL-positive CA-MRSA in and around Japan, with the possibility of causing serious life-threatening disease. The potential of linezolid for the treatment of MRSA meningitis as one of the alternative MRSA therapeutic drugs is also discussed.

Infantile Aspergillus fumigatus ventriculitis successfully treated with monitoring of plasma and cerebrospinal fluid voriconazole concentration level.

Aspergillosis is a rare fungal infection in newborns, and its morbidity and mortality are high. Voriconazole (VRCZ) is the first-line antifungal agent for invasive Aspergillus infection, but little data is available about its pharmacokinetics in infants. We report a case of a premature infant who developed ventriculitis due to Aspergillus fumigatus and received combination antifungal therapy including VRCZ. ß-D glucan and Aspergillus antigen index were elevated in the cerebrospinal fluid (CSF). We titrated the dose of VRCZ by monitoring plasma and CSF concentrations. The CSF to plasma concentration ratio of VRCZ ranged from 0.47 to 1.36 (median 0.71). While VRCZ adequately penetrates the blood-brain barrier, its concentration is highly variable in infants.

Identification of Haemophilus influenzae serotype e strains missing the fucK gene in clinical isolates from Japan.

Introduction. Certain nontypeable Haemophilus influenzae cannot be assigned a sequence type (ST) by Multilocus Sequence Typing (MLST) due to the lack of the fucK gene, one of seven MLST loci in H. influenzae, which encodes a fucose-operon enzyme.Aims. To confirm whether the loss of fucK is also found in the encapsulated strains, we analysed clinical isolates of H. influenzae serotype e (Hie).Methodology. We conducted MLST, PFGE, and antimicrobial susceptibility tests of 45 Hie strains; the majority (n=43) were derived from respiratory samples of pediatric patients at Chiba Children's Hospital between 2000 and 2016. The two remaining strains were obtained from the blood of elderly patients with invasive H. influenzae diseases (IHiDs) between 2015 and 2016 at general hospitals. For the fucK-negative strains, PCR analysis for fucose operon was also performed.Results. Four STs (ST18, 122, 621 and 1758) were assigned to 13 strains, and remaining 32 (including one associated with IHiD) were fucK-negative, completely missing the fucose operon. The allelic profiles of six other loci were identical among 31 strains and to that of ST18, 122 and 621, and these strains were genetically closely related. Forty of 45 isolates were ampicillin-sensitive.Conclusions. The loss of fucK was frequently observed in clinical isolates of Hie from children. Moreover, fucK-negative Hie may be the cause of IHiD in adult patients. The majority of Hie, including fucK-negative strains, were shown to be clonally related and were ampicillin sensitive. This represents the first report examining fucK losses in encapsulated H. influenzae.

[Comparison of Chemical Behavior of Original and Generic Docetaxel Formulations as Non-alcoholic Preparations: Discussion about Diluent Solvents for Docetaxel].

　Although generic anti-tumor agents are in wide clinical use, they have not in all cases been shown to be equivalent to the original agents after preparation. In the present study, original and generic docetaxel formulations were compared with respect to stability when prepared as a non-alcoholic solution for use. When the original formulation was diluted with physiological saline solution to make a non-alcoholic preparation, the concentration decreased with time, whereas no such decrease occurred when a preparation of the generic formulation was made in a similar manner. With both the original and generic formulations, no decrease in docetaxel concentration with time was found after dilution with 5% glucose solution. On the basis of these results, it is concluded that the behaviors of original and generic docetaxel formulations are not equivalent when prepared, but that the original and generic formulations can be taken to be equivalent if they are diluted with 5% glucose solution at preparation.

Comparative analysis of lactic acidosis induced by linezolid and vancomycin therapy using cohort and case-control studies of incidence and associated risk factors.

PURPOSE: Lactic acidosis is a rare complication of linezolid (LZD) therapy, and its incidence and risk factors remain unknown. This study aimed to compare the incidence of LZD-associated lactic acidosis (LALA) and vancomycin (VAN)-associated lactic acidosis (VALA) and investigate the risk factors for LALA. METHODS: We performed a retrospective cohort study using propensity score-matched analyses comparing the incidence of lactic acidosis between LZD and VAN therapy. We included adult patients administered LZD or VAN between April 2014 and March 2016 and extracted patient baseline data. In a case-control study, we identified the risk factors of lactic acidosis in patients treated with LZD. RESULTS: We identified 94 and 313 patients who were administered LZD and VAN, respectively. The incidence of lactic acidosis after LZD and VAN therapy was 10.6 and 0.3%, respectively. After propensity score-matched analyses, the incidence of lactic acidosis with LZD therapy was significantly higher than that with VAN therapy [10.0% (8/80) vs. 0% (0/80), respectively; risk difference, 0.1; 95% confidence interval (CI), 0.03-0.17; p = 0.004]. In a case-control study, 10 patients with LALA were matched to 20 non-lactic acidosis patients by age and sex. Patients with LALA were more likely to have renal insufficiency than non-lactic acidosis patients that were in the univariate analysis (odds ratio, 7.4; 95% CI, 1.0-84.4; p = 0.02). CONCLUSIONS: This study indicates that LALA occurs more frequently than VALA does and is associated with renal insufficiency. Therefore, close monitoring of kidney function and serum lactate is recommended during LZD therapy.

Prevalence and characteristics of human parechovirus and enterovirus infection in febrile infants.

BACKGROUND: Human parechovirus (HPeV) and human non-polio enterovirus (EV) are important causes of fever without source (FWS) in young infants. Their prevalence and clinical characteristics are largely unknown in Asian countries. This study was conducted to elucidate the epidemiology and clinical characteristics of HPeV and EV infection in febrile young infants in Japan. METHODS: During February 2010-August 2015, we obtained 53 stool, 44 throat swab, and 20 cerebrospinal fluid samples from 56 infants (<3 months) with FWS at a single hospital. To each sample, we applied reverse transcription-polymerase chain reaction for HPeV and EV. We compared the clinical characteristics of HPeV and EV patients. RESULTS: HPeV was detected in 11 and EV in 17 patients. HPeV was detected during July-September. HPeV patients, compared with EV patients, had lower age (32 vs 47 days; P = n.s.), higher prevalence of exclusive breast-feeding (81.8 vs 29.4%; P = 0.024), and lower prevalence of sick contacts (36.4 vs 88.2%; P = 0.010). More HPeV than EV patients met the systemic inflammatory response syndrome criteria (90.9 vs 52.9%; P = 0.049). In the HPeV group, leukopenia, thrombopenia, and elevated deviation enzyme were observed, although the prevalence of abnormal cerebrospinal fluid was significantly lower than in the EV group. HPeV patients had longer hospital stay (7 vs 5 days; P = 0.025). CONCLUSION: HPeV and EV are important causal viruses of FWS. Characteristic clinical pictures exist in these virus infections, but further research is needed to accumulate more cases to produce a comprehensive picture of these virus infections.

Analysis of Streptococcus pneumoniae and Haemophilus influenzae isolated from middle ear fluid before and after the introduction of government subsidies for pneumococcal and H. influenzae type b vaccines in Japan.

This study aimed to identify trends in frequency, serotype, and antimicrobial susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolated from middle ear fluid specimens of children aged≤15 years (mean, 2 years), before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and the H. influenzae type b vaccine, at a pediatric facility in Japan. Sixty-six S. pneumoniae and 88 H. influenzae strains were isolated from 820 middle ear fluid samples. Serotyping and antimicrobial susceptibility testing were performed. The study time-frame was divided into period 1 (2007-2010) and period 2 (2011-2014), according to the availability of vaccine public funding. The S. pneumoniae detection rate decreased from 9.6% in period 1-6.1% in period 2 (p = 0.042). PCV7 serotypes decreased from 56.8% to 9.1% (p = 0.0002). No significant change was observed for the 13-valent pneumococcal conjugate vaccine (PCV13) serotypes: 72.7% in period 1 and 59.1% in period 2. Penicillin-resistant strains (penicillin G-MIC ≥2 µg/mL) decreased from 25% to 4.5% (p = 0.038). Detection rates for H. influenzae did not change significantly: 10.3% in period 1 and 11.3% in period 2. Serotypes were mostly non-typeable: 97.9% in period 1 and 90.2% in period 2, and only one serotype b strain was isolated in each period. The frequency of ampicillin-resistant strains (MIC ≥4 µg/mL) did not change. These results show a preventative effect of PCV7 on otitis media due to S. pneumoniae. PCV7 was replaced with PCV13 in 2013 in Japan; therefore, a further decrease in pneumococcal otitis media is anticipated in the future.