The prevalence and antimicrobial susceptibility of Streptococcus pneumoniae isolated from patients at Jikei University Hospitals after the implementation of the pneumococcal vaccination program in Japan

Studies have shown that pneumococcal vaccination reduces the incidence of Streptococcus pneumoniae infections but does not change the prevalence of S. pneumoniae nasopharyngeal colonization. To comprehensively and longitudinally assess the epidemiology of S. pneumoniae after the introduction of pneumococcal vaccination, we monitored the prevalence and antimicrobial susceptibility of S. pneumoniae, irrespective of its serotypes or pathogenicity, by analyzing specimens collected from a large number of patients at Jikei University Hospitals from 2009 to 2017. A total of 5763 S. pneumoniae isolates were identified out of 375,435 specimens from various sources of patients in different age groups. The prevalence of S. pneumoniae isolated only from patients <5 years old was significantly reduced with the widespread use of pneumococcal vaccines, although this reduction differed by areas where patients resided. The incidence of pneumococcal infections, including bacteremia and otitis media, clearly decreased among patients <5 years old after the introduction of pneumococcal vaccination, while the prevalence of S. pneumoniae isolated from blood specimens of patients 15–64 years old increased, suggesting the involvement of non-vaccine serotypes in the incidence of invasive pneumococcal infections. The antimicrobial susceptibility of S. pneumoniae improved after the introduction of pneumococcal vaccination. Our results show that pneumococcal vaccination has a suppressive effect on the prevalence of S. pneumoniae and the incidence of pneumococcal infections, at least for children <5 years old, in association with an improvement in the antimicrobial susceptibility of S. pneumoniae. However, further measures will be needed to control invasive pneumococcal infections caused by non-vaccine serotypes.     

When It Hurts,a Positive Attitude May Help. The Moderating Effect of Positive Affect on the Relationship Between Walking,Depression, and Symptoms in Women with Fibromyalgia

Background: Increased exercise is a marker of health in fibromyalgia (FM). However, patients frequently avoid physical activity as a way of minimizing the pain they feel. This deprives them of opportunities to obtain positive reinforcement, increasing functional impact. Aims: This study examines the mediating role of depressive symptoms between walking (as physical exercise), functional impact, and pain, at different levels of positive affect (PA) among women with fibromyalgia. Design: Cross-sectional correlational study. Settings: Mutual aid associations for fibromyalgia in Spain. Participants: 231 women diagnosed with FM. Methods: Moderate mediation analyses were conducted using PROCESS. Results: First, a simple mediation model showed that depression mediated the effect of walking on functional impact, but not on pain. Additionally, the moderated mediated model showed that this effect was significant at medium and high levels of PA, but not when levels of PA were low. Conclusions: Provision of resources focused on positive affect seem to increase the positive effects of walking on functional impact through the reduction of depressive symptoms. Nurses can improve adherence of patients with FM to walking behavior through increasing positive affect.     

A Target Antigen–Based Approach to the Classification of Membranous Nephropathy

ObjectiveTo describe the clinical and pathological phenotype of membranous nephropathy (MN) associated with M-type-phospholipase–A₂-receptor (PLA₂R), thrombospondin-type-1-domain-containing-7A (THSD7A), semaphorin 3B (SEMA3B), neural-epidermal-growth-factor-like-1-protein (NELL-1), protocadherin 7 (PCDH7), exostosin 1/exostosin 2 (EXT1/EXT2) and neural cell adhesion molecule 1 (NCAM-1) as target antigens.MethodsA retrospective cohort of 270 adult patients with biopsy-proven MN diagnosed between January 2015 and April 2020 was classified as PLA₂R-, THSD7A-, SEMA3B-, NELL-1–, PCDH7-, EXT1/EXT2-, NCAM-1–associated or septuple-negative MN using serologic tests, immunostaining, and/or mass spectrometry. Clinical, biochemical, pathologic, and follow-up data were systematically abstracted from the medical records, including disease activity of conditions traditionally associated with MN and occurring within 5 years of MN diagnosis.ResultsPatients with PLA₂R-associated MN were predominantly middle-aged white men without associated disease. The presence of associated disease did not affect the clinical and pathologic characteristics of PLA₂R-associated MN, suggesting that they were coincidental rather than causally linked. THSD7A-, NELL-1–, PCDH7-, and NCAM-1–associated MN were rare and SEMA3B-associated MN was not discovered in our cohort. EXT1/EXT2-associated MN was primarily diagnosed in younger women with active systemic autoimmunity. A significant proportion of septuple-negative patients had associated malignancy or systemic autoimmunity.ConclusionThe widely used distinction between primary and secondary MN has limitations. We propose a refined terminology that combines the target antigen and associated disease to better classify MN and guide clinical decision making.     

First description of a clinical glutamine-dependent Escherichia coli with a missense mutation in the glnA

IntroductionSmall-colony variants (SCVs) of bacteria are subpopulations with a small colony size, low growth rate, and atypical colony morphology. The purpose of this study was to comprehensively elucidate the characteristics and underlying mechanism of the development of a glutamine-dependent SCV of E. coli, GU-92_SCV, isolated from the blood of a patient with pyelonephritis.MethodsThe GU-92_SCV strain was tested for auxotrophy testing for glutamine. DNA mutations in genes related to glutamine synthesis were analysed by sequencing. The isolate's proliferation and antimicrobial susceptibility in Mueller-Hinton II medium supplemented with glutamine were examined.ResultsThe colony of the GU-92_SCV strain did not grow on Mueller-Hinton II agar, but growth around the filter paper containing l-glutamine was enhanced on Mueller-Hinton II agar. The GU-92_SCV strain had a single nucleotide substitution in glnA, c.193G>A, corresponding to p.Asp65Asn. Changing c.193G>A to the wild-type sequence in glnA restored these phenotypes. Because GU-92_SCV did not grow in Mueller-Hinton II broth, antimicrobial susceptibility test results were not obtained; however, in the presence of 10 mg mL^?1 l-glutamine, the results were consistent with those of the revertant strain GU-92_REV.ConclusionTo the best of our knowledge, this is the first clinical isolation of a glutamine-dependent E. coli SCV from a patient blood culture. Our data showed that glnA was important for the growth of E. coli in Mueller-Hinton II medium, which also required the presence of glutamine when performing antimicrobial susceptibility testing for glutamine-dependent SCV strains.     

Antimicrobial activity of ozenoxacin and other antimicrobials against Staphylococcus aureus strains isolated from clinical skin specimens in Japan in 2019 and 2020

Skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and the spread of antimicrobial resistance are a major problem in Japan. Here, we investigated the susceptibility of S. aureus clinical isolates to ozenoxacin (OZNX), a topical antimicrobial approved for superficial skin infection treatment in Japan. Susceptibility to OZNX was measured in 110 skin-derived methicillin-susceptible S. aureus (MSSA) and 130 MRSA strains isolated in 2019 and 2020 in Japan. The broth microdilution method was performed, and results were analyzed according to the Clinical and Laboratory Standard Institute (M07 and M100) guidelines. The results were compared with those of other antimicrobials used against S. aureus. The minimum inhibitory concentrations (MIC)₉₀ of OZNX for MSSA and MRSA were 0.12 and 0.25 μg/mL, respectively, indicating that OZNX exhibited the same or stronger antibacterial activity than that of the other antimicrobials tested, such as nadifloxacin, fucidic acid, and gentamicin. No strains exhibited reduced OZNX susceptibility. Notably, a low MIC of OZNX was observed even for strains with reduced susceptibility to nadifloxacin, a similar quinolone-based topical antimicrobial. OZNX is a highly potent antimicrobial used in Japan for superficial skin infections caused by S. aureus, such as impetigo contagiosa and related diseases.     

Mortality changes for patients with pneumococcal pneumonia from 2012 to 2017 in Japan

IntroductionPneumococcal pneumonia has a high morbidity and mortality in adults, especially those ≥65 years old. In the past decade, pneumococcal vaccination programs have been initiated worldwide, however, few data concerning mortality changes are available in pneumococcal pneumonia patients and there are no reports clarifying these current changes in Japan.MethodsJapanese patients ≥65 years old hospitalized with pneumococcal pneumonia between April 2012 and March 2018 were analyzed using the Diagnostic Procedure Combination database. In-hospital mortality was evaluated, and the odds ratios for this outcome in each fiscal year compared with that in 2012 was analyzed using multivariable logistic regression models.ResultsBetween 2012 and 2017, data of 47,375 pneumococcal pneumonia patients ≥65 years old were extracted. The incidence per 1000 person-years for in-hospital mortality was 60.4 in 2012, 56.8 in 2013, 63.2 in 2014, 56.1 in 2015, 73.0 in 2016, and 67.4 in 2017 and the odds ratios for in-hospital mortality in 2013, 2014, 2015, 2016, and 2017 compared with that in 2012 were 1.00, 1.05, 1.04, 1.06, and 0.98, respectively. There were no significant differences between 2012 and each year from 2013 to 2017. Low BMI; low ADL score; high A-DROP score; comorbid malignancy and heart failure; the coexistence of invasive pneumococcal infection; and the use of invasive mechanical ventilation were independent risk factors for in-hospital mortality.ConclusionsThere were no changes in in-hospital mortality in pneumococcal pneumonia patients between 2012 or each year from 2013 to 2017 and further epidemiological observations are necessary.     

Bacteriological analysis of Neisseria lactamica isolated from the respiratory tract in Japanese children

IntroductionNeisseria lactamica is a commensal bacterium of the upper respiratory tract in humans and is closely related to Neisseria meningitidis. N. lactamica colonization may contribute to preventing N. meningitidis colonization and invasive meningococcal disease. However, the transference of antimicrobial resistance genes from N. lactamica to N. meningitidis has been reported.MethodsIn this study, we aimed to identify N. lactamica using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and performed multilocus sequence typing of seven N. lactamica strains isolated from Japanese children. We also analyzed the antimicrobial susceptibility of these strains and the mutations in their antimicrobial resistance genes (penA, gyrA, and parC).ResultsAll the N. lactamica strains could be identified using MALDI-TOF MS. All strains were of different sequence types (STs), including five new STs. Five strains had intermediate susceptibility, two were resistant to ampicillin, and all had five out of the five known PBP2 mutations. Six strains were resistant to levofloxacin. Among the quinolone-resistant strains, three had GyrA mutations, and three had both ParC and GyrA mutations.ConclusionsN. lactamica STs may vary in Japanese children, and penicillin- and quinolone-resistant strains may be prevalent. We should pay attention not only to the drug resistance of N. meningitidis but also to the drug susceptibility of N. lactamica whose drug-resistance genes may transfer to N. meningitidis.