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Background: Although the individual expression of heterogeneous vancomycin-intermediate resistance (hVISA) and β-lactam antibiotic-induced vancomycin resistance (BIVR) phenotypes has been associated with treatment failure and recurrence in methicillin-resistant Staphylococcus aureus (MRSA) infections, the effect of the co-expression of these phenotypic profiles on clinical outcome has not been fully elucidated. The aim of this study was to determine the impact of the combination of hVISA and BIVR phenotypes on the clinical outcome in MRSA bacteremia. Methods: One hundred and sixty-two MRSA blood isolates from a 21-y period, 1987-2007, were randomly selected. Screening for hVISA was done by the macromethod Etest and confirmed by population analysis profiles. BIVR was identified using Mu3 agar containing 4 μg/ml of vancomycin. Results: Thirty (18.5%) and 39 (24.1%) of the 162 MRSA blood isolates were positive for the hVISA and BIVR phenotypes, respectively. Eighteen (11.1%) isolates possessed both hVISA and BIVR phenotypes (hVISA(+)/BIVR(+)). In a subset of patients who received initial treatment with glycopeptides, only the patients whose isolates were hVISA(+)/BIVR(+) displayed a significantly higher mortality rate in comparison to those with non-hVISA(+)/BIVR(+) (80.0% vs 31.3%, p = 0.004). The presence of both hVISA and BIVR phenotypes was a predictor of mortality using a logistic regression analysis ( p = 0.025). Conclusions: The combined phenotype of hVISA and BIVR was associated with a higher probability of mortality in patients with MRSA bacteremia. Further prospective studies are warranted to delineate the clinical significance of the combined phenotype of hVISA and BIVR. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) infections have been the most common cause of nosocomial infections in Japan, but their genetic characteristics related to bloodstream infections have not been well studied. The aim of this study was to investigate a comprehensive molecular characterization of MRSA blood isolates during the historical 18-year study period between 1987 and 2004 in a tertiary care university hospital. A total of 137 MRSA isolates recovered from the blood of inpatients at Fukuoka University Hospital were analyzed. Clinical information and antimicrobial susceptibility profiles were reviewed, and staphylococcal chromosomal cassette mec (SCC mec), accessory gene regulator ( agr), and a battery of bacterial genes were tested by PCR-based assays. The relatedness of these isolates was determined by the repetitive sequence-based PCR (rep-PCR) and pulsed-field gel electrophoresis (PFGE). Although low numbers of agr type III/SCC mec type IV isolates circulated between 1987 and 1992, agr type II/SCC mec type II isolates started circulating in 1993 and were responsible for the increased MRSA isolates until 2004. The rep-PCR and PFGE identified 104 epidemic and 33 sporadic isolates. Among the 104 epidemic isolates, six major rep-PCR/PFGE types were identified, which occupied 67.3% of epidemic isolates. The SCC mec type II and agr type II isolates were observed in significantly higher proportion in epidemic isolates than in sporadic isolates ( P = 0.0318, P = 0.0123, respectively). In contrast, SCC mec type IV strains were observed in significantly higher proportion in sporadic isolates than in epidemic isolates ( P = 0.0494). Although isolates with sec were detected in higher rates in epidemic isolates ( P = 0.0397), seh was detected in higher rates in sporadic isolates ( P = 0.0350). Multivariate logistic regression analysis with forward stepping revealed that SCC mec type II was independently associated with epidemic isolates ( P = 0.0067; odds ratio, 1.75; 95% confidence interval, 1.17-2.64). These data indicated that SCC mec type II MRSA isolates were responsible for the increased MRSA bloodstream infections for inpatients during the 18-year study period in the hospital. [ABSTRACT FROM AUTHOR]

Abstract: The role of a dprA ortholog (Cj0634) in Campylobacter jejuni transformation was phenotypically assessed using two strains. C. jejuni strain 11168 was naturally competent for transformation by chromosomal DNA, while efficiency decreased 100-fold in a Cj0634::aphA mutant, whereas C. jejuni strain 480 was not naturally competent. C. jejuni strain 480 but not 11168 could be electro-transformed by shuttle plasmid pRY111, an effect completely abolished by Cj0634 interruption. Complementation of the Cj0634 mutation in C. jejuni strain 480 in trans with vectors containing the dprA homologs from C. jejuni, Helicobacter pylori, or Haemophilus influenzae, completely (for Cj0634) or partially (H. pylori > H. influenzae) restored electro-transformation. Thus, C. jejuni expresses a DprA ortholog that functionally most closely resembles that of H. pylori and is involved in DNA transformation. [Copyright &y& Elsevier]

Helicobacter pylori, Gram-negative, curved bacteria colonizing the human stomach, possess strain-specific complements of functional restriction–modification (R–M) systems. Restriction–modification systems have been identified in most bacterial species studied and are believed to have evolved to protect the host genome from invasion by foreign DNA. The large number of R–Ms homologous to those in other bacterial species and their strain-specificity suggest that H. pylori may have horizontally acquired these genes. A type IIs restriction–modification system, hpyIIRM, was active in two out of the six H. pylori strains studied. We demonstrate now that in most strains lacking M.HpyII function, there is complete absence of the R–M system. Direct DNA repeats of 80 bp flanking the hpyIIRM system allow its deletion, resulting in an ‘empty-site’ genotype. We show that strains possessing this empty-site genotype and strains with a full but inactive hpyIIRM can reacquire the hpyIIRM cassette and functional activity through natural transformation by DNA from the parental R–M+ strain. Identical isolates divergent for the presence of an active HpyII R–M pose different restriction barriers to transformation by foreign DNA. That H. pylori can lose HpyII R–M function through deletion or mutation, and can horizontally reacquire the hpyIIRM cassette, is, in composite, a novel mechanism for R–M regulation, supporting the general hypothesis that H. pylori populations use mutation and transformation to regulate gene function. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) due to severe coronavirus disease 2019 (COVID-19) pneumonia is associated with a high incidence of ventilator-associated pneumonia (VAP). We aimed to evaluate the epidemiology of VAP associated with severe COVID-19 pneumonia. This retrospective observational study recruited patients with COVID-19-associated ARDS admitted to our center from April 1, 2020, to September 30, 2021. The primary outcome was the survival-to-discharge rate. The secondary outcomes were the VAP rate, time to VAP, length of ICU stay, length of ventilator support, and isolated bacteria. Sixty-eight patients were included in this study; 23 developed VAP. The survival-to-discharge rate was 60.9 % in the VAP group and 84.4 % in the non-VAP group. The median time to VAP onset was 16 days. The median duration of ventilator support and of ICU stay were higher in the VAP group than in the non-VAP group. The VAP rate was 33.8 %. The most common isolated species was Stenotrophomonas maltophilia. On admission, carbapenems were used in a maximum number of cases (75 %). Furthermore, the median body mass index (BMI) was lower and the median sequential organ failure assessment (SOFA) score on admission was higher in the VAP group than in the non-VAP group. The survival-to-discharge rate in VAP patients was low. Moreover, VAP patients tended to have long ICU stays, low BMI, and high SOFA scores on admission. Unusually, S. maltophilia was the most common isolated bacteria, which may be related to the frequent use of carbapenems. [ABSTRACT FROM AUTHOR]

We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97–39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors. [ABSTRACT FROM AUTHOR]

Background: Hypervirulent Klebsiella pneumoniae (HVKp) infections have distinct clinical manifestations from classical K. pneumoniae infections. The hallmark of HVKp infections are liver abscess formation and metastatic infections. Due to the severe sequelae of these complications, method to identify patients at-risk of HVKp infections should be developed. Results: A retrospective cohort study of 222 patients with K. pneumoniae bloodstream infections (BSIs) was performed. Patient demographics, clinical manifestations, and bacterial characteristics were investigated. Ten cases of liver abscesses were identified. Characteristics such as community-onset BSIs, hypermucoviscosity phenotype, and capsular serotype K1 were identified as risk factors for HVKp infections. A scoring system was developed based on the risk factors. The area under the receiver operating characteristic curve for the scoring system was 0.90. A score of ≥ 2 points provided sensitivity and specificity of 0.70 and 0.94, respectively. Conclusions: Simple scoring system was developed for the diagnosis of HVKp infections. The system allows early identification of patients with K. pneumoniae BSIs in whom hypervirulent infections should be evaluated. Prospective evaluation is expected. [ABSTRACT FROM AUTHOR]

Vancomycin-intermediately resistant Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are associated with treatment failure. hVISA contains only a subpopulation of cells with increased minimal inhibitory concentrations, and its detection is problematic because it is classified as vancomycin-susceptible by standard susceptibility testing and the gold-standard method for its detection is impractical in clinical microbiology laboratories. Recently, a research group developed a machine-learning classifier to distinguish VISA and hVISA from vancomycin-susceptible S. aureus (VSSA) according to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) data. Nonetheless, the sensitivity of hVISA classification was found to be 76%, and the program was not completely automated with a graphical user interface. Here, we developed a more accurate machine-learning classifier for discrimination of hVISA from VSSA and VISA among MRSA isolates in Japanese hospitals by means of MALDI-TOF MS data. The classifier showed 99% sensitivity of hVISA classification. Furthermore, we clarified the procedures for preparing samples and obtaining MALDI-TOF MS data and developed all-in-one software, hVISA Classifier, with a graphical user interface that automates the classification and is easy for medical workers to use; it is publicly available at . This system is useful and practical for screening MRSA isolates for the hVISA phenotype in clinical microbiology laboratories and thus should improve treatment of MRSA infections. [ABSTRACT FROM AUTHOR]

Introduction: Few studies have investigated the effect of increased creatinine clearance (CrCl) on linezolid (LZD) concentration. Herein, we report the pharmacokinetic/pharmacodynamic (PK/PD) profile of LZD used in the management of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia with concomitant bacteremia in a patient with high CrCl caused by diabetes insipidus (DI). Case Report: A 19-year-old man was admitted to the intensive care unit following a traumatic brain injury. After admission, he underwent a craniotomy for the severe brain injury. However, he developed DI after the operation. Despite treatment with vasopressin, his urine output reached 5-6 L/day as a result of the DI, and his CrCl increased to 180-278 mL/min. We were required to administer 6-7 L of fluid a day to compensate for the high urinary fluid output. On day 55, MRSA pneumonia with sepsis was suspected and, consequently, LZD was administrated intravenously (600 mg every 12 h). He was treated with LZD for 14 days. The patient has since successfully recovered from MRSA pneumonia with concomitant bacteremia, and was transferred to the general ward on day 82. Blood LZD levels from days 60-68, which were measured after the patient's transfer to the general ward, showed that the trough levels were lower than the threshold level of detection. The blood 24-h area under the plasma LZD concentration-time curve (AUC)/minimum inhibitory concentration (MIC) was 69.3. Conclusion: In spite of the low level of LZD AUC/MIC caused by the high CrCl with DI, MRSA pneumonia with concomitant bacteremia was successfully treated with LZD. [ABSTRACT FROM AUTHOR]

Ninety-four episodes of Klebsiella pneumoniae bloodstream infection were identified at a university hospital in Japan. After excluding extended-spectrum beta lactamase-producing strains, 83 blood isolates from these patients were assayed in terms of their bacterial phenotypes such as the mucoid and hypermucoviscosity phenotypes. Bacterial phenotypes were correlated with the patients' clinical manifestations. The hypermucoviscosity phenotype was significantly associated with septic shock at the onset of infections (odds ratio, 15.92; 95% confidence interval, 1.27–468.12), but was not associated with liver abscess formation. Mortality was determined by the presence of septic shock. RmpA gene was associated with the induction of the hypermucoviscosity phenotype. These results reveal unique roles of bacterial phenotypes on the patient's clinical condition in K. pneumoniae bacteremia. [ABSTRACT FROM AUTHOR]

We conducted an antibiotic susceptibility survey of 830 blood-borne methicillin resistant Staphylococcus aureus collected from nationwide hospitals in Japan over a three-year period from January 2008 through May 2011. Antibiotic susceptibility was judged according to the criteria recommended by the Clinical Laboratory Standard Institute. Over 99% of the MRSA showed to be susceptible to teicoplanin, linezolid, sulfamethoxazole/trimethoprim and vancomycin, and over 97% of them were susceptible to daptomycin, arbekacin and rifampin. The majority of the MRSA strains showed resistant to minocycline, meropenem, imipenem, clindamycin, ciprofloxacin, cefoxitin, and oxacillin in the rates of 56.6, 72.9, 73.7, 78.7, 89.0, 99.5, and 99.9%, respectively. Among the MRSA strains, 72 showed reduced susceptibility to vancomycin, including 8 strains (0.96%) of vancomycin-intermediate S. aureus (VISA), 54 (6.51%) of heterogeneous vancomycin-intermediate S. aureus (hVISA), and 55 (5.63%) of β-lactam antibiotics-induced vancomycin resistant S. aureus (BIVR). Unexpectedly, among the 54 hVISA and 55 BIVR, 45 isolates (83.3% and 81.8%, respectively) showed both hVISA and BIVR phenotypes. A new trend of vancomycin resistance found in this study was that VISA strains were still prevalent among the bacteremic specimens. The high rates of the hVISA/BIVR two-phenotypic vancomycin resistance, and the prevalence of VISA in the bloodborne MRSA call attention in the MRSA epidemiology in Japan. [ABSTRACT FROM AUTHOR]

• Emerging resistance to beta-lactams was observed in P. ananatis bacteremia case. • Whole genome analysis showed the presence of inducible class A beta-lactamase gene. • Careful follow-up is necessary during the treatment of P. ananatis infection. We observed an emerging resistance to β-lactams in a P. ananatis bacteremia case. Whole genome sequence analysis detected two β-lactamase genes as well as related genes that regulate the β-lactamase genes in the chromosome. The induction experiment resulted in the expression of the class A β-lactamase gene in the isolate. [ABSTRACT FROM AUTHOR]

The novel conceptual disease model, the oral–gut axis, which represents the immunomodulatory mutual relationship between oral and gut microbial compartments, has been attracting attention in relation to systemic health issues. We investigated whether this unique crosstalk influences the systemic condition of patients with COVID-19 infections who received extracorporeal membrane oxygenation (ECMO) in the intensive care unit (ICU) during April and December 2020. In this case-control study, patients were divided into two groups according to their survival (total entry size, n = 21; survivors, n = 13; non-survivors, n = 8). Patients were evaluated using the oral assessment guide from Fukuoka University (OAG-F) and the Bristol Stool Form Scale (BSFS) to examine the oral and fecal conditions. A blood-based inflammatory factor, the neutrophil-to-lymphocyte ratio (NLR), was used as an indicator of systemic immunity. The high total OAG-F scores were associated with both elevated BSFS and NLR values, and a mutually positive correlation between BSFS and NLR was observed. This indicated an interplay between oral deterioration, gut dysbiosis, and the impairment of immunity. Furthermore, oral deterioration was more frequently observed in non-survivors on day 14 of ICU admission. In addition, on days 7 and 21 of ICU admission, impaired immunity, reflected by an elevated NLR, was observed in non-survivors. However, the distribution of the gut microbiome—reflected by increased BSFS values—with the time it was examined was not directly observed in non-survivors. Taken together, these findings suggested that oral–gut health may be specifically associated with mortality in COVID-19 patients receiving ECMO in the ICU. [ABSTRACT FROM AUTHOR]

The oral health of coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU) is an important issue in treatment of respiratory failure. We retrospectively investigated the oral health history of severe COVID-19 patients who received extracorporeal membrane oxygenation (ECMO) from April 2020 to December 2020 using the oral assessment guide from Fukuoka University (OAG-F). Nineteen consecutive patients (median age: 62 years) were divided into two groups according to survival (survivors, n = 12; non-survivors, n = 7). A univariate analysis revealed no significant differences between the groups in sex, age, body mass index (BMI), or the number of remaining teeth, whereas the ECMO assistance of non-survivors (median: 34 days) was prolonged in comparison to survivors (median: 8 days; p < 0.05). Among the factors of OAG-F, significant differences were observed between the groups in the conditions of the saliva, mucous membrane, and gingiva. The total scores in non-survivors (median: 19) were significantly higher in comparison to survivors (Median: 15.5), suggesting that the frequency of oral health deterioration was higher in non-survivors (p < 0.05). Taken together, these findings suggest that poor oral health is associated with mortality in COVID-19 patients receiving ECMO in the ICU. [ABSTRACT FROM AUTHOR]

Cites clinical reports related to infectious diseases. Fungemia caused by azole-resistant Candida albicans in neutropenic patients with acute leukemia; Campylobacter fetus bacteremia in a patient with adult T cell leukemia; Cholelithiasis possibly induced by protease inhibitors in three patients.