Clinical characteristics and antimicrobial susceptibility of Fusobacterium species isolated over 10 years at a Japanese university hospital.

PURPOSE: Anaerobic bacteria, existing on human skin and mucous membranes, can cause severe infections with complications or mortality. We examined the clinical characteristics of patients infected with Fusobacterium spp. and assessed their antibiotic susceptibility. METHODS: Clinical data were collated from patients diagnosed with Fusobacterium infections in a Japanese university hospital between 2014 and 2023. Antibiotic susceptibility tests were conducted following the Clinical and Laboratory Standards Institute guidelines. RESULTS: We identified 299 Fusobacterium isolates. The median age was 61 years (range, 14-95 years), with females constituting 43.1% of the patients. Most infections were community-acquired (84.6%, 253/299). Multiple bacterial strains were isolated simultaneously in 74.6% of cases. One-fourth of the patients had solid organ malignancies (25.4%, 76/299), and 14.5% (11/76) of those had colorectal cancer. The 30-day mortality rate was 1.3%. Fusobacterium species were isolated from blood cultures in 6% (18/299) of the patients. Patients, aged 75 years or older, with cerebrovascular disease or hematologic malignancy exhibited significantly higher prevalence of blood culture isolates in univariate analysis. Each Fusobacterium species had its characteristic infection site. Approximately 5% F. nucleatum and F. necrophorum isolates showed penicillin G resistance. Moxifloxacin resistance was observed in varying degrees across strains, ranging from 4.6 to 100% of isolates. All isolates were sensitive to ß-lactam/ß-lactamase inhibitors, carbapenems, and metronidazole. CONCLUSION: We show a link between Fusobacterium species and solid organ malignancies. We observed resistance to penicillin, cefmetazole, clindamycin, and moxifloxacin, warranting caution in their clinical use. This study offers valuable insights for managing Fusobacterium infections and guiding empirical treatments.

Retrospective study to investigate appropriate duration of antibiotic treatment for uncomplicated Staphylococcus aureus bacteremia in patients with immunodeficiency.

BACKGROUND: Since the appropriate antibiotic duration for uncomplicated Staphylococcus aureus (S. aureus) bacteremia (u-SAB) in an immunocompromised state is still unclear, physicians are likely to extend antibiotic therapy from 2 weeks to 4-6 weeks. To examine the appropriate duration of antibiotic therapy for u-SAB, we performed this study. PATIENTS AND METHODS: We reviewed all patients with u-SAB at our institute seen between January 2020 and August 2023. A total of 51 patients were enrolled, and they were divided into the following two groups by antibiotic duration: longer duration group ≥28 days after blood culture negativity, and shorter duration group. Then, the patients were matched by a propensity score using the covariates of age, sex, qSOFA, and CCI. The primary outcome was to identify the prognosis by duration of antibiotic treatment. RESULTS: After propensity score matching, all-cause 30-day mortality was 0 % in both groups. Hence, there was no significant difference in all-cause 90 days mortality (19.0% vs 9.5%, p = 0.33) or recurrence (9.5%% vs 0%, p = 0.22). Before propensity-score matching, we found that a serum level of CRP 2.0 mg/dL and greater after intravenous antibiotic treatment was one of the poor prognostic factors. The cut-off value of serum CRP level was 2.0 mg/dL with a sensitivity of 82.1% and a specificity of 75.0%. CONCLUSION: We suggested that 4-6 weeks of antibiotic treatment for immunodeficient u-SAB patients was unnecessary. Moreover, the serum level of CRP after completion of IV antibiotic treatment could be a prognostic marker for u-SAB.

Epidemiological study of respiratory syncytial virus infection in adults during the pandemic of COVID-19.

INTRODUCTION: While respiratory syncytial virus (RSV) is one of the most common pathogens in adults admitted to the ICU due to respiratory diseases, no reports regarding the occurrence rate of RSV infections in adults in Japan during the COVID-19 pandemic exist. PATIENTS AND METHODS: We conducted this retrospective study to examine the exact occurrence rate of RSV infections in adults. We reviewed all patients (≥18 years) with any respiratory symptoms who received quantitative polymerase chain reaction (PCR) using nasopharyngeal samples for respiratory viruses by GeneLEAD at the Aichi Medical University Hospital between November 2022 and November 2023. RESULTS: A total of 541 adult patients who underwent PCR test were enrolled in this study. RSV was identified in 18 cases (3.3 %); 8 (1.5 %) upper and 10 (1.8 %) lower respiratory tract infections. Influenza A and SARS-CoV-2 were found in 10 (1.8 %) and 61 (11.3 %), respectively. Patients with RSV infections and COVID-19 had more comorbidities than those with Influenza virus infections. As for RSV-associated with lower respiratory tract infection cases, 10 developed acute respiratory failure, resulting in 1 fatal case due to pneumonia and 1 died of septic shock due to ileus. The 30-, 90-day mortality rates were 1 (6 %) and 2 (11 %) respectively. CONCLUSION: About 3 % of adults had RSV infections during the COVID-19 pandemic. The outcomes of RSV infections in adults were similar to those by COVID-19. Those with comorbidities should have a preventive method against RSV infections, the same as for COVID-19.

Complicated pyelonephritis caused by Proteus alimentorum in a woman with peritoneal cancer: a case report.

BACKGROUND: Proteus spp. are widespread in the environment and comprise a part of the normal flora of the human gastrointestinal tract. Only six species in this genus, including Proteus mirabilis, Proteus vulgaris, Proteus terrae, Proteus penneri, Proteus hauseri, and Proteus faecis, have been isolated from human clinical specimens. However, there are no reports of Proteus alimentorum isolated from humans, and the clinical characteristics of P. alimentorum infection are unknown. CASE PRESENTATION: An 85-year-old female patient with peritoneal cancer was hospitalized for complicated pyelonephritis and bacteremia caused by P. alimentorum. The patient received antimicrobial therapy and was discharged on day 7 of hospitalization. No recurrence was observed 14 days after the treatment. Various methods were used to identify the Proteus sp. Furthermore, the VITEK-2 GN ID card resulted in low discrimination between P. hauseri and P. penneri. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry showed P. hauseri with a spectral score of 2.22 as the best match. Nevertheless, the pathogen was identified as P. alimentorum based on genetic investigation using 16 S rRNA gene sequencing and biochemical tests. CONCLUSION: Proteus alimentorum is a human pathogen, and its infection has an excellent therapeutic response to antimicrobials based on antimicrobial susceptibility. Genomic methods may be helpful for the precise identification of P. alimentorum.

Prescribed probiotic usage to prevent Clostridioides difficile infection among older patients receiving antibiotics: A retrospective cohort study.

OBJECTIVES: Clostridioides difficile infection (CDI) is a leading cause of antimicrobial-associated colitis and is a global clinical concern. Probiotics are considered a CDI-preventive measure; however, highly inconsistent data have been previously reported. Thus, we evaluated the CDI-preventive effect of prescribed probiotics in high-risk older patients receiving antibiotics. METHODS: Older patients (aged ≥65 years) admitted to the emergency department who received antibiotics between 2014 and 2017 were enrolled in this single-center retrospective cohort study. Propensity score-matched analysis was used to compare the CDI incidence in patients who took the prescribed probiotics within 2 days of receiving antibiotics for at least 7 days with those who did not. The rates of severe CDI and associated hospital mortality were also evaluated. RESULTS: Among 6148 eligible patients, 221 were included in the prescribed probiotic group. A propensity score-matched (221 matched pairs) well-balanced for patient characteristics was obtained. The incidence of primary nosocomial CDI did not differ significantly between the prescribed and non-prescribed probiotic groups (0% [0/221] vs. 1.0% [2/221], p = 0.156). Of the 6148 eligible patients, 0.5% (30/6148) developed CDI, with a severe CDI rate of 33.3% (10/30). Furthermore, no CDI-associated in-hospital mortality was observed in the study cohort. CONCLUSIONS: The evidence from this study does not support recommendations for the routine use of prescribed probiotics to prevent primary CDI in older patients receiving antibiotics in situations where the CDI is infrequent.

Usefulness of the FilmArray blood culture identification panel for identifying causative pathogens of bone and joint infections.

As bone and joint infections (BJIs) require long-term treatment, identifying their causative pathogens is vital. However, the detection rate of conventional culturing remains inadequate. This study aimed to evaluate the usefulness of the FilmArray blood culture identification (BCID) panel for identifying causative pathogens in patients with BJIs. We tested a BCID panel using collected samples, in addition to conventional cultures. The primary outcome was to evaluate the diagnostic performance of the BCID panel, calculated using conventional culturing methods. A total of 44 patients who underwent BJI-related specimen collection were enrolled. Of the 44 patients, 22 were diagnosed with a BJI. Conventional culture identified 15 of 22 organisms (68.2%), whereas the BCID panel identified 14 of 22 organisms (63.4%). The overall sensitivity and specificity of the BCID panel were 73.3% and 57.1%, respectively, compared to those of the conventional culture. However, the sensitivity reached 100% when only pathogens included in the BCID panel were considered. In seven culture-negative cases, the BCID panel identified three organisms (42.9%). The BCID panel also indicated the appropriate therapy against a BJI caused by methicillin-resistant Staphylococcus aureus by detecting the mecA gene. This study demonstrated that the BCID panel has the potential for early and accurate diagnosis of the causative organism of BJI using specimens such as joint fluid and bone tissue. Our results suggest that BCID panels, in addition to routine culture, may improve our ability to diagnose the causative microorganisms of BJI in clinical practice, thereby contributing to the selection of appropriate antimicrobial agents.

Diagnostic significance of secondary bacteremia in patients with COVID-19.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A systematic review and meta-analysis of efficacy and safety of isavuconazole for the treatment and prophylaxis of invasive fungal infections.

BACKGROUND: Isavuconazole is a novel triazole antifungal agent. However, the previous outcomes were highlighted by statistical heterogeneity. This meta-analysis aimed to validate the efficacy and safety of isavuconazole for the treatment and prophylaxis of invasive fungal infections (IFIs) compared with other antifungal agents (amphotericin B, voriconazole and posaconazole). METHODS: Scopus, EMBASE, PubMed, CINAHL and Ichushi databases were searched for relevant articles that met the inclusion criteria through February 2023. Mortality, IFI rate, discontinuation rate of antifungal therapy and incidence of abnormal hepatic function were evaluated. The discontinuation rate was defined as the percentage of therapy discontinuations due to adverse events. The control group included patients who received other antifungal agents. RESULTS: Of the 1784 citations identified for screening, 10 studies with an overall total of 3037 patients enrolled. Isavuconazole was comparable with the control group in mortality and IFI rate in the treatment and prophylaxis of IFIs, respectively (mortality, odds rate (OR) 1.11, 95% confidential interval (CI) 0.82-1.51; IFI rate, OR 1.02, 95% CI 0.49-2.12). Isavuconazole significantly reduced the discontinuation rate in the treatment (OR 1.96, 95% CI 1.26-3.07) and incidence of hepatic function abnormalities in the treatment and prophylaxis, compared with the control group (treatment, OR 2.31, 95% CI 1.41-3.78; prophylaxis, OR 3.63, 95% CI 1.31-10.05). CONCLUSIONS: Our meta-analysis revealed that isavuconazole was not inferior to other antifungal agents for the treatment and prophylaxis of IFIs, with substantially fewer drug-associated adverse events and discontinuations. Our findings support the use of isavuconazole as the primary treatment and prophylaxis for IFIs.

Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study.

BACKGROUND: Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19. METHODS: We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections. RESULTS: Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil-lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality. CONCLUSIONS: Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.

Invasive pectoral abscess and costal osteomyelitis with bloodstream infection caused by methicillin-resistant Staphylococcus aureus after nasal septoplasty in an immunocompetent adult patient.

There are few reports of multilocus sequence type (ST) 5/staphylococcal cassette chromosome (SCC) mec type IVc/toxic shock syndrome toxin (TSST)-1- positive methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections. We report a case of community-onset MRSA (CO-MRSA) bloodstream infection in a healthy 41-year-old Japanese man after nasal septoplasty, followed by pectoral abscess and costal osteomyelitis. The patient presented with right anterior chest pain and fever. After admission, MRSA was isolated from two sets of blood cultures, and vancomycin was administered. On the fifth day, contrast-enhanced computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging (MRI) scan showed an abscess in the right anterior chest to the right subpleural region. The dosage of vancomycin (4 g/day) did not reach the effective blood concentration; therefore, there was a switch to daptomycin. On the 23rd day, contrast-enhanced MRI revealed osteomyelitis of the right first rib, and as a result, linezolid was initiated. Two weeks later, contrast-enhanced CT of the chest showed improvement in the abscess. The patient was treated for 6 weeks during hospitalization and then switched to minocycline for 10 weeks. Molecular characterization of this isolate showed that it was ST5/SCCmec type IVc/TSST-1-positive/Panton-Valentine leucocidin (PVL)-negative. PVL-negative CO-MRSA can lead to hematogenous osteomyelitis and abscess even if the patient is immunocompetent, and if isolated from blood cultures, it is important to repeat imaging studies, even if the initial imaging studies were normal. It is possible that this strain contributes to the pathogenesis of invasive CO-MRSA, but further case accumulation is needed.

Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Fidaxomicin (FDX) has received considerable attention as a novel therapeutic alternative agent to vancomycin (VCM) for Clostridioides difficile infection (CDI). However, the superiority and efficacy profile of FDX are not sufficiently determined by high-quality evidence. This study aimed to clarify the superiority of FDX for CDI treatment through a systematic review and meta-analysis. METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) which evaluated the efficacy and safety of FDX and VCM in patients with CDI. Electronic databases (PubMed, Cochrane Library, Web of Science, and Clinicaltrials.gov) were searched for studies published until October 15, 2021. The primary endpoint was global cure. The secondary endpoints were clinical cure, recurrence, and adverse event. Risk ratios (RRs), risk differences (RDs), and 95% confidence intervals were calculated using Mantel-Haenszel random-effects model. The risk of bias was assessed using Cochrane Handbook for Systematic Reviews of Interventions and Assessment Criteria. RESULTS: Six RCTs were included in this meta-analysis. Compared to VCM, FDX was associated with significantly higher global cure rates (RR = 1.18, P < 0.00001; RD = 0.11, 95% CI = 0.07-0.16). In addition, clinical cure rates were comparable between FDX and VCM (P = 0.31). FDX was associated with significantly lower recurrence rates compared to VCM (RR = 0.59, P < 0.0001). In addition, adverse event rates were not significantly different between the drugs (P = 0.41). CONCLUSION: FDX achieves significantly higher global cure rates and lower recurrence rates and is comparable to VCM in clinical cure rates and adverse event rates in patients with CDI. Collectively, FDX is superior to VCM as a therapeutic agent for CDI.

Multisystem Inflammatory Syndrome in Adults after Mild SARS-CoV-2 Infection, Japan.

In Japan, a 51-year-old man had minimally symptomatic severe acute respiratory syndrome coronavirus 2 infection. Multisystem inflammatory syndrome was diagnosed ≈5 weeks later; characteristics included severe inflammation, cardiac dysfunction, and IgG positivity. Clinicians should obtain detailed history and examine IgG levels for cases of inflammatory disease with unexplained cardiac decompensation.

Photo-on-Demand Synthesis of Vilsmeier Reagents with Chloroform and Their Applications to One-Pot Organic Syntheses.

The Vilsmeier reagent (VR), first reported a century ago, is a versatile reagent in a variety of organic reactions. It is used extensively in formylation reactions. However, the synthesis of VR generally requires highly toxic and corrosive reagents such as POCl3, SOCl2, or COCl2. In this study, we found that VR is readily obtained from a CHCl3 solution containing N,N-dimethylformamide or N,N-dimethylacetamide upon photo-irradiation under O2 bubbling. The corresponding Vilsmeier reagents were obtained in high yields with the generation of gaseous HCl and CO2 as byproducts to allow their isolations as crystalline solid products amenable to analysis by X-ray crystallography. With the advantage of using CHCl3, which bifunctionally serves as a reactant and a solvent, this photo-on-demand VR synthesis is available for one-pot syntheses of aldehydes, acid chlorides, formates, ketones, esters, and amides.

Disseminated Mycobacterium abscessus subspecies massiliense infection and subsequent prosthetic joint infection in a hemodialysis patient: A case report.

A 74-year-old man with diabetic nephropathy undergoing dialysis after total knee arthroplasty presented to our hospital with dyspnea and abnormal behavior such as wearing his pants on his head. The patient was in shock with ventricular tachycardia. Urine and blood cultures showed MAM with sterile pyuria. We administered amikacin and imipenem cilastatin, but repeated cultures were persistently positive. Although we initially chose not to administer azithromycin because of a higher risk of fatal arrhythmia, we had no choice but to administer azithromycin because of treatment failure. Upon close monitoring, we observed no arrhythmia, and the blood cultures became negative. The patient was discharged on day 106 without any symptoms. However, 2 months after discontinuation of antibiotics, he was readmitted and diagnosed with prosthetic joint infection due to MAM. He could not undergo total knee arthroplasty resection because of his low tolerance to surgery. We re-administered same antibiotics, and repeated draining and cleaning of his left knee for several weeks. The inflammation in the knee joint gradually improved, and the patient was discharged while treatment with azithromycin and amikacin was continued. After being discharged, the patient did not experience recurrent disease for at least 6 months. Our case suggests that MAM can cause sterile pyuria and infection in a patient with diabetic nephropathy. The macrolide agent is a key drug for MAM infection, and repeated joint lavage in addition to administering antibiotics may be an alternative treatment for prosthetic joint infection in patients with intolerance to surgery.

Comparison of 0.5% chlorhexidine gluconate alcohol with 10% povidone-iodine for skin disinfection in children to prevent blood culture contamination.

INTRODUCTION: Various disinfectants, such as povidone iodine (PVI)1, alcohol preparations, and chlorhexidine gluconate ethanol (CHG-ALC), are used for disinfection prior to blood sampling for culture. METHODS: This retrospective cohort study compared the usefulness and effectiveness of CHG-ALC and PVI in pediatric venipuncture. We applied 0.5% w/v CHG-ALC or 10% PVI as an antiseptic for phlebotomies on pediatric outpatients and inpatients with suspected bacterial infection between November 2017 and April 2019. We conducted logistic regression analysis to define the differences associated with the choice of disinfectant, collection site, and the staff member collecting the blood sample (explanatory variables) and the presence of contamination (objective variable). Based on these results, we performed propensity score matching. RESULTS: The total number of specimens was 1460. The propensity score matching indicated that CHG-ALC reduced the incidence of blood culture contamination more effectively than PVI (0.4%, 2/479 cultures versus 2.5%, 12/479 cultures; relative risk, 0.163 [95% confidence interval, 0.036 to 0.733]; P = 0.012). There were no differences in the contamination rates between cultures of blood drawn from a vascular catheter and those of blood obtained percutaneously. Higher contamination rates were found when junior residents performed the venipuncture. CONCLUSIONS: Compared with PVI, CHG-ALC dries rapidly with no pigmentation and has a long-lasting antiseptic effect. Overall, CHG-ALC skin preparations were more efficacious than the PVI preparations for blood sampling in children.

Epstein-Barr virus-related encephalitis in a young woman: A case report.

Although infectious mononucleosis due to Epstein-Barr virus (EBV) is a common disease among young individuals, central nervous system (CNS) complications are rare. In this report, we describe a case of CNS complications caused by EBV in a previously healthy young woman. She presented to our hospital with a 9-day history of headache and sore throat, followed by the development of fever and facial edema 6 days prior to admission. On Day 2 of admission, she was confused (Glasgow Coma Scale score: 10 points) and had fever, muscle weakness in her right arm and leg, stiff neck, and roving eye movement. We detected EBV in a cerebrospinal fluid (CSF) sample using a polymerase chain reaction (PCR) test. The magnetic resonance imaging of her brain revealed dural enhancement and right parietal and temporal lobe lesions. She was treated with acyclovir and high-dose steroid therapy. She responded well to treatment, recovered without neurologic sequelae, and was discharged home on Day 12. Our experience suggests that PCR detection of EBV DNA in CSF may be useful in diagnosing EBV encephalitis and that prognosis may be associated with an area of the brain that is affected and the time from symptom onset to starting treatment.

Clinical and molecular analyses of bloodstream infections caused by IMP metallo-ß-lactamase-producing Enterobacteriaceae in a tertiary hospital in Japan.

Carbapenemase-producing Enterobacteriaceae infection has been reported worldwide and is a major threat to public health. However, reports of bloodstream infection (BSI) caused by metallo-ß-lactamase (MBL), especially the IMP-type, are limited. Therefore, we aimed to investigate the clinical and microbial characteristics of patients with BSI caused by IMP-type MBL-producing Enterobacteriaceae (MBL-E) in a tertiary care hospital in Japan. The clinical data were collected from medical charts for all the patients. A next-generation sequencing approach and multilocus sequence typing were used to identify antimicrobial resistance genes. Six patients were enrolled and had severe conditions on admission. The sources of MBL-E BSI were as follows: catheter-related BSI, pyelonephritis, cholangitis, and bacterial peritonitis. No isolate was resistant to levofloxacin or aminoglycoside. Microbiological response rates were 100%. The all-cause 30-day mortality rate was 50%. Of the six isolates, three were Enterobacter hormaechei sequence type 78, one was Enterobacter cloacae Hoffman cluster IV ST997, and two were Klebsiella pneumoniae (ST134 and ST252). All isolates produced IMP-1 and carried blaIMP-1 gene and various antimicrobial resistance genes. The results of this study showed that MBL-E BSI was fatal, although rare, in patients with severe diseases and long-term hospitalization. Further research is necessary to determine the appropriate treatment strategies for MBL-producing BSI.

Streptococcal toxic shock syndrome following group A streptococcal vulvovaginitis in a breastfeeding woman.

Streptococcal toxic shock syndrome (STSS) is a systemic, life-threatening illness usually caused by invasive respiratory tract or skin and soft tissue infections of Streptococcus pyogenes (group A streptococcus, GAS). We report the case of an adult woman with lactational amenorrhea and GAS vulvovaginitis progressing to STSS. She was admitted to our hospital because of fever, lethargy, and a 2-week history of vaginal discharge; she also had hypotension and multiple organ failure. Blood and urine cultures yielded gram-positive cocci and GAS. After 14 days of antimicrobial therapy, she fully recovered without any complications. The vulvovaginitis was most likely the portal of entry for GAS, which is rarely recognized as a causative pathogen of vulvovaginitis. Lactational amenorrhea is thought to be a risk factor for GAS vulvovaginitis. It is important for clinicians to recognize the possibility of GAS vulvovaginitis in breastfeeding women with vaginal symptoms and consider the necessity of prompt antibiotic treatment.

Performance of laboratory tests for detection for Clostridioides difficile: A multicenter prospective study in Japan.

BACKGROUND: The optimal and practical laboratory diagnostic approach for detection of Clostridioides difficile to aid in the diagnosis of C. difficile infection (CDI) is controversial. A two-step algorithm with initial detection of glutamate dehydrogenase (GDH) or nucleic acid amplification test (NAAT) alone are recommended as a predominant method for C. difficile detection in developed countries. The aim of this study was to compare the performance of enzyme immunoassays (EIA) detecting toxins A and B, NAAT detecting the toxin B gene, and GDH compared to toxigenic culture (TC) for C. difficile as the gold standard, in patients prospectively and actively assessed with clinically significant diarrhea in 12 medical facilities in Japan. METHODS: A total of 650 stool specimens were collected from 566 patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h. EIA and GDH were performed at each hospital, and NAAT and toxigenic C. difficile culture with enriched media were performed at the National Institute of Infectious Diseases. All C. difficile isolates recovered were analyzed by PCR-ribotyping. RESULTS: Compared to TC, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EIA were 41%, 96%, 75% and 84%, respectively, and for NAAT were 74%, 98%, 91%, and 92%, respectively. In 439 specimens tested with GDH, the sensitivity, specificity, PPV, and NPV were 73%, 87%, 65%, and 91%, and for an algorithm (GDH plus toxin EIA, arbitrated by NAAT) were 71%, 96%, 85%, and 91%, respectively. Among 157 isolates recovered, 75% of isolates corresponded to one of PCR-ribotypes (RTs) 002, 014, 018/018", and 369; RT027 was not isolated. No clear differences in the sensitivities of any of EIA, NAAT and GDH for four predominant RTs were found. CONCLUSION: The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile in this study were lower than most previous reports. This study also found low PPV of EIAs. The optimal method to detect C. difficile or its toxins to assist in the diagnosis of CDI needs further investigation.

Clostridioides (Clostridium) difficile infection burden in Japan: A multicenter prospective study.

Clostridioides (Clostridium) difficile is the leading cause of healthcare-associated infectious diarrhea in the developed world. Retrospective studies have shown a lower incidence of C. difficile infection (CDI) in Japan than in Europe or North America. Prospective studies are needed to determine if this is due lack of testing for C. difficile or a true difference in CDI epidemiology. A prospective cohort study of CDI was conducted from May 2014 to May 2015 at 12 medical facilities (20 wards) in Japan. Patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h were enrolled. CDI was defined by positive result on enzyme immunoassay for toxins A/B, nucleic acid amplification test for the toxin B gene or toxigenic culture. C. difficile isolates were subjected to PCR-ribotyping (RT), slpA-sequence typing (slpA-ST), and antimicrobial susceptibility testing. The overall incidence of CDI was 7.4/10,000 patient-days (PD). The incidence was highest in the five ICU wards (22.2 CDI/10,000 PD; range: 13.9-75.5/10,000 PD). The testing frequency and CDI incidence rate were highly correlated (R2 = 0.91). Of the 146 isolates, RT018/018″ was dominant (29%), followed by types 014 (23%), 002 (12%), and 369 (11%). Among the 15 non-ICU wards, two had high CDI incidence rates (13.0 and 15.9 CDI/10,000 PD), with clusters of RT018/slpA-ST smz-02 and 018"/smz-01, respectively. Three non-RT027 or 078 binary toxin-positive isolates were found. All RT018/018" isolates were resistant to moxifloxacin, gatifloxacin, clindamycin, and erythromycin. This study identified a higher CDI incidence in Japanese hospitals than previously reported by actively identifying and testing patients with clinically significant diarrhea. This suggests numerous patients with CDI are being overlooked due to inadequate diagnostic testing in Japan.