Antimicrobial therapy and outcome of methicillin-resistant Staphylococcus aureus endocarditis: A retrospective multicenter study in Japan.

BACKGROUND: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis. METHODS: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019. RESULTS: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis. CONCLUSION: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents.

Clinical characteristics and analysis of prognostic factors in methicillin-resistant Staphylococcus aureus endocarditis: A retrospective multicenter study in Japan.

BACKGROUND: Infective endocarditis (IE) caused by MRSA (methicillin-resistant Staphylococcus aureus) is associated with a high mortality rate. This study aimed to elucidate the characteristics of patients with MRSA-IE in Japan and identify the factors associated with prognosis. METHODS: This retrospective study included patients with a confirmed diagnosis of IE caused by MRSA, between January 2015 and April 2019. RESULTS: A total of 65 patients from 19 centers were included, with a mean age of 67 years and 26 % were female. Fifty percent of the patients with IE were had nosocomial infections and 25 % had prosthetic valve involvement. The most common comorbidities were hemodialysis (20 %) and diabetes (20 %). Congestive heart failure was present in 86 % of patients (NYHA class I, II: 48 %; III, IV: 38 %). The 30-day and in-hospital mortality rates were 29 % and 46 %, respectively. Multi-organ failure was the primary cause of death, accounting for 43 % of all causes of death. Prognostic factors for in-hospital mortality were age, disseminated intravascular coagulation, daptomycin and/or linezolid as initial antibiotic therapy, and surgery. Surgical treatment was associated with a lower mortality rate (odds ratio [OR], 0.026; 95 % confidence interval [CI], 0.002-0.382; p = 0.008 for 30-day mortality and OR, 0.130; 95 % CI; 0.029-0.584; p = 0.008 for in-hospital mortality). CONCLUSION: Mortality due to MRSA-IE remains high. Surgical treatment is a significant prognostic predictor of MRSA-IE.

Is trimethoprim/sulfamethoxazole-associated increase in serum creatinine a pseudo-elevation or true nephrotoxicity?

INTRODUCTION: The aim of this study was to determine the rates of trimethoprim/sulfamethoxazole (TMP/SMX)-associated pseudo-elevation and true nephrotoxicity by comparison of creatinine-estimated and cystatin C-estimated GFRs (glomerular filtration rates) before and after TMP/SMX administrations. METHODS: Patients in whom serum creatinine and cystatin C were simultaneously measured are the cohort of this study. A decreasing of creatinine-estimated GFR posterior to TMP/SMX by ≥ 20% and a decreasing of cystatine C-estimated GFR posterior to TMP/SMX by ≥ 20% were defined as true nephrotoxicity. A decreasing of creatinine-estimated GFR posterior to TMP/SMX by ≥ 20% and a decreasing of cystatine C-estimated GFR posterior to TMP/SMX by < 20% were defined as pseudo-elevation. RESULTS: A total of 66 patients were enrolled. Within the 19 patients in whom serum creatinine and cystatin C were measured simultaneously both before and after TMP/SMX administrations, 10 patients (52.6%) had nephrotoxicity. Fewer random error and systematic bias between creatinine- and cystatine C-estimated GFR were observed after TMP/SMX than before TMP/SMX by Bland-Altman analysis. CONCLUSIONS: Using cystatin C, we reveled TMP/SMX-associated nephrotoxicity is not uncommon. We should equally pay attention to TMP/SMX-associated nephrotoxicity and pseudo-elevation. In spite of pseudo-elevation, creatinine-estimated GFR after receiving TMP/SMX is ironically reliable as surrogate maker for renal clearance.

Clinical pharmacokinetic and pharmacodynamic analysis of daptomycin and the necessity of high-dose regimen in Japanese adult patients.

The objective of this study was to explore the optimal dosage regimen of daptomycin and to determine the necessity and validity of a high-dose regimen from the perspectives of PK/PD parameters using Monte Carlo Simulation (MCS) and therapeutic drug monitoring (TDM) in a Japanese clinical setting. The volume of distribution (0.13 ± 0.012 L/kg) in this study was greater than that in healthy volunteers reported in Japan. The range of half-lives was between 8.9 and 34.9 h, which were gradually prolonged as creatinine clearance decreased. In MCS, the cumulative fractions of response (CFR) of the peak/MIC â‰§ 60 and the AUC/MIC â‰§ 666 at the 6 mg/kg q 24 h were 72.0% and 78.8% but at the 10 mg/kg q 24 h, the CFRs improved to both 99%. In TDM with 6 mg/kg q 24 h regimen, the patients who reached the peak and AUC target were 40% (2 out of 5 patients), respectively. The intraindividual variability in daptomycin PK may indicate the necessity of TDM and high-dose regimen, such as over 8 mg/kg, may be needed to ensure the effectiveness especially on Japanese patients with normal renal function.

Clinical utility of direct application of matrix-assisted laser desorption ionization time-of-flight mass spectrometry and rapid disk diffusion test in presumptive antimicrobial therapy for bacteremia.

OBJECTIVE: To study how and to what degree the rapid pathogen identification by MALDI-TOF MS coupled with rapid disk diffusion test improve the current clinical practice of patients with bacteremia in a tertiary teaching hospital with full-time ID consultation service. PATIENTS AND METHODS: MALDI-TOF MS and 8H disk diffusion tests were directly applied to the positive blood cultures samples and the results were reflected on antimicrobial therapy (n = 119). The appropriateness of antimicrobial selection through these interventions was verified with conventional culture results in comparison with historical control (n = 129). The mortality of patients between the two periods was also compared. RESULTS: The appropriateness of antimicrobial selection was higher (99.2%) in the intervention than in the control group (93.8%) (p 0.024), but there was no difference in 28-day mortality between the two periods (16.8%, 14.8%) (p 0.668). The duration of presumptive antimicrobial therapy with anti-MRSA agents and carbapenem antibiotics did not differ between the two periods indicating that the intervention was not effective in decreasing the unnecessary antibiotics. On the other hand, some bacteremic patients with pathogens whose drug susceptibilities were invariably sensitive to the standard class of antibiotics definitely benefitted from the intervention. CONCLUSION: The intervention utilizing MALDI-TOF MS and the rapid disk diffusion test may not demonstrate overall improvement in bacteremia mortality in the institution with full-time infectious disease consultants. Its utility has yet to be evaluated in different setting hospitals.

Staphylococcus saprophyticus native valve endocarditis in a diabetic patient with neurogenic bladder: A case report.

A 61-year-old man was admitted to our hospital with 2-day history of malaise and dyspnea. He had mitral prolapse and type II diabetes mellitus with neurogenic bladder, which was cared for by catheterization on his own. On arrival the patient was in septic condition with hypoxemia, and physical examination revealed systolic murmur at the apex. Transthoracic echocardiography revealed vegetation of the mitral and the aortic valve. The presence of continuous bacteremia was confirmed by multiple sets of blood culture, whereby gram-positive cocci was retrieved and identified as Staphylococcus saprophyticus (S. saprophyticus) both phenotypically and genetically. Because two major criteria of the Modified Duke Criteria were met, the patient was diagnosed with native valve endocarditis due to S. saprophyticus. The urine culture was also positive for gram-positive cocci, phenotypically identified as Staphylococcus warneri, which was subsequently identified as S. saprophyticus with the use of 16S rRNA gene sequence analysis and MALDI-TOF MS (matrix-assisted laser desorption ionization time of flight mass spectrometry), indicating strongly that the intermittent catheterization-associated urinary tract infection resulted in bacteremia that eventually lead to infective endocarditis. This patient was treated with vancomycin and clindamycin. Because of multiple cerebral infarctions, the patient underwent mitral and aortic valve replacement on hospital day 5. Blood culture turned negative at 6th hospital day. Antibiotic therapy was continued for six weeks after surgery. The patient's clinical course was uneventful thereafter, and was discharged home. This is the first case report of native valve endocarditis caused by S. saprophyticus of confirmed urinary origin.

Clinical features of enterococcal bacteremia due to ampicillin-susceptible and ampicillin-resistant enterococci: An eight-year retrospective comparison study.

Enterococcus consists human bowel flora, but sometimes behave as an important nosocomial pathogen. In order to identify clinical characteristics that help discriminate between ampicillin-susceptible and ampicillin-resistant enterococcal bacteremia in advance for antimicrobial susceptibility testing, a retrospective eight-year study was carried out in patients with enterococcal bacteremia experienced in Saga University Hospital, Japan. A total of 143 patients were included in the analysis: 85 (59.4%) with bacteremia caused by ampicillin-susceptible enterococci and 58 (40.6%) by ampicillin-resistant strains. Hospital-acquired bacteremia was present in 79.0% (113/143) of patients. Abdominal infections, urinary tract infections, and unknown source were predominant foci for the two groups. Patients with ampicillin-resistant enterococcal bacteremia was significantly associated with hematological cancer, immunosuppressive therapy, prior use of antibiotics, and mucositis associated with febrile neutropenia. The 28-day mortality was significantly higher in ampicillin-resistant enterococcal bacteremia. On multivariate analysis, independent risk factors for ampicillin-resistant enterococci were as follows: prior exposures to penicillins and carbapenems, and bacteremia related to mucositis with febrile neutropenia. These findings would assist physicians in deciding whether glycopeptide antibiotics should be included as an empiric antibiotic therapy in patients with suspected enterococcal infections and also those with persistent neutropenic fever refractory to fourth generation cephalosporin. A few cases of MALDI-TOF MS-identified Enterococcus faecium that turned out ampicillin-sensitive were also described to emphasize the importance of taking epidemiological aspects of patients into considerations when deciding initial antimicrobial treatment.

Cumulative exposure to ritonavir-boosted atazanavir is associated with cholelithiasis in patients with HIV-1 infection.

OBJECTIVES: This study aimed to examine the effect of long-term treatment with ritonavir-boosted atazanavir (atazanavir/ritonavir) on cholelithiasis. METHODS: A single-centre, cross-sectional study was conducted to elucidate the prevalence of cholelithiasis in patients with HIV-1 infection who underwent abdominal ultrasonography between January 2004 and March 2013. Univariate and multivariate logistic regression analyses were applied to estimate the effects of >2 years of atazanavir/ritonavir exposure on cholelithiasis as the primary exposure. RESULTS: Of the 890 study patients, 84 (9.4%) had >2 years of atazanavir/ritonavir exposure. Cholelithiasis was twice as frequent in those treated for >2 years with atazanavir/ritonavir [15 (18%) of 84 patients] compared with those treated for <2 years [72 (8.9%) of 806 patients] (P = 0.018). Univariate analysis showed a significant association between >2 years of atazanavir/ritonavir exposure and cholelithiasis (OR = 2.216; 95% CI = 1.206-4.073; P = 0.010) and the association almost persisted in multivariate analysis (adjusted OR = 1.806; 95% CI = 0.922-3.537; P = 0.085). Long-term treatment (>2 years) with other commonly used protease inhibitors, such as ritonavir-boosted lopinavir and ritonavir-boosted darunavir, was not associated with cholelithiasis in univariate and multivariate analysis. Additional analysis showed that >1 year of exposure to atazanavir/ritonavir was significantly associated with cholelithiasis (OR = 1.857; 95% CI = 1.073-3.214; P = 0.027), whereas >1 year of exposure to ritonavir-boosted lopinavir and ritonavir-boosted darunavir was not. CONCLUSIONS: Long-term treatment of patients with HIV-1 infection for >2 years with atazanavir/ritonavir was associated with an increased risk of cholelithiasis compared with patients with shorter exposure. Long-term exposure to atazanavir/ritonavir appears to increase the risk of cholelithiasis in patients with HIV-1 infection.

Single-nucleotide polymorphisms in the UDP-glucuronosyltransferase 1A-3' untranslated region are associated with atazanavir-induced nephrolithiasis in patients with HIV-1 infection: a pharmacogenetic study.

OBJECTIVES: Ritonavir-boosted atazanavir (atazanavir/ritonavir) is a widely used antiretroviral drug, though it can potentially cause nephrolithiasis. The aim of this study was to determine the relationship between polymorphisms in genes encoding proteins involved in metabolism and transportation of atazanavir, and atazanavir/ritonavir-induced nephrolithiasis in HIV-1-infected patients treated with atazanavir/ritonavir. METHODS: Nineteen SNPs in the ABCB1, NR1I2, UGT1A1, SLCO1B1 and CYP3A5 genes were examined in case patients with atazanavir/ritonavir-induced nephrolithiasis (n = 31) and controls (n = 47). Case patients were those with a clinical diagnosis of nephrolithiasis while on atazanavir/ritonavir, based on new-onset acute flank pain plus one of the following: (i) new-onset haematuria; (ii) documented presence of stones by either abdominal ultrasonography or CT; or (iii) confirmed stone passage. Control patients were consecutively enrolled among those with >2 years of atazanavir/ritonavir exposure free of nephrolithiasis. Genotyping was performed by allelic discrimination using TaqMan 5'-nuclease assays with standard protocols. Associations between alleles and atazanavir/ritonavir-induced nephrolithiasis were tested by univariate and multivariate logistic regression analyses. RESULTS: Multivariate analysis showed a significant association between atazanavir/ritonavir-induced nephrolithiasis and genotype T/C versus C/C at position c.211 (adjusted OR = 3.7; 95% CI, 1.13-11.9; P = 0.030), genotype G/C versus C/C at 339 (adjusted OR = 5.8; 95% CI, 1.56-21.3; P = 0.009) and genotype G/G or G/C versus C/C at 440 (adjusted OR = 5.8; 95% CI, 1.56-21.3; P = 0.009) of the UGT1A-3' untranslated region (UTR). CONCLUSIONS: This is the first known study to identify the association between SNPs in the UGT1A-3'-UTR and atazanavir-induced nephrolithiasis. Further studies are warranted to confirm this association and to elucidate how these SNPs might influence atazanavir exposure.

Enterococcal endocarditis complicated with ruptured infected-intracranial aneurysm: with pharmacokinetic-pharmacodynamic documentation in proof of the successful antimicrobial treatment.

A 74-year-old man presented with sudden onset of aphasia and apraxia. Magnetic resonance image (MRI) of the brain disclosed a left frontal hemorrhage. The concomitant low grade fever suggestive of infection was unresponsive to cefazolin 1 g q12h, and refractory to piperacillin (PIPC) 2 g q8h. Blood culture grew enterococci, establishing together with echocardiography the diagnosis of infective endocarditis. The angiography revealed cerebral hemorrhage to have resulted from the rupture of the infected intracranial aneurysm. The antimicrobial therapy was switched to ampicillin (ABPC) 2 g q4h plus gentamicin (GM) 60 mg q8h. The positive blood culture was subsequently identified Enterococcus faecium to which the minimum inhibitory concentration (MIC) of PIPC, and ABPC was 16 mcg/mL, and 4 mcg/mL, respectively. The peak concentration of serum ABPC was 83.1, median 50.8, and trough 25.8 mcg/mL. Thus, the percent time > MIC for ABPC was 100%, and the time > minimum bactericidal concentration (MBC) as well. On the other hand, time > MIC for PIPC, was found nearly 30% in retrospective analysis using population pharmacokinetics. The neurological deficit of the patient was completely restored to the normal status after 4-weeks' antimicrobial therapy with ABPC plus GM, then he underwent cardiac surgery for valvular replacement, where microbiological culture of the resected valve was negative. The constellation of the clinical, pharmacological and microbiological outcome in our case provides scientific evidence that the antibiotic therapy given to our case is the best available strategy as an antimicrobial treatment of severe enterococcal endocarditis complicated by disseminated lesion as infected intracranial aneurysm.

Three cases of IMP-type metallo-ß-lactamase-producing Enterobacter cloacae bloodstream infection in Japan.

We report three cases of IMP-type metallo-ß-lactamase-producing Enterobacter cloacae bloodstream infection, which showed minimum inhibitory concentration values for imipenem with 2 µg/ml in all isolates. Although carbapenems were initiated empirically in all cases, two of three cases died. The Clinical and Laboratory Standards Institute lowered the breakpoints of carbapenems for Enterobacteriaceae in 2010. However, the previous breakpoints are still used in many clinical laboratories, which can result in failure to detect carbapenem-resistant Enterobacteriaceae. Therefore, lower breakpoints of carbapenems should be used in clinical settings, and alternative tests for detecting metallo-ß-lactamase such as polymerase chain reaction and immunochromatographic assays may contribute to better detection of carbapenem-resistant isolates.

[Clinical and microbiological analysis of community-acquired bacteremia admitted to a tertiary teaching hospital].

OBJECTIVES: To investigate clinical and microbiological characteristics of community-acquired bacteremia (CAB). METHODS: We retrospectively analyzed subjects with CAB hospitalized at Saga University Hospital between January 2009 and September 2011. We investigated causative organisms, primary infection sites, and subject summaries and complications, and analyzed the mortality factor. RESULTS: CAB incidence was 185 cases, with 192 organisms cultured. Causative organisms were gram-positive bacteria in 81 strains (42%), 9 (11%) of which were methicillin-resistant Staphylococcus aureus (MRSA). Gram-negative bacteria were identified in 111 strains (58%), with 80% Enterobacteriaceae. Five of the 111 (5%) were caused by extended-spectrum beta-lactamase (ESBL) producing bacteria. The most frequent bacteremia portal was intraabdominal infection (29%, 54/185). During hospitalization of 1-180 days, 20 subjects eventually died. Neutropenia on admission was associated with significantly higher mortality than without (30% vs. 3%, p < 0.001). Septic shock rates were higher in non-survivors than survivors (45% vs. 14%, p = 0.002), and more complications were documented in non-survivors than survivors (50% vs. 25%, p = 0.017). No specific pathogen or primary infection site was associated with higher mortality. CONCLUSIONS: Antimicrobial-resistant pathogens such as MRSA and ESBL producers should be considered even in CAB, especially in subjects with healthcare-associated infection, regardless of how small the number. The CAB treatment course should consider subjects summaries, severity, and complications.

On-site Gram staining that increases a post-test probability of an ominous infection: a case of necrotizing fasciitis caused by Vibrio vulnificus: a case report.

BACKGROUND: Gram staining is a classic but standard and essential procedure for the prompt selection of appropriate antibiotics in an emergency setting. Even in the era of sophisticated medicine with technically developed machinery, it is not uncommon that a classic procedure such as Gram staining is the most efficient for assisting physicians in making therapeutic decisions in a timely fashion. CASE PRESENTATION: A 65-year-old Asian man with alcoholic cirrhosis complicated by esophageal varices was brought to the emergency division of Saga Medical School Hospital in early August, complaining of severe pain, redness, swelling, and purpura of the lower extremities. On physical examination he appeared in a critically ill condition suggestive of deep-seated soft tissue infection, raising a pre-test probability of streptococci, staphylococci, Vibrio sp., or Aeromonas sp. as a causative pathogen. A characteristic of his residency in an estuarine area is that raw seafood ingestion, as documented in this patient prior to the current admission, predisposes those who have a chronic liver disease to a life-threatening Vibrio vulnificus infection. Given the pathognomonic clinical features suggestive of necrotizing fasciitis, our immediate attempt was to narrow down the differential list of candidate pathogens by obtaining clinical specimens for microbiological investigation, thus inquiring about the post-test probability of the causative pathogen. The Gram stain of the small amount of discharge from the test incision of the affected lesion detected Gram-negative rods morphologically compatible with V. vulnificus. After two sets of blood culture, intravenous meropenem and minocycline were immediately administered before the patient underwent emergency surgical debridement. The next day, both blood culture and wound culture retrieved Gram-negative rods, which were subsequently identified as V. vulnificus by mass spectrometry, matrix-assisted laser desorption/ionization. The antibiotics were switched to intravenous ceftriaxone and minocycline. CONCLUSION: The pre-test probability of V. vulnificus infection was further validated by on-site Gram staining in the emergency division. This case report highlights the significance of a classic procedure.

Upper-plate conduits linked to plate boundary that hosts slow earthquakes.

In shallow subduction zones, fluid behavior impacts various geodynamic processes capable of regulating slip behaviors and forming mud volcanoes. However, evidence of structures that control the fluid transfer within an overriding plate is limited and the physical properties at the source faults of slow earthquakes are poorly understood. Here we present high-resolution seismic velocity models and reflection images of the Hyuga-nada area, Japan, where the Kyushu-Palau ridge subducts. We image distinct kilometer-wide columns in the upper plate with reduced velocities that extend vertically from the seafloor down to 10-13 km depth. We interpret the low-velocity columns as damaged zones caused by seamount subduction and suggest that they serve as conduits, facilitating vertical fluid migration from the plate boundary. The lateral variation in upper-plate velocity and seismic reflectivity along the plate boundary correlates with the distribution of slow earthquakes, indicating that the upper-plate drainage system controls the complex pattern of seismic slip at subduction faults.

High incidence of renal stones among HIV-infected patients on ritonavir-boosted atazanavir than in those receiving other protease inhibitor-containing antiretroviral therapy.

BACKGROUND: Little information is available on the incidence of renal stones with ritonavir-boosted atazanavir (ATV/r) use. METHODS: In a single-center study, the incidence of renal stones was compared between human immunodeficiency virus (HIV)-infected patients who commenced ritonavir-boosted atazanavir (ATV/r)-containing antiretroviral (ARV) therapy (the ATV/r group) and those who were receiving other protease inhibitors (the other PIs group). The effects of ATV/r were estimated by univariate and multivariate Cox proportional hazards regression models. Other possible risk factors were evaluated by univariate analysis, and those found to be significant were entered into multivariate analysis. RESULTS: Renal stones were diagnosed in 31 patients (23.7 cases per 1000 person-years) in the ATV/r group (n = 465) and 4 in patients (2.2 cases per 1000 person-years) in the other PIs group (n = 775). ATV/r use was significantly associated with renal stones, by univariate and multivariate analyses (adjusted hazard ratio, 10.44; 95% confidence interval [CI], 3.685-29.59; P < .001). ATV/r remained a significant risk factor for renal stones in all subgroups stratified by the median values of baseline variables. In the 31 patients receiving ATV/r who developed renal stones, the median time from commencement of ATV/r to diagnosis was 24.5 months (interquartile range, 14.7-34.6 months). Of the 18 patients who continued ATV/r despite the diagnosis of renal stones, 6 (33.3%) experienced recurrence. No patient who discontinued ATV/r experienced recurrence during the observation period (250.6 person-months). CONCLUSIONS: The incidence of renal stones was substantially higher among patients in the ATV/r group, compared with patients in the other PIs group. Continuation of ATV/r after diagnosis of renal stones was associated with a high rate of recurrence. Switching ATV/r to other ARVs is warranted in patients who develop renal stones.

Clinical characteristics and treatment outcomes of carbapenem-resistant Enterobacterales infections in Japan.

OBJECTIVES: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan. METHODS: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality. RESULTS: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality. CONCLUSION: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.

Early prophylaxis of central venous catheter-related thrombosis using 1% chlorhexidine gluconate and chlorhexidine-gel-impregnated dressings: a retrospective cohort study.

To determine the prophylactic effect of using combined 1% alcoholic chlorhexidine gluconate and chlorhexidine gel-impregnated dressings (CGCD) on catheter-related thrombosis (CRT) in critically ill patients. This retrospective cohort study was performed in an intensive care unit from November 2009 to August 2014. The CRT incidence diagnosed with ultrasound examination was compared between patients applying CGCD and combined 10% aqueous povidone-iodine and standard transparent dressings (PITD) after central venous catheter insertion into the internal jugular vein for ≥ 48 h. CRT was stratified into early (within 7 days) and late (days 8-14) thromboses. Multivariate analyses using logistic regression models clarified the relationships between early- and late-CRT risks and skin antiseptic and catheter site dressing combinations. CRT occurred in 74 of 134 patients (55%), including 52 with early CRT and 22 with late CRT. Patients receiving CGCD had a significantly lower incidence of early CRT than those receiving PITD (odds ratio = 0.18; 95% confidence interval = 0.07-0.45, p < .001). No significant association was evident between using CGCD and late CRT (p = .514). Compared to PITD, CGCD reduced the CRT risk over 7 days in critically ill patients.UMIN Clinical Trials Registry: UMIN000037492.

Construction of Two Box-Like Head-and-Face Shields by Japanese Origami Folding for Use During the COVID-19 Pandemic.

A worldwide shortage of personal protective equipment during the COVID-19 pandemic has led to the development of new alternatives. We introduce two new disposable box-like head-and-face shields constructed using Japanese origami-style folding. The design comprises a single sheet of thick paper and a shield made of a thin, transparent plastic sheet. The first design, Model 1, is a head-and-face shield designed to cover the wearer's head and neck. Model 2 was designed to solve the problem of heat and moisture buildup inside the shield. This version can be used as face shields for patients, and it allows clinicians to collect swabs from the nasopharynx for virus detection via polymerase chain reaction through pre-cut incisions near the nasal orifices. These two new box-like face shields are excellent alternatives to traditional face shields because of the low cost, compatibility with mass production, lightweight, and disposability.

Temperature limits to deep subseafloor life in the Nankai Trough subduction zone.

Microorganisms in marine subsurface sediments substantially contribute to global biomass. Sediments warmer than 40°C account for roughly half the marine sediment volume, but the processes mediated by microbial populations in these hard-to-access environments are poorly understood. We investigated microbial life in up to 1.2-kilometer-deep and up to 120°C hot sediments in the Nankai Trough subduction zone. Above 45°C, concentrations of vegetative cells drop two orders of magnitude and endospores become more than 6000 times more abundant than vegetative cells. Methane is biologically produced and oxidized until sediments reach 80° to 85°C. In 100° to 120°C sediments, isotopic evidence and increased cell concentrations demonstrate the activity of acetate-degrading hyperthermophiles. Above 45°C, populated zones alternate with zones up to 192 meters thick where microbes were undetectable.