How an Antimicrobial Stewardship Team Treated a Nocardia farcinica-Associated Brain Abscess: A Case Report.

Nocardia species, which are ubiquitous in the environment, form lesions primarily in immunocompromised patients via oral or cutaneous infection. Some of these Nocardia species, such as N. farcinica, also infect the central nervous system via hematogenous dissemination, which rarely results in brain abscesses. Notably, N. farcinica is resistant to numerous antimicrobial drugs used in empirical therapy, necessitating the intervention of an infectious disease specialist. To date, no case of antimicrobial stewardship teams (ASTs) playing a central role in community hospitals without an infectious disease specialist has been reported. Here, we describe a case of N. farcinica-associated brain abscess in a small-to-medium-sized hospital with no infectious disease department or specialist, in which the AST assisted in the identification of the causative organism and in selecting appropriate therapeutic agents, ultimately leading to a cure. The patient was an 88-year-old man with a high fever. He had been taking prednisolone (10-15 mg/day) for approximately 1 year for pemphigoid. Considering the possibility of fever owing to bacteremia of cutaneous origin, ampicillin/sulbactam antimicrobial therapy at 6 g/day was initiated. A subsequent close examination led to the diagnosis of a brain abscess. Emergency abscess drainage was performed by a neurosurgeon, and postoperative antimicrobial combination therapy comprising ceftriaxone (4 g/day), vancomycin (2 g/day), and metronidazole (1,500 mg/day) was commenced. The AST suspected Nocardia infection earlier, but further testing was difficult to perform at this facility. Therefore, by requesting assistance from Nagoya University Hospital, we performed early bacterial identification by mass spectrometry and appropriate antimicrobial susceptibility testing by a custom panel on day 11. The patient was non-responsive to all the previously used antibiotics at the time of admission. On day 13 after admission, the patient was successfully treated with trimethoprim-sulfamethoxazole (TMP-SMX) and imipenem/cilastatin sodium, and the patient was cured. The AST can be as effective as an infectious disease specialist when a strong working relationship is established between the team and clinicians. Further, the activities of the AST can improve patient survival via active medical support in collaboration with attending physicians.

Comparison of disease and economic burden between MRSA infection and MRSA colonization in a university hospital: a retrospective data integration study.

BACKGROUND: Although there is a growing concern and policy regarding infections or colonization caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), the prognosis of MRSA infections compared to that of methicillin-susceptible Staphylococcus aureus (MSSA) infections remains controversial. Moreover, there have not been any studies comparing both the burden of disease and its impact on the healthcare economy between MRSA infection and colonization while adjusting for confounding factors. These comparisons are crucial for developing effective infection control measures and healthcare policies. We aimed to compare the disease and economic burden between MRSA and MSSA infections and between MRSA infection and colonization. METHODS: We retrospectively investigated data of 496 in-patients with MRSA or MSSA infections and of 1178 in-patients with MRSA infections or MRSA colonization from a university hospital in Japan from 2016 to 2021. We compared in-hospital mortality, length of stay, and hospital charges between in-patients with MRSA and MSSA infections and those with MRSA infections and MRSA colonization using multiple regressions. We combined surveillance data, including all microbiological test results, data on patients with infections, treatment histories, and clinical outcomes, to create the datasets. RESULTS: There was no statistically significant difference in in-hospital mortality rates between matched MRSA vs. MSSA infections and MRSA infection vs. colonization. On the contrary, the adjusted effects of the MRSA infection compared to those of MSSA infection on length of stay and hospital charges were 1.21-fold (95% confidence interval [CI] 1.03-1.42, P = 0.019) and 1.70-fold (95% CI 1.39-2.07, P < 0.00001), respectively. The adjusted effects of the MRSA infection compared to those of MRSA colonization on length of stay and hospital charges were 1.41-fold (95% CI 1.25-1.58, P < 0.00001) and 1.53-fold (95% CI 1.33-1.75, P < 0.00001), respectively. Regarding confounding factors, hemodialysis or hemofiltration was consistently identified and adjusted for in the multiple regression analyses comparing MRSA and MSSA infections, as well as MRSA infection and MRSA colonization. CONCLUSIONS: MRSA infection was associated with longer length of stay and higher hospital charges than both MSSA infection and MRSA colonization. Furthermore, hemodialysis or hemofiltration was identified as a common underlying factor contributing to increased length of stay and hospital charges.

Catheter-related bloodstream infection caused by Lacticaseibacillus paracasei: A case report and literature review.

Catheter-related bloodstream infections (CRBSIs) caused by Lactobacillus spp. and Lacticaseibacillus spp. are rare, and their clinical course and optimal treatment remain uncertain. In this report, we present a 46-year-old male patient who experienced clinically diagnosed Lacticaseibacillus paracasei CRBSI on four separate occasions, despite receiving systemic administration of antibiotics and antimicrobial lock therapy. The patient did not develop L. paracasei bacteremia after catheter removal. This case report furthers our knowledge of CRBSI caused by Lactobacillus and related genera and highlights the need for further research.

Surgical antimicrobial prophylaxis in Japanese hospitals: Real status and challenges.

BACKGROUND: Information regarding the status of surgical antimicrobial prophylaxis (SAP) in Japanese hospitals is lacking. This study aimed to explore the status of SAP prescriptions for surgeries and adherence to Japanese SAP guidelines. METHODS: From February to July 2020, a 1-day multicentre point prevalent survey was conducted at 27 hospitals in Aichi Prefecture, Japan. Patients prescribed SAP were included in this study. The appropriateness of the SAP was evaluated based on the guidelines for selection of antimicrobials and their duration. Surgery was defined as appropriate when all the items were appropriate. RESULTS: A total of 728 patients (7.1 %; 728/10,199) received antimicrobials for SAP. Among them, 557 patients (76.5 %, 557/728) underwent the surgeries described in the guidelines. The overall appropriateness of all surgeries was 33.9 % (189/557). The appropriate selection of antimicrobial before/during and after surgery and their durations were 67.5 % (376/557), 67.5 % (376/557), and 43.3 % (241/557), respectively. The overall appropriateness ranged from 0 % (0/37, oral and maxillofacial surgery) to 58.7 % (88/150, orthopaedic surgery) and 27.7 % (36/130, community hospitals with 400-599 beds) to 47.2 % (17/36, specific hospitals). Cefazolin was the most prevalent antimicrobial prescribed before/during (55.5 %, 299/539), and after (45.1 %, 249/552) surgery. In total, 101 oral antimicrobials were prescribed postoperatively. CONCLUSIONS: SAP adherence by specific surgical fields and hospitals was shown in this study. Intensive intervention and repeated surveillance are necessary to improve SAP prescriptions in Japanese hospitals.

Mycobacterium obuense bacteremia: A case report and literature review.

An 84-year-old man visited our hospital with a high fever. He had cut his right index finger 7 days previously. Blood culture became positive on day 3. Gram staining was negative, and acid-fast staining was positive. The organism was subsequently identified as Mycobacterium obuense using a MALDI Biotyper. M. obuense was also detected in the soil at the patient's house, suggesting that it had entered his bloodstream through the cut on his finger. He was treated with a combination of imipenem/cilastatin, amikacin, and clarithromycin for 2 weeks. His clinical condition improved, and he was discharged after 2 weeks and was prescribed clarithromycin and levofloxacin therapy. Only two cases of human infection with M. obuense have been reported previously.

Time course of skin rash, computed tomography findings, and viral load in a rheumatoid arthritis patient with severe varicella pneumonia.

Varicella-zoster virus (VZV) infection in adults or immunocompromised patients has a more severe presentation compared to the mild disease in children. To the best of our knowledge, no reports have described the clinical course of VZV pneumonia focusing on time course of skin rash, chest computed tomography (CT) findings, and viral load. Furthermore, no reports have described the reactivation of human herpes virus 6 (HHV-6) in VZV pneumonia. Here, we report a case of severe VZV pneumonia that resulted in reactivation of HHV-6 in a patient with rheumatoid arthritis (RA). A 66-year-old female treated for RA was admitted to our hospital with papules. Her chest CT showed granular infiltrates, micronodules, and ground-glass opacities. The day after admission, because the typical skin rashes and chest CT findings were observed, she was diagnosed with VZV pneumonia and treated with acyclovir. Her skin rash then crusted over five days and entered the healing process, whereas it took approximately two weeks for her respiratory condition and chest CT findings to improve. In addition, VZV deoxyribonucleic acid (DNA) gradually decreased with treatment. On the 34th day of admission, VZV DNA was not found in the serum sample but remained in the sputum sample. Furthermore, although reactivation of HHV-6 was observed, viremia resolved without treatment. Clinicians should be able to recognize the differences in the improvement of skin rashes, respiratory status, and chest CT findings. In addition, treatment for HHV-6 reactivation should be carefully determined for each case.

First Case Report of Peritoneal Dialysis-associated Peritonitis Caused by Lysinibacillus sphaericus.

We herein report a case of peritoneal dialysis-associated peritonitis caused by Lysinibacillus sphaericus in a 40s-year-old patient. Treatment was initiated with intermittent intraperitoneal cefazolin and ceftazidime. Later, both peritoneal dialysate and blood cultures detected L. sphaericus, so the antibiotic was changed to ampicillin (ABPC). The patient was treated with a combination of intraperitoneal intermittent and intravenous ABPC for 7 days, followed by 14 days of amoxicillin. The patient experienced no adverse events and no recurrence for 30 days. The patient had four dogs, and the infection was deemed likely to have been caused by environmental contamination and inadequate catheter replacement.

＜Editors' Choice＞ Multicenter survey for carbapenemase-producing Enterobacterales in central Japan.

Carbapenemase-producing Enterobacterales (CPE) raise concerns about the treatment options for infectious diseases and infection control. We conducted a multicenter study to clarify the molecular epidemiology of CPE in the Aichi Prefecture during the first 3-month period from 2015 to 2019. Carbapenemase production was screened using a modified carbapenem inactivation method, and the genotypes of the carbapenemase genes were determined by polymerase chain reaction sequencing. Genetic relatedness was analyzed using multilocus sequence typing (MLST). Twenty-four hospitals participated in this study. Of the 56,494 Enterobacterales strains detected during the study period, 341 (0.6%) that met the susceptibility criteria were analyzed. Sixty-five of the 341 strains were determined to be CPE, with an incidence rate of 0.12% (65/56,494). The bacterial species responsible for CPE were Klebsiella pneumoniae (n = 24), Enterobacter cloacae complex (n = 23), Klebsiella oxytoca (n = 10), and Escherichia coli (n = 8). Most of the carbapenemase genotypes were IMP-1 (58/65), and only three were IMP-6 types. Three E. coli strains that produced NDM-5 were detected. MLST analysis showed that Sequence type (ST) 78 was predominant in E. cloacae complex CPE (14/23, 60.9%). Meanwhile, various STs were detected in carbapenemase-producing (CP) K. pneumoniae, of which ST37 and ST517 were the most common. The incidence rate of CPE in this region was comparable to national data. This 3-month surveillance revealed the spread of ST78 of CP E. cloacae complex and ST517 and ST592 of CP K. pneumoniae across hospitals, indicating the need to strengthen regional infection control programs.

A case of acute focal bacterial nephritis caused by methicillin-resistant Staphylococcus saprophyticus in a 13-year-old adolescent girl treated with daptomycin.

Staphylococcus saprophyticus is a gram-positive, coagulase-negative member of the Staphylococcus genus and is second only to Escherichia coli as a cause of urinary tract infections in the young female population. S. saprophyticus usually has good susceptibility to drugs commonly used to treat urinary tract infections, but it is often methicillin-resistant. Here we report a case of acute focal bacterial nephritis in a 13-year-old female patient caused by methicillin-resistant S. saprophyticus and treated with daptomycin (DAP). The patient had a history of unilateral hearing loss and presented to her previous physician with a 3-day history of fever, right-sided abdominal pain, and diarrhea. Cefotaxime antimicrobial chemotherapy was initiated as an empiric therapy targeting E. coli, the most frequent cause of community-onset pyelonephritis. Vancomycin (VCM) was started for acute focal bacterial nephritis caused by methicillin-resistant S. saprophyticus but was stopped due to allergy and replaced with DAP. After 13 days of treatment with DAP, the patient received 17 days of treatment with sulfamethoxazole-trimethoprim combination therapy. The patient experienced no adverse events and did not relapse. DAP is a relatively new anti-methicillin-resistant Staphylococcus aureus drug used to treat gram-positive cocci infections. It is primarily excreted by the kidneys, which may be desirable in treating urinary tract infections. For children who cannot receive VCM for any reason, DAP may be a viable alternative.

Genetic and epidemiological analysis of ESBL-producing Klebsiella pneumoniae in three Japanese university hospitals.

INTRODUCTION: We aimed to clarify the genetic background and molecular epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) at three geographically separated university hospitals in Japan. METHODS: From January 2014 to December 2016, 118 ESBL-producing K. pneumoniae (EPKP) strains that were detected and stored at three university hospitals were collected. Molecular epidemiological analysis was performed using enterobacterial repetitive intergenic consensus (ERIC)-polymerase chain reaction (PCR) and multi-locus sequence typing (MLST). The ESBL type was determined using the PCR-sequence method. The presence of plasmid-mediated fluoroquinolone resistance (PMQR) genes was analyzed by PCR. We compared the relationships between PMQR gene possession/quinolone resistance-determining region (QRDR) mutation and levofloxacin (LVFX)/ciprofloxacin (CPFX) susceptibility. RESULTS: The detection rate of EPKP was 4.8% (144/2987 patients). MLST analysis revealed 62 distinct sequence types (STs). The distribution of STs was diverse, and only some EPKP strains had the same STs. ERIC-PCR showed discriminatory power similar to that of MLST. The major ESBL genotypes were CTX-M-15-, CTX-M-14-, and SHV-types, which were detected in 47, 30, and 27 strains, respectively. Ninety-one out of 118 strains had PMQR genes and 14 out of 65 strains which were not susceptible to CPFX had QRDR mutations, and the accumulation of PMQR genes and QRDR mutations tended to lead to higher minimum inhibitory concentrations (MICs) of LVFX. CONCLUSIONS: At three geographically separated university hospitals in Japan, the epidemiology of EPKP was quite diverse, and no epidemic strains were found, whereas CTX-M-14 and CTX-M-15 were predominant.

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.

Difficulties in diagnosing Malassezia furfur bloodstream infection and possibility of spontaneous resolution in a patient undergoing chemotherapy for neuroblastoma: A case report.

Malassezia furfur is a lipophilic, yeast-like fungus that forms part of the normal human skin microflora and is associated with a wide range of infections, such as pityriasis versicolor, folliculitis, and systemic infections in immunocompromised patients. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has enabled rapid identification of Malassezia species, it is still a challenge to diagnose systemic infections because Malassezia fungemia can often be missed by automated blood culture systems. We report a case in which M. furfur in blood was detected by the presence of yeast-like fungi in blood smears. Yeast-like organisms were observed in the blood smears of a 3-year-old boy, taken over 2 weeks without any symptoms. He had undergone several courses of chemotherapy for neuroblastoma via an indwelling central venous catheter (CVC) that was placed in his right anterior chest for 11 months. Although the blood cultures obtained from an automated blood culture system were negative, M. furfur growth was detected in the subcultured blood taken from the CVC. The CVC was removed, and the scheduled chemotherapy was postponed. No systemic M. furfur bloodstream infection occurred; the infection resolved spontaneously without any specific treatment; only prophylactic fluconazole was administered. M. furfur fungemia may not be diagnosable by an automated blood culture system. Further, M. furfur may not cause infections in humans even when administered intravenously. This report may lead to the discovery of factors related to human infectivity of this disease in the future.

Epidemiology and molecular characterization of fecal carriage of third-generation cephalosporin-resistant Enterobacterales among elderly residents in Japan.

INTRODUCTION: The spread of third-generation cephalosporin-resistant Gram-negative bacteria is a serious concern in acute and post-acute care settings. This study aimed to understand the epidemiology and molecular background of fecal colonization of resistant Enterobacterales in elderly people. METHODS: In December 2015-December 2017, stool or rectal swab samples were collected from 101 elderly patients receiving home care, using long-term care facilities (LTCF), and living in nursing homes repeatedly at 3-9-month intervals. Patient clinical background data were collected from medical records. After phenotypic screening for extended-spectrum ß-lactamase (ESBL), AmpC-type ß-lactamase or carbapenemase production, drug resistance genes of isolates were analyzed using polymerase chain reaction (PCR). ESBL-producing Escherichia coli isolates obtained from the same patients in repetitive screenings were analyzed using PCR-based ORF typing. Risk factors for persistent carriage of resistant Enterobacterales were analyzed using multivariate analysis. RESULTS: Resistant Enterobacterales isolates were detected in 37 of 101 (36.6%) and 29 of 80 (36.3%) residents in first and second screenings, respectively. ESBL-producing E. coli accounted for 80% isolates, the most common being CTX-M-9-group ß-lactamase producers. Molecular epidemiological analysis revealed probable transmissions of ESBL-producing E. coli; 58% of ESBL-producing E. coli colonizers were persistent colonizers at least after 3 -month intervals. Age > 87 years and LTCF residence were independent risk factors for persistent carriage of ESBL-producing E. coli. CONCLUSIONS: We showed, for the first time, high persistent colonization rate of ESBL-producing E. coli among elderly people in post-acute care settings with probable horizontal transmission. We also identified significant risk factors for persistent colonization.

Lysinibacillus fusiformis bacteremia: Case report and literature review.

A 93-year-old woman was diagnosed with Lysinibacillus fusiformis bacteremia complicated with coma blisters. Initial gram staining for L. fusiformis indicated the presence of gram-negative rods; however, subsequent staining of colonies from Mueller-Hinton agar revealed the presence of gram-positive and gram-negative rods with spherical endospores, and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (VITEK ® MS and microflex® LT/SH) definitively identified the organism as L. fusiformis. The two-week administration of piperacillin/tazobactam and ampicillin resulted in an improvement of the patient's general condition, and the skin lesions gradually improved.

Bursitis, Bacteremia, and Disseminated Infection of Mycobacteroides (Mycobacterium) abscessus subsp. massiliense.

We herein report a 59-year-old woman with a 2-year history of chronic bursitis of the hand who took 50 mg/day prednisolone for several autoimmune diseases. Mycobacteroides abscessus subsp. massiliense was isolated from the abscess and blood culture. Combination therapy (imipenem/cilastatin, amikacin, and clarithromycin) was administered for a month. Two months later, M. massiliense was detected from a blood culture again, and disseminated lesions were found. Clarithromycin and sitafloxacin were administered following eight weeks of the same regimen. Six months after the diagnosis, M. massiliense was isolated from a blood culture, and she expired due to multiple organ failure.

Molecular epidemiological analysis and risk factors for acquisition of carbapenemase-producing Enterobacter cloacae complex in a Japanese university hospital.

Background: To clarify the molecular epidemiology of carbapenem-resistant Enterobacter cloacae complex (CREC) and the risk factors for acquisition of carbapenemase-producing E. cloacae complex (CPEC). Methods: Using clinical CREC isolates detected in a Japanese university hospital over 4 years, carbapenemase production was screened with phenotypic methods. Carbapenemase genes were analysed by PCR and sequencing. Molecular epidemiological analyses were conducted with repetitive extragenic palindromic (REP)-PCR and multilocus sequence typing (MLST). CRECs were identified to the subspecies level by hsp60 sequencing. Whole-genome sequencing of plasmids was conducted. A case-control study was performed to identify risk factors for acquisition of CPEC among patients with CREC. Results: Thirty-nine CRECs including 20 CPECs carrying blaIMP-1 were identified. Patients with CPEC had longer hospital stay before detection (26.5 days vs. 12 days, p = 0.008), a urinary catheter (odds ratio [OR], 5.36; 95% confidence interval [CI], 1.14-30.9; p = 0.023), or intubation (OR, 7.53; 95% CI, 1.47-53.8; p = 0.008) compared to patients without CPEC. Four genetically closely related CPEC clusters were observed, which showed that three of four CPEC clusters corresponded to E. asburiae (ST 53), E. hormaechei subsp. steigerwaltii (ST 113 and ST 1047) and E. cloacae subsp. cloacae (ST 513) by MLST and hsp60 sequencing. Seven representative plasmids shared structures with class I integron containing blaIMP-1 and IncHI2A replicon type. Conclusions: A longer hospital stay, presence of a urinary catheter, and intubation are risk factors for CPEC acquisition. In addition to horizontal transmission of genetically indistinguishable CPECs, IncHI2A plasmid carrying blaIMP-1 appeared to be transferred among genetically different ECs.

Scaling effect on unipolar and bipolar resistive switching of metal oxides.

Electrically driven resistance change in metal oxides opens up an interdisciplinary research field for next-generation non-volatile memory. Resistive switching exhibits an electrical polarity dependent "bipolar-switching" and a polarity independent "unipolar-switching", however tailoring the electrical polarity has been a challenging issue. Here we demonstrate a scaling effect on the emergence of the electrical polarity by examining the resistive switching behaviors of Pt/oxide/Pt junctions over 8 orders of magnitudes in the areas. We show that the emergence of two electrical polarities can be categorised as a diagram of an electric field and a cell area. This trend is qualitatively common for various oxides including NiOx, CoOx, and TiO(2-x). We reveal the intrinsic difference between unipolar switching and bipolar switching on the area dependence, which causes a diversity of an electrical polarity for various resistive switching devices with different geometries. This will provide a foundation for tailoring resistive switching behaviors of metal oxides.