A case report of native vertebral osteomyelitis caused by Cutibacterium modestum.

BACKGROUND: Cutibacterium modestum was named in 2020. C. modestum was previously called Propionibacterium humerusii. Several implant-associated infections caused by Cutibacterium species have been previously reported, but native vertebral osteomyelitis due to these bacteria has rarely been reported. CASE PRESENTATION: A 72-year-old man, who had previously received several nerve block injections for low back pain, was referred to our hospital for deterioration in back pain in the last 1 month. MRI findings were suggestive of L5-S1 vertebral osteomyelitis. Blood cultures and bone biopsy culture revealed the presence of Gram-positive bacilli. The isolate was identified as C. modestum by 16SrRNA gene sequencing. A diagnosis of vertebral osteomyelitis caused by C. modestum was made. Minocycline followed by oral amoxicillin was administered for 3 months. His symptom improved and did not recur after treatment completion. CONCLUSION: A case of vertebral osteomyelitis caused by C. modestum was encountered. Although C. modestum is very similar to C. acnes, it could be accurately identified by 16SrRNA gene sequencing. This case represents the first documented C. modestum infection in humans.

Sustained Improvements in Antimicrobial Therapy and Clinical Outcomes following a Pharmacist-Led Antimicrobial Stewardship Intervention: Uncontrolled Before-After Study.

Our antimicrobial pharmacist-led intervention included: (a) a structured review of antibiotic prescriptions; (b) educating prescribers on antimicrobial therapy; (c) monthly reporting of department-level rates of blood sampling for culture. Daily review began in May 2018 and was discontinued after 10 months; however, the other interventions were conducted throughout the study period. This study aimed to evaluate the sustained impact of pharmacist's interventions on antimicrobial therapy and clinical outcomes between the baseline (May-December 2017), intervention (May-December 2018), and post-intervention (May-December 2019) periods. The rate of blood culture collections before starting antipseudomonal agent therapy was significantly increased from the baseline to post-intervention periods (71% vs. 85%, p < 0.001). Antipseudomonal agent therapy was more frequently de-escalated in the post-intervention period than in the baseline period (73% vs. 54%, p = 0.038). Total use of antipseudomonal agents was reduced from the baseline to intervention periods and persisted during the post-intervention period (50.5 vs. 41.8 and 42.6 DDD per 1000 patient-days, p = 0.016 and p = 0.022, respectively). During the study period, there were significant reductions in the incidence of hospital-acquired Clostridioides difficile infection (1.12, 0.54, and 0.51 per 10,000 patient-days, respectively, p = 0.031) and 30-day mortality with bacteremia (19%, 18%, and 12%, respectively, p = 0.005). Our pharmacist-led interventions sustainably achieved appropriate antimicrobial therapy and improved clinical outcomes.

Effect of Antimicrobial Stewardship on Oral Quinolone Use and Resistance Patterns over 8 Years (2013-2020).

Since 2014, several global and national guidelines have been introduced to address the problem of antimicrobial resistance. We conducted a campaign in a tertiary hospital to promote appropriate quinolone use through educational lectures in 2018. The aim of this retrospective study was to evaluate the changes in the following: prescription characteristics, trend of oral quinolone use, and antibiotic susceptibility of bacteria from 2013 to 2020. Antimicrobial use was assessed as days of therapy per 1000 patient-days. We found a significant reduction in unnecessary antibiotic prescriptions between December 2013 and December 2020. Significant negative trends were detected in the use of quinolones over 8 years (outpatients, coefficient = -0.15655, p < 0.001; inpatients, coefficient = -0.004825, p = 0.0016). In particular, the monthly mean use of quinolones among outpatients significantly decreased by 11% from 2013 to 2014 (p < 0.05) and reduced further by 31% from 2017 to 2020 (p < 0.001). A significant positive trend was observed in the susceptibility of Pseudomonas aeruginosa to levofloxacin (p < 0.001). These results demonstrate that the use of oral quinolones was further reduced following educational intervention and the bacterial susceptibility improved with optimal quinolone usage compared to that in 2013.

Evaluation of five Legionella urinary antigen detection kits including new Ribotest Legionella for simultaneous detection of ribosomal protein L7/L12.

Urinary antigen tests are a widely used rapid diagnostic method for Legionella pneumonia. However, conventional urinary antigen tests are unable to detect anything other than Legionella pneumophila serogroup 1. The Ribotest Legionella (Ribotest) can detect all serogroups by using antibodies recognizing L. pneumophila ribosomal protein L7/L12 in addition to the conventional L. pneumophila serogroup 1 lipopolysaccharide. The aim of this study was to evaluate the performance of Ribotest against conventional urinary antigen tests, including the detection of Legionellaceae other than L. pneumophila. We investigated the detection sensitivity of various kits using in-vitro culture-soluble antigen extracts of ATCC strains and 22 clinical isolates collected from multiple medical facilities in the Kinki region of Japan. For L. pneumophila serogroup 1, four kits, including Ribotest, had a detection sensitivity of 105 CFU/mL, with only Check Legionella having a sensitivity of 106 CFU/mL. L. pneumophila non-serogroup 1 and Legionellaceae of other species were undetectable by the four conventional kits, whereas Ribotest could detect them with a sensitivity of 105-108 CFU/mL. The Ribotest was also able to detect other species such as Legionella hackeliae, Legionella feeleii, Legionella anisa, Fluoribacter bozemanae, and Fluoribacter dumoffii, but the detection sensitivity of L. hackeliae and L. feeleii was 108 CFU/mL, which was much lower than that of the other strains. The Ribotest has high potential to be applied as a rapid diagnostic method for pneumonia caused by other species of Legionella and Fluoribacter.

Impact of Infectious Disease Consultation on Management and Outcomes of Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) is associated with significant morbidity and mortality, and successful management requires expertise in both cardiac surgery and infectious disease (ID). However, the impact of ID consultation on the clinical outcomes of IE is not clear. METHODS: The present study was a quasi-experimental, interrupted time series analysis of the clinical outcomes of patients with IE before (April 1998-April 2008) and after (May 2008-March 2019) the establishment of an ID department at a tertiary care hospital in Japan. The primary outcome was clinical failure within 90 days, defined as a composite of all-cause mortality, unplanned cardiac operation, new-onset embolic events, and relapse of bacteremia caused by the original pathogen. RESULTS: Of 238 IE patients, 59 (25%) were treated in the preintervention period, and 179 (75%) were treated in the postintervention period. Establishment of an ID department was associated with a 54% reduction in clinical failure (relative risk, 0.46; 95% confidence interval, 0.21-1.02; P = .054) and a 79% reduction in new-onset embolic events (relative risk, 0.21; 95% confidence interval, 0.07-0.71; P = .01). In addition, the rate of inappropriate IE management significantly decreased (relative risk, 0.06; 95% confidence interval, 0.02-0.22; P < .01). CONCLUSIONS: Establishment of an ID department at a tertiary care hospital was associated with improved management, better clinical outcomes, and reduced embolic events in patients with IE admitted to the hospital.

Efficacy of educational intervention on reducing the inappropriate use of oral third-generation cephalosporins.

PURPOSE: This study aimed to evaluate the efficacy of an educational intervention on reducing the inappropriate use of oral third-generation cephalosporins, the prevalence of resistant bacteria, and clinical outcomes. METHODS: A before-after study was conducted to compare the data for 1 year before and after intervention at a Japanese university hospital. Educational intervention included lectures for all medical staff on oral antibiotics and educational meetings with each medical department. The primary outcome was the use of oral third-generation cephalosporins in inpatients as measured by the monthly median days of therapy (DOTs) per 1000 patient days. Secondary outcomes included the use of each oral antibiotic in inpatients and outpatients, proportion of ß-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae (BLNAR), penicillin-resistant Streptococcus pneumoniae (PRSP) and extended-spectrum ß-lactamase producing Escherichia coli (ESBLEC), the incidence of hospital-acquired Clostridioides difficile infection (HA-CDI), and hospital mortality. RESULTS: The use of oral third-generation cephalosporins in inpatients was significantly decreased after intervention [DOTs (interquartile range): 24.2 (23.5-25.1) vs. 3.7 (0.0-7.1), P < 0.001], and the value in outpatients was also decreased significantly. The use of fluoroquinolones and macrolides did not increase after intervention. The proportion of BLNAR, PRSP and ESBLEC did not change significantly during the study period. The incidence of HA-CDI was significantly decreased, and hospital mortality did not change after intervention. CONCLUSION: Educational intervention was effective in reducing the use of oral third-generation cephalosporins without increasing the use of broad-spectrum antibiotics and worsening clinical outcome. The prevalence of resistant bacteria did not change during the study period.

Acquisition of antimicrobial-resistant variants in repeated infections caused by Pseudomonas aeruginosa revealed by whole genome sequencing.

Pseudomonas aeruginosa, responsible for serious nosocomial-acquired infections, possesses intrinsic antibiotic resistance mechanisms and commonly exhibits multidrug resistance. Here, we report the evolving resistance profiles of strains isolated from the sputum of a patient being treated for repeated P. aeruginosa infections following cancer resection. Whole genome sequencing of six isolates obtained over a 2-month period revealed two key single nucleotide polymorphisms in the mexR and gyrB genes that affected efflux pump expression and antimicrobial resistance.

Determination of the antimicrobial susceptibility and molecular profile of clarithromycin resistance in the Mycobacterium abscessus complex in Japan by variable number tandem repeat analysis.

Mycobacterium abscessus complex, including three subspecies-M. abscessus, M. massiliense, and M. bolletii-is resistant to a variety of antibiotics so limited treatment options are available. The susceptibility of these subspecies to antimicrobial agents depends in particular on the erm(41) sequevar and rrl mutations in the 23S rRNA, which are potentially related to clarithromycin (CLR) resistance. The purpose of this study was to carry out identification and molecular characterization of these subspecies based on variable number of tandem repeats (VNTR) analysis. Twenty-four M. abscessus complex strains were identified as M. abscessus and M. massiliense and these subspecies could be discriminated between based on their resistance to CLR, as determined by truncation or mutation of erm(41) or mutation of rrl, as illustrated by their VNTR patterns. In conclusion, we confirmed that the CLR susceptibility profiles could be differentiated according to the subspecies of M. abscessus complex strains by their VNTR patterns.

Case of Mycobacterium haemophilum misdiagnosed as Mycobacterium intracellulare due to one base insertion in the bacterial genome.

Mycobacterium haemophilum is a slow-growing, non-tuberculous mycobacteria that causes cutaneous infection. We describe a case of cutaneous infection in a 68-year-old Japanese man with polymyositis. This was caused by M. haemophilum harboring one base insertion in gene sequence. At first, the causal microorganism was misidentified as M. intracellulare by COBAS® TaqMan® MAI test. However, poor growth on Ogawa media and growth enhancement on 7H11C agar around a hemin-containing disk prompted us to reinvestigate the causal microorganisms, which were revealed to be M. haemophilum. Amplified polymerase chain reaction products were sequenced, and the 16S rRNA gene, rpoB, hsp65 and internal transcribed spacer region sequences showed a 100%, 100%, 99.66% and 99.7% match, respectively, with the corresponding regions of M. haemophilum, but it harbored a novel gene sequence in hsp65. The sequences determined by gene analysis of the M. haemophilum strain were deposited into the International Nucleotide Sequence Database. Although numerous cases of M. haemophilum infection have been reported in other countries, only six cases have been reported in Japan to date. It could be possible that this novel mutation lead to misdiagnosis. As M. haemophilum prefers a lower growth temperature (30-32°C) and it requires iron in the culture medium, M. haemophilum could be misidentified or overlooked. Accordingly, a M. haemophilum infection should be considered in cases of cutaneous infection of the body sites, of which surface temperature is low.

Long-term efficacy of comprehensive multidisciplinary antibiotic stewardship programs centered on weekly prospective audit and feedback.

OBJECTIVE: To evaluate the long-term effects of comprehensive antibiotic stewardship programs (ASPs) on antibiotic use, antimicrobial-resistant bacteria, and clinical outcomes. DESIGN: Before-after study. SETTING: National university hospital with 934 beds. INTERVENTION: Implementation in March 2010 of a comprehensive ASPs including, among other strategies, weekly prospective audit and feedback with multidisciplinary collaboration. METHODS: The primary outcome was the use of antipseudomonal antibiotics as measured by the monthly mean days of therapy per 1000 patient days each year. Secondary outcomes included overall antibiotic use and that of each antibiotic class, susceptibility of Pseudomonas aeruginosa, the proportion of patients isolated methicillin-resistant Staphylococcus aureus (MRSA) among all patients isolated S. aureus, the incidence of MRSA, and the 30-day mortality attributable to bacteremia. RESULTS: The mean monthly use of antipseudomonal antibiotics significantly decreased in 2011 and after as compared with 2009. Susceptibility to levofloxacin was significantly increased from 2009 to 2016 (P = 0.01 for trend). Its susceptibility to other antibiotics remained over 84% and did not change significantly during the study period. The proportion of patients isolated MRSA and the incidence of MRSA decreased significantly from 2009 to 2016 (P < 0.001 and = 0.02 for trend, respectively). There were no significant changes in the 30-day mortality attributable to bacteremia during the study period (P = 0.57 for trend). CONCLUSION: The comprehensive ASPs had long-term efficacy for reducing the use of the targeted broad-spectrum antibiotics, maintaining the antibiotic susceptibility of P. aeruginosa, and decreasing the prevalence of MRSA, without adversely affecting clinical outcome.

[The Deveroppment of Screening Methods Using the Disk Diffusion Method for Carbapenemase-producing Enterobacteriaceae].

Carbapenem-resistant Enterobacteriaceae (CRE) are increasing globally. Particularly, carbapenemase-producing Enterobacteriaceae (CPE) are of concern. Rapid and accurate detection of these strains is critical for appropriate antimicrobial use and hospital infection control. In the present study, criteria for CPE screening were examined using a carbapenem susceptibility disk. Carbapenemase producers showed minimal inhibition zones for faropenem (5 µg): 6-12 mm (mean: 6.9 mm). Some strains with the IMP-6 genotype showed inhibition zones of >30 mm for imipenem (10 µg) and biapenem (10 µg). All strains that formed inhibition zones for FRPM had the IMP-6 genotype. The cut off values of carbapenemase-producers, determined by ROC analysis, were 12 mm for FRPM, 24 mm for meropenem (10 µg), 29 mm for BIPM, 25 mm for doripenem (10 µg), 26 mm for IPM, and 24 mm for panipenem (10 µg). Thus, the sensitivity was the highest (100%) for FRPM. Specificities were 93.44% for MEPM and DRPM and 85.25% for FRPM. Consequently, a drug sensitivity test using FRPM (5 µg) disks facilitates simple and accurate CPE screening.

Molecular characteristics of extended-spectrum ß-lactamase-producing Escherichia coli in a university teaching hospital.

The prevalence of extended-spectrum ß-lactamases (ESBLs) has been increasing worldwide. Recently, a pandemic clone of Escherichia coli O25:H4, sequence type 131 (ST131), producing ESBL-type CTX-M-15 has been reported as a major problem. In this study, we investigated the molecular characteristics of 72 ESBL-producing E. coli isolates. We detected the ESBL blaCTX-M gene and nine virulence factor genes (papC, papEF, fimH, hlyA, iutA, sfa, eaeA, bfpA, and aggR) by PCR and DNA sequencing, plasmid replicon typing, phylogenetic grouping, repetitive-sequence-based PCR (rep-PCR), and multilocus sequence typing. All strains were positive for blaCTX-M. Twenty-two (30.6%) strains in CTX-M-1 group included 9 (12.5%) of CTX-M-15, 3 (4.2%) in CTX-M-2 group, and 47 (65.3%) strains in CTX-M-9 group. The CTX-M-15-producing E. coli O25:H4 ST131 was derived from phylogenetic group B2 and rep-PCR pattern d. The most prevalent virulence factor was fimH (72 strains; 100%) and the most common replicon type was the IncF type (65 strains; 90.3%). The CTX-M-9 group was significantly associated with the presence of papC and papEF [OR (95% CI)=9.22 (1.32-64.7), p=0.025] or hlyA [OR (95% CI)=5.57 (1.17-26.4), p=0.031]. In conclusion, we confirmed that CTX-M-15-producing E. coli O25:H4 ST131 has emerged in Japan and found significant virulence factors with CTX-M-9 group.

[Contribution of medical technologists in team medical care of diabetics].

For the effective treatment of diabetic mellitus (DM), patients are encouraged to self-manage their disease according to the doctor's instructions and advice from certified diabetes educators (CDE) and other comedical staff. Therefore, the cooperation of medical staff consisting of a doctor, CDE, nurse, pharmacist, dietitian, and medical technologist is important for DM education. Medical technologists licensed for CDE (MT-CDE) have been participating in the DM education team in Kobe University Hospital since 2000. MT-CDE are in charge of classes for medical tests, guidance for self-monitoring of blood glucose and teaching how to read the fluctuation graph of the blood glucose level in the education program for hospitalized DM patients. MT-CDEs teach at the bedside how to read the results of medical tests during the first few days of hospitalization using pamphlets for medical tests. The pamphlets are made comprehensible for patients by using graphics and photographs as much as possible. It is important to create a friendly atmosphere and answer frank questions from patients, since they often feel stress when having medical tests at the early stage of hospitalization. This process of questions and answers promotes their understanding of medical tests, and seems to reduce their anxiety about having tests. We repeatedly evaluate their level of understanding during hospitalization. By showing them the fluctuation graph of the glucose level, patients can easily understand the status of their DM. When prescriptions are written on the graph, their therapeutic effects are more comprehensible for the patients. The items written on the graph are chosen to meet the level of understanding of each patient to promote their motivation. In summary, the introduction of MT-CDE has been successful in the education program for DM patients in our hospital. We plan to utilize the skills and knowledge of MT-CDE more in our program so that our DM education program will help patients cope with life with DM.

The lipoprotein fraction between VLDL and LDL detected by biphasic agarose gel electrophoresis reflects serum remnant lipoprotein and Lp(a) concentrations.

We analyzed lipoprotein profiles in 616 Japanese by biphasic agarose gel electrophoresis using Chol/Trig Combo(TM) to yield HDL, VLDL, LDL and CM fractions which were stained with cholesterol and triglyceride reagents, respectively. To further evalute the pattern of electrophoresis, we analyzed the fraction between VLDL and LDL to confirm the possibility of a MidBand by using an automatic-five-fraction function. The cholesterol concentrations in MidBand (MidBand-C) showed a good correlation to remnant-like particle-cholesterol (RLP-C) (r = 0.95) in 23 consecutive samples (TC < 220 mg/dl, Lp(a) < 30 mg/dl). However, MidBand-C concentrations of subjects with high Lp(a) levels (Lp(a) > 30 mg/dl) were also high compared to RLP-C concentrations. The average MidBand-C levels in elderly normolipidemic control subjects (TC < 220, TG < 150) were 5.2 +/- 2.4 mg/dl in 30 males (mean age, 70 +/- 10 years) and 5.4 +/- 2.0 mg/dl in 40 females (64 +/- 11 years). The average MidBand-C levels of normolipidemic patients with coronary artery diseases (CAD; TC < 220, TG < 150) were 9.4 +/- 4.1 mg/dl in 126 males (mean age, 66 +/- 10 years) and 9.1 +/- 4.0 mg/dl in 44 females (67 +/- 10 years). These levels were significantly higher than control values (p < 0.0001). Areas under ROC curves were greater for MidBand-C than for TC, LDL-C and TG when used to discriminate between the patients with CAD and normolipidemic control subjects for each sex. There results suggest that the MidBand-C level may be useful as an indicator of risk for CAD.