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.

Prolonged infective SARS-CoV-2 omicron variant shedding in a patient with diffuse large B cell lymphoma successfully cleared after three courses of remdesivir.

We report a case of prolonged shedding of the infective SARS-CoV-2 omicron variant BA.1.1.2 in a 79-year-old male patient with diffuse large B-cell lymphoma, after receiving chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). The patient was admitted to our hospital in late March 2022 for the sixth course of R-CHOP chemotherapy. Initially, the patient tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using an in-hospital loop-mediated amplification assay with a nasopharyngeal swab, both on the day of admission and three days later. However, the patient developed fever and was diagnosed with coronavirus disease (COVID-19) six days after admission and was suspected to have contracted the infection in the ward. Viral shedding continued for more than three months, with confirmed viral infectivity. As compared to the original Wuhan-Hu-1/2019 strain, amino acid substitutions including S36 N in non-structural protein (NSP)2, S148P, S1265del and L1266I in NSP3, G105D in NSP4, G496S, A831V, or V987F in spike protein, and I45T in open-reading frame (ORF)9b were randomly detected in isolated viruses. Although the patient had received two doses of the BNT162b2 vaccine approximately six months earlier and the third dose on day 127 after the infection, both serum anti-spike and anti-nuclear protein IgG and IgM tests were negative at day 92, 114, and 149 after the infection. The patient finally cleared the virus after the third course of remdesivir and did not have further recurrence.

Detection of Clostridioides difficile toxin B gene in clinical stool specimens using rapid diagnostic quenching probe-polymerase chain reaction assay.

We tested the accuracy of quenching probe-polymerase chain reaction (QP-PCR) for detecting Clostridioides difficile toxin B gene (tcdB) in stools from inpatients with suspected C. difficile infection and compared the results with other nucleic acid amplification tests (NAATs). Toxigenic culture results were used as reference for comparison. QP-PCR had comparable diagnostic accuracy with other NAATs and prior bead-beating enabled detection of tcdB in specimens judged as negative, without bead-beating. Taken together, the QP-PCR either with or without bead-beating showed sufficient effectiveness for detecting tcdB in stool specimens.

Clinical effect of early administration of tocilizumab following the initiation of corticosteroid therapy for patients with COVID-19.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in Wuhan in December 2019, and has since caused a global pandemic. The efficacy of several drugs has been evaluated, and it is now evident that tocilizumab has a beneficial effect, especially combined with corticosteroids, in patients with Coronavirus Disease 2019 (COVID-19). However, the optimal timing of tocilizumab administration has not yet been established. The goal of the present study was to determine the optimal timing of tocilizumab administration after starting corticosteroid therapy in patients with COVID-19. METHODS: We retrospectively analyzed the clinical characteristics of patients who were hospitalized for COVID-19 and treated with tocilizumab and corticosteroids in our hospital. The patients were divided into concurrent and sequential groups. The concurrent group received tocilizumab ≤24 h after corticosteroids, and the sequential group received tocilizumab >24 h after corticosteroid administration. RESULTS: The baseline clinical characteristics of tocilizumab administration were similar between the two groups. White blood cell counts were significantly lower and C-reactive protein levels were significantly higher in the concurrent group than the sequential group. In the concurrent group, tocilizumab administration led to a significant decrease in maximum body temperature. In addition, there were significantly more oxygen-free days in the concurrent group than in the sequential group. However, survival rate was not significantly different between the concurrent and the sequential groups. CONCLUSIONS: In the combination therapy with tocilizumab and corticosteroids, early administration of tocilizumab after starting corticosteroid treatment is effective when treating COVID-19.

Evaluation of microbial contamination on cuff syringe, cuff pressure gauge, and their surroundings in the operating room.

BACKGROUND: Some institutions reuse cuff syringes and do not periodically sterilize cuff pressure gauges. Pathogenic bacterial contamination of such equipment may increase the probability of pathogen transmission to patients during anesthetic procedures. Therefore, microbial contamination on cuff syringes, cuff pressure gauges, and their surroundings was assessed in the operating rooms of a university-affiliated tertiary care hospital in Japan. METHODS: This study was conducted between April and May 2019 in 14 operating suites at a hospital. The following sites in each operating suite were sampled: cuff syringe (inner/outer components), outer components of cuff pressure gauge, cuff syringe and cuff pressure gauge storage drawers, and computer mice. The swabs were directly streaked onto agar plates and incubated. Then, the bacterial species were identified using mass spectrometry. RESULTS: The highest bacterial isolation was observed in computer mice, followed by the outside of cuff pressure gauges and the drawers of cuff pressure gauges (92.9, 78.6, and 64.3%, respectively). Most of the identified bacteria belonged to the Bacillus species, with colonization rates of 85.7, 57.1, and 57.1% on computer mice, cuff pressure gauges, and cuff pressure gauge storage drawers, respectively. Coagulase-negative Staphylococcus was found in 35.7% of the specimens and was more prevalent on computer mice (71.4%), followed by on cuff pressure gauges (64.3%). CONCLUSION: Anesthesiologists should be aware of the possible pathogen contamination risk from cuff syringes, cuff pressure gauges, or associated equipment and take appropriate infection control measures to minimize the risk of pathogenic transmission.

Evaluation of the Antimicrobial Effectiveness of Ozonated Water for Hand Washing in the Presence of Organic Material Contamination Using the ASTM E2946-13 Standard Test Method.

ABSTRACT: Ozonated water is a possible hand washing alternative to antimicrobial soap and water. In a previous report, 4 ppm of ozonated water removed artificially contaminated bacteria from the hands of healthy volunteers as effectively as antimicrobial or nonantimicrobial soap and water. Currently, there is a lack of data on the efficacy of ozonated water in removing bacteria from hands loaded with organic materials. This study aimed to evaluate the effectiveness of ozonated water in removing bacteria from hands contaminated with organic material, according to the American Society for Testing and Materials E2946-13. Sixteen healthy volunteers were randomly assigned to the ozonated water group and the antimicrobial soap and water group. Their hands were contaminated with an avirulent strain of Escherichia coli in beef broth suspension. Approximately 3-log CFU bacterial reductions between baseline and postwash colonies were observed on the hands in both groups. Ozonated water may remove bacteria from hands contaminated with organic material with similar effectiveness as antimicrobial soap and water.

Severe Coronavirus Disease 2019 That Recovered from Respiratory Failure by Treatment That Included High-dose Intravenous Immunoglobulin.

We herein report a case of severe coronavirus disease 2019 (COVID-19) in which high-dose intravenous immunoglobulin (IVIg) treatment achieved significant clinical improvement of deterioration of pulmonary inflammation after temporary clinical improvement. In the present case, clinical and radiological deterioration occurred despite a decrease in viral load, suggesting that deterioration was caused by reactivation of proinflammatory factors, such as tumor necrosis factor-α and interleukin-6, rather than direct viral effects. IVIg treatment may provide not only immunosuppressive effects but also inhibition of proinflammatory cytokines, indicating that treatment including IVIg may be effective by inhibiting cytokine storm in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.

Evaluation of the Cytotoxicity of Various Hand Disinfectants and Ozonated Water to Human Keratinocytes in a Cultured Epidermal Model.

OBJECTIVE: To evaluate the cytotoxicity of various hand disinfectants and ozonated water to human keratinocytes using a cultured epidermal model. DESIGN: Using a test protocol from the Organization for Economic Co-operation and Development, investigators applied hand disinfectants containing either 83% ethanol, 0.2% benzalkonium chloride, 0.5% povidone-iodine, 1% chlorhexidine, 1% chlorhexidine ethanol, or ozonated water to a cultured human epidermal model. Surface morphology and histologic changes were evaluated by scanning electron microscopy and hematoxylin-eosin staining. MAIN OUTCOME MEASURES: Production of inflammatory cytokine interleukin 1α by keratinocytes and cell death rate. MAIN RESULTS: Electron microscopic analysis revealed the creation of small holes on the stratum corneum, and hematoxylin-eosin staining revealed perinuclear vacuolation of keratinocytes and cells with a condensed nucleus. Interleukin 1α was detected in the culture supernatants. More than 80% of keratinocytes did not survive after a 15-minute application of disinfectants. However, no significant damage was detected with ozonated water. CONCLUSIONS: Ozonated water did far less damage to keratinocytes than the tested disinfectants. Although the ability of ozonated water to disinfect hands of medical staff members requires further study, it might serve as an alternative with minimum cytotoxicity.

Analysis of Clinical Isolates of Extended-Spectrum ß-Lactamase-Producing Bacteria with Primer and Probe Sets Developed to Detect blaCTX-M, blaTEM, and blaSHV Using a Fully Automated Gene Detection System.

In this study, we evaluated extended-spectrum ß-lactamase (ESBL)-producing bacteria with the newly developed primer and probe sets to detect blaCTX-M, blaTEM, and blaSHV using BD MAXTM, a fully automated multiplex polymerase chain reaction assay system. In 36 isolates confirmed by whole-genome sequencing to have blaCTX-M, blaTEM, or blaSHV, the developed primer and probe sets accurately detected each gene without being influenced by the presence of other ß-lactamase genes. In nine control strains that do not harbor either blaCTX-M, blaTEM, or blaSHV no cross-reaction was observed. In 191 strains phenotypically determined to be ESBL-producers by conventional antimicrobial susceptibility tests, 189 strains were blaCTX-M-, blaTEM-, or blaSHV-positive as assessed by BD MAXTM using the developed primer and probe sets, and two strains were negative for these genes. Whole-genome sequencing revealed that these two strains were phenotypically false-positive ESBL-producers. The accuracy of the primer and probe sets seems to be satisfactory, and they may be applicable to detect CTX-M-type ESBL-producing bacteria.

IL-13 attenuates early local CXCL2-dependent neutrophil recruitment for Candida albicans clearance during a severe murine systemic infection.

To investigate the role of IL-13 during a severe systemic Candida albicans infection, BALB/c control and IL-13-/- mice were examined for colony forming units (CFU) in the kidneys and survival days after intravenous infection. Proinflammatory mediators and cell recruitment into the tissue were measured by quantitative real-time PCR, a multiple ELISA system, and morphological cell differentiation. The IL-13-/- group exhibited a lower CFU number in the kidneys at 4 days and survived longer than the control mice, which was accompanied by significantly higher expression of C-X-C motif ligand 2 (CXCL2), IFN-γ, and polymorphonuclear neutrophils (PMNs) in the infected kidneys. By contrast, the expression of transforming growth factor ß (TGF-ß) and IL-17 A on day 10 were significantly higher in the control mice than in the IL-13-/- group. When using an intratracheal infection model, the IL-13-/- group recruited a greater number of PMNs in 6 h, with rapidly increased CXCL2 in the alveolar space. In vitro testing with cultured bone-marrow-derived cells demonstrated rapid CXCL2 mRNA upregulation at 3 h after contact with C. albicans, which decreased with recombinant IL-13 pretreatment, whereas rIL-13 retained TGF-ß upregulation. In a murine model of Candida systemic infection, preexistent IL-13 limits both the rapid CXCL2 elevation and PMN aggregation in the target organ to suppress inflammatory mediators, which also attenuates local pathogen clearance within four days.

Severe epidemic myalgia with an elevated level of serum interleukin-6 caused by human parechovirus type 3: a case report and brief review of the literature.

BACKGROUND: Human parechovirus type 3 (HPeV-3) is known to cause cold-like symptoms, diarrhea, or severe infections such as sepsis in infants and children. In adults, HPeV-3 infection is rarely diagnosed because the symptoms are generally mild and self-limiting; however, this infection has been linked to epidemic myalgia, regardless of the presence of underlying diseases, immunosuppression, or sex. CASE PRESENTATION: We describe an adult case of severe systemic myalgia and orchiodynia after infection with HPeV-3, which was transmitted from the child of the patient. Interleukin-6 (IL-6) level was found to be elevated in the patient's serum. CONCLUSION: Severe myalgia associated with HPeV-3 infection is potentially caused by an elevated serum level of IL-6.

Neonatal meningitis and recurrent bacteremia with group B Streptococcus transmitted by own mother's milk: A case report and review of previous cases.

This article reports a case of neonatal meningitis and recurrent bacteremia caused by group B Streptococcus (GBS) transmitted via the mother's milk. A 3-day-old neonate suffered early-onset meningitis due to GBS, from which he recovered after antibiotic treatment for 4 weeks. GBS was not detected in the vaginal or stool cultures of the neonate's mother before delivery. However, 4days after treatment of GBS meningitis, the neonate developed GBS bacteremia. As the mother repeatedly showed signs of mastitis after the delivery, bacterial culture tests were performed on her breast milk, in addition to vaginal and stool culture tests. GBS was exclusively detected in the mother's breast milk. The GBS strains detected in the cerebrospinal fluid of the neonate and the mother's breast milk were both serotype III, and were confirmed to be identical through pulsed-field gel electrophoresis analysis. As horizontal GBS transmission between the mother and neonate was indicated, breastfeeding was ceased and replaced with formula milk. No recurrence of bacterial meningitis or bacteremia due to GBS was observed thereafter. Physicians need to consider culturing breast milk in cases of recurrent neonatal GBS infections, even in mothers without prior detection of GBS in conventional vaginal or stool cultures before delivery.

A case of typhoidal tularemia in a male Japanese farmer.

In Japan, most tularemia cases occur after contact with hares (hunting, cooking) and involve the glandular or ulceroglandular form. Here, we present a case of typhoidal tularemia in a 72-year-old Japanese male farmer who presented with fever, fatigue, and right lower abdominal pain. Computed tomography revealed intestinal wall thickening at the ascending colon, pleural effusion, and ascites. Following an initial diagnosis of bacterial enteric infection, his symptoms deteriorated after a week-long cephalosporin treatment course. The patient lived in an area endemic for scrub typhus; the antibiotic was changed to a tetracycline on suspicion of scrub typhus infection. His symptoms rapidly improved after initiation of minocycline treatment. Later, blood tests revealed marked increases in serological tests against Francisella tularensis exclusively, and the patient was diagnosed with typhoidal tularemia. Typhoidal tularemia may be characterized by any combination of general symptoms, but does not exhibit the local manifestations associated with other forms of tularemia. The patient, in this case, had no direct contact with hares or other wild animals and did not present with local manifestations of tularemia. Physicians should consider this disease, especially when tick-borne disease is suspected in the absence of local wounds, eschar, ulcers, or lymphadenopathy.

Severe Disseminated Mycobacterium avium Infection in a Patient with a Positive Serum Autoantibody to Interferon-γ.

We herein report a case of disseminated Mycobacterium avium infection that involved both optic nerves, the conjunctiva, the right lower lung, and multiple skin lesions, including a thoracic nodule. The patient was a 65-year-old man without any significant medical history. The pathogen was detected in the patient's eye discharge, sputum, bronchial lavage fluid, and thoracic nodule. Anti-mycobacterial chemotherapy, including clarithromycin, rifampicin, and ethambutol, was administered, and the thoracic nodule was resected. An autoantibody to interferon-γ was detected in the patient's serum. Bilateral swelling of his optic nerves and facial dermatitis improved after initiating anti-mycobacterial chemotherapy.

[Importance of Clinical Laboratory and Molecular Epidemiology for Investigation of MRSA Outbreak].

MRSA has been a major pathogen associated with nosocomial outbreaks. Moreover, the isolation of community-acquired MRSA(CA-MRSA) is increasing even in Japanese hospitals. It is necessary to carry out outbreak investigations in cooperation with the clinical laboratory as it is the site where MRSA is identi- fied. "Timing of information on MRSA from the clinical laboratory" is crucial for the ICT. To detect signs of an outbreak, information on the number of MRSA isolates is essential in every ward per week or month. It is desirable to perform active surveillance routinely. However, there are problems to be solved such as the cost of active surveillance, workload of laboratory technicians, and shortage of private rooms for isolation. It is necessary that the infection control department confirms clonal spread on analysis of the molecular epi- demiology, including the PCR-based open reading frame typing (POT) method. When the number of MRSA isolates increased and some strains had the same POT number on a ward, we suspected MRSA outbreak and strengthened infection control measures. We describe herein the importance of the relationship with the clinical laboratory for infection control and how to control an MRSA outbreak rapidly. [Review].

Expression of activation-induced cytidine deaminase enhances the clearance of pneumococcal pneumonia: evidence of a subpopulation of protective anti-pneumococcal B1a cells.

We describe a protective early acquired immune response to pneumococcal pneumonia that is mediated by a subset of B1a cells. Mice deficient in B1 cells (xid), or activation-induced cytidine deaminase (AID(-/-) ), or invariant natural killer T (iNKT) cells (Jα18(-/-) ), or interleukin-13 (IL-13(-/-) ) had impaired early clearance of pneumococci in the lung, compared with wild-type mice. In contrast, AID(-/-) mice adoptively transferred with AID(+/+) B1a cells, significantly cleared bacteria from the lungs as early as 3 days post infection. We show that this early bacterial clearance corresponds to an allergic contact sensitivity-like cutaneous response, probably due to a subpopulation of initiating B1a cells. In the pneumonia model, these B1a cells were found to secrete higher affinity antigen-specific IgM. In addition, as in contact sensitivity, iNKT cells were required for the anti-pneumococcal B1a cell initiating response, probably through early production of IL-13, given that IL-13(-/-) mice also failed to clear infection. Our study is the first to demonstrate the importance of AID in generating an appropriate B1a cell response to pathogenic bacteria. Given the antibody affinity and pneumonia resistance data, natural IgM produced by conventional B1a cells are not responsible for pneumonia clearance compared with the AID-dependent subset.

[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2012].

The nationwide surveillance of antibacterial susceptibility to meropenem (MEPM) and other parenteral antibiotics against clinical isolates during 2012 in Japan was conducted. A total of 2985 strains including 955 strains of Gram-positive bacteria, 1782 strains of Gram-negative bacteria, and 248 strains of anaerobic bacteria obtained from 31 medical institutions were examined. The results were as follows; 1. MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). 2. Of all species tested, there were no species, which MIC90 of MEPM was more than 4-fold higher than those in our previous studies in 2009 or 2006. Therefore, the tendency to increase in antimicrobial resistance rates was not observed. 3. MEPM resistance against Pseudomonas aeruginosa was 17.8% (56/315 strains). Compared to our previous results, it was the lowest than that in 2006 and 2009. 4. Carbapenem-resistant Klebsiella pneumoniae, and multi-drug-resistant Acinetobacter species, which emerged in worldwide, were not observed. 5. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 6.2% (59/951 strains) in enterobacteriaceae, which increased compared with that of our previous studies in 2009 or before. Whereas, the proportion of metallo-beta-lactamase strains was 1.6% (5/315 strains) in P. aeruginosa, which was stable. In conclusion, the results from this surveillance suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 17 years passed after available for commercial use in Japan.

Efficacy of 1.0% chlorhexidine-gluconate ethanol compared with 10% povidone-iodine for long-term central venous catheter care in hematology departments: a prospective study.

The efficacy of 1% chlorhexidine-gluconate ethanol and 10% povidone-iodine for skin antisepsis of central venous catheter (CVC) sites were compared among hematology patients. The CVC site colonization rates of those groups were 11.9% and 29.2%, respectively, and the catheter-associated blood stream infections were 0.75 and 3.62 per 1,000 catheter-days, respectively. One percent chlorhexidine-gluconate ethanol was superior to povidone-iodine to reduce skin colonizers at CVC sites even when catheters were used for long duration.