Japanese journal of infectious diseases最新文献

Using anticancer drugs as examples, we examined the possibility of reusing residual drugs. The use of residual drugs is not widespread owing to concerns regarding bacterial contamination. We combined anticancer drugs and bacteria to investigate their effects on bacterial growth. The anticancer drugs carboplatin, paclitaxel, etoposide, irinotecan, methotrexate, and 5-fluorouracil (5-FU) were mixed with Staphylococcus aureus, Enterococcus faecalis, Serratia marcescens, and Escherichia coli. After a certain period, the bacteria were counted. Irinotecan showed no antibacterial activity, whereas 5-FU exhibited high antibacterial activity against the tested bacteria. The 5-FU also showed a minimum inhibitory concentration value in the range of 8-80 μg/mL, depending on the bacterial species. 5-FU dose-dependently inhibited S. aureus growth at more than 0.8 µg/mL. Because protein synthesis systems are reportedly antibiotic targets, we used a cell-free protein synthesis system to confirm the mechanism of the antibacterial activity of the anticancer agent. 5-FU and methotrexate had direct inhibitory effects on protein synthesis. It has been suggested that even if residual drugs are contaminated with bacteria, there will be no microbial growth, or the microbes will be killed by the drug. With careful monitoring, 5-FU can potentially be used for antimicrobial purposes.

Legionella pneumophila serogroup (SG) 1, the main cause of Legionnaires' disease, can be diagnosed using urinary antigen testing kits. However, lower respiratory tract specimen cultures are required to identify L. pneumophila SG 2-15. We attempted to detect L. pneumophila SG-specific genes in a culture-negative sputum specimen from a patient with pneumonia who was suspected to have Legionnaires' disease. Two multiplex PCR methods targeting L. pneumophila were modified and amplicons considered to be SG13 specific were detected. Direct sequencing revealed that the amplicons were identical to the nucleotide sequence of L. pneumophila SG13. Based on the presentation and clinical course (fever, muscle pain, disturbance of consciousness, high C-reactive protein titer, rhabdomyolysis, hypophosphatemia, and symptomatic improvement with levofloxacin treatment), in combination with the detection of L. pneumophila SG-specific genes, we suspected L. pneumophila SG13 pneumonia. L. pneumophila non-SG1 pneumonia is thought to be underestimated because of its difficult laboratory diagnosis. The modified multiplex PCR system for lower respiratory tract specimens revealed in this study is likely to improve the diagnosis of Legionnaires' disease caused by L. pneumophila SG13 and other SGs.

The patient was a 22-year-old woman with no comorbidities who was transferred to our hospital due to cardiac arrest. Treatment enabled return to spontaneous circulation in the patient before arriving at the hospital. At the hospital, the patient's vital signs were unstable. Vasopressors and hyperhydration therapy were administered. Computed Tomography (CT) showed no remarkable change that caused the cardiac arrest. Antibiotics were prescribed after a blood culture exam. The patient was admitted to the ICU. In the ICU, the high-capacity vasopressors, hyperhydration therapy and transfusion of fresh frozen plasma were continued. Two hours after examining the blood culture, the results remained positive. Gram staining revealed Streptococcus, and the antibiotics were switched to penicillin G potassium, clindamycin and immunoglobulin was added. Hyperhydration therapy caused respiratory failure. Ten hours after admission to the ICU, extracorporeal membrane oxygenation was introduced, but the patient's general status did not improve. The patient died at 40 hours after admission. Blood culture results proved Streptococcus pyogenes; T and M serotypes were unclassifiable. The emm genotype was emm22. Regarding fever toxin genes, speA and speB were positive, and speC was negative. Among CsrS, CsrR and Rgg amino acid sequences, mutations in CsrS were detected.

COVID-19 is an pandemic that is still affecting today and has caused many deaths. Toll-like receptor (TLR) have an important role in the binding of disease agents to host cell, disease susceptibility and severity, host disease resistance, In this study, we investigated frequencies of TLR7 (C.4-151 A/G), TLR9 (T-1486C and G2848A), and TLR10 (720A/C and 992T/A) single nucleotide polymorphisms (SNPs) in 150 cases with COVID-19 and 171 control samples. We also observed whether TLR7, 9, and 10 were related with the COVID-19 disease severity. Furthermore, we analyzed the association between COVID-19 and some clinical parameters. Polymerase chain reaction (PCR) based on restriction fragment length polymorphism (RFLP) was performed for TLR7, 9 and 10 SNPs. TLR7 C.4-151 A/G G allele and GG genotype; TLR9 T-1486C C allele and TC, CC genotypes; and TLR10 720A/C C allele; TLR10 992T/A A allele and AA genotype frequencies were statistic significant in cases compared with controls (P<0.05*). In addition, there was a statistic significant difference in the distribution of TLR7, 9, and 10 allele and genotype frequencies between severity groups (P<0.05*). Our findings suggest that TLR7, 9, and 10 polymorphisms may be crucial on clinical course or susceptibility of the infection.

Since 2019, many studies on COVID-19, which has caused extensive damage as a pandemic, have been ongoing worldwide. These include serological and biochemical studies using sera from patients and animal models. Testing with these sera must be performed after the inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Heat treatment, UV irradiation, and/or gamma-ray irradiation are used to inactivate viruses in serum. Determining the inactivation conditions that ensure the inactivation of viruses and minimize the effect on test results after inactivation is important to ensure worker safety and accuracy of test results. In this study, serum samples containing SARS-CoV-2 were subjected to heat, UV irradiation, and gamma irradiation to determine their inactivation conditions. The viral titers were below the detection limit after heating at 56°C for 1 h or 60°C for 15 min, UV-B irradiation with a transilluminator for 30 min, or gamma ray irradiation with ⁶⁰Co at 10 kGy. These results provide useful information for safe serological and biochemical experiments.

Human parainfluenza virus type 3 (HPIV-3, Human respirovirus 3) is the second most frequently detected virus after human respiratory syncytial virus (HRSV) in lower respiratory tract infections in children. HPIV-3, like its close relative respiratory viruses, HRSV and influenza virus, may cause encephalopathy, but the relevance of HPIV-3 as a pathogenic factor in encephalopathy is unknown. We attempted to detect HPIV-1 through 4, HRSV, and human metapneumovirus (HMPV) in 136 patients with encephalitis/encephalopathy, or suspected encephalitis/encephalopathy during a 6-year period from 2014 to 2019. As a result, HPIV-3 was detected most frequently in 6 patients, followed by HRSV in 3. The HPIV-3 strains detected were closely related to those detected in a patient with respiratory disease at the same period. Although HPIV-3 is less recognized than HRSV as a triggering virus of encephalopathy, our results suggest that HPIV-3 is at least as important as HRSV. Surveillance of the causative virus of encephalopathy, including HPIV-3, would help to clarify the actual status of encephalopathy, the cause of which is currently reported in less than half of cases in Japan.

All clinical isolates of Streptococcus dysgalactiae subsp. equisimilis (SDSE) are considered susceptible to β-lactams, the first-line drugs used for SDSE infections. However, penicillin-non-susceptible SDSE has been reported from Denmark. In this study, we attempted to detect β-lactam-non-susceptible clinical isolates of SDSE in Japan. One hundred and fifty clinical isolates of S. dysgalactiae were collected in 2018, and species identification was performed using Rapid ID Strep API. The minimum inhibitory concentrations (MIC) of six β-lactams (penicillin G, oxacillin, ceftizoxime, ceftibuten, cefoxitin, and cefaclor) were determined for 85 clinical isolates of SDSE using the agar dilution method standardized by the Clinical Laboratory Standards Institute. For the 85 isolates identified as SDSE, the MIC ranges of penicillin G, oxacillin, ceftizoxime, ceftibuten, cefoxitin, and cefaclor were 0.007–0.06, 0.03–0.12, 0.015–0.06, 0.25–2, 0.12–2, and 0.06–0.5 μg/mL, respectively. None of the clinical isolates were non-susceptible to penicillin G, indicating that all 85 clinical isolates of SDSE were susceptible to β-lactams. Our findings indicate that almost all clinical isolates of SDSE in several prefectures of Japan remain susceptible to β-lactams. Nevertheless, there remains a need for continuous and careful monitoring of drug susceptibility among clinical isolates of SDSE in Japan.

Nafamostat mesylate, a synthetic serine protease inhibitor, has demonstrated early antiviral activity against SARS-CoV-2 and anticoagulant properties that may be beneficial in COVID-19. We conducted a meta-analysis evaluating the efficacy and safety of nafamostat mesylate for COVID-19 treatment. PubMed, Embase, Cochrane Library, Scopus, Web of Science, medRxiv and bioRxiv were searched up to July 2023 for studies comparing outcomes between nafamostat mesylate treatment and no nafamostat mesylate treatment in COVID-19 patients. Mortality, disease progression and adverse events were analyzed. Six studies involving 16,195 patients were included. Meta-analysis revealed no significant difference in mortality (OR=0.88, 95%CI: 0.20-3.75, P=0.86) or disease progression (OR=2.76, 95%CI: 0.31-24.68, P=0.36) between groups. However, nafamostat mesylate was associated with increased hyperkalemia risk (OR=7.15, 95%CI: 2.66 to 19.24, P<0.0001). Nafamostat mesylate does not improve mortality or morbidity in hospitalized COVID-19 patients compared to no nafamostat mesylate treatment. The significant hyperkalemia risk is a serious concern requiring monitoring and preventative measures. Further research is needed in different COVID-19 populations.

This cross-sectional study investigated the antimicrobial resistance (AMR) patterns of Gram-negative pathogens isolated from 4,789 hospitalized patients with lower respiratory tract infections (LRTIs). Of the collected specimens, 1,325 (27.7%) specimens tested positive for Gram-negative bacteria. The most prevalent isolates were Acinetobacter baumannii (38.6%), Pseudomonas aeruginosa (33.5%), Klebsiella pneumoniae (18.7%), Escherichia coli (5.6%), and Klebsiella aerogenes (3.5%). Antimicrobial resistance analysis revealed high resistance rates among A. baumannii isolates, showing resistance (79.9%-100%) to multiple classes of antibiotics, except amikacin, trimethoprim/sulfamethoxazole, and colistin. P. aeruginosa displayed lower resistance to colistin (<10%), but resistance to other antibiotics was high. K. pneumoniae displayed elevated resistance rates against most penicillins, ranging from 90.0% to 100.0%. In contrast, the resistance rates were notably lower for colistin (7.1%) and amikacin (16.7%). K. aerogenes showed high resistance to various antibiotics, while sensitivity was observed for amikacin (95.1%), ampicillin (100.0%), and colistin (100.0%). E. coli exhibited resistance to ampicillin (96.9%) but showed maximum sensitivity to several antibiotics. The study identified significant antimicrobial resistance trends and highlighted the prevalence of multidrug-resistant strains (93.6% for K. aerogenes and 69.1%-92.4% for other isolates). These findings emphasize the urgent need for appropriate antibiotic stewardship practices to combat antimicrobial resistance in Gram-negative pathogens associated with LRTIs.

Multidrug-resistant Acinetobacter baumannii (MDRAB) is an important pathogen that causes nosocomial infections and is resistant to almost all antibiotics, including carbapenems. Cefiderocol is a novel siderophore cephalosporin that is active against a broad spectrum of Gram-negative bacteria. However, the susceptibility of MDRAB from Japan to cefiderocol has not yet been reported. In this study, we measured the minimum inhibitory concentrations (MICs) of antibiotics, including cefiderocol, against MDRAB clinical isolates collected during a nosocomial outbreak from 2009 to 2010 at Teikyo University Hospital in Japan. We found that all 10 MDRAB clinical isolates tested were susceptible to cefiderocol, with an MIC range of 0.12 to 1 μg/mL, all isolates were resistant to ampicillin-sulbactam, nine of the 10 isolates were susceptible to tigecycline, and all 10 isolates had an intermediate phenotype to colistin. DNA sequencing revealed that all strains harbored an OXA-51-like carbapenemase, one of the major causes of carbapenem resistance in A. baumannii in Japan. In conclusion, this study showed that susceptibility to cefiderocol of MDRAB clinical isolates in Japan was equivalent to that of colistin or tigecycline. Cefiderocol could be a possible choice for the treatment of MDRAB infections.