OP-145 is a synthetic antimicrobial peptide developed from the human cathelicidin LL-37. The purpose of this investigation was to evaluate the effect of the antimicrobial peptide OP-145 against clinically isolated drug-resistant strains. Ten methicillin-resistant Staphylococcus aureus (MRSA) strains were obtained from our hospital's clinical inspection center, and the activity of OP-145 on growth and biofilm formation of these strains was evaluated by colony counts and scanning electron microscopy. The antimicrobial peptide OP-145 showed significant antibacterial activity against 9 MRSA strains. For the biofilm experiments, MRSA counts in the biofilms decreased significantly after 24 h (P ＜ 0.05). OP-145 strongly reduced growth and biofilm formation of clinically isolated drug-resistant strains in vitro, and the use of this class of antimicrobial agents may be an important new approach in controlling bacterial infections.
The incidence of severe hand-foot-mouth disease (HFMD) in Southeast and East Asia has increased in recent years. This study explored spatial clusters of the incidence and proportion of severe HFMD cases on Hainan Island, where the prevalence and mortality of HFMD were the highest in China during 2011. A spatial autocorrelation statistic (Anselin’s Local Moran I) was calculated for the Empirical Bayesian (EB)-smoothed dataset of severe HFMD cases. Significant spatial clusters were detected for both the incidence and proportion of severe HFMD cases. Population density was higher in spatial clusters with a high proportion of severe HFMD cases among total HFMD cases. We speculate that a higher proportion of severe HFMD cases were diagnosed in densely populated townships. This should be considered when analyzing the HFMD database of Hainan Island.
In norovirus and Campylobacter food poisonings, the frequencies of the number of patients per incident and that of the number of eaters per incident followed a lognormal distribution, with medians of 12–27 and 23–48 for norovirus and 5–8 and 9–21 for Campylobacter food poisonings, respectively. The lognormal frequency distribution of eaters could be simulated by assuming that people find a dish more appealing if that dish has already been found to be appealing to others. The numbers of patients and eaters per incident were not necessarily inter-correlated; the frequencies of the attack rates (number of patients/number of eaters) were distributed evenly from 0.01 to 1; that is, the attack rates of these food poisonings could not be represented by means and standard deviations. The frequency distributions of the attack rates were nevertheless not entirely disordered; plotting the attack rate against the number of patients in individual incidents produced fingerprint-like patterns that were repeatedly produced at the prefectural and national levels.
The pharmacokinetic–pharmacodynamic (PK–PD) breakpoints (BPs) of garenoxacin (GRNX) and other oral quinolones were calculated using Monte Carlo simulation (MCS) based on the distribution of changes in their plasma concentrations. PK–PD BPs of 400 mg once a day (QD) of GRNX for the free area under the curve/minimum inhibitory concentration (fAUC/MIC) for 30 strains of Streptococcus pneumoniae and 100 strains of gram-negative bacteria (G [－]) were 0.5 and 0.125 μg/mL, respectively. PK–PD BPs of other quinolones for S. pneumoniae/G (－) were 1/0.25 μg/mL for levofloxacin (LVFX) 500 mg QD, 0.5/0.125 μg/mL for moxifloxacin (MFLX) 400 mg QD, 0.0625/0.0156 μg/mL for sitafloxacin (STFX) 50 mg twice a day (BID) (100 mg QD), and 0.125/0.0313 μg/mL for STFX 100 mg BID. We also investigated the hypothetical probability of target attainments (PTAs) of fAUC/MIC for community-acquired pneumonia (CAP) using MCS, in consideration of the isolation frequencies of the three main causative pathogens of CAP: S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. For hypothetical CAP in adults, PTA of fAUC/MIC was 100% with GRNX and MFLX, 96%–97% with STFX at 100 mg BID, 45%–46% with LVFX, and 53%–58% with STFX at 100 mg QD and 50 mg BID. Based on the PK–PD BP, GRNX showed higher fAUC/MIC than the other quinolones tested against the three main pathogens of respiratory infections.
We studied the prevalence of HIV drug resistance among high-risk groups such as injecting drug users (IDUs), female sex workers (FSWs), and men having sex with men (MSM) in central Vietnam. We used HIV-positive blood samples from 2012–2013 sentinel surveillance surveys. Study subjects were screened for HIV infection by standardized screening assays, and the HIV-positive samples were further tested for HIV viral load and drug-resistance mutations (DRMs) by in-house assays. DRMs were identified using the Stanford University online sequence analysis tool. Their risk behaviors were also investigated. During the study period, 6,016 (high-risk) subjects were screened, and 97 tested positive for HIV infection (IDUs: n = 63, 3.0%; FSWs: n = 24, 0.9%; and MSM: n = 10, 1.0%). Ninety-two of the 97 samples (45 from 2012 and 47 from 2013) were available for further testing. HIV RNA was detected in 56 (60.9%) of the 92 samples, and drug resistance genotyping was successfully performed on 40 (71.4%) samples. All these isolates were subtype CRF01_AE, except for 1 (2.5%) IDU whose HIV belongs to subtype B. Thirteen individuals (32.5%) were carrying HIV with at least 1 DRM: 9 IDUs, 1 FSW, and 3 MSM. Thus, HIV seroprevalence among high-risk individuals in central Vietnam is low, but a high proportion of drug resistant HIV-1 isolates is observed in the high-risk group.
Twelve nonreplicate carbapenemase-negative ertapenem (ETP)-nonsusceptible (CNENS) Escherichia coli isolates obtained at a Thai university hospital between 2010 and 2014 were characterized and compared with 2 carbapenemase-producing E. coli isolates from the same hospital. Eight unique pulsed-field gel electrophoresis patterns were obtained. All the isolates produced CTX-M-15 β-lactamase and 2 either coexpressed CMY-2 cephalosporinase or showed increased efflux pump activity. Amino acid sequence analysis revealed that an OmpF defect (in 7 isolates) due to mutations generating truncated proteins or an IS1 insertion was more prevalent than a defect in OmpC was (no truncated proteins detected). Seven out of 10 isolates possessing OmpC variants with any OmpF defect were weakly ETP-resistant (minimum inhibitory concentrations [MICs] of 1–4 μg/mL) and imipenem (IPM)- and meropenem (MEM)-susceptible (MICs 0.125–0.5 μg/mL). Two isolates with ompC PCR-negative results and an OmpF defect showed higher carbapenem MICs (8–32, 1–8, and 1–4 μg/mL for ETP, IPM, and MEM, respectively) with the highest MICs associated with the additional efflux pump activity. Both carbapenemase producers possessing CTX-M-15 and a porin background identical to that in the CNENS isolates showed ETP, IPM, and MEM MICs of 128–256, 8, and 2–32 μg/mL, respectively. These findings suggest that a porin defect combined with CTX-M-15 production is the major mechanism of low carbapenem susceptibility among our CNENS isolates, which have potential to become strongly carbapenem-resistant because of additional carbapenemase or efflux pump activities.
This is the first report on large-scale experimental production of an equine antivenom against the redback spider (Latrodectus hasseltii) lived in Japan. We captured 10,000 redback spiders in Japan and prepared the toxoids of crude venom extract, mixed the toxoids with a mineral oil adjuvant, and immunized healthy horses repeatedly over a period of several weeks. Thereafter, we separated the horse plasma, purified the γ-globulin fraction, and stocked it as a purified antivenom concentrate. Consequently, we manufactured approximately 6,500 vials of a single-dose freeze-dried test lot from a portion of the purified γ-globulin fraction, equivalent to the extract derived from 520 spiders. This test lot had an antitoxin titer comparable to that of a similar drug commercially available overseas (a liquid preparation), and the other quality met all quality reference specifications based on the Minimum Requirements for Biological Products and other guidelines relevant to existing antivenom drug products in Japan.
Multiple-locus variable-number tandem-repeat analysis (MLVA) typing was performed for Mycoplasma pneumoniae strains isolated between 2004 and 2014 in Yamagata, Japan. The results were examined by considering the combination of the P1 type and prevalence of macrolide resistance-associated mutations. Four-locus (Mpn13–16) MLVA classified 347 strains into 9 MLVA types, including 3 major types: 3-5-6-2, 4-5-7-2, and 4-5-7-3. All type 3-5-6-2 strains (77 strains) were P1 type 2 variants (2a or 2c), while types 4-5-7-2 (181 strains) and 4-5-7-3 (75 strains) were P1 type 1. MLVA type 4-5-7-2 strains circulated and were dominant until 2010, accounting for 88.4% of the 121 strains isolated between 2004 and 2010. The prevalence of types 4-5-7-3 and 3-5-6-2 strains increased rapidly in 2011 and 2012, respectively, resulting in cocirculation of 3 MLVA types, including type 4-5-7-2, between 2011 and 2013. The prevalence of macrolide resistance-associated mutations in MLVA types 4-5-7-2, 4-5-7-3, and 3-5-6-2 strains was 59.7% (108/181), 25.3% (19/75), and 0% (0/77), respectively. Because the prevalence of macrolide resistance-associated mutations differed by current MLVA types in Yamagata, continued surveillance combined with molecular typing and identification of macrolide resistance-associated mutations is necessary.
Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome are an important factor in low therapeutic effectiveness. Nonetheless, the prevalence of these mutations in HBV strains isolated previously in Indonesia has not been systematically examined. Therefore, in this study, we investigated the profile of mutations in the RT region and the associations of these mutations with amino acid changes in the surface protein in the virus of treatment-naïve Indonesian HBV carriers. Overall, 96 sequences of the full-length Indonesian HBV genomes (genotype B, n = 54; genotype C, n = 42) were retrieved from the National Center for Biotechnology Information. Naturally occurring primary and/or compensatory drug resistance mutations were found in 6/54 (11.1%) genotype B strains and in 1/42 (2.4%) genotype C strains. The potential mutations underlying resistance to a nucleos(t)ide analog and/or pretreatment mutations were more frequent in both genotypes but more frequent in genotype C strains than in genotype B strains. The A–B interdomain region in the RT gene was more frequently mutated in genotype C than in genotype B (3.51 ± 2.53 vs. 1.08 ± 1.52, P ＜ 0.001). Knowledge about the mutational profiles of the RT gene and changes in the surface protein may help clinicians to select the most appropriate antiviral drug and vaccination or HBV immunoglobulin regimen for management of HBV infection in Indonesia.
Chronic kidney disease (CKD) has been shown to be a poor prognostic factor in HIV patients. This study aimed to identify risk factors in HIV-infected patients with early decline in renal function or an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m2. The study was retrospectively conducted at Panyananthaphikkhu Chonprathan Medical Center, Thailand. The inclusion criteria were HIV-infected adult patients who were treated at the hospital’s HIV clinic and whose eGFR levels at the first visit had been evaluated. Eligible patients were categorized according to their eGFR level being lesser or greater than 90 mL/min/1.73 m2. Multivariate logistic analysis was performed to evaluate the association of risk factors with an eGFR of less than 90 mL/min/1.73 m2. There were 301 HIV-infected patients included in the study. Of those, 89 patients (29.57%) had an eGFR of less than 90 mL/min/1.73 m2. Age was the only significant risk factor associated with an eGFR of less than 90 mL/min/1.73 m2 with an adjusted odds ratio of 1.072 (95% confidence interval: 1.015–1.132). Age of over 37 years predicted an eGFR of less than 90 mL/min/1.73 m2 as a risk factor in HIV-infected patients, with a sensitivity of 80.9% and specificity of 34.91%. Age was independently associated with eGFRs of less than 90 mL/min/1.73 m2 in HIV-infected patients. Close monitoring of eGFR should be performed in HIV-infected patients aged over 37 years.
Legionella species are important causative pathogens for severe community-acquired pneumonia (CAP). Most cases of Legionella pneumonia are due to Legionella pneumophila serogroup 1, and CAP due to L. pneumophila serogroup 9 is rare. A fourth case of CAP due to L. pneumophila serogroup 9 has been reported, and initial treatment using single-dose oral azithromycin appeared useful. Azithromycin or fluoroquinolone injection is usually recommended for the treatment of Legionella pneumonia, and no previous reports have shown the effectiveness of single-dose oral azithromycin. This case report is therefore valuable from the perspective of possible treatment for mild to moderate Legionella pneumonia using single-dose oral azithromycin.
Dengue is the most prevalent arboviral disease affecting humans, with tropical and subtropical regions having the highest risk of dengue virus infections. The clinical symptoms often range from mild fever to fever with hemorrhagic manifestations and shock. Since 2010, India has been witnessing a marked increase in the number of dengue virus serotype 1 (DENV-1) infections, apart from those of serotypes 2 (DENV-2) and 3 (DENV-3). The present study was undertaken to understand the circulating genotypes of DENV-1 in South West India, by sequencing the envelope gene of DENV-1 samples representative of the 2014–2015 time period. The extracted RNAs from dengue NS1 antigen ELISA-positive samples, archived at the APEX Referral Laboratory for Arboviruses (National Vector Borne Disease Control Programme, Manipal Centre for Virus Research), were used for the study. The currently circulating genotypes of DENV-1 identified from the study area belong to genotypes V and I. Multicentric laboratory-based studies analyzing the envelope gene of all dengue serotypes are required from endemic countries like India.
Human adenovirus (HAdV) strains isolated from respiratory specimens of 139 children were analyzed to evaluate the endemic situation of HAdV infections in Osaka, Japan, between 2008 and 2015. The cases increased during spring and winter, and the infections were confirmed mainly in children aged ≤ 5 years, comprising 91.9% of the total population examined. Molecular typing of the isolates revealed that the most common types belonged to HAdV-B and -C. Co-infection of HAdV-C1 and -C2 was also confirmed in a case. The median age of HAdV-E cases was higher than that of the HAdV-B and -C cases. These results revealed age and seasonal distribution of respiratory HAdV infections in children from Osaka, and indicate that majority of these children might have acquired immunity through endemic HAdV infection before reaching school age.
In Japan, 20–50 cases of leptospirosis are reported annually, typically involving farmers or returnees from tropical areas. Here, we report on 5 indigenous leptospirosis cases that occurred in the Tokyo urban area. All patients were men (mean age, 66.4 ± 4.6 [SD] years) and presented with clinical features that included high fever, acute kidney injury, and jaundice. Three patients presented with pulmonary infiltration and ground-glass opacity on admission. Two of the 5 patients were intubated and underwent continuous hemodiafiltration. The mean length of hospitalization was 38.0 ± 17.0 days, and all patients were treated successfully with antibiotics. Notably, all patients had a history of exposure to rats prior to becoming symptomatic, suggesting that exposure to rats is a risk factor for urban leptospirosis. Although rare, even in metropolitan areas, leptospirosis should be considered by physicians when patients present with severe sepsis, acute kidney injury, and a history of exposure to rats.
Brucellosis is endemic in Iran. Several studies have shown that brucellosis is associated with other infectious diseases. This study aimed to determine the relationship between Helicobacter pylori (HP) and brucellosis. In this case-control study, 100 patients with brucellosis as cases and 200 participants without brucellosis as controls were evaluated. To compare the prevalence of HP in the 2 groups, odds ratios and confidence intervals for every variable were analyzed using logistic regression models after adjustment for confounding factors. The results obtained in patients with brucellosis showed that fever, sweating, and joint pain were the most prevalent clinical symptoms. In addition, compared with the control group, there was a significant relationship between the IgM antibody to HP and brucellosis infection (estimated odds ratio 2.74; 95% CI: 1.5–4.9) (p = 0.001). Acute infection with HP was associated with brucellosis and increased the risk of brucellosis infection.
Dengue fever remains underreported in Africa due to a lack of awareness among healthcare providers, the presence of other febrile illnesses, and insufficient laboratory testing. We present a case of dengue fever imported from Burkina Faso to Japan, where an outbreak of dengue was reported on October 18, 2016. Phylogenetic analysis revealed that the isolate from our patient belonged to a distinct cluster of sylvatic dengue viruses, suggesting that dengue viruses have been maintained in mosquitoes and human cycles in Burkina Faso for more than 30 years.
Oxazolidinones constitute a novel class of antimicrobials as inhibitors of bacterial ribosomal protein synthesis. In this study, we identified 15 novel oxazolidinone analogs with potent antituberculosis activities. Compounds sy124 and sy125 showed the best activity in vitro (better than that of the linezolid) against various clinically relevant bacterial species, including most Gram-positive bacteria, Mycobacterium spp., and Helicobacter pylori. A cell-based assay indicated that these compounds have a strong ability to kill intracellular pathogens. Our results reveal that the newly identified compounds may be further developed as novel antimicrobial agents.
Trueperella bernardiae (T.bernardiae) is a gram-positive curved rod that is considered an uncommon pathogen involved in few infections. The true incidence of infections with this bacterium, and the clinical implications, remain unknown. We report 2 cases of wound infections in 2 patients who underwent different surgical procedures, although in the second case the microorganism was isolated in mixed culture. Culture of wound secretions resulted in isolation of T. bernardiae. Treatment was performed and resolution of the infections was documented.
An increasing number of invasive infections due to Streptococcus agalactiae in non-pregnant adults have been reported. We report a case of infective endocarditis complicated by intraventricular abscesses, pericarditis, and mycotic aneurysm due to S. agalactiae belonging to ST681 with a capsular serotype VI in a woman with diabetes. The patient also had a myocardial infarction and was treated with percutaneous coronary intervention, pericardiocentesis, and 6 weeks of antibiotic treatment. Invasive infections due to serotype VI S. agalactiae are common in Asian countries such as Taiwan and Japan, so continuous monitoring of invasive S. agalactiae strains is warranted.