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Fatal pneumonia with repeated detection of Talaromyces columbinus two years after haploidentical transplantation
IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-02-06 DOI: 10.1016/j.jiac.2025.102649
Yuya Nakata , Nozomu Yoshino , Machiko Kusuda , Shun-ichi Kimura , Akari Matsuoka , Tomohiro Meno , Takuto Ishikawa , Yuhei Nakamura , Masakatsu Kawamura , Junko Takeshita , Shunto Kawamura , Yukiko Misaki , Kazuki Yoshimura , Ayumi Gomyo , Masaharu Tamaki , Yasutaka Hoshino , Takayuki Shinohara , Yoshitsugu Miyazaki , Hideki Nakasone , Shinichi Kako , Yoshinobu Kanda
Talaromyces columbinus was previously reported in two patients with lung infections under the name Penicillium piceum and one case of dual infection with Aspergillus calidoustus was recently reported.; currently, no treatment has been established. We identified a 61-year-old woman with fatal pneumonia with repeated detection of T. columbinus that developed two years after haploidentical transplantation using alemtuzumab for chronic myeloid leukemia in the blast phase. Seven months after transplantation, her minimal residual disease (MRD) turned positive. Thus, ponatinib was restarted, which resulted in MRD becoming negative again. Nine months after transplantation, she developed autoimmune hemolytic anemia (AIHA); treatment with prednisone (PSL) 35 mg was started. PSL was discontinued one year ten months after transplantation, but was resumed at 5 mg after relapse one year eleven months after transplantation. Two years after transplantation, she developed cough, and a CT scan showed bilateral pulmonary infiltrates. Initiation of antibiotics, voriconazole (VRCZ), posaconazole (PSCZ) and liposomal amphotericin B (L-AMB) did not improve her condition. Sputum culture detected Penicillium species, which was identified as T. columbinus by polymerase chain reaction (PCR). Since the minimal inhibitory concentration (MIC)/minimal effective concentration (MEC) ratio was lower for echinocandins, micafungin (MCFG) was added to L-AMB. However, the patient died of respiratory failure on day 38 of admission. This is the first reported case of T. columbinus infection in Japan. Managing this infection is challenging due to the lack of established diagnostic methods and treatments. Proactive diagnostic testing and case accumulation are needed.
{"title":"Fatal pneumonia with repeated detection of Talaromyces columbinus two years after haploidentical transplantation","authors":"Yuya Nakata ,&nbsp;Nozomu Yoshino ,&nbsp;Machiko Kusuda ,&nbsp;Shun-ichi Kimura ,&nbsp;Akari Matsuoka ,&nbsp;Tomohiro Meno ,&nbsp;Takuto Ishikawa ,&nbsp;Yuhei Nakamura ,&nbsp;Masakatsu Kawamura ,&nbsp;Junko Takeshita ,&nbsp;Shunto Kawamura ,&nbsp;Yukiko Misaki ,&nbsp;Kazuki Yoshimura ,&nbsp;Ayumi Gomyo ,&nbsp;Masaharu Tamaki ,&nbsp;Yasutaka Hoshino ,&nbsp;Takayuki Shinohara ,&nbsp;Yoshitsugu Miyazaki ,&nbsp;Hideki Nakasone ,&nbsp;Shinichi Kako ,&nbsp;Yoshinobu Kanda","doi":"10.1016/j.jiac.2025.102649","DOIUrl":"10.1016/j.jiac.2025.102649","url":null,"abstract":"<div><div><em>Talaromyces columbinus</em> was previously reported in two patients with lung infections under the name <em>Penicillium piceum</em> and one case of dual infection with <em>Aspergillus calidoustus</em> was recently reported.; currently, no treatment has been established. We identified a 61-year-old woman with fatal pneumonia with repeated detection of <em>T. columbinus</em> that developed two years after haploidentical transplantation using alemtuzumab for chronic myeloid leukemia in the blast phase. Seven months after transplantation, her minimal residual disease (MRD) turned positive. Thus, ponatinib was restarted, which resulted in MRD becoming negative again. Nine months after transplantation, she developed autoimmune hemolytic anemia (AIHA); treatment with prednisone (PSL) 35 mg was started. PSL was discontinued one year ten months after transplantation, but was resumed at 5 mg after relapse one year eleven months after transplantation. Two years after transplantation, she developed cough, and a CT scan showed bilateral pulmonary infiltrates. Initiation of antibiotics, voriconazole (VRCZ), posaconazole (PSCZ) and liposomal amphotericin B (L-AMB) did not improve her condition. Sputum culture detected <em>Penicillium</em> species, which was identified as <em>T. columbinus</em> by polymerase chain reaction (PCR). Since the minimal inhibitory concentration (MIC)/minimal effective concentration (MEC) ratio was lower for echinocandins, micafungin (MCFG) was added to L-AMB. However, the patient died of respiratory failure on day 38 of admission. This is the first reported case of <em>T. columbinus</em> infection in Japan. Managing this infection is challenging due to the lack of established diagnostic methods and treatments. Proactive diagnostic testing and case accumulation are needed.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"31 4","pages":"Article 102649"},"PeriodicalIF":1.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Isepamicin alone as antimicrobial prophylaxis for transrectal prostate needle biopsy: “Do we still need levofloxacin? ”
IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-02-05 DOI: 10.1016/j.jiac.2025.102645
Hiroki Yamada , Kojiro Tashiro , Yusuke Takahashi , Mariko Honda , Hajime Ohnuma , Keiji Yasue , Mahito Atsuta , Kei-Ichiro Miyajima , Mimu Ishikawa , Yuki Takiguchi , Hiroshi Kiyota , Takahiro Kimura
The purpose of this study was to investigate whether conventional levofloxacin (LVFX) administration is unnecessary for transrectal ultrasound-guided prostate needle biopsy (TRP-Bx) in view of the increase in LVFX-resistant Escherichia coli and appropriate use of antibiotics. The study included 636 cases undergoing TRP-Bx, divided into two groups based on the prophylactic antibiotic regimen. Group 1 (n = 308) received both oral levofloxacin (LVFX) 500 mg and intravenous isepamicin (ISP) 400 mg. Group 2 (n = 328) received only intravenous ISP 400 mg. Biopsies involved sampling 12 cores using an 18G needle. A high-risk subgroup included patients with a large prostate (>75 ml), severe dysuria, diabetes mellitus, or steroid use. Significantly more high-risk cases were in Group 2 than in Group 1 (35.7 % vs. 24.4 %, p = 0.003). Febrile genitourinary tract infections (fGUTIs) occurred in three patients (0.5 %), with no significant difference between the groups (0.3 % in Group 1 vs. 0.6 % in Group 2). No fGUTI complications were noted among high-risk cases in either group. Of the fGUTI cases, one involved LVFX-resistant E. coli; another involved E. coli susceptible to both LVFX and amikacin, isolated from blood. The single- and short-duration intravenous dose of ISP 400 mg would appear to be one of possible options in preventing TRP-Bx-related fGUTIs in both low-risk and high-risk patients.
{"title":"Isepamicin alone as antimicrobial prophylaxis for transrectal prostate needle biopsy: “Do we still need levofloxacin? ”","authors":"Hiroki Yamada ,&nbsp;Kojiro Tashiro ,&nbsp;Yusuke Takahashi ,&nbsp;Mariko Honda ,&nbsp;Hajime Ohnuma ,&nbsp;Keiji Yasue ,&nbsp;Mahito Atsuta ,&nbsp;Kei-Ichiro Miyajima ,&nbsp;Mimu Ishikawa ,&nbsp;Yuki Takiguchi ,&nbsp;Hiroshi Kiyota ,&nbsp;Takahiro Kimura","doi":"10.1016/j.jiac.2025.102645","DOIUrl":"10.1016/j.jiac.2025.102645","url":null,"abstract":"<div><div>The purpose of this study was to investigate whether conventional levofloxacin (LVFX) administration is unnecessary for transrectal ultrasound-guided prostate needle biopsy (TRP-Bx) in view of the increase in LVFX-resistant <em>Escherichia coli</em> and appropriate use of antibiotics. The study included 636 cases undergoing TRP-Bx, divided into two groups based on the prophylactic antibiotic regimen. Group 1 (n = 308) received both oral levofloxacin (LVFX) 500 mg and intravenous isepamicin (ISP) 400 mg. Group 2 (n = 328) received only intravenous ISP 400 mg. Biopsies involved sampling 12 cores using an 18G needle. A high-risk subgroup included patients with a large prostate (&gt;75 ml), severe dysuria, diabetes mellitus, or steroid use. Significantly more high-risk cases were in Group 2 than in Group 1 (35.7 % vs. 24.4 %, p = 0.003). Febrile genitourinary tract infections (fGUTIs) occurred in three patients (0.5 %), with no significant difference between the groups (0.3 % in Group 1 vs. 0.6 % in Group 2). No fGUTI complications were noted among high-risk cases in either group. Of the fGUTI cases, one involved LVFX-resistant <em>E. coli;</em> another involved <em>E. coli</em> susceptible to both LVFX and amikacin, isolated from blood. The single- and short-duration intravenous dose of ISP 400 mg would appear to be one of possible options in preventing TRP-Bx-related fGUTIs in both low-risk and high-risk patients.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"31 4","pages":"Article 102645"},"PeriodicalIF":1.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Days of antibiotic spectrum coverage (DASC) as predictors of recurrent Clostridioides difficile infection: A retrospective cohort study
IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-02-04 DOI: 10.1016/j.jiac.2025.102650
Nobuaki Mori , Yuichi Shibata , Jun Hirai , Nobuhiro Asai , Hiroshige Mikamo

Background

Broad-spectrum antibiotic use increases the risk of Clostridioides difficile infection (CDI), with recurrence rates varying by antibiotic type, spectrum, and treatment duration. We assessed CDI recurrence risk using the days of antibiotic spectrum coverage (DASC) score, considering antibiotic spectrum and use duration.

Methods

We retrospectively analyzed patients with hospital-acquired CDI. A logistic regression analysis was used to evaluate CDI recurrence, incorporating three variables: DASC score prior to CDI diagnosis, type of anti-CDI drugs, or DASC score after CDI diagnosis.

Results

Overall, 246 patients were included, with 31 (12.6 %) cases of recurrence. Median DASC scores within 30 days prior to CDI diagnosis were higher in the recurrent group than in the non-recurrent group (128 [interquartile range: 106–217] vs. 80 [interquartile range: 39–142], p < 0.01). Using the lowest quartile of DASC scores as the reference, the analysis indicated higher relative risks of CDI recurrence in the upper quartiles. However, daily DASC scores post-CDI diagnosis did not correlate with recurrence. Compared to metronidazole, fidaxomicin lowered the risk of CDI recurrence (relative risk 0.2, 95 % confidence interval: 0.1–0.8, p = 0.03).

Conclusions

The DASC score within 30 days prior to CDI diagnosis appears to be a predictive risk factor for CDI recurrence.
{"title":"Days of antibiotic spectrum coverage (DASC) as predictors of recurrent Clostridioides difficile infection: A retrospective cohort study","authors":"Nobuaki Mori ,&nbsp;Yuichi Shibata ,&nbsp;Jun Hirai ,&nbsp;Nobuhiro Asai ,&nbsp;Hiroshige Mikamo","doi":"10.1016/j.jiac.2025.102650","DOIUrl":"10.1016/j.jiac.2025.102650","url":null,"abstract":"<div><h3>Background</h3><div>Broad-spectrum antibiotic use increases the risk of <em>Clostridioides difficile</em> infection (CDI), with recurrence rates varying by antibiotic type, spectrum, and treatment duration. We assessed CDI recurrence risk using the days of antibiotic spectrum coverage (DASC) score, considering antibiotic spectrum and use duration.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed patients with hospital-acquired CDI. A logistic regression analysis was used to evaluate CDI recurrence, incorporating three variables: DASC score prior to CDI diagnosis, type of anti-CDI drugs, or DASC score after CDI diagnosis.</div></div><div><h3>Results</h3><div>Overall, 246 patients were included, with 31 (12.6 %) cases of recurrence. Median DASC scores within 30 days prior to CDI diagnosis were higher in the recurrent group than in the non-recurrent group (128 [interquartile range: 106–217] vs. 80 [interquartile range: 39–142], p &lt; 0.01). Using the lowest quartile of DASC scores as the reference, the analysis indicated higher relative risks of CDI recurrence in the upper quartiles. However, daily DASC scores post-CDI diagnosis did not correlate with recurrence. Compared to metronidazole, fidaxomicin lowered the risk of CDI recurrence (relative risk 0.2, 95 % confidence interval: 0.1–0.8, p = 0.03).</div></div><div><h3>Conclusions</h3><div>The DASC score within 30 days prior to CDI diagnosis appears to be a predictive risk factor for CDI recurrence.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"31 4","pages":"Article 102650"},"PeriodicalIF":1.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
First reported case of disseminated Cunninghamella phaeospora infection with multidrug resistance in acute myeloid leukemia
IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-02-04 DOI: 10.1016/j.jiac.2025.102646
Tomohito Shimada , Akira Watanabe , Kaori Akita , Kana Bando , Atsushi Takahata , Kazuhiro Ishikawa , Shigeo Toyota
Mucormycosis is a severe mold infection primarily affecting immunocompromised patients. Neutropenia, steroid use, hyperglycemia, and diabetes are recognized as significant risk factors. Cunninghamella species are rare pathogenic fungi associated with high mortality rates and multidrug resistance. However, there have been no reports of C. phaeospora being identified as the causative agent of clinical infection. We report a case of a 71-year-old man who developed right middle lobe pneumonia during salvage induction therapy for relapsed acute myeloid leukemia. Based on the clinical course, mucormycosis was suspected, and antifungal therapy was initiated with isavuconazole (200 mg every 8 hours for six doses, followed by 200 mg daily) and later switched to liposomal amphotericin B (5 mg/kg/day). Despite these interventions, the patient's respiratory failure progressed, culminating in a fatal hemorrhagic infarction of the right lung. An autopsy revealed invasive fungal involvement in multiple organs, including the lungs and liver. Genetic identification of the isolated fungi demonstrated C. phaeospora, confirming disseminated C. phaeospora infection. Susceptibility testing showed high Minimum Inhibition Concentrations/Minimum Effective Concentrations to all tested antifungal agents. This is the first reported case of disseminated infection caused by C. phaeospora with multidrug resistance. This case highlights the diagnostic and therapeutic challenges associated with rare pathogenic fungi. It underscores the importance of early identification of Mucorales, including susceptibility testing, to optimize antifungal therapy and consider appropriate surgical interventions. Further research is required to elucidate the mechanisms of antifungal resistance and clinical characteristics of C. phaeospora.
{"title":"First reported case of disseminated Cunninghamella phaeospora infection with multidrug resistance in acute myeloid leukemia","authors":"Tomohito Shimada ,&nbsp;Akira Watanabe ,&nbsp;Kaori Akita ,&nbsp;Kana Bando ,&nbsp;Atsushi Takahata ,&nbsp;Kazuhiro Ishikawa ,&nbsp;Shigeo Toyota","doi":"10.1016/j.jiac.2025.102646","DOIUrl":"10.1016/j.jiac.2025.102646","url":null,"abstract":"<div><div>Mucormycosis is a severe mold infection primarily affecting immunocompromised patients. Neutropenia, steroid use, hyperglycemia, and diabetes are recognized as significant risk factors. <em>Cunninghamella</em> species are rare pathogenic fungi associated with high mortality rates and multidrug resistance. However, there have been no reports of <em>C. phaeospora</em> being identified as the causative agent of clinical infection. We report a case of a 71-year-old man who developed right middle lobe pneumonia during salvage induction therapy for relapsed acute myeloid leukemia. Based on the clinical course, mucormycosis was suspected, and antifungal therapy was initiated with isavuconazole (200 mg every 8 hours for six doses, followed by 200 mg daily) and later switched to liposomal amphotericin B (5 mg/kg/day). Despite these interventions, the patient's respiratory failure progressed, culminating in a fatal hemorrhagic infarction of the right lung. An autopsy revealed invasive fungal involvement in multiple organs, including the lungs and liver. Genetic identification of the isolated fungi demonstrated <em>C. phaeospora</em>, confirming disseminated <em>C. phaeospora</em> infection. Susceptibility testing showed high Minimum Inhibition Concentrations/Minimum Effective Concentrations to all tested antifungal agents. This is the first reported case of disseminated infection caused by <em>C. phaeospora</em> with multidrug resistance. This case highlights the diagnostic and therapeutic challenges associated with rare pathogenic fungi. It underscores the importance of early identification of Mucorales, including susceptibility testing, to optimize antifungal therapy and consider appropriate surgical interventions. Further research is required to elucidate the mechanisms of antifungal resistance and clinical characteristics of <em>C. phaeospora</em>.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"31 4","pages":"Article 102646"},"PeriodicalIF":1.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effectiveness of transurethral enucleation with bipolar for benign prostatic hyperplasia patients with chronic prostatitis/chronic pelvic pain syndrome – Single center retrospective study
IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-02-04 DOI: 10.1016/j.jiac.2025.102647
Yoshikazu Togo, Shimpei Yoshioka, Yohei Kaizuka, Seiji Nagasawa

Introduction

Transurethral prostate surgery is the standard procedure for patients with benign prostatic hyperplasia (BPH), while the efficacy of surgical treatment for patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains unclear. This study was conducted to evaluate the usefulness of transurethral enucleation with bipolar (TUEB) of the prostate for BPH patients with CP/CPPS.

Methods

Between February 2018 and May 2024, 53 BPH patients with CP/CPPS underwent TUEB of the prostate at our institution and were followed for more than three months. Changes in the National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score before and after surgery were retrospectively examined. Patients with bladder stones or indwelling urethral catheters before surgery were excluded.

Results

Mean values for NIH-CPSI total, pain domain, urinary symptoms domain, and quality of life impact domain scores at the baseline were 21.7, 7.0, 6.4, and 8.3, respectively. Follow-up examinations showed scores of 11.1, 2.5, 3.3, and 5.3, respectively, after one month, 7.9, 1.3, 2.9, and 3.6, respectively, after three months, 4.8, 0.5, 1.7, and 2.5, respectively, after six months, and 4.5, 0.6, 1.7, and 2.3, respectively, after 12 months, with all domain scores significantly reduced as compared with the baseline (P < 0.001).

Conclusions

The present results suggest that TUEB of the prostate is effective for alleviating not only urinary symptoms but also pain in BPH patients with CP/CPPS.
{"title":"Effectiveness of transurethral enucleation with bipolar for benign prostatic hyperplasia patients with chronic prostatitis/chronic pelvic pain syndrome – Single center retrospective study","authors":"Yoshikazu Togo,&nbsp;Shimpei Yoshioka,&nbsp;Yohei Kaizuka,&nbsp;Seiji Nagasawa","doi":"10.1016/j.jiac.2025.102647","DOIUrl":"10.1016/j.jiac.2025.102647","url":null,"abstract":"<div><h3>Introduction</h3><div>Transurethral prostate surgery is the standard procedure for patients with benign prostatic hyperplasia (BPH), while the efficacy of surgical treatment for patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains unclear. This study was conducted to evaluate the usefulness of transurethral enucleation with bipolar (TUEB) of the prostate for BPH patients with CP/CPPS.</div></div><div><h3>Methods</h3><div>Between February 2018 and May 2024, 53 BPH patients with CP/CPPS underwent TUEB of the prostate at our institution and were followed for more than three months. Changes in the National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score before and after surgery were retrospectively examined. Patients with bladder stones or indwelling urethral catheters before surgery were excluded.</div></div><div><h3>Results</h3><div>Mean values for NIH-CPSI total, pain domain, urinary symptoms domain, and quality of life impact domain scores at the baseline were 21.7, 7.0, 6.4, and 8.3, respectively. Follow-up examinations showed scores of 11.1, 2.5, 3.3, and 5.3, respectively, after one month, 7.9, 1.3, 2.9, and 3.6, respectively, after three months, 4.8, 0.5, 1.7, and 2.5, respectively, after six months, and 4.5, 0.6, 1.7, and 2.3, respectively, after 12 months, with all domain scores significantly reduced as compared with the baseline (P &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>The present results suggest that TUEB of the prostate is effective for alleviating not only urinary symptoms but also pain in BPH patients with CP/CPPS.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"31 4","pages":"Article 102647"},"PeriodicalIF":1.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of fosfomycin susceptibility testing methods: A focus on multidrug-resistant Klebsiella pneumoniae using ECOFF values
IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-02-04 DOI: 10.1016/j.jiac.2025.102643
Zeycan Semerci , Fatih Mehmet Akıllı , Arzu İlki

Introduction

We aimed to evaluate the performance of two methods; disc diffusion and gradient test with the gold standard agar dilution method in determining the susceptibility of fosfomycin, in multidrug-resistant (MDR) K. pneumoniae isolates causing urinary tract infections.

Methods

K. pneumoniae producing carbapenemase and extended-spectrum beta-lactamase (ESBL) isolated from urine samples submitted to the clinical microbiology laboratory were included in the study. The isolates were tested using gradient test (MTS, Liofilchem, Italy) and disc diffusion (Oxoid, UK). Agar dilution was employed as the reference method. Since there is no MIC value for K. pneumoniae in EUCAST, epidemiological cut-off values (ECOFFs) were determined and susceptibility and error rates were calculated.

Results

In this study, among the 251 ESBL-positive K. pneumoniae isolates, 20(8 %) were also positive for carbapenemase. The ECOFF was determined as 128 mg/L for K. pneumoniae. When all study isolates (n:251) were considered, 87.6%(220/251) were wild-type (WT) for fosfomycin (MIC≤128 mg/L). Among ESBL-positive but carbapenemase-negative isolates (n:231), 87.8%(203/231) were WT for fosfomycin, and among ESBL and carbapenemase-positive isolates (n:20), 85.0%(17/20) were WT. The MIC50/90 values were determined to be 8/256 mg/L. When compared to agar dilution, the categorical agreement was 96.8% for the gradient test and 94.8 % for disc diffusion. While the gradient test showed a 16.1% very major error (VME) rate with no major errors (ME), disk diffusion revealed 35.4 % VME rate and 5.8 % ME rate.

Conclusion

A significant proportion of ESBL-positive K. pneumoniae isolates were WT for fosfomycin. The gradient test with 96.8% categorical agreement appears to be a good alternative, but agar dilution remains the gold Standard for reference laboratories.
{"title":"Evaluation of fosfomycin susceptibility testing methods: A focus on multidrug-resistant Klebsiella pneumoniae using ECOFF values","authors":"Zeycan Semerci ,&nbsp;Fatih Mehmet Akıllı ,&nbsp;Arzu İlki","doi":"10.1016/j.jiac.2025.102643","DOIUrl":"10.1016/j.jiac.2025.102643","url":null,"abstract":"<div><h3>Introduction</h3><div>We aimed to evaluate the performance of two methods; disc diffusion and gradient test with the gold standard agar dilution method in determining the susceptibility of fosfomycin, in multidrug-resistant (MDR) <em>K. pneumoniae</em> isolates causing urinary tract infections.</div></div><div><h3>Methods</h3><div><em>K. pneumoniae</em> producing carbapenemase and extended-spectrum beta-lactamase (ESBL) isolated from urine samples submitted to the clinical microbiology laboratory were included in the study. The isolates were tested using gradient test (MTS, Liofilchem, Italy) and disc diffusion (Oxoid, UK). Agar dilution was employed as the reference method. Since there is no MIC value for <em>K. pneumoniae</em> in EUCAST, epidemiological cut-off values (ECOFFs) were determined and susceptibility and error rates were calculated.</div></div><div><h3>Results</h3><div>In this study, among the 251 ESBL-positive <em>K. pneumoniae</em> isolates, 20(8 %) were also positive for carbapenemase. The ECOFF was determined as 128 mg/L for <em>K. pneumoniae</em>. When all study isolates (n:251) were considered, 87.6%(220/251) were wild-type (WT) for fosfomycin (MIC≤128 mg/L). Among ESBL-positive but carbapenemase-negative isolates (n:231), 87.8%(203/231) were WT for fosfomycin, and among ESBL and carbapenemase-positive isolates (n:20), 85.0%(17/20) were WT. The MIC<sub>50/90</sub> values were determined to be 8/256 mg/L. When compared to agar dilution, the categorical agreement was 96.8% for the gradient test and 94.8 % for disc diffusion. While the gradient test showed a 16.1% very major error (VME) rate with no major errors (ME), disk diffusion revealed 35.4 % VME rate and 5.8 % ME rate.</div></div><div><h3>Conclusion</h3><div>A significant proportion of ESBL-positive <em>K. pneumoniae</em> isolates were WT for fosfomycin. The gradient test with 96.8% categorical agreement appears to be a good alternative, but agar dilution remains the gold Standard for reference laboratories.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"31 4","pages":"Article 102643"},"PeriodicalIF":1.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fully automated identification of Neisseria meningitidis using the BD MAX system in a clinical laboratory setting: A preliminary study
IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-02-03 DOI: 10.1016/j.jiac.2025.102648
Rika Inose , Yoshifumi Uwamino , Wataru Aoki , Yuka Kamoshita , Mika Nagata , Osamu Ishihara , Hiromitsu Yokota , Hiromichi Matsushita
The rapid and accurate identification of Neisseria meningitidis, a pathogen that causes invasive infections and meningitis, is crucial for its effective clinical management and infection control. However, identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry may misidentify other Neisseria species as N. meningitidis, thus necessitating confirmatory tests based on biochemical properties. These tests require high bacterial concentrations that are achieved through subculturing, which can increase biosafety risks in laboratories.
In this study, we developed a real-time polymerase chain reaction detection system for N. meningitidis using the BD MAX automated genetic testing platform. We then evaluated its accuracy using 25 strains of clinically isolated Neisseria species, including N. meningitidis. Our detection results were in full agreement with those of sequencing-based identification, with a minimum detection sensitivity of 10 CFU/mL. The BD MAX system completes all measurements in a closed system, allowing for the rapid and precise identification of N. meningitidis while reducing laboratory biosafety risks.
{"title":"Fully automated identification of Neisseria meningitidis using the BD MAX system in a clinical laboratory setting: A preliminary study","authors":"Rika Inose ,&nbsp;Yoshifumi Uwamino ,&nbsp;Wataru Aoki ,&nbsp;Yuka Kamoshita ,&nbsp;Mika Nagata ,&nbsp;Osamu Ishihara ,&nbsp;Hiromitsu Yokota ,&nbsp;Hiromichi Matsushita","doi":"10.1016/j.jiac.2025.102648","DOIUrl":"10.1016/j.jiac.2025.102648","url":null,"abstract":"<div><div>The rapid and accurate identification of <em>Neisseria meningitidis</em>, a pathogen that causes invasive infections and meningitis, is crucial for its effective clinical management and infection control. However, identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry may misidentify other <em>Neisseria</em> species as <em>N. meningitidis</em>, thus necessitating confirmatory tests based on biochemical properties. These tests require high bacterial concentrations that are achieved through subculturing, which can increase biosafety risks in laboratories.</div><div>In this study, we developed a real-time polymerase chain reaction detection system for <em>N. meningitidis</em> using the BD MAX automated genetic testing platform. We then evaluated its accuracy using 25 strains of clinically isolated <em>Neisseria</em> species, including <em>N. meningitidis</em>. Our detection results were in full agreement with those of sequencing-based identification, with a minimum detection sensitivity of 10 CFU/mL. The BD MAX system completes all measurements in a closed system, allowing for the rapid and precise identification of <em>N. meningitidis</em> while reducing laboratory biosafety risks.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"31 4","pages":"Article 102648"},"PeriodicalIF":1.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Culture-negative infective endocarditis due to Neisseria bacilliformis identified via 16S rRNA gene analysis from resected valve tissue: Case report and review of the literature 通过对切除的瓣膜组织进行 16S rRNA 基因分析,发现奈瑟氏菌类杆菌引起的培养阴性感染性心内膜炎:病例报告和文献综述。
IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.jiac.2024.08.017
Yoshinori Takahashi , Junya Nakade , Yoshitaka Zaimoku , Naoki Watanabe , Tomohisa Watari , Yoshihito Otsuka , Yasunori Iwata , Hajime Kanamori
Blood culture-negative infective endocarditis (BCNE) has a poorer prognosis than culture-positive cases. Thus, it is crucial to determine the pathogenic microorganism using molecular diagnostic techniques, in addition to conventional techniques, including cultures of blood and/or resected valve tissue. Herein, we report a case of culture-negative infective endocarditis (IE) caused by Neisseria bacilliformis, as identified by 16S rRNA analysis of valve tissue. N. bacilliformis a non-gonococcal and non-meningococcal Neisseria species that partially comprises the oropharyngeal microbiome, and reports of invasive infections have increased recently. We conducted a literature review of IE caused by N. bacilliformis and found that beta-lactam antibiotics were effective with a relatively favorable prognosis. To the best of our knowledge, this is the first case of culture-negative IE in which N. bacilliformis was identified via 16S rRNA analysis.
与培养阳性病例相比,血培养阴性的感染性心内膜炎(BCNE)预后较差。因此,除了血液和/或切除的瓣膜组织培养等传统技术外,使用分子诊断技术确定病原微生物至关重要。在此,我们报告了一例培养阴性的感染性心内膜炎(IE)病例,该病例是通过对瓣膜组织进行 16S rRNA 分析而确定的奈瑟氏菌(Neisseria bacilliformis)引起的。巴氏奈瑟菌是一种非淋球菌和非脑膜炎球菌奈瑟菌,部分构成了口咽部微生物群,最近关于侵袭性感染的报道有所增加。我们对由巴氏奈瑟菌引起的 IE 进行了文献综述,发现β-内酰胺类抗生素有效,且预后相对较好。据我们所知,这是第一例通过 16S rRNA 分析鉴定出杆菌噬菌体的培养阴性 IE 病例。
{"title":"Culture-negative infective endocarditis due to Neisseria bacilliformis identified via 16S rRNA gene analysis from resected valve tissue: Case report and review of the literature","authors":"Yoshinori Takahashi ,&nbsp;Junya Nakade ,&nbsp;Yoshitaka Zaimoku ,&nbsp;Naoki Watanabe ,&nbsp;Tomohisa Watari ,&nbsp;Yoshihito Otsuka ,&nbsp;Yasunori Iwata ,&nbsp;Hajime Kanamori","doi":"10.1016/j.jiac.2024.08.017","DOIUrl":"10.1016/j.jiac.2024.08.017","url":null,"abstract":"<div><div>Blood culture-negative infective endocarditis (BCNE) has a poorer prognosis than culture-positive cases. Thus, it is crucial to determine the pathogenic microorganism using molecular diagnostic techniques, in addition to conventional techniques, including cultures of blood and/or resected valve tissue. Herein, we report a case of culture-negative infective endocarditis (IE) caused by <em>Neisseria bacilliformis</em>, as identified by 16S rRNA analysis of valve tissue. <em>N. bacilliformis</em> a non-gonococcal and non-meningococcal <em>Neisseria</em> species that partially comprises the oropharyngeal microbiome, and reports of invasive infections have increased recently. We conducted a literature review of IE caused by <em>N. bacilliformis</em> and found that beta-lactam antibiotics were effective with a relatively favorable prognosis. To the best of our knowledge, this is the first case of culture-negative IE in which <em>N. bacilliformis</em> was identified via 16S rRNA analysis.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"31 2","pages":"Article 102502"},"PeriodicalIF":1.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Descriptive analysis of safety and immunogenicity profiles of a 15-valent pneumococcal conjugate vaccine between subcutaneous and intramuscular administration in a phase 1 study of healthy Japanese infants (V114-028) 在一项针对日本健康婴儿的 1 期研究中,对皮下注射和肌肉注射 15 价肺炎球菌结合疫苗的安全性和免疫原性进行描述性分析 (V114-028)。
IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.jiac.2024.10.007
Keiko Wan, Masayoshi Shirakawa, Miyuki Sawata

Introduction

Subcutaneous (SC) administration is typically used for pediatric inactivated vaccines in Japan, whereas intramuscular (IM) administration is used outside Japan. We previously reported the safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), administered subcutaneously and intramuscularly in a Japanese phase 1 study (V114-028). Here, we report secondary descriptive analyses on V114 groups of the study to further assess the safety and immunogenicity profiles of V114 between the administration routes.

Methods

A total of 133 healthy Japanese infants were randomized to receive V114-SC (n = 44), V114-IM (n = 45), or PCV13-SC (n = 44) at approximately 3, 4, 5, and 12–15 months of age. Adverse events (AEs) from Days 1–14 post-vaccination and vaccine-related serious AEs from Day 1 to 1-month post-dose 4 were reported. Serotype-specific immunoglobulin G (IgG) responses were measured across the vaccination series.

Results

Proportions of participants with solicited systemic AEs (irritability, somnolence, decreased appetite, and urticaria) and pyrexia were generally comparable between the groups. Compared with V114-SC, patients receiving V114-IM had a lower incidence of irritability and somnolence, and higher incidence of decreased appetite. Proportion of participants with solicited injection-site erythema was lower with V114-IM (82.2%) than V114-SC (100.0%). Those with other solicited injection-site AEs (induration, swelling, and pain) were generally comparable between the groups, with lower observed proportions with V114-IM. Serotype-specific IgG responses were also generally comparable between the groups, including at pre-toddler dose.

Conclusions

These results suggest the utility of IM administration as an option for V114 vaccination in Japanese infants.
简介:在日本,小儿灭活疫苗通常采用皮下注射 (SC),而在日本以外则采用肌肉注射 (IM)。我们曾在日本的一项 1 期研究(V114-028)中报告了 15 价肺炎球菌结合疫苗 (PCV) V114 皮下注射和肌肉注射的安全性和免疫原性。在此,我们报告该研究中 V114 组的二次描述性分析,以进一步评估 V114 不同给药途径的安全性和免疫原性概况:共有 133 名健康的日本婴儿被随机分配到 V114-SC(44 人)、V114-IM(45 人)或 PCV13-SC(44 人)组,分别在婴儿约 3、4、5 和 12-15 个月大时给药。报告了接种后第 1-14 天的不良事件 (AE) 以及第 1 天至第 4 剂后 1 个月的疫苗相关严重不良事件。测量了整个接种系列的血清型特异性免疫球蛋白 G (IgG) 反应:结果:两组接种者出现全身性不良反应(烦躁、嗜睡、食欲下降和荨麻疹)和发热的比例基本相当。与V114-SC相比,接受V114-IM治疗的患者烦躁和嗜睡的发生率较低,食欲下降的发生率较高。V114-IM患者出现注射部位红斑的比例(82.2%)低于V114-SC(100.0%)。两组中出现其他注射部位AE(压痕、肿胀和疼痛)的人数基本相当,但V114-IM观察到的比例较低。各组之间的血清型特异性 IgG 反应(包括幼儿期前的剂量)也基本相当:这些结果表明,在日本婴儿接种 V114 疫苗时,IM 给药是一种有效的选择。
{"title":"Descriptive analysis of safety and immunogenicity profiles of a 15-valent pneumococcal conjugate vaccine between subcutaneous and intramuscular administration in a phase 1 study of healthy Japanese infants (V114-028)","authors":"Keiko Wan,&nbsp;Masayoshi Shirakawa,&nbsp;Miyuki Sawata","doi":"10.1016/j.jiac.2024.10.007","DOIUrl":"10.1016/j.jiac.2024.10.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Subcutaneous (SC) administration is typically used for pediatric inactivated vaccines in Japan, whereas intramuscular (IM) administration is used outside Japan. We previously reported the safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), administered subcutaneously and intramuscularly in a Japanese phase 1 study (V114-028). Here, we report secondary descriptive analyses on V114 groups of the study to further assess the safety and immunogenicity profiles of V114 between the administration routes.</div></div><div><h3>Methods</h3><div>A total of 133 healthy Japanese infants were randomized to receive V114-SC (n = 44), V114-IM (n = 45), or PCV13-SC (n = 44) at approximately 3, 4, 5, and 12–15 months of age. Adverse events (AEs) from Days 1–14 post-vaccination and vaccine-related serious AEs from Day 1 to 1-month post-dose 4 were reported. Serotype-specific immunoglobulin G (IgG) responses were measured across the vaccination series.</div></div><div><h3>Results</h3><div>Proportions of participants with solicited systemic AEs (irritability, somnolence, decreased appetite, and urticaria) and pyrexia were generally comparable between the groups. Compared with V114-SC, patients receiving V114-IM had a lower incidence of irritability and somnolence, and higher incidence of decreased appetite. Proportion of participants with solicited injection-site erythema was lower with V114-IM (82.2%) than V114-SC (100.0%). Those with other solicited injection-site AEs (induration, swelling, and pain) were generally comparable between the groups, with lower observed proportions with V114-IM. Serotype-specific IgG responses were also generally comparable between the groups, including at pre-toddler dose.</div></div><div><h3>Conclusions</h3><div>These results suggest the utility of IM administration as an option for V114 vaccination in Japanese infants.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"31 2","pages":"Article 102539"},"PeriodicalIF":1.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High plasma concentration of tenofovir alafenamide in people living with HIV with ABCB1 genetic variants 具有 ABCB1 基因变异的 HIV 感染者体内替诺福韦-阿拉非那胺的血浆浓度较高。
IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.jiac.2024.10.009
Kiyoto Tsuchiya , Hieu Trung Tran , Akira Kawashima , Koji Watanabe , Akinobu Hamada , Shinichi Oka , Hiroyuki Gatanaga

Objectives

We aimed to analyze the relationships between single nucleotide polymorphisms in the ATP-binding cassette transporter B1 (ABCB1) and G2 (ABCG2) genes and plasma concentrations of tenofovir alafenamide (TAF), tenofovir (TFV), and emtricitabine (FTC).

Methods

We recruited 10 people living with HIV receiving once-daily treatment with a single tablet containing TAF (25 mg), FTC (200 mg), and bictegravir (50 mg). Peripheral blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 12, and 24 h after administration. Plasma concentrations of TAF, TFV, and FTC were quantified using liquid chromatography-tandem mass spectrometry. Genotyping for allelic variants of ABCB1, including 1236C > T (rs1128503), 2677 G > T/A (rs2032582), 3435C > T (rs1045642), 4036 A > G (rs3842) and ABCG2 421C > A (rs2231142), was performed using TaqMan Drug Metabolism Assays.

Results

None of the genotypes for ABCB1 1236C > T, 2677 G > T/A, 3435C > T, and ABCG2 421C > A exhibited correlations with plasma concentrations of TAF, TFV, and FTC. In contrast, individuals with the ABCB1 4036 AG genotype (188.7 ng/mL, n = 3) exhibited a significantly higher mean peak plasma concentration of TAF than those with the ABCB1 4036 AA genotype (67.7 ng/mL, n = 7) (p = 0.0167). However, these genotypes did not affect the elimination of terminal half-lives of TAF.

Conclusions

The allelic variant ABCB1 4036 A > G is associated with reduced protein expression and function of ABCB1. Individuals with this genetic variant exhibited significantly high peak plasma concentrations of TAF, potentially due to the reduced expression of efflux transporters in the intestines linked to this variant.
研究目的我们旨在分析ATP结合盒转运体B1(ABCB1)和G2(ABCG2)基因的单核苷酸多态性与替诺福韦-阿拉非那胺(TAF)、替诺福韦(TFV)和恩曲他滨(FTC)血浆浓度之间的关系:我们招募了 10 名艾滋病病毒感染者,他们每天接受一次含 TAF(25 毫克)、FTC(200 毫克)和 bictegravir(50 毫克)的片剂治疗。在服药后 0、1、2、3、4、6、8、12 和 24 小时采集外周血样本。采用液相色谱-串联质谱法对血浆中 TAF、TFV 和 FTC 的浓度进行定量。使用 TaqMan 药物代谢测定法对 ABCB1 的等位基因变异进行了基因分型,包括 1236 C>T (rs1128503)、2677 G>T/A (rs2032582)、3435 C>T (rs1045642)、4036 A>G (rs3842) 和 ABCG2 421 C>A (rs2231142):结果:ABCB1 1236 C>T、2677 G>T/A、3435 C>T和ABCG2 421 C>A的基因型均与TAF、TFV和FTC的血浆浓度无关。相比之下,ABCB1 4036 AG 基因型个体(188.7 纳克/毫升,n = 3)的 TAF 平均血浆峰值浓度明显高于 ABCB1 4036 AA 基因型个体(67.7 纳克/毫升,n = 7)(p = 0.0167)。然而,这些基因型并不影响 TAF 末端半衰期的消除:结论:等位基因变体 ABCB1 4036 A>G 与 ABCB1 蛋白表达和功能降低有关。具有该基因变异的个体血浆中 TAF 的峰值浓度明显较高,这可能是由于与该变异相关的肠道中外排转运体的表达减少所致。
{"title":"High plasma concentration of tenofovir alafenamide in people living with HIV with ABCB1 genetic variants","authors":"Kiyoto Tsuchiya ,&nbsp;Hieu Trung Tran ,&nbsp;Akira Kawashima ,&nbsp;Koji Watanabe ,&nbsp;Akinobu Hamada ,&nbsp;Shinichi Oka ,&nbsp;Hiroyuki Gatanaga","doi":"10.1016/j.jiac.2024.10.009","DOIUrl":"10.1016/j.jiac.2024.10.009","url":null,"abstract":"<div><h3>Objectives</h3><div>We aimed to analyze the relationships between single nucleotide polymorphisms in the ATP-binding cassette transporter B1 (ABCB1) and G2 (ABCG2) genes and plasma concentrations of tenofovir alafenamide (TAF), tenofovir (TFV), and emtricitabine (FTC).</div></div><div><h3>Methods</h3><div>We recruited 10 people living with HIV receiving once-daily treatment with a single tablet containing TAF (25 mg), FTC (200 mg), and bictegravir (50 mg). Peripheral blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 12, and 24 h after administration. Plasma concentrations of TAF, TFV, and FTC were quantified using liquid chromatography-tandem mass spectrometry. Genotyping for allelic variants of ABCB1, including 1236C &gt; T (rs1128503), 2677 G &gt; T/A (rs2032582), 3435C &gt; T (rs1045642), 4036 A &gt; G (rs3842) and ABCG2 421C &gt; A (rs2231142), was performed using TaqMan Drug Metabolism Assays.</div></div><div><h3>Results</h3><div>None of the genotypes for ABCB1 1236C &gt; T, 2677 G &gt; T/A, 3435C &gt; T, and ABCG2 421C &gt; A exhibited correlations with plasma concentrations of TAF, TFV, and FTC. In contrast, individuals with the ABCB1 4036 AG genotype (188.7 ng/mL, n = 3) exhibited a significantly higher mean peak plasma concentration of TAF than those with the ABCB1 4036 AA genotype (67.7 ng/mL, n = 7) (<em>p</em> = 0.0167). However, these genotypes did not affect the elimination of terminal half-lives of TAF.</div></div><div><h3>Conclusions</h3><div>The allelic variant ABCB1 4036 A &gt; G is associated with reduced protein expression and function of ABCB1. Individuals with this genetic variant exhibited significantly high peak plasma concentrations of TAF, potentially due to the reduced expression of efflux transporters in the intestines linked to this variant.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"31 2","pages":"Article 102541"},"PeriodicalIF":1.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Infection and Chemotherapy
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