Pub Date : 2026-01-13DOI: 10.1016/j.jiac.2026.102908
Ho Won Kim , Hoe Sun Yoon , Jake Whang , Jong-Seok Kim
Nontuberculous mycobacteria (NTM), particularly Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABC), are increasingly recognized as major opportunistic pathogens. Standard therapy requires prolonged multidrug regimens, often extending for more than 12 months, yet treatment success remains limited, especially for MABC. One of the greatest barriers to effective therapy is not antimicrobial resistance alone but also the high burden of drug-related toxicities. Hepatotoxicity, ototoxicity, nephrotoxicity, myelosuppression, neuropathy, gastrointestinal intolerance, and dermatologic complications frequently lead to dose reduction, interruption, or discontinuation, undermining therapeutic efficacy and patient adherence.
This review summarizes current standard regimens for MAC and MABC, details the spectrum of toxicities associated with commonly used agents, and evaluates emerging supportive and adjunctive strategies. Hepatoprotective agents such as ursodeoxycholic acid, silymarin, and N-acetylcysteine, antioxidants and aspirin for aminoglycoside-related ototoxicity, liposomal inhaled amikacin as an alternative to intravenous administration, dose optimization and pyridoxine supplementation for linezolid, and prophylactic antiemetics for tigecycline represent pragmatic approaches with varying levels of evidence. While most supportive measures are extrapolated from tuberculosis cohorts or small pilot studies, they collectively highlight the potential to improve tolerability and adherence.
Future research should prioritize prospective, NTM-specific trials to validate these interventions and develop structured toxicity management frameworks. By embedding supportive strategies alongside antimicrobial regimens, NTM care can move toward a more holistic paradigm that not only enhances microbiological outcomes but also improves patient quality of life.
{"title":"Adjunctive and supportive strategies to mitigate drug toxicities in the treatment of nontuberculous mycobacterial disease with future directions","authors":"Ho Won Kim , Hoe Sun Yoon , Jake Whang , Jong-Seok Kim","doi":"10.1016/j.jiac.2026.102908","DOIUrl":"10.1016/j.jiac.2026.102908","url":null,"abstract":"<div><div>Nontuberculous mycobacteria (NTM), particularly <em>Mycobacterium avium</em> complex (MAC) and <em>Mycobacterium abscessus</em> complex (MABC), are increasingly recognized as major opportunistic pathogens. Standard therapy requires prolonged multidrug regimens, often extending for more than 12 months, yet treatment success remains limited, especially for MABC. One of the greatest barriers to effective therapy is not antimicrobial resistance alone but also the high burden of drug-related toxicities. Hepatotoxicity, ototoxicity, nephrotoxicity, myelosuppression, neuropathy, gastrointestinal intolerance, and dermatologic complications frequently lead to dose reduction, interruption, or discontinuation, undermining therapeutic efficacy and patient adherence.</div><div>This review summarizes current standard regimens for MAC and MABC, details the spectrum of toxicities associated with commonly used agents, and evaluates emerging supportive and adjunctive strategies. Hepatoprotective agents such as ursodeoxycholic acid, silymarin, and N-acetylcysteine, antioxidants and aspirin for aminoglycoside-related ototoxicity, liposomal inhaled amikacin as an alternative to intravenous administration, dose optimization and pyridoxine supplementation for linezolid, and prophylactic antiemetics for tigecycline represent pragmatic approaches with varying levels of evidence. While most supportive measures are extrapolated from tuberculosis cohorts or small pilot studies, they collectively highlight the potential to improve tolerability and adherence.</div><div>Future research should prioritize prospective, NTM-specific trials to validate these interventions and develop structured toxicity management frameworks. By embedding supportive strategies alongside antimicrobial regimens, NTM care can move toward a more holistic paradigm that not only enhances microbiological outcomes but also improves patient quality of life.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 2","pages":"Article 102908"},"PeriodicalIF":1.5,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979951","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}
Cefiderocol (CFDC) exhibits potent in vitro activity against multidrug-resistant Gram-negative bacilli (MDR-GNB), yet standardized susceptibility testing remains technically demanding. This study evaluated the reproducibility and categorical agreement (CA) of broth microdilution (BMD), MIC dry plate (DP), and disk diffusion (DD) using MDR-GNB from Japan and Bangladesh. To our knowledge, this is the first systematic assessment of Japan-specific commercial platforms for CFDC testing.
Methods
A total of 452 MDR-GNB isolates, including 272 Enterobacterales and 180 non-fermenters (Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia), were tested using BMD and two commercial platforms. Reproducibility was assessed in triplicate, and essential agreement, CA, and error rates were determined with BMD as the reference.
Results
BMD demonstrated >90 % reproducibility across species. DP and DD showed reduced reproducibility and agreement for NDM-producing Enterobacterales, with CA of 54 % for DP and 63 % for DD. Most discrepancies were minor errors. Trailing effects and visual artifacts contributed to elevated MICs, particularly in DP.
Conclusions
The performance of simplified CFDC susceptibility methods varies by species and resistance mechanism, with notable limitations for NDM producers. While DP and DD remain practical tools for routine laboratories, their use requires caution. Parallel DP–DD testing does not replace BMD but can help identify discrepant results requiring confirmation, particularly for NDM-producing isolates.
{"title":"Evaluation of Japan-specific cefiderocol susceptibility testing methods in multidrug-resistant gram-negative isolates from Japan and Bangladesh","authors":"Takashi Okanda , Niinyo Nakajima , Takuro Koshikawa , Tadatomo Oyanagi , Tomonori Takano , Tetsuo Yamaguchi , Hiroyuki Kunishima , Mitsuo Kaku , Hiromu Takemura","doi":"10.1016/j.jiac.2026.102903","DOIUrl":"10.1016/j.jiac.2026.102903","url":null,"abstract":"<div><h3>Background</h3><div>Cefiderocol (CFDC) exhibits potent in vitro activity against multidrug-resistant Gram-negative bacilli (MDR-GNB), yet standardized susceptibility testing remains technically demanding. This study evaluated the reproducibility and categorical agreement (CA) of broth microdilution (BMD), MIC dry plate (DP), and disk diffusion (DD) using MDR-GNB from Japan and Bangladesh. To our knowledge, this is the first systematic assessment of Japan-specific commercial platforms for CFDC testing.</div></div><div><h3>Methods</h3><div>A total of 452 MDR-GNB isolates, including 272 Enterobacterales and 180 non-fermenters (<em>Pseudomonas aeruginosa</em>, <em>Acinetobacter baumannii</em>, <em>Stenotrophomonas maltophilia</em>), were tested using BMD and two commercial platforms. Reproducibility was assessed in triplicate, and essential agreement, CA, and error rates were determined with BMD as the reference.</div></div><div><h3>Results</h3><div>BMD demonstrated >90 % reproducibility across species. DP and DD showed reduced reproducibility and agreement for NDM-producing Enterobacterales, with CA of 54 % for DP and 63 % for DD. Most discrepancies were minor errors. Trailing effects and visual artifacts contributed to elevated MICs, particularly in DP.</div></div><div><h3>Conclusions</h3><div>The performance of simplified CFDC susceptibility methods varies by species and resistance mechanism, with notable limitations for NDM producers. While DP and DD remain practical tools for routine laboratories, their use requires caution. Parallel DP–DD testing does not replace BMD but can help identify discrepant results requiring confirmation, particularly for NDM-producing isolates.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 2","pages":"Article 102903"},"PeriodicalIF":1.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952232","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}
Amid a large-scale resurgence of pertussis in Japan in 2025, concern is growing about the spread of macrolide-resistant Bordetella pertussis (MRBP)—prevalent in China—posing a clinical challenge, particularly in infants. We describe a term 6-week-old unvaccinated infant with life-threatening MRBP. Diagnosis was confirmed by culture and multiplex PCR. The isolate harbored the 23S rRNA A2047G mutation. Daily microbiology (Gram stain, culture, quantitative PCR) was performed on nasopharyngeal swabs and lower-airway aspirates. The infant received empiric azithromycin and a 14-day course of sulfamethoxazole–trimethoprim (SMX-TMP) and recovered without sequelae. Nasopharyngeal cultures became negative by Day 2 of SMX-TMP therapy, and lower-airway aspirate cultures by Day 3. Nasopharyngeal quantitative PCR was below the detection limit by Day 7. Lower-airway quantitative PCR declined through Day 7, and sampling ceased after extubation. These observations suggest that bacteriologic clearance with SMX-TMP may occur on a time frame similar to that used to discontinue precautions for macrolide-susceptible disease, commonly five days after starting effective therapy. During the current resurgence in Japan, transmission appears concentrated among school-aged children, whereas the national vaccination program targets only those under two years of age. Introducing booster doses at 5–6 and 11–12 years may help reduce school-based transmission. In addition, maternal booster vaccination during pregnancy could protect young infants through the transplacental transfer of maternal pertussis antibodies.
{"title":"Microbiologic clearance in macrolide-resistant Bordetella pertussis: An infant treated with sulfamethoxazole-trimethoprim — A case timeline","authors":"Yu Kuramochi , Meiwa Shibata , Mikako Morinaga , Tomoyuki Tame , Kazue Kinoshita , Osamu Saito , Yuho Horikoshi","doi":"10.1016/j.jiac.2026.102907","DOIUrl":"10.1016/j.jiac.2026.102907","url":null,"abstract":"<div><div>Amid a large-scale resurgence of pertussis in Japan in 2025, concern is growing about the spread of macrolide-resistant <em>Bordetella pertussis</em> (MRBP)—prevalent in China—posing a clinical challenge, particularly in infants. We describe a term 6-week-old unvaccinated infant with life-threatening MRBP. Diagnosis was confirmed by culture and multiplex PCR. The isolate harbored the 23S rRNA A2047G mutation. Daily microbiology (Gram stain, culture, quantitative PCR) was performed on nasopharyngeal swabs and lower-airway aspirates. The infant received empiric azithromycin and a 14-day course of sulfamethoxazole–trimethoprim (SMX-TMP) and recovered without sequelae. Nasopharyngeal cultures became negative by Day 2 of SMX-TMP therapy, and lower-airway aspirate cultures by Day 3. Nasopharyngeal quantitative PCR was below the detection limit by Day 7. Lower-airway quantitative PCR declined through Day 7, and sampling ceased after extubation. These observations suggest that bacteriologic clearance with SMX-TMP may occur on a time frame similar to that used to discontinue precautions for macrolide-susceptible disease, commonly five days after starting effective therapy. During the current resurgence in Japan, transmission appears concentrated among school-aged children, whereas the national vaccination program targets only those under two years of age. Introducing booster doses at 5–6 and 11–12 years may help reduce school-based transmission. In addition, maternal booster vaccination during pregnancy could protect young infants through the transplacental transfer of maternal pertussis antibodies.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 2","pages":"Article 102907"},"PeriodicalIF":1.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952276","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}
Non-O1 and non-O139 Vibrio cholerae (NOVC) strains rarely harbor the cholera toxin gene and are typically associated with mild, self-limiting gastroenteritis. However, an increasing number of reports in recent years have described severe gastroenteritis or extraintestinal infections with fatal outcomes, particularly in immunocompromised individuals, such as those with underlying conditions including cirrhosis. Here, we describe a case of severe gastroenteritis caused by V. cholerae serogroup O24, following the consumption of seafood during prolong prednisolone treatment for systemic lupus erythematosus. Stool culture upon admission yielded yellow colonies on thiosulfate-citrate-bile salt-sucrose agar, and Gram staining of the colonies revealed Gram-negative, curved, comma-shaped rods, suggestive of Vibrio species. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) yielded low-confidence identifications, suggesting either Vibrio mimicus or Vibrio albensis, the isolate was ultimately identified as NOVC based on its biochemical characteristics and salt tolerance. Subsequent genetic analysis confirmed the isolate as V. cholerae serogroup O24, a strain not included in the MALDI-TOF MS identification database. This case underscores the diagnostic value of conventional methods, such as biochemical profiling, in identifying V. cholerae strains not detectable by current mass spectrometry-based systems.
{"title":"Severe gastroenteritis caused by Vibrio cholerae serogroup O24 in an immunocompromised patient: A case report","authors":"Tomoko Azuma , Yoshinori Takahashi , Megumi Oshima , Megumi Ikeda , Daiki Hayasi , Hatsumi Otani , Akiko Maekawa , Hiroyasu Oe , Aya Noguchi , Mika Mori , Hajime Kanamori","doi":"10.1016/j.jiac.2026.102906","DOIUrl":"10.1016/j.jiac.2026.102906","url":null,"abstract":"<div><div>Non-O1 and non-O139 <em>Vibrio cholerae</em> (NOVC) strains rarely harbor the cholera toxin gene and are typically associated with mild, self-limiting gastroenteritis. However, an increasing number of reports in recent years have described severe gastroenteritis or extraintestinal infections with fatal outcomes, particularly in immunocompromised individuals, such as those with underlying conditions including cirrhosis. Here, we describe a case of severe gastroenteritis caused by <em>V. cholerae</em> serogroup O24, following the consumption of seafood during prolong prednisolone treatment for systemic lupus erythematosus. Stool culture upon admission yielded yellow colonies on thiosulfate-citrate-bile salt-sucrose agar, and Gram staining of the colonies revealed Gram-negative, curved, comma-shaped rods, suggestive of <em>Vibrio</em> species. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) yielded low-confidence identifications, suggesting either <em>Vibrio mimicus</em> or <em>Vibrio albensis</em>, the isolate was ultimately identified as NOVC based on its biochemical characteristics and salt tolerance. Subsequent genetic analysis confirmed the isolate as <em>V. cholerae</em> serogroup O24, a strain not included in the MALDI-TOF MS identification database. This case underscores the diagnostic value of conventional methods, such as biochemical profiling, in identifying <em>V. cholerae</em> strains not detectable by current mass spectrometry-based systems.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 2","pages":"Article 102906"},"PeriodicalIF":1.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928990","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}
Introduction: Carbapenem-resistant Gram-negative bacteria (CRGNB) pose a major clinical threat. This study evaluated the in vitro activity of cefiderocol and other recently approved β-lactam/β-lactamase inhibitor combinations against major CRGNB.
Materials and methods: A total of 292 CRGNB clinical isolates were analyzed, comprising 146 Enterobacterales, 106 Pseudomonas aeruginosa, and 40 Stenotrophomonas maltophilia, all collected from hospitals across Japan. Antimicrobial susceptibility testing was performed by broth microdilution (BMD). Disk diffusion testing was also conducted for cefiderocol, and categorical agreement with BMD was assessed. Whole-genome sequencing (WGS) was used for species confirmation and characterization of resistance determinants.
Results: Carbapenemase producers accounted for 64.4% of Enterobacterales (94/146) and 8.5% of P. aeruginosa (9/106), with metallo-β-lactamase (MBL) producers comprising 92.6% (87/94) and 77.8% (7/9), respectively. Based on CLSI breakpoints, 94.5% (276/292) of isolates were susceptible to cefiderocol, including 91.8% of Enterobacterales, 99.1% of P. aeruginosa, and 92.5% of S. maltophilia. Ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam were active against 12.3%, 44.5% and 45.9% of Enterobacterales, and 89.6%, 86.8% and 72.6% of P. aeruginosa, respectively. Categorical agreement between cefiderocol disk diffusion and BMD exceeded 92% across all groups, although very major errors occurred in Enterobacterales (n=2) and S. maltophilia (n=3). Cefiderocol-non-susceptible Enterobacterales isolates frequently harbored carbapenemase and extended-spectrum β-lactamase (ESBL) genes, together with mutations in ftsI (encoding PBP3), ompK35, or siderophore receptor genes (cirA, tonB).
Discussion: Cefiderocol showed potent in vitro activity against CRGNB in Japan, including MBL producers. Disk diffusion correlated well with BMD results; however, confirmatory BMD testing should be considered when resistance is clinically suspected.
{"title":"In vitro activity of cefiderocol against carbapenem-resistant Gram-negative pathogens in Japan.","authors":"Kenjiro Matsui, Aki Sakurai, Yasufumi Matsumura, Takuya Hosoda, Masahiro Suzuki, Sho Saito, Ryota Hase, Hideaki Kato, Takehiro Hashimoto, Takashi Matono, Naoya Itoh, Momoko Mawatari, Kohei Uemura, Kayoko Hayakawa, Hiroyasu Ito, Yohei Doi","doi":"10.1016/j.jiac.2026.102905","DOIUrl":"https://doi.org/10.1016/j.jiac.2026.102905","url":null,"abstract":"<p><strong>Introduction: </strong>Carbapenem-resistant Gram-negative bacteria (CRGNB) pose a major clinical threat. This study evaluated the in vitro activity of cefiderocol and other recently approved β-lactam/β-lactamase inhibitor combinations against major CRGNB.</p><p><strong>Materials and methods: </strong>A total of 292 CRGNB clinical isolates were analyzed, comprising 146 Enterobacterales, 106 Pseudomonas aeruginosa, and 40 Stenotrophomonas maltophilia, all collected from hospitals across Japan. Antimicrobial susceptibility testing was performed by broth microdilution (BMD). Disk diffusion testing was also conducted for cefiderocol, and categorical agreement with BMD was assessed. Whole-genome sequencing (WGS) was used for species confirmation and characterization of resistance determinants.</p><p><strong>Results: </strong>Carbapenemase producers accounted for 64.4% of Enterobacterales (94/146) and 8.5% of P. aeruginosa (9/106), with metallo-β-lactamase (MBL) producers comprising 92.6% (87/94) and 77.8% (7/9), respectively. Based on CLSI breakpoints, 94.5% (276/292) of isolates were susceptible to cefiderocol, including 91.8% of Enterobacterales, 99.1% of P. aeruginosa, and 92.5% of S. maltophilia. Ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam were active against 12.3%, 44.5% and 45.9% of Enterobacterales, and 89.6%, 86.8% and 72.6% of P. aeruginosa, respectively. Categorical agreement between cefiderocol disk diffusion and BMD exceeded 92% across all groups, although very major errors occurred in Enterobacterales (n=2) and S. maltophilia (n=3). Cefiderocol-non-susceptible Enterobacterales isolates frequently harbored carbapenemase and extended-spectrum β-lactamase (ESBL) genes, together with mutations in ftsI (encoding PBP3), ompK35, or siderophore receptor genes (cirA, tonB).</p><p><strong>Discussion: </strong>Cefiderocol showed potent in vitro activity against CRGNB in Japan, including MBL producers. Disk diffusion correlated well with BMD results; however, confirmatory BMD testing should be considered when resistance is clinically suspected.</p>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":" ","pages":"102905"},"PeriodicalIF":1.5,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933602","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}
Pub Date : 2026-01-05DOI: 10.1016/j.jiac.2026.102904
Fatih Çubuk , Caner Öksüz , Murtaza Öz
Objective
A substantial proportion of urine cultures in patients with suspected urinary tract infections (UTIs) yield negative results. This study aimed to evaluate whether parameters from automated urinalysis could predict the likelihood of significant bacterial growth, thereby aiding in reducing unnecessary cultures.
Methods
A total of 696 patients (402 females, 294 males) undergoing urinalysis with the FUS-200 automated analyzer were evaluated. Urine cultures were processed using the BD Phoenix 100 system. Demographic data and urinalysis parameters were compared according to culture results.
Results
Among culture-negative patients, females were younger (median age: 45 vs. 58 years, p = 0.000) and had significantly higher leukocyte, erythrocyte, and bacterial counts (p = 0.000). In culture-positive cases, females were younger than males (55 vs. 72.5 years, p = 0.000), though they had lower leukocyte counts (p = 0.029). Gram-negative infections were associated with significantly higher leukocyte and bacterial counts compared to gram-positive infections (p < 0.05), along with increased nitrite and leukocyte esterase positivity. ROC analysis identified optimal cut-off values for predicting significant culture growth: leukocyte count ≥16.5 (sensitivity, 79.5 %; specificity, 79.9 %) and bacterial count ≥2.5 (sensitivity, 77.6 %; specificity, 79.3 %). Cut-off values were higher in females (leukocytes: 23.5, bacteria: 5.5) than in males (leukocytes: 11.5, bacteria: 0.5).
Conclusion
The practical utility of the defined normal range values for urinary leukocyte count is limited. The predictive power of urinalysis parameters for culture results is affected by patient gender. For predicting significant bacterial growth in males, we recommend leukocyte and bacteria cut-off values of 11.5/HPF and 0.5/HPF, respectively (with >85 % sensitivity and specificity). In females, leukocyte and bacterial counts in urine provide poor predictive value for culture positivity.
{"title":"Diagnostic utility of urinalysis parameters in predicting urine culture positivity: A gender-stratified evaluation","authors":"Fatih Çubuk , Caner Öksüz , Murtaza Öz","doi":"10.1016/j.jiac.2026.102904","DOIUrl":"10.1016/j.jiac.2026.102904","url":null,"abstract":"<div><h3>Objective</h3><div>A substantial proportion of urine cultures in patients with suspected urinary tract infections (UTIs) yield negative results. This study aimed to evaluate whether parameters from automated urinalysis could predict the likelihood of significant bacterial growth, thereby aiding in reducing unnecessary cultures.</div></div><div><h3>Methods</h3><div>A total of 696 patients (402 females, 294 males) undergoing urinalysis with the FUS-200 automated analyzer were evaluated. Urine cultures were processed using the BD Phoenix 100 system. Demographic data and urinalysis parameters were compared according to culture results.</div></div><div><h3>Results</h3><div>Among culture-negative patients, females were younger (median age: 45 vs. 58 years, p = 0.000) and had significantly higher leukocyte, erythrocyte, and bacterial counts (p = 0.000). In culture-positive cases, females were younger than males (55 vs. 72.5 years, p = 0.000), though they had lower leukocyte counts (p = 0.029). Gram-negative infections were associated with significantly higher leukocyte and bacterial counts compared to gram-positive infections (p < 0.05), along with increased nitrite and leukocyte esterase positivity. ROC analysis identified optimal cut-off values for predicting significant culture growth: leukocyte count ≥16.5 (sensitivity, 79.5 %; specificity, 79.9 %) and bacterial count ≥2.5 (sensitivity, 77.6 %; specificity, 79.3 %). Cut-off values were higher in females (leukocytes: 23.5, bacteria: 5.5) than in males (leukocytes: 11.5, bacteria: 0.5).</div></div><div><h3>Conclusion</h3><div>The practical utility of the defined normal range values for urinary leukocyte count is limited. The predictive power of urinalysis parameters for culture results is affected by patient gender. For predicting significant bacterial growth in males, we recommend leukocyte and bacteria cut-off values of 11.5/HPF and 0.5/HPF, respectively (with >85 % sensitivity and specificity). In females, leukocyte and bacterial counts in urine provide poor predictive value for culture positivity.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 2","pages":"Article 102904"},"PeriodicalIF":1.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903896","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jiac.2025.102902
Nesrin Türker , Ozge Eren Korkmaz , Figen Kaptan Aydogmus , Nur Miray Ayhan Geniş , Tuba Müderris , Murat Aksun
Background
Carbapenem-resistant Gram-negative bloodstream infections (CR-GNB BSIs) are increasingly prevalent in intensive care units (ICUs) and associated with high mortality. Accurate early risk stratification tools are lacking.
Objectives
To develop and internally validate a nomogram-based model predicting 30-day mortality in ICU patients with CR-GNB BSIs.
Methods
We conducted a retrospective cohort study of adult ICU patients with CR-GNB BSIs at a tertiary hospital in western Turkey (January 2020–October 2024). Demographic, clinical, laboratory, and microbiological data were collected. Patients were randomly split into training (70 %) and validation (30 %) cohorts. Univariable and multivariable logistic regression analyses identified independent mortality predictors, which were incorporated into a nomogram. Model discrimination, calibration, and decision-curve utility were evaluated.
Results
A total of 281 patients were included (median age 66 years; 60.9 % male); 30-day mortality was 58 %. Acinetobacter spp. predominated (51.6 %), followed by Klebsiella spp. (42.3 %) and Pseudomonas spp. (6.1 %). Independent predictors of 30-day mortality included older age, immunosuppression, hypoalbuminemia, elevated white blood cell count, and absence of microbiological cure. The nomogram demonstrated excellent discrimination (AUC 0.895 training; 0.854 validation), good calibration (mean absolute error 0.022–0.059), and meaningful clinical net benefit across intermediate risk thresholds.
Conclusions
We developed and internally validated a nomogram using routine clinical and laboratory variables to predict 30-day mortality in ICU patients with CR-GNB BSIs. This tool may support early prognostic assessment at bedside and guide individualized management. Prospective multicenter validation is warranted.
{"title":"Carbapenem resistant gram negative bacteremia in intensive care unit patients: Development and validation of a nomogram-based 30-day mortality risk prediction model","authors":"Nesrin Türker , Ozge Eren Korkmaz , Figen Kaptan Aydogmus , Nur Miray Ayhan Geniş , Tuba Müderris , Murat Aksun","doi":"10.1016/j.jiac.2025.102902","DOIUrl":"10.1016/j.jiac.2025.102902","url":null,"abstract":"<div><h3>Background</h3><div>Carbapenem-resistant Gram-negative bloodstream infections (CR-GNB BSIs) are increasingly prevalent in intensive care units (ICUs) and associated with high mortality. Accurate early risk stratification tools are lacking.</div></div><div><h3>Objectives</h3><div>To develop and internally validate a nomogram-based model predicting 30-day mortality in ICU patients with CR-GNB BSIs.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study of adult ICU patients with CR-GNB BSIs at a tertiary hospital in western Turkey (January 2020–October 2024). Demographic, clinical, laboratory, and microbiological data were collected. Patients were randomly split into training (70 %) and validation (30 %) cohorts. Univariable and multivariable logistic regression analyses identified independent mortality predictors, which were incorporated into a nomogram. Model discrimination, calibration, and decision-curve utility were evaluated.</div></div><div><h3>Results</h3><div>A total of 281 patients were included (median age 66 years; 60.9 % male); 30-day mortality was 58 %. <em>Acinetobacter spp</em>. predominated (51.6 %), followed by <em>Klebsiella spp</em>. (42.3 %) and <em>Pseudomonas spp</em>. (6.1 %). Independent predictors of 30-day mortality included older age, immunosuppression, hypoalbuminemia, elevated white blood cell count, and absence of microbiological cure. The nomogram demonstrated excellent discrimination (AUC 0.895 training; 0.854 validation), good calibration (mean absolute error 0.022–0.059), and meaningful clinical net benefit across intermediate risk thresholds.</div></div><div><h3>Conclusions</h3><div>We developed and internally validated a nomogram using routine clinical and laboratory variables to predict 30-day mortality in ICU patients with CR-GNB BSIs. This tool may support early prognostic assessment at bedside and guide individualized management. Prospective multicenter validation is warranted.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102902"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145856988","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}
A man in his 50's with a history of acute lymphoblastic leukemia underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) over 20 years earlier and later developed bilateral giant pulmonary bullae, presumed secondary to pulmonary chronic graft-versus-host disease (cGVHD), requiring bilateral lung transplantation. Six months after lung transplantation, he developed rapid-onset severe normocytic anemia with reticulocytopenia. Cytomegalovirus (CMV) reactivation was initially suspected, and antiviral therapy was commenced, but the anemia persisted. Subsequent Polymerase chain reaction (PCR) testing revealed parvovirus B19 viremia, and bone marrow examination demonstrated erythroid hypoplasia with giant proerythroblasts, confirming parvovirus B19–associated pure red cell aplasia (PRCA). Treatment with intravenous immunoglobulin (IVIG) led to rapid hematologic improvement and complete recovery without recurrence.
This case underscores the importance of considering parvovirus B19 infection as a potential cause of anemia in immunocompromised individuals, especially following solid organ transplantation, where overlapping viral infections and immunosuppressive agents complicate diagnosis. Early recognition and prompt IVIG therapy can result in excellent outcomes and prevent unnecessary interventions.
{"title":"Parvovirus B19 infection induces pure red cell aplasia after lung transplantation","authors":"Yusuke Okamoto , Kenichi Ishiyama , Akira Matsumoto , Yusuke Tsuda , Miki Nagao , Masahiro Hirata , Masakazu Fujimoto , Hironori Haga , Yojiro Yutaka , Akifumi Takaori-Kondo","doi":"10.1016/j.jiac.2025.102901","DOIUrl":"10.1016/j.jiac.2025.102901","url":null,"abstract":"<div><div>A man in his 50's with a history of acute lymphoblastic leukemia underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) over 20 years earlier and later developed bilateral giant pulmonary bullae, presumed secondary to pulmonary chronic graft-versus-host disease (cGVHD), requiring bilateral lung transplantation. Six months after lung transplantation, he developed rapid-onset severe normocytic anemia with reticulocytopenia. Cytomegalovirus (CMV) reactivation was initially suspected, and antiviral therapy was commenced, but the anemia persisted. Subsequent Polymerase chain reaction (PCR) testing revealed parvovirus B19 viremia, and bone marrow examination demonstrated erythroid hypoplasia with giant proerythroblasts, confirming parvovirus B19–associated pure red cell aplasia (PRCA). Treatment with intravenous immunoglobulin (IVIG) led to rapid hematologic improvement and complete recovery without recurrence.</div><div>This case underscores the importance of considering parvovirus B19 infection as a potential cause of anemia in immunocompromised individuals, especially following solid organ transplantation, where overlapping viral infections and immunosuppressive agents complicate diagnosis. Early recognition and prompt IVIG therapy can result in excellent outcomes and prevent unnecessary interventions.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102901"},"PeriodicalIF":1.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786657","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}
We investigated the long-term impact of an antimicrobial stewardship program (ASP) led by a dedicated intensive care unit (ICU) pharmacist belonging to an antimicrobial stewardship team (AST) on trends in antimicrobial use and patient outcomes.
Methods
This was a single-center, retrospective study of patients admitted in an open ICU. Days of therapy (DOT) and number of patients receiving antimicrobial drug (NAD) of carbapenems, anti-pseudomonal β-lactams and non-anti-pseudomonal β-lactams, and all-cause mortality at 28 days were compared between the pre-ASP period (April 2012 to March 2016) and post-ASP period (April 2016 to March 2024). We divided patients into the sepsis, non-sepsis, and non-infection groups and compared outcomes. De-escalation rates and number of days until de-escalation of carbapenems and anti-pseudomonal β-lactams were investigated in sepsis and non-sepsis cases.
Results
DOT decreased significantly for carbapenems, anti-pseudomonal and non-anti-pseudomonal β-lactams post-ASP. In sepsis cases, the number of days until de-escalation of carbapenems and anti-pseudomonal β-lactams significantly decreased post-ASP; the ICU pharmacist intervened in all cases for sepsis and non-sepsis post-ASP. DOT of carbapenems and anti-pseudomonal β-lactams decreased significantly in non-sepsis and non-infection cases post-ASP. NAD significantly decreased in patients treated with carbapenems, anti-pseudomonal β-lactams and non-anti-pseudomonal β-lactams post-ASP. In non-infection cases, NAD significantly decreased in patients treated with carbapenems, anti-pseudomonal β-lactams post-ASP. No significant difference occurred in all-cause mortality rate between groups.
Conclusion
ASP led by a pharmacist belonging to an AST in the open ICU contributed to long-term appropriate antimicrobial use of carbapenems and anti-pseudomonal β-lactams, and DOT for non-pseudomonal β-lactams.
{"title":"The effect of pharmacist-led antimicrobial stewardship on antimicrobial use in an intensive care unit: a single-center, retrospective, observational study","authors":"Yoshihiro Nishita , Natsuko Ishida , Masatoshi Taga , Ryoji Takata , Yoshitsugu Iinuma , Togen Masauji , Junko Ishizaki","doi":"10.1016/j.jiac.2025.102898","DOIUrl":"10.1016/j.jiac.2025.102898","url":null,"abstract":"<div><h3>Purpose</h3><div>We investigated the long-term impact of an antimicrobial stewardship program (ASP) led by a dedicated intensive care unit (ICU) pharmacist belonging to an antimicrobial stewardship team (AST) on trends in antimicrobial use and patient outcomes.</div></div><div><h3>Methods</h3><div>This was a single-center, retrospective study of patients admitted in an open ICU. Days of therapy (DOT) and number of patients receiving antimicrobial drug (NAD) of carbapenems, anti-pseudomonal β-lactams and non-anti-pseudomonal β-lactams, and all-cause mortality at 28 days were compared between the pre-ASP period (April 2012 to March 2016) and post-ASP period (April 2016 to March 2024). We divided patients into the sepsis, non-sepsis, and non-infection groups and compared outcomes. De-escalation rates and number of days until de-escalation of carbapenems and anti-pseudomonal β-lactams were investigated in sepsis and non-sepsis cases.</div></div><div><h3>Results</h3><div>DOT decreased significantly for carbapenems, anti-pseudomonal and non-anti-pseudomonal β-lactams post-ASP. In sepsis cases, the number of days until de-escalation of carbapenems and anti-pseudomonal β-lactams significantly decreased post-ASP; the ICU pharmacist intervened in all cases for sepsis and non-sepsis post-ASP. DOT of carbapenems and anti-pseudomonal β-lactams decreased significantly in non-sepsis and non-infection cases post-ASP. NAD significantly decreased in patients treated with carbapenems, anti-pseudomonal β-lactams and non-anti-pseudomonal β-lactams post-ASP. In non-infection cases, NAD significantly decreased in patients treated with carbapenems, anti-pseudomonal β-lactams post-ASP. No significant difference occurred in all-cause mortality rate between groups.</div></div><div><h3>Conclusion</h3><div>ASP led by a pharmacist belonging to an AST in the open ICU contributed to long-term appropriate antimicrobial use of carbapenems and anti-pseudomonal β-lactams, and DOT for non-pseudomonal β-lactams.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102898"},"PeriodicalIF":1.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786750","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}
A 69-year-old woman with hypertension had undergone total arch replacement with an open stent graft 7 years prior. She was referred to our hospital for evaluation after experiencing fever (>38 °C) and cough. Chest radiography revealed a prominent aortic arch, and contrast-enhanced computed tomography demonstrated aortic arch enlargement and peri-graft fluid collection containing air. These findings indicated graft infection and prompted immediate intervention. Blood cultures grew Streptococcus equi subspecies zooepidemicus, a zoonotic pathogen associated with horses. Notably, the patient worked as a horse trainer. On hospital day 6, she developed severe hemoptysis due to an aortobronchial fistula caused by stent graft infection and underwent emergency re-replacement of the aortic arch. Intraoperative specimens also yielded the same pathogen. Consequently, she was treated with ampicillin, and her postoperative course was uneventful. Although rare, zoonotic pathogens can cause vascular graft infections.
{"title":"Zoonotic aortic graft infection by Streptococcus equi","authors":"Haruka Karaushi , Akihiro Yoshitake , Yuta Kanazawa , Noriyuki Watanabe , Mieko Tokano , Masafumi Seki , Kotaro Mitsutake","doi":"10.1016/j.jiac.2025.102900","DOIUrl":"10.1016/j.jiac.2025.102900","url":null,"abstract":"<div><div>A 69-year-old woman with hypertension had undergone total arch replacement with an open stent graft 7 years prior. She was referred to our hospital for evaluation after experiencing fever (>38 °C) and cough. Chest radiography revealed a prominent aortic arch, and contrast-enhanced computed tomography demonstrated aortic arch enlargement and peri-graft fluid collection containing air. These findings indicated graft infection and prompted immediate intervention. Blood cultures grew <em>Streptococcus equi</em> subspecies <em>zooepidemicus</em>, a zoonotic pathogen associated with horses. Notably, the patient worked as a horse trainer. On hospital day 6, she developed severe hemoptysis due to an aortobronchial fistula caused by stent graft infection and underwent emergency re-replacement of the aortic arch. Intraoperative specimens also yielded the same pathogen. Consequently, she was treated with ampicillin, and her postoperative course was uneventful. Although rare, zoonotic pathogens can cause vascular graft infections.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102900"},"PeriodicalIF":1.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781349","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}
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