Infection and Chemotherapy最新文献

Background: For infections caused by metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE), ceftazidime-avibactam (CZA) alone is inactive because avibactam does not inhibit MBLs. Co-administration with aztreonam can restore activity but requires simultaneous delivery and harmonization of non-aligned renal dose adjustments. Pharmacodynamic (PD) targets for MBL producers may also differ from those for serine β-lactamase producers. This study aimed to define practical CZA plus aztreonam dosing regimens across renal function strata using Monte Carlo simulation.

Materials and methods: Pharmacokinetic (PK) parameters from infected patients receiving concomitant CZA plus aztreonam were modeled using a one-compartment structure with CKD-EPI renal function as the key covariate. Monte Carlo simulations (n=5,000) evaluated concentration-time profiles during the first 24 hours and at steady state across renal strata. Both conventional and stringent PK/PD targets were assessed. Probability of target attainment (PTA) was estimated at clinically relevant minimal inhibitory concentrations (MICs) for ceftazidime and aztreonam and threshold concentrations (CT 2.5 and 4 mg/L) for avibactam. Joint PTA was defined as the probability of simultaneous attainment of aztreonam and avibactam targets. A ceftazidime C_min >80 mg/L was applied as a neurotoxicity risk threshold.

Results: Across simulations, aztreonam and ceftazidime achieved ≥90% PTA at MIC breakpoints under conventional targets. Avibactam achieved ≥90% PTA only at steady-state CT 2.5 mg/L and failed at 4 mg/L or under stringent targets, reflecting limited avibactam exposure relative to higher PD thresholds. In preserved renal function, q6h regimens provided higher joint PTA than q8h dosing, though neither achieved ≥90% joint PTA under stringent targets. Most regimens in reduced renal function (eGFR ≤90 mL/min) maintained ≥90% joint PTA under conventional targets, while attainment under stringent targets was limited. Neurotoxicity risk (C_min >80 mg/L) remained low across renal strata.

Conclusion: Co-administration of CZA and aztreonam using renal-adjusted doses provides a practical and effective strategy for MBL-CRE infections. This approach ensures high joint PTA attainment while maintaining a low neurotoxicity risk across all renal function strata.

This retrospective study analyzed the antimicrobial susceptibility of pneumococcus isolated from eye discharge of pediatric patients. It included 65 patients, stratified by age (<2 years vs. ≥2 years) and date of isolation of pneumococcus (earlier period, 1994-2013 vs. later period, 2014-2024). There were no differences between the age groups in antimicrobial susceptibility. Between the periods, antibiotic susceptibility showed no significant difference for cefotaxime (83.3% vs. 63.8%) and levofloxacin (100% vs. 95.5%), but there was a significant difference for penicillin susceptibility (48.5% vs. 16.7%, P=0.035). The results suggest an increase in non-susceptibility to penicillin in the later period.

Background: Varicella, caused by the varicella-zoster virus, is a highly contagious pediatric infection that can lead to severe complications. SKYVaricella Inj. (SK bioscience Co., Ltd, Incheon, Korea), a live-attenuated varicella vaccine developed by SK bioscience, was approved in Korea in 2018. This post-marketing surveillance study aimed to evaluate the safety profile of SKYVaricella Inj. (SK bioscience Co., Ltd, Incheon, Korea) in children aged 12 months to 12 years in routine clinical practice.

Materials and methods: This multicenter, prospective, non-interventional study was conducted across 25 sites in Korea from June 4, 2018, to June 3, 2022. A total of 623 subjects were included in the safety analysis. Adverse events (AEs), including those assessed as adverse drug reactions (ADRs), and serious adverse events (SAEs), were monitored for 42 days post-vaccination. Events were further categorized by causality and expectedness based on regulatory definitions. Descriptive statistics were used to summarize AE incidence and to explore potential associations with participant characteristics.

Results: Among the 623 participants, 263 (42.2%) reported 514 AEs, and 56 (9.0%) experienced ADRs. The most frequently reported ADRs were injection site pain (4.0%), erythema (3.9%), and irritability (3.7%). Two SAEs (0.3%) - bronchitis and hand-foot-and-mouth disease - were reported and assessed as unrelated to vaccination. Varicella-like rashes occurred in 10 subjects (1.6%) and were mostly mild or moderate in severity. No unexpected serious adverse drug reactions were observed.

Conclusion: SKYVaricella Inj. (SK bioscience Co., Ltd, Incheon, Korea) demonstrated an acceptable safety profile in pediatric use in Korea, with most AEs being mild and consistent with expected vaccine-related reactions. Continued pharmacovigilance and larger-scale studies are warranted to further support its long-term public health impact.

Background: Antimicrobial resistance is driven by inappropriate antibiotic use. In Cambodia, young children frequently receive antibiotics despite declining rates of common illnesses. We analyzed nationally representative data to describe trends and determinants of antibiotic use for acute respiratory infection (ARI), fever, and diarrhea among under-five children.

Materials and methods: We performed a secondary analysis of the Cambodia Demographic and Health Surveys from 2010, 2014, and 2021-2022. Caregivers reported whether children (<60 months) experienced ARI, fever, or diarrhea in the two weeks preceding the survey and whether antibiotics were administered. We calculated weighted prevalence estimates of each illness and the proportion of episodes treated with antibiotics. For fever and diarrhea separately, we fitted multivariable logistic regression models-stratified by survey year-to identify associations between antibiotic receipt and child age, sex, urban vs. rural residence, household wealth quintile, and maternal education, accounting for sampling weights and clustering.

Results: Between 2010 and 2021-2022, the two-week prevalence of fever declined from 26.8% to 13.2% (P<0.001) and diarrhea from 14.5% to 6.9% (P<0.001), yet antibiotic use remained high. In 2021-2022, 53% of fever episodes and 29% of diarrheal episodes were treated with antibiotics. Urban residence was associated with higher odds of antibiotic use for fever (adjusted odds ratio [aOR], 1.85; 95% confidence interval [CI], 1.05-3.25) and diarrhea (aOR, 2.38; 95% CI, 1.02-5.54) vs. rural residence. In 2010, children in the richest quintile had greater odds of antibiotic use for fever (aOR, 2.10; 95% CI, 0.89-4.97) and diarrhea (aOR, 3.39; 95% CI, 1.61-7.11) compared to those in the poorest quintile; these disparities persisted, though attenuated, in later surveys.

Conclusion: Despite substantial declines in childhood illness, antibiotic use among Cambodian children under five remains disproportionately high-especially in urban and wealthier households. Antimicrobial stewardship initiatives should focus on reducing overuse in privileged populations while ensuring equitable access in underserved areas.

As the life expectancy of people living with HIV (PLWH) continues to rise with the success of antiretroviral therapy (ART), long-term complications such as reduced bone mineral density (BMD) and osteoporosis have become increasingly prevalent. PLWH exhibit a higher risk of bone loss and fractures compared to the general population, driven by multiple factors including chronic immune activation, systemic inflammation, and ART-related toxicity. Tenofovir disoproxil fumarate is known to induce proximal renal tubular dysfunction and hypophosphatemia, contributing to reduced BMD. Tenofovir alafenamide is associated with improved renal and bone safety profiles. Recent data on integrase inhibitor-based or tenofovir-sparing regimens such as dolutegravir/lamivudine and long-acting cabotegravir plus rilpivirine suggest favorable effects on bon health. However, bone loss may still occur following ART initiation, regardless of regimen, and long-term skeletal outcomes remain under investigation. Given the increasing burden of bone disease in aging PLWH, timely assessment using dual-energy X-ray absorptiometry and fracture risk tools such as FRAX is essential. Management strategies should include lifestyle modification, calcium and vitamin D supplementation, and pharmacologic interventions including bisphosphonates or denosumab. Optimizing ART selection to minimize bone toxicity is also an important consideration. As PLWH age, bone health must be integrated into comprehensive HIV care.

We present the results of the 4^th year surveillance period of a prospective, multicenter, observational, post-marketing surveillance study that evaluates the safety and effectiveness of Biktarvy in routine clinical practice in Korea. A total of 1,157 patients were included in the safety analysis set. Most patients were male (93.3%) and ART experienced (treatment-experienced [89.3%]). Adverse events occurred in 425 patients (36.7%) and of those 63 patients reported adverse drug reactions (ADRs [5.5%]). No serious ADRs were reported. The virological success rate (HIV-1 RNA <50 copies/mL) of Biktarvy treatment at last visit was 96.7%.

Background: In Korea, data on circulating Chlamydia trachomatis strains and their antimicrobial susceptibility profiles remain limited despite its significance in terms of public health. To date, their antimicrobial susceptibility or related genes are not fully characterized yet. This study aimed to determine the distribution of C. trachomatis genotypes and antimicrobial susceptibility profiles, and the presence of antimicrobial susceptibility related genes in Korea from 2016 to 2019.

Materials and methods: A total number of 118 clinical C. trachomatis isolates were obtained from 1,011 samples for analysis. We characterized patient demographics and performed ompA genotyping and multilocus sequence typing (MLST) on the isolates, determined their in vitro susceptibilities to tetracycline, levofloxacin, azithromycin, and rifampicin, and screened for susceptibility-associated genes in both isolates and clinical samples.

Results: The genotype D/Ep6, which is rarely reported globally, was the predominant strain (82, 69.5%), followed by genotypes F (14, 11.9%), Ja (12, 10.2%), E (9, 7.6%), and J (1, 0.9%) out of 118 C. trachomatis isolates. The MLST revealed eight sequence types (STs), including two novel STs. Of clinically isolated C. trachomatis (n=118), many isolates were susceptible to tetracycline at 125 ng/ml (52, 44.1%), levofloxacin at 250 ng/ml (81, 68.6%), azithromycin at 62.5 ng/ml (50, 42.4%), and rifampicin at 7.81 ng/ml (50, 42.4%). In antimicrobial susceptibility profiling. One isolate was susceptible to both azithromycin at 256 µg/ml and rifampicin at 8 µg/ml. Also, several single nucleotide polymorphisms (SNPs) on rpoB genes and tet(C) gene of C. trachomatis L2/tet9 were detected.

Conclusion: A rarely reported genotype, D/Ep6, was the dominant C. trachomatis variant in Korea during 2016 to 2019. The detection of SNPs and novel rpoB mutations may suggest unique C. trachomatis landscape in Korea. Our findings provide meaningful distribution landscape and antimicrobial susceptibility profiling of C. trachomatis in Korea.

Streptococcus gallolyticus subsp. pasteurianus is a rare pathogen causing bacteremia and meningitis in neonates and infants. We present a case of septic shock with cardiac arrest due to S. gallolyticus subsp. pasteurianus infection in a previously healthy infant and review of the literature. Although S. gallolyticus subsp. pasteurianus infections are typically considered to follow a mild clinical course in infants, this case highlights the potential for aggressive progression even in the absence of comorbidities. Evidence points that infants without apparent perinatal insults or immune dysfunction are susceptible. Therefore, clinical awareness is crucial for early diagnosis and prompt treatment.

Paragonimiasis, most commonly caused by Paragonimus westermani, is endemic in East and Southeast Asia and commonly transmitted through ingestion of raw or undercooked freshwater crab or crayfish. While pulmonary manifestations predominate, extrapulmonary involvement such as cerebral paragonimiasis can occur. We describe three cases of imported familial pulmonary and extrapulmonary paragonimiasis from Southeast Asia and diagnosed in Korea. A 12-year-old boy presented with dizziness, headache, nausea, and vomiting. Brain magnetic resonance imaging revealed a hemorrhagic mass-like lesion with leptomeningeal enhancement, and chest tomography showed serpiginous tubular opacities with multifocal consolidations. Laboratory evaluation revealed marked eosinophilia (46.2%). Further history revealed habitual consumption of raw crayfish while residing in Cambodia. Serology was positive for P. westermani and Clonorchis sinensis IgG. Treatment with albendazole and praziquantel resulted in resolution of symptoms and normalization of eosinophil counts. Further evaluation identified similar findings in his parents who were misdiagnosed as tuberculosis and cerebral hemorrhage, and the family was treated with praziquantel. This familial cluster highlights the importance of detailed dietary and travel history in patients with eosinophilia and neurological symptoms. This case was discussed at the Clinical Grand Round of the Korean Society of Infectious Diseases on November 7, 2024.