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23 pages, 2562 KB  
Article
Non-Vaccine Serotype Replacement and Subdominant Persistence of Vaccine Types in Nepalese Infants Following PCV10 Introduction
by Fleurette Mbuyakala Domai, Dhruba Shrestha, Raj Kumar Shrestha, Monika Thimi, Desmond Opoku Ntiamoah, Yumiko Hayashi, Chris Smith, Yoshinao Kubo, Shunmay Yeung, Motoi Suzuki, Konosuke Morimoto, Koya Ariyoshi and Bhim Gopal Dhoubhadel
Vaccines 2026, 14(1), 73; https://doi.org/10.3390/vaccines14010073 - 8 Jan 2026
Abstract
Background: Streptococcus pneumoniae is a leading cause of child mortality in Nepal despite the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10). Vaccine effectiveness is threatened by the emergence of non-vaccine serotypes (NVTs) and the multiple serotypes carriage which often fail to [...] Read more.
Background: Streptococcus pneumoniae is a leading cause of child mortality in Nepal despite the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10). Vaccine effectiveness is threatened by the emergence of non-vaccine serotypes (NVTs) and the multiple serotypes carriage which often fail to be detected by traditional methods. We aimed to study changes in serotype distribution before and after PCV10 immunization among infants, including serotype dominance in Nepalese infants in the post-vaccine era. Methods: We enrolled infants in a longitudinal cohort study (2020–2022) conducted in Bhaktapur, Nepal. Nasopharyngeal swabs were collected before PCV10 dose 1 (6 weeks) and at 9 and 12 months post-immunization. We used a sensitive nanofluidic qPCR platform to detect multiple serotypes and establish their hierarchy by quantifying the bacterial load of each strain. Inverse Probability Weighting (IPW) adjusted risk factor analysis was used to account for loss to follow-up. Results: PCV10 successfully reduced vaccine-type (VT) carriage, declining sharply from 32.8% at 6 weeks to 4.8% at 12 months. VTs were pushed from being the dominant strain to occupying subdominant roles in co-colonization. Conversely, NVTs rapidly filled the vacated niche, showing a significant increase in their dominant status (p < 0.001). The most common replacing NVTs that rose to dominance were 35B, 19A, 6C/6D, and 15B/15C. Significant risk factors for carriage included older infancy (aOR 3.4, 95%CI: 2.6–4.5 at 9 months), a household kitchen in the living area (aOR 1.4, 95%CI: 1.0–1.9), and winter (aOR 1.7, 95%CI: 1.5–2.7) and pre-monsoon seasons (aOR 2.0, 95%CI: 1.5–2.8). Conclusions: While PCV10 reduced overall VT circulation, the persistence of VTs in subdominant niches creates a continuous reservoir for potential re-emergence and antibiotic resistance. This clear hierarchical shift in dominance towards NVTs underscores the urgent need for a public health strategy that includes the adoption of a higher-valent PCV to provide broader protection, and interventions targeting environmental risk factors are essential to sustain long-term reductions in pneumococcal colonization. Full article
(This article belongs to the Section Epidemiology and Vaccination)
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12 pages, 699 KB  
Article
Timing of Antibiotics in ICU Pneumonia: An Observational Association Between Early Treatment and Higher Mortality
by Josef Yayan and Kurt Rasche
Antibiotics 2026, 15(1), 49; https://doi.org/10.3390/antibiotics15010049 - 3 Jan 2026
Viewed by 151
Abstract
Background: Early administration of antibiotics is commonly recommended for pneumonia in intensive care unit (ICU) patients. However, the clinical benefit of very early empirical treatment remains uncertain and may reflect differences in illness severity, baseline risk, or care pathways, particularly in non-septic or [...] Read more.
Background: Early administration of antibiotics is commonly recommended for pneumonia in intensive care unit (ICU) patients. However, the clinical benefit of very early empirical treatment remains uncertain and may reflect differences in illness severity, baseline risk, or care pathways, particularly in non-septic or hemodynamically stable ICU populations. Methods: We performed a retrospective cohort study using the Medical Information Mart for Intensive Care IV (v2.2) database to evaluate the observational association between antibiotic timing and in-hospital mortality among adult ICU patients with pneumonia. Patients were categorized as receiving early (<3 h) or delayed (≥3 h) antibiotic therapy after ICU admission. A multivariable logistic regression model adjusted only for age and sex. Given the absence of detailed severity-of-illness measures, no causal inference was intended, and all analyses were considered hypothesis-generating. Additional analyses exploring antibiotic class, dosing frequency, and combination therapy were conducted in an exploratory manner, given substantial variation in sample sizes and a high risk of confounding by indication, misclassification, immortal-time, and survivorship bias. Results: Among 7569 ICU patients with pneumonia, 56.5% received antibiotics within three hours of ICU admission. Early antibiotic initiation was associated with higher in-hospital mortality than delayed therapy (26.1% vs. 21.5%; OR 1.30, 95% CI 1.16–1.44; p < 0.001). Because validated severity-of-illness measures were unavailable, residual confounding and confounding by indication are likely and may largely explain this association. A potential signal of increased mortality was observed in patients receiving ≥3 doses of levofloxacin (OR 4.39, 95% CI 1.13–17.02); however, this subgroup was small and the finding is highly susceptible to survivorship and indication bias. Mortality appeared lower in patients receiving two or three antibiotics compared with monotherapy, but marked group imbalances, lack of restriction or stratification, and clinical selection effects limit interpretability. Regimens involving ≥4 agents were rare and primarily associated with prolonged ICU length of stay rather than a clear mortality difference. Conclusions: In this large retrospective ICU cohort, very early antibiotic administration for pneumonia was observationally associated with higher in-hospital mortality. Causality cannot be inferred, and early treatment likely represents a marker of higher baseline risk or clinical urgency rather than a harmful exposure. These findings challenge the assumption that earlier antibiotic initiation is uniformly beneficial and underscore the importance of individualized, stewardship-aligned, and context-dependent decision-making regarding antimicrobial timing and intensity in critically ill patients. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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18 pages, 4873 KB  
Article
Effect of N-Acetyl-L-Cysteine (NAC) on Inflammation After Intraperitoneal Mesh Placement in an Escherichia coli Septic Rat Model: A Randomized Experimental Study
by Styliani Parpoudi, Ioannis Mantzoros, Orestis Ioannidis, Konstantinos Zapsalis, Thomai Gamali, Dimitrios Kyziridis, Christos Gekas, Elissavet Anestiadou, Savvas Symeonidis, Stefanos Bitsianis, Efstathios Kotidis, Manousos-Georgios Pramateftakis, Dimosthenis Miliaras, Anastasia Bikouli, Georgios Iosifidis and Stamatios Angelopoulos
Med. Sci. 2025, 13(4), 318; https://doi.org/10.3390/medsci13040318 - 14 Dec 2025
Viewed by 504
Abstract
Background/Objectives: The safety of intraperitoneal mesh placement in contaminated fields remains controversial because of the increased risk of inflammation and adhesion formation. N-acetyl-L-cysteine (NAC) has antioxidant, pro-fibrinolytic and antibiofilm actions that could attenuate this response. The aim of this study is to [...] Read more.
Background/Objectives: The safety of intraperitoneal mesh placement in contaminated fields remains controversial because of the increased risk of inflammation and adhesion formation. N-acetyl-L-cysteine (NAC) has antioxidant, pro-fibrinolytic and antibiofilm actions that could attenuate this response. The aim of this study is to determine whether NAC reduces mesh-related inflammation in a septic model created by intraperitoneal Escherichia coli (E.coli) inoculation. The primary comparison was prospectively defined between E. coli–inoculated animals treated with NAC (D) and those without NAC (B). Groups without E. coli (A,C,E) are presented for context and were compared previously. Methods: In this randomized, double-blind experimental model (five groups, n = 20 per group), all rats underwent midline laparotomy with intraperitoneal placement of a composite mesh, followed by standardized ciprofloxacin administration. The septic groups received intraperitoneal E. coli, while the NAC-treated groups additionally received intraperitoneal NAC (150 mg/kg). Serum levels of IL-1α, IL-6, and TNF-α were measured on postoperative days 7, 14, and 21. On day 21, adhesions were graded using the Modified Diamond system, histology (inflammatory infiltration, fibrosis, neovascularization) was scored, and mesh cultures were obtained. Cytokine data were analyzed with repeated-measures ANOVA, while categorical or ordinal outcomes were assessed using χ2 or Fisher’s exact tests with Bonferroni-adjusted pairwise comparisons. Results: E. coli inoculation significantly increased adhesion burden and worsened histologic scores compared with controls (both p < 0.001). NAC administration in the septic model significantly reduced adhesions and improved all histologic domains relative to E. coli alone (all p ≤ 0.003), with values comparable to controls (non-significant across domains). For cytokines, there was a significant overall group effect for IL-1α, IL-6, and TNF-α (all p < 0.001), without a main effect of time or time × group interaction. Pairwise contrasts showed lower IL-1α (p = 0.024), IL-6 (p < 0.001), and TNF-α (p < 0.001) levels in group D versus B, and lower IL-6 and TNF-α in group D versus A (both p < 0.001). Mesh culture positivity rate was higher in group B than A (p < 0.001) and showed a non-significant reduction in group D versus B (p = 0.10). No perioperative deaths occurred. Conclusions: NAC attenuated septic, mesh-associated inflammation—normalizing adhesions and histology and reducing IL-6 and TNF-α— supporting its role as a host-directed adjunct alongside antibiotics. Further translational studies are warranted to define the optimal dose, timing, and clinical indications. Full article
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14 pages, 3688 KB  
Article
Chelerythrine-Mediated Growth Inhibition and Resistance Mechanism in Bacillus tropicus
by Jueyu Wang, Hongxia Wan, Wenqi Chai, Daizong Cui and Min Zhao
Microorganisms 2025, 13(12), 2731; https://doi.org/10.3390/microorganisms13122731 - 29 Nov 2025
Viewed by 289
Abstract
Chelerythrine (CHE) is a naturally occurring benzophenanthridine alkaloid obtained from plants such as Chelidonium majus L. It has received notable attention in pharmacology and microbial control because of its broad-spectrum activity and marked anti-inflammatory, apoptosis-inducing, and antibacterial effects. In this study, Bacillus tropicus [...] Read more.
Chelerythrine (CHE) is a naturally occurring benzophenanthridine alkaloid obtained from plants such as Chelidonium majus L. It has received notable attention in pharmacology and microbial control because of its broad-spectrum activity and marked anti-inflammatory, apoptosis-inducing, and antibacterial effects. In this study, Bacillus tropicus, which frequently presents in the soil environment, was selected as the target microorganism to systematically examine the dose-dependent inhibitory influence of CHE on its growth curve, biofilm development, and survival rate. Furthermore, by simulating an antibiotic pressure environment in vitro, the original strain was subjected to continuous subculturing (30 times), and a highly drug-resistant B. tropicus strain capable of stable growth under high concentrations of CHE (300 mg/L) was successfully acclimated. After that, transcriptomics analysis was employed to compare the genetic differences between the wild-type bacterium and drug-resistant bacterium to determine how bacterial cells are able to resist CHE. A total of 868 genes in the CHE-resistant bacterium were revealed to be more active, while 539 genes were less active. These results indicate that the CHE resistance characteristics of the strain may be related to the adjustment of its sugar metabolism pathway and the biofilm formation pathway. As a widely used biological control bacterial strain, the successful acclimation of the B. tropicus strain with resistance to CHE has made it possible to use the combined formulation of these two agents for the prevention and control of plant diseases. Full article
(This article belongs to the Section Environmental Microbiology)
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44 pages, 552 KB  
Review
Modulation of Surgical Site Infection Risk in Spinal and Thoracic Surgeries Through Operative Parameters: A Narrative Review
by Joanna Suszczyńska, Michał Grabala and Paweł Grabala
J. Clin. Med. 2025, 14(22), 8124; https://doi.org/10.3390/jcm14228124 - 17 Nov 2025
Viewed by 1627
Abstract
Background: Surgical site infections (SSIs) following spinal and thoracic procedures are associated with prolonged hospitalization and increased morbidity, with incidence rates of 2–15% in spinal surgery and 3–12% in thoracic procedures. Multiple patient-related and procedure-specific factors contribute to wound complications, including diabetes mellitus, [...] Read more.
Background: Surgical site infections (SSIs) following spinal and thoracic procedures are associated with prolonged hospitalization and increased morbidity, with incidence rates of 2–15% in spinal surgery and 3–12% in thoracic procedures. Multiple patient-related and procedure-specific factors contribute to wound complications, including diabetes mellitus, obesity, smoking, extended surgical time, excessive tissue dissection, and hardware implantation. Implementing evidence-based prevention and early intervention strategies is essential in high-risk surgical cohorts. Methods: This narrative review followed searches in PubMed, Scopus, ScienceDirect, Cochrane Library, and Embase for studies published between January 2000 and October 2025. Eligible peer-reviewed articles examined SSI incidence, risk factors, or prevention strategies in adult patients undergoing thoracic or spinal surgery. Data extraction focused on operative parameters, antibiotic prophylaxis regimens, negative-pressure wound therapy (NPWT) use, and patient outcomes. Results: Evidence from found recent studies was synthesized. Key findings demonstrated that operative duration > 4 h increased SSI odds by 41% per additional hour, and blood loss > 500 mL doubled infection risk. Prophylactic NPWT reduced deep SSI rates by 50% in high-risk patients (BMI ≥ 35, diabetes, multilevel instrumentation). Intrawound vancomycin powder reduced deep SSIs by 50–60%, particularly in multilevel fusions. Administering prophylactic antibiotics within 30 min of incision was significantly more effective than at 60 min, with a 23% relative risk reduction. Weight-adjusted antibiotic dosing in obese patients lowered SSI rates from 5.1% to 2.9%. Conclusions: Operative parameters strongly predict SSI risk. An integrated risk- and evidence-based approach to wound management following spinal and thoracic surgeries—combining optimized antibiotic prophylaxis, risk-stratified NPWT application, and operative technique modifications—can significantly reduce SSI incidence. Successful implementation requires institutional commitment, multidisciplinary collaboration, and continuous quality improvement to optimize patient outcomes. Full article
19 pages, 564 KB  
Review
β-Lactam/β-Lactamase Inhibitor Combinations in Sepsis-Associated Acute Kidney Injury and Renal Replacement Therapy
by Antonio Lacquaniti, Valentina Pistolesi, Antonella Smeriglio, Domenico Santoro, Cristina Iannetti, Giuseppe Lentini, Roberto Chimenz, Valeria Chirico, Domenico Trombetta, Santo Morabito and Paolo Monardo
Antibiotics 2025, 14(11), 1097; https://doi.org/10.3390/antibiotics14111097 - 1 Nov 2025
Viewed by 1150
Abstract
Sepsis-associated acute kidney injury (SA-AKI) often requires renal replacement therapy (RRT), which markedly alters antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations broaden options against multidrug-resistant Gram-negative bacteria, but dosing during RRT remains uncertain. This review summarizes PK/PD features, extracorporeal [...] Read more.
Sepsis-associated acute kidney injury (SA-AKI) often requires renal replacement therapy (RRT), which markedly alters antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations broaden options against multidrug-resistant Gram-negative bacteria, but dosing during RRT remains uncertain. This review summarizes PK/PD features, extracorporeal clearance, and practical dosing considerations about ceftolozane–tazobactam, ceftazidime–avibactam, aztreonam–avibactam, cefiderocol, meropenem–vaborbactam, imipenem–relebactam, and newer agents including sulbactam–durlobactam, cefepime–enmetazobactam, and cefepime–taniborbactam. Pharmacokinetic data, RRT impact, PK/PD targets, pediatric aspects, and clinical outcomes were extracted from experimental models, case reports, and clinical studies. Drug exposure varies with RRT modality, effluent flow, membrane properties, and patient-specific factors such as augmented renal clearance, hypoalbuminemia, and fluid overload. Standard renal-adjusted dosing often yields subtherapeutic concentrations in critically ill patients. Pediatric data remain scarce and largely limited to case reports. Optimal BL/BLI use in septic patients with SA-AKI on RRT requires individualized dosing that accounts for PK/PD variability and dialysis settings. Full-dose initiation during the first 24–48 h, followed by careful adjustment, appears prudent. Therapeutic drug monitoring should be used when available, and institution-specific protocols should be integrated into stewardship programs to improve efficacy and minimize resistance. Full article
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14 pages, 414 KB  
Article
Optimising Meropenem and Piperacillin Dosing in Patients Undergoing Extracorporeal Membrane Oxygenation Without Renal Dysfunction (MEPIMEX)
by Mar Ronda, M Paz Fuset, Erika Esteve-Pitarch, Josep Llop, Victor Daniel Gumucio-Sanguino, Evelyn Shaw, Daniel Marco Mula, Kristel Maisterra-Santos, Joan Sabater, Xose L. Pérez, Sara Cobo-Sacristan, Raül Rigo, Fe Tubau, Jordi Carratalà, Helena Colom-Codina and Ariadna Padullés
Antibiotics 2025, 14(9), 939; https://doi.org/10.3390/antibiotics14090939 - 17 Sep 2025
Viewed by 1251
Abstract
Background/Objectives: Antibiotic pharmacokinetics (PK) and pharmacodynamics (PD) are altered during extracorporeal membrane oxygenation (ECMO). Meropenem and piperacillin are among the most commonly prescribed antibiotics for infections in this population. However, guidance on dosage adjustments in the ECMO setting remains limited. We aim [...] Read more.
Background/Objectives: Antibiotic pharmacokinetics (PK) and pharmacodynamics (PD) are altered during extracorporeal membrane oxygenation (ECMO). Meropenem and piperacillin are among the most commonly prescribed antibiotics for infections in this population. However, guidance on dosage adjustments in the ECMO setting remains limited. We aim to assess differences in meropenem and piperacillin concentrations achieved and identify the clinical, physiological, and mechanical factors influencing antibiotic exposure. Methods: This is a retrospective, single-centre, observational study comparing an ECMO cohort with a population control group from a prior study, without renal dysfunction. Demographic, clinical, PK/PD parameters, and ECMO-related data were analysed using univariate and generalised estimating equations. For both antimicrobials, the PK/PD target was set at 100%fT>4xMIC. Results: A total of 130 critically ill patients were included: 18 in the ECMO group and 112 in the control group. The mean age was 65 years (23), 67% were male and 26.9% were classified as obese. For meropenem, renal function and ECMO support significantly influenced drug exposure, with PK/PD targets being achieved in 67% of measurements; in contrast, piperacillin exposure exhibited greater variability, primarily driven by renal function and mechanical ventilation. Notably, PK/PD targets for piperacillin were met in only 20% of measurements. Conclusions: Our findings highlight the considerable variability in β-lactam exposures and PK/PD target attainment in critically ill patients. This study underscores the importance of therapeutic drug monitoring and individualised dosing in attempts to improve antimicrobial efficacy and patient outcomes in this challenging setting. Full article
(This article belongs to the Special Issue Antibiotic Stewardship Implementation Strategies)
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14 pages, 1307 KB  
Article
Impact of Obesity on Serum Concentrations of Vancomycin Administered as Continuous Infusion and on Clinical Outcomes in Critically Ill Patients—A Retrospective Observational Study
by Stefanie Nothofer, Rico Angeli, Manfred Weiss, Christian Dumps, Felix Berger, Josephin Eckert, Felix Girrbach, Nadin Scheidt, Susan Menzel, Mirko Lange, Hermann Wrigge and Philipp Simon
Antibiotics 2025, 14(9), 895; https://doi.org/10.3390/antibiotics14090895 - 4 Sep 2025
Viewed by 1088
Abstract
Background/Objectives: Vancomycin is a commonly used antibiotic in critically ill patients with severe methicillin-resistant Staphylococcus aureus infections. Due to its narrow therapeutic window, under- or overdosing is likely to result in adverse effects, especially in patients with conditions associated with altered pharmacokinetics such [...] Read more.
Background/Objectives: Vancomycin is a commonly used antibiotic in critically ill patients with severe methicillin-resistant Staphylococcus aureus infections. Due to its narrow therapeutic window, under- or overdosing is likely to result in adverse effects, especially in patients with conditions associated with altered pharmacokinetics such as obesity. The objective of this study was to investigate the impact of obesity on serum concentrations of vancomycin in critically ill patients receiving intravenous vancomycin by continuous infusion based on ideal body weight (IBW). Methods: This retrospective observational study performed at the University Hospital of Leipzig, Germany, included all patients admitted to the intensive care unit (ICU) between January 2009 and December 2015 who received guideline-based vancomycin therapy based on IBW. Serum concentrations were obtained through routinely performed therapeutic drug monitoring (TDM). Results: A total of 1066 patients with a median age of 62 years were included in this study. The median (25%; 75% quantile) vancomycin treatment duration was 4 (2; 7) days and the median time to reach target concentrations of 20–25 mg L−1 was 3 (2; 4) days without a significant difference between BMI groups. Overall, only 25.9% of patients were in the therapeutic range of 20–25 mg L−1 in the entire treatment interval. 47.8% of vancomycin concentrations obtained from TDM were below the desired target range with no differences between the BMI groups (p = 0.077). 26.3% of measurements exceeded the target range, with a significant increase in the morbidly obese group (p < 0.001). A higher BMI was associated with an increased ICU, in-hospital, 28- and 90-day mortality in morbidly obese patients (p < 0.05). Age, BMI and high SAPS-II and SOFA scores were significant predictors of an increased risk of death. Conclusions: Our preliminary findings suggest that IBW-based dosing may help reduce the risk of supratherapeutic concentrations in morbidly obese patients. The high rates of sub- and supratherapeutic vancomycin serum concentrations across all patients highlight the need for close TDM and dose adjustments, particularly in morbidly obese patients with the highest rates of supratherapeutic vancomycin serum concentrations and of RRT. Full article
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11 pages, 894 KB  
Article
Immunoglobulin G Trough Levels and Infection Risk in Adults with Inborn Errors of Immunity Receiving Immunoglobulin Therapy
by Özge Öztürk Aktaş, Nagihan Orhan Özer, Ceren Kaplankıran, Begüm Görgülü Akın, Betul Ozdel Ozturk, Makbule Seda Bayrak Durmaz, Fikriye Kalkan and Şadan Soyyiğit
Medicina 2025, 61(9), 1549; https://doi.org/10.3390/medicina61091549 - 29 Aug 2025
Viewed by 995
Abstract
Background and Objectives: Inborn errors of immunity are increasingly diagnosed in developing countries. Immunoglobulin replacement therapy (IGRT) remains the cornerstone of treatment in these patients, and its monitoring has gained importance for optimizing outcomes. We conducted a retrospective study to evaluate the relationship [...] Read more.
Background and Objectives: Inborn errors of immunity are increasingly diagnosed in developing countries. Immunoglobulin replacement therapy (IGRT) remains the cornerstone of treatment in these patients, and its monitoring has gained importance for optimizing outcomes. We conducted a retrospective study to evaluate the relationship between IgG trough levels and infections in adults with inborn errors of immunity receiving IGRT. Materials and Methods: Adults diagnosed with primary immunodeficiency and receiving IGRT for at least six months were included. Serum IgG trough levels were measured, and infections during follow-up were systematically recorded. Results: A total of 31 adult patients (CVID: 29, XLA: 2) were analyzed. The mean follow-up was 13 months, with a mean serum IgG trough level of 815.8 ± 205.9 mg/dL, achieved with an average IGRT dose of 498.8 ± 93.0 mg/kg/month. Dose adjustments were made in 35.5% of patients, mostly due to weight changes and clinical indications. Overall, 74.2% of patients had at least one infection requiring antibiotics. Patients with mean IgG trough levels below 850 mg/dL had significantly higher rates of antibiotic-requiring infections (p = 0.032, Mann–Whitney U; mean difference = 0.109, 95% CI: 0.037–0.182; p = 0.005 via t-test). Multivariate regression confirmed that lower IgG trough levels were independently associated with higher antibiotic-requiring infection rates (B = −0.024, 95% CI: −0.045 to −0.002, p = 0.033), while IGRT dose and comorbidities were not significant. Conclusions: IGRT plays a key role in reducing antibiotic-requiring infections in patients with primary immunodeficiency. Regular monitoring and individualized dose adjustments may help optimize outcomes. Further prospective studies are needed to confirm these findings. Full article
(This article belongs to the Section Hematology and Immunology)
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21 pages, 11899 KB  
Article
The Long-Term Efficacy of Cephalosporin in Elderly Hip Fracture Patients: A Comprehensive Analysis
by Huiqing Pan, Xiao Wang, Qingjian Ou, Juan Wang and Zisheng Ai
J. Clin. Med. 2025, 14(17), 6086; https://doi.org/10.3390/jcm14176086 - 28 Aug 2025
Viewed by 1509
Abstract
Objectives: This study aims to evaluate the association between antibiotic prophylaxis (particularly cephalosporins) and clinical outcomes in elderly hip fracture patients. Methods: We analyzed 4044 elderly hip fracture patients (2008–2022) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database using [...] Read more.
Objectives: This study aims to evaluate the association between antibiotic prophylaxis (particularly cephalosporins) and clinical outcomes in elderly hip fracture patients. Methods: We analyzed 4044 elderly hip fracture patients (2008–2022) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database using inverse probability treatment weighting (IPTW). Cox proportional hazards models assessed mortality risk, while logistic regression evaluated infection and Intensive Care Unit (ICU) admission risks. Dose–response and subgroup analyses were performed for significant findings. Results: In total, 166 patients received no antibiotics, 2589 received Cephalosporin monotherapy, 403 received non-cephalosporin therapy, and 886 received Cephalosporin combination therapy. After IPTW adjustment, monotherapy showed significantly lower mortality risk versus combination therapy at all timepoints (hazard ratio (HR) for 28-day mortality: 0.46, 95% confidence interval (95% CI): 0.28–0.75; HR for 90-day mortality: 0.60, 95% CI: 0.44–0.82; HR for 180-day mortality: 0.67, 95% CI: 0.51–0.87; HR for 1-year mortality: 0.71, 95% CI: 0.57–0.89). The SII cut-off values were 1310.1 for 28-day mortality, 2077.5 for both 90-day and 180-day mortality, 1742.2 for 1-year mortality, 2199.7 for ICU admission, and 1930.7 for infection. Subgroup analyses showed that males and internal fixation patients derived more benefits after cephalosporin monotherapy treatment at all time nodes. Patients with multiple injuries had a lower risk of 28-day mortality, while high-comorbidity patients (CCI ≥ 5) and those with osteoporosis exhibited particular advantages with cephalosporin monotherapy. Conclusions: Cephalosporin monotherapy appears non-inferior to combination therapy for elderly hip fracture patients, potentially reducing long-term mortality risk, especially in males, internal fixation cases, and patients with CCI ≥ 5 and osteoporosis. Full article
(This article belongs to the Section Orthopedics)
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12 pages, 441 KB  
Article
Optimizing Safety and Efficacy of Intravenous Vancomycin Therapy in Orthopedic Inpatients Through a Standardized Dosing Protocol: A Pre-Post Cohort Study
by Moritz Diers, Juliane Beschauner, Maria Felsberg, Alexander Zeh, Karl-Stefan Delank, Natalia Gutteck and Felix Werneburg
Antibiotics 2025, 14(8), 775; https://doi.org/10.3390/antibiotics14080775 - 31 Jul 2025
Cited by 1 | Viewed by 1429
Abstract
Background: Intravenous vancomycin remains a key agent in the treatment of complex orthopedic infections, particularly those involving methicillin-resistant Staphylococcus aureus (MRSA). However, its use is associated with significant risks, most notably nephrotoxicity. Despite guideline recommendations, standardized dosing and monitoring protocols are often [...] Read more.
Background: Intravenous vancomycin remains a key agent in the treatment of complex orthopedic infections, particularly those involving methicillin-resistant Staphylococcus aureus (MRSA). However, its use is associated with significant risks, most notably nephrotoxicity. Despite guideline recommendations, standardized dosing and monitoring protocols are often absent in orthopedic settings, leading to inconsistent therapeutic drug exposure and preventable adverse events. This study evaluated the clinical impact of implementing a structured standard operating procedure (SOP) for intravenous vancomycin therapy in orthopedic inpatients. Methods: We conducted a single-center, pre-post cohort study at a university orthopedic department. The intervention consisted of a standard operating procedure (SOP) for intravenous vancomycin therapy, which mandated weight-based loading doses, renal function-adjusted maintenance dosing, trough level monitoring, and defined dose adjustments. Patients treated before SOP implementation (n = 58) formed the control group; those treated under the SOP (n = 56) were prospectively included. The primary outcome was the incidence of vancomycin-associated acute kidney injury (VA-AKI) defined by KDIGO Stage 1 criteria. Secondary outcomes included therapeutic trough level attainment and infusion-related or ototoxic adverse events. Results: All patients in the post-SOP group received a loading dose (100% vs. 31% pre-SOP, p < 0.001). The range of measured vancomycin trough levels narrowed substantially after SOP implementation (7.1–36.2 mg/L vs. 4.0–80.0 mg/L). The proportion of patients reaching therapeutic trough levels increased, although this was not statistically significant. Most notably, VA-AKI occurred in 17.2% of patients in the control group, but in none of the patients after SOP implementation (0%, p = 0.0013). No cases of ototoxicity were observed in either group. Infusion-related reactions decreased after the implementation of the SOP, though not significantly. Conclusions: The introduction of a structured vancomycin protocol significantly reduced adverse drug events and improved dosing control in orthopedic inpatients. Incorporating such protocols into routine practice represents a feasible and effective strategy to strengthen antibiotic stewardship and clinical quality in surgical disciplines. Full article
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11 pages, 239 KB  
Article
Targeted Antibiotic Prophylaxis in Percutaneous Nephrolithotomy: Results of a Protocol Based on Preoperative Urine Culture and Risk Assessment
by Felipe Osorio-Ospina, Gonzalo Bueno-Serrano, María Pilar Alcoba-García, Juan Tabares-Jiménez, Blanca Gómez-Jordana-Mañas, Elena García-Criado, Joaquin Ruiz-de-Castroviejo, Xabier Pérez-Aizpurua, Jaime Jorge Tufet-I-Jaumot, Raúl González-Páez, Jose Carlos Matta-Pérez, Beatriz Yanes-Glaentzlin, Juan Francisco Jiménez-Abad, José Maria Alcázar Peral, Nerea Carrasco Antón, Elizabet Petkova-Saiz and Carmen González-Enguita
J. Clin. Med. 2025, 14(15), 5249; https://doi.org/10.3390/jcm14155249 - 24 Jul 2025
Viewed by 1779
Abstract
Background: Infectious complications are common after percutaneous nephrolithotomy (PCNL). Clinical guidelines recommend, previous to surgery, prolonged antibiotic regimens in patients with preoperative positive urine cultures to reduce infectious risk. However, such strategies may increase selective pressure and promote antimicrobial resistance. Evidence supporting the [...] Read more.
Background: Infectious complications are common after percutaneous nephrolithotomy (PCNL). Clinical guidelines recommend, previous to surgery, prolonged antibiotic regimens in patients with preoperative positive urine cultures to reduce infectious risk. However, such strategies may increase selective pressure and promote antimicrobial resistance. Evidence supporting the use of a single antibiotic dose tailored to culture sensitivity in these cases is limited but emerging. Methods: We conducted a retrospective observational study including 187 PCNL procedures performed between 2021 and 2023 under an individualized antibiotic prophylaxis protocol. Patients with negative or contaminated urine cultures received a single empirical dose, while those with recent positive cultures received a single dose based on antimicrobial susceptibility testing. Postoperative complications—including fever, sepsis, and a composite outcome—were analyzed through multivariable logistic regression, comparing high- and low-risk patients. Results: A total of 67.9% of procedures were performed in patients meeting at least one high-risk criterion, including a positive preoperative urine culture in 32.1%. The overall incidence of infectious complications was 11.9% (fever 8.7%, sepsis 3.2%), with no significant differences between risk groups. A low concordance was observed between preoperative and intraoperative urine cultures (Spearman = 0.3954). Conclusions: A single preoperative antibiotic dose adjusted to the antibiogram, even in patients with a positive urine culture, was not associated with increased infectious complications. This approach is an initial step that supports a rational and individualized prophylactic strategy aligned with the goals of antimicrobial stewardship programs (ASPs). Full article
(This article belongs to the Special Issue Targeted Treatment of Kidney Stones)
14 pages, 1422 KB  
Article
Preclinical Study of Pharmacokinetic/Pharmacodynamic Analysis of Tebipenem Using Monte Carlo Simulation for Extended-Spectrum β-Lactamase-Producing Bacterial Urinary Tract Infections in Japanese Patients According to Renal Function
by Fumiya Ebihara, Takumi Maruyama, Hidefumi Kasai, Mitsuru Shiokawa, Nobuaki Matsunaga and Yukihiro Hamada
Antibiotics 2025, 14(7), 648; https://doi.org/10.3390/antibiotics14070648 - 26 Jun 2025
Cited by 1 | Viewed by 1638
Abstract
Background/Objectives: The increasing prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing organisms poses a significant clinical challenge worldwide due to limited oral treatment options. Tebipenem (TBPM), an oral carbapenem antibiotic, is currently approved only for pediatric use in Japan, with [...] Read more.
Background/Objectives: The increasing prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing organisms poses a significant clinical challenge worldwide due to limited oral treatment options. Tebipenem (TBPM), an oral carbapenem antibiotic, is currently approved only for pediatric use in Japan, with no adult indication established. International studies have shown promising results for ESBL-producing infections, but optimal dosing regimens for Japanese adults with varying renal function have not been established. This study aimed to determine the optimal TBPM dosing regimens for ESBL-producing Enterobacterales UTIs in Japanese patients stratified by renal function, providing evidence for potential adult approval applications in Japan. Methods: Monte Carlo simulations (MCSs) were performed using pharmacokinetic parameters derived from clinical trials in Japanese subjects. Various dosing regimens were evaluated across different creatinine clearance (CCR) ranges and minimum inhibitory concentrations (MICs). The pharmacokinetic/pharmacodynamic target was set at fAUC0–24/MIC·1/tau ≥ 34.58, with a ≥90% probability of target attainment (PTA) considered optimal. Results: For patients with severe renal impairment (CCR < 30 mL/min), 150 mg q12 h achieved a >90% PTA against ESBL-producing organisms with an MIC of 0.03 mg/L. For moderate-to-severe renal impairment (30 ≤ CCR < 50 mL/min) and moderate renal impairment (50 ≤ CCR < 80 mL/min), 300 mg q8 h maintained a >90% PTA. For normal renal function (CCR ≥ 80 mL/min), 600 mg q8 h was required to achieve the target PTA. Conclusions: This first Japanese PK/PD analysis of TBPM in ESBL-producing UTIs provides evidence-based dosing recommendations across various renal function levels. TBPM, with appropriate renal-adjusted dosing, may offer an effective oral treatment option for patients who have traditionally required hospitalization for parenteral therapy. Full article
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18 pages, 321 KB  
Review
The Effect of Antibiotics on the Nervous System: Importance for Anesthesiology and Intensive Care
by Paweł Radkowski, Julia Oszytko, Kamil Sobolewski, Florian Trachte, Dariusz Onichimowski and Marta Majewska
Antibiotics 2025, 14(6), 622; https://doi.org/10.3390/antibiotics14060622 - 19 Jun 2025
Cited by 2 | Viewed by 7338
Abstract
Background: Due to the high prevalence of severe infections, antibiotics are frequently administered in anaesthesia and intensive care units. Despite their therapeutic efficacy, several antibiotics exhibit neurotoxic potential, resulting in central and peripheral neurological complications in patients. This review aims to summarise the [...] Read more.
Background: Due to the high prevalence of severe infections, antibiotics are frequently administered in anaesthesia and intensive care units. Despite their therapeutic efficacy, several antibiotics exhibit neurotoxic potential, resulting in central and peripheral neurological complications in patients. This review aims to summarise the current evidence on antibiotic-induced neurotoxicity, particularly in critical care settings. Methods: A comprehensive literature analysis was performed to assess the neurotoxic profiles, underlying mechanisms, and clinical manifestations associated with different antibiotic classes, including beta-lactams, fluoroquinolones, macrolides, aminoglycosides, and others. Results: Beta-lactam antibiotics (especially cephalosporins and carbapenems) are strongly associated with seizures, encephalopathy, and EEG abnormalities, mainly through GABAergic inhibition and mitochondrial dysfunction. Fluoroquinolones and macrolides can cause psychosis, insomnia, and neuropathy via NMDA activation and oxidative stress. Linezolid carries the risk of serotonin syndrome and optic neuropathy, while glycopeptides and aminoglycosides are primarily associated with ototoxicity. Risk factors include advanced age, renal or hepatic impairment, and high serum drug levels. Conclusions: The neurotoxic potential of antibiotics is a critical but under-recognised aspect of pharmacotherapy in intensive care. Improved awareness, pharmacovigilance, dose adjustment, and drug monitoring are crucial for mitigating adverse neurological effects. Full article
14 pages, 680 KB  
Article
Point-Prevalence Survey of Antimicrobial Use in Benin Hospitals: The Need for Antimicrobial Stewardship Programs
by Sarah Delfosse, Carine Laurence Yehouenou, Angèle Dohou, Dessièdé Ariane Fiogbe and Olivia Dalleur
Antibiotics 2025, 14(6), 618; https://doi.org/10.3390/antibiotics14060618 - 18 Jun 2025
Viewed by 1184
Abstract
Background: Antimicrobial resistance (AMR) is a public health concern worldwide, particularly in low-to-middle-income countries with few antimicrobial stewardship programs and few laboratories equipped for diagnosis. Methods: As point-prevalence surveys (PPSs) are a well-known tool for assessing antimicrobial use, we adjusted standardized Global-PPS for [...] Read more.
Background: Antimicrobial resistance (AMR) is a public health concern worldwide, particularly in low-to-middle-income countries with few antimicrobial stewardship programs and few laboratories equipped for diagnosis. Methods: As point-prevalence surveys (PPSs) are a well-known tool for assessing antimicrobial use, we adjusted standardized Global-PPS for use in two hospitals in Benin and included an analysis based on the 2021 WHO AWaRe classification. Results: Of the 450 patients enrolled, 148 received antimicrobials (AMs) (overall prevalence 32.9%), most of them orally (54.2%). Both hospitals had a high rate of Access and Watch antibiotics use, and both prescribed mainly metronidazole. In four prescriptions, hospital A used a non-recommended association of antibiotics, such as ceftriaxone + sulbactam and ofloxacin + ornidazole. While hospital A prescribed predominantly amoxicillin + clavulanic acid (19/92; 21%) and ceftriaxone (14/92; 15%), hospital B prescribed ampicillin (24/120; 20%) and cefuroxime (14/120; n = 12%). In hospital B, surgical antimicrobial prophylaxis (SAP) was suboptimal. While there were no single-dose prophylaxis prescriptions, all one-day prophylaxis (SP2) involved ampicillin for cesarean sections. In patients in intensive care units, prolonged prophylaxis (>1 day, SP3) accounted for all postoperative prescriptions. Conclusions: These findings highlight the critical need for implementing antimicrobial stewardship programs, expanding diagnostic laboratory capacity to minimize empirical prescribing, and strengthening medical student training to ensure quality and rational antibiotic use, thereby addressing the growing challenge of resistance in resource-limited settings. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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