Search Results (19)

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

Drug-induced nephrotoxicity is a common and serious problem in clinical practice. We conducted a systematic review of studies reporting nephrotoxicity events associated with antibiotics approved since 2018. The agents assessed included aztreonam/avibactam, cefepime/enmetazobactam, cefiderocol, ceftobiprole, contezolid, gepotidacin, imipenem/cilastatin/relebactam, lascufloxacin, lefamulin, levonadifloxacin, plazomicin, and sulbactam/durlobactam. Literature searches were conducted in PubMed, Scopus, Web of Science, and major pharmacovigilance databases (Vigibase, FAERS, EudraVigilance, EMA, FDA, NMPA, PMDA, and CDSCO) in May 2025, along with reference citation tracking. Studies were included if they reported safety or adverse event data. The risk of bias was assessed using validated tools in accordance with the study design. Out of 2105 potentially relevant records, 74 studies met inclusion criteria, comprising 52 clinical trials, 17 observational studies, 1 registry-based study, 3 case series, and 1 case report. Nephrotoxicity was rarely reported for any of the newly approved antibiotics. No renal adverse events were found in the available studies for aztreonam/avibactam, levonadifloxacin, and contezolid. Most studies were of moderate to high quality; two were classified as low quality. However, nephrotoxicity was inconsistently assessed, with variable definitions and methodologies used. Although current data suggest a low frequency of nephrotoxicity, limitations in study design and reporting preclude firm conclusions. There is a need for post-marketing studies to better characterize renal safety. Clinicians should remain vigilant and continue to monitor for and report renal-related adverse events. Full article

Background: Immune checkpoint inhibitors (ICIs) have significantly modified the management of metastatic cancers; however, their nephrotoxic potential remains underappreciated. While acute kidney injury (AKI) is a known immune-related adverse event, the subacute spectrum of kidney injury—termed acute kidney disease (AKD)—has not been adequately explored in this setting. Methods: We conducted a retrospective cohort study in 226 adult patients with metastatic solid tumors who received ICIs between 2017 and 2023 at a single tertiary care center. AKD was defined according to the 2024 “Kidney Disease: Improving Global Outcomes” (KDIGO) criteria. Multivariable logistic regression was used to identify predictors of AKD. Results: AKD occurred in 46 patients (20.4%) within 90 days of ICI initiation, with 16 (7.1%) experiencing persistent dysfunction beyond 30 days. Independent predictors of AKD included higher body surface area (OR 8.17, p = 0.03) and baseline use of nonsteroidal anti-inflammatory drugs (OR 29.74, p = 0.014). Baseline antibiotics showed a trend toward association (p = 0.054). Concurrent chemotherapy was associated with a trend toward protection. The predictive model showed good discrimination (AUC 0.778). No significant differences in other grade ≥2 immune-related adverse events were observed between the AKD and non-AKD groups. Conclusions: AKD is a frequent and underrecognized renal complication in patients receiving ICIs, with implications for both renal and oncological outcomes. Identifying high-risk patients and integrating longitudinal renal monitoring into immunotherapy care pathways may improve safety and treatment continuity. Full article

Piperacillin/tazobactam (PT), a widely utilized broad-spectrum antibiotic, has been associated with acute kidney injury (AKI). Although the precise mechanism remains uncertain, and most cases of PT-associated AKI are mild, this report describes a rare and severe complication of PT, which manifested as severe AKI with necrotizing glomerulonephritis requiring hemodialysis. A 42-year-old man was transferred to the nephrology clinic due to progressive deterioration of kidney function. Prior to the transfer, the patient had been diagnosed with appendicitis complicated by peritonitis and received intravenous PT for 8 days. Baseline kidney function was normal, but serum creatinine subsequently increased to 7.2 mg/dL. Hemodialysis was initiated to address metabolic acidosis and edema. Kidney biopsy revealed severe acute tubular injury and necrotizing glomerulonephritis. Steroid therapy was initiated based on the biopsy findings, and serum creatinine returned to normal levels after 4 weeks of treatment. This case demonstrates that severe AKI with necrotizing glomerulonephritis can occur after PT use. Prompt kidney biopsy and the timely initiation of immunosuppressive therapy are essential for a favorable outcome. Full article

In children with acute leukemia (AL), the mortality rate from Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infection (KPC-KpBSI) exceeds 50%, highest when active treatment is delayed. Neutropenic KPC-K. pneumoniae carriers are at high risk of KPC-KpBSI, and preemptive empiric antibiotic treatment (EAT) of febrile neutropenic episodes (FNEs) active against KPC-K. pneumoniae may reduce this mortality. We conducted an 8-year (2014–2021) retrospective observational study of 112 febrile neutropenic episodes (FNEs) in 32 children with AL who were KPC-K. pneumoniae carriers: standard EAT for 39 FNEs and active EAT for 73 FNEs (52 ceftazidime/avibactam (CAZAVI)-based and 21 colistin-based combinations, and 5 CAZAVI monotherapy). Successful outcomes (survival from FNE) were observed in 94%; seven were fatal, with four due to infectious causes. KPC-KpBSIs caused 10/112 FNEs, 10/20 g-negative BSIs, and 3 deaths. The mortality rate of KPC-KpBSI was 30%. Active EAT was successful in 97% of the FNEs, compared to 87% with standard EAT. All deaths from KPC-KpBSI occurred in patients who received standard EAT, while none occurred with active EAT. KPC-KpBSI mortality rate with initial inactive treatment was 60%. CAZAVI-based EAT was successful in all FNEs, with a higher success rate without any modification compared to colistin-based EAT, where nephrotoxicity occurred in 14%. Therefore, active EAT, mainly a CAZAVI-based combination, was effective, safe, and associated with low overall and KPC-KpBSI-related mortality. Full article

The objective was to evaluate the incidence of nephrotoxicity related to vancomycin and other anti-MRSA antibiotics (linezolid and daptomycin). Patients receiving any of these drugs between July 2014 and December 2020 at a tertiary hospital were included. Renal failure was evaluated using the acute renal injury (AKIN) system. Univariate analysis was conducted on the 5806 patients who were included. Among them, 1023 patients (17.62%) developed renal failure. The renal damage incidence was 14.74% (496/3365) for vancomycin, 19.13% (367/1918) for linezolid, and 30.59% (160/523) for daptomycin. Patients with lower basal glomerular filtration had a higher risk of AKIN. In the vancomycin group, the risk factors were high creatinine and urea serum basal values, duration of treatment (DOT), body mass index (BMI), ICU stay, age, and low CKDEPI and albumin levels. In the linezolid group, AKIN was linked to high creatinine and urea levels, BMI, age, and ICU stay and to low CKDEPI levels; for daptomycin, AKIN was associated with low CKDEPI and albumin levels and a long DOT. Patients with AKIN showed higher mortality rates. Vancomycin-associated nephrotoxicity remains a great concern. However, linezolid and daptomycin could also cause nephrotoxicity. Bearing in mind risk factors that may prompt nephrotoxicity in hospitalized patients taking anti-staphylococcal antibiotics will result in better pharmacotherapeutic management. Full article

Compounds that potentiate the activity of clinically available antibiotics provide a complementary solution, except for developing novel antibiotics for the rapid emergence of multidrug-resistant Gram-negative bacteria (GNB). We sought to identify compounds potentiating polymyxin B (PMB), a traditional drug that has been revived as the last line for treating life-threatening GNB infections, thus reducing its nephrotoxicity and heterogeneous resistance in clinical use. In this study, we found a natural product, sanguinarine (SA), which potentiated the efficacy of PMB against GNB infections. The synergistic effect of SA with PMB was evaluated using a checkerboard assay and time–kill curves in vivo and the murine peritonitis model induced by Escherichia coli in female CD-1 mice in vivo. SA assisted PMB in accelerating the reduction in bacterial loads both in vitro and in vivo, improving the inflammatory responses and survival rate of infected animals. The subsequent detection of the intracellular ATP levels, membrane potential, and membrane integrity indicated that SA enhanced the bacterial-membrane-breaking capacity of PMB. A metabolomic analysis showed that the inhibition of energy metabolism, interference with nucleic acid biosynthesis, and the blocking of L-Ara4N-related PMB resistance may also contribute to the synergistic effect. This study is the first to reveal the synergistic activity and mechanism of SA with PMB, which highlights further insights into anti-GNB drug development. Full article

This retrospective cross-sectional study aims to investigate the prevalence and seriousness of drug-induced nephrotoxicity and to identify clinical predictors intensifying the seriousness of nephrotoxicity. Adverse drug events (ADEs) reported to the Korean Adverse Event Reporting System Database (KAERS DB) from January 2012 to December 2021 were investigated. The association between the seriousness and the etiologic drug was estimated in reporting odds ratio (ROR) based on disproportionality analysis. Logistic regression was utilized to recognize predictors associated with serious nephrotoxicity. The majority of ADEs were reported in ages 30 to 59, and immunosuppressants were the most etiologic medications. ADEs involving antibiotics, including vancomycin (ROR 0.268; 95% CI 0.129–0.557), were less likely to be serious. More than 93% of cyclosporine-related ADEs were serious nephrotoxicity, whereas tacrolimus was less likely to report serious nephrotoxicity (ROR 0.356; 95% CI 0.187–0.680). The risk of serious nephrotoxicity was decreased with aging (ROR 0.955; 95% CI 0.940–0.972) while increased in women (OR 2.700; 95% CI 1.450–5.008). Polypharmacy was associated with increased risk of interstitial nephritis (OR 1.019; 95% CI 1.001–1.038). However, further studies investigating the impact of clinical practice on ADE incidences as well as clinical prognosis related to nephrotoxicity are obligated. Full article

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis. Full article

The objective was to compare clinical characteristics, outcomes, and economic differences in complicated urinary tract infections (cUTI) caused by extensively drug-resistant Pseudomonas aeruginosa (XDR P. aeruginosa) and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-K. pneumoniae). A retrospective study was conducted at a tertiary care hospital. Patients with XDR P. aeruginosa and ESBL-K. pneumoniae cUTIs were compared. The primary outcome was clinical failure at day 7 and at the end of treatment (EOT). Secondary outcomes: 30- and 90-day mortality, microbiological eradication, and economic cost. Two-hundred and one episodes were included, of which 24.8% were bloodstream infections. Patients with XDR P. aeruginosa cUTI more frequently received inappropriate empirical therapy (p < 0.001). Nephrotoxicity due to antibiotics was only observed in the XDR P. aeruginosa group (26.7%). ESBL-K. pneumoniae cUTI was associated with worse eradication rates, higher recurrence, and higher infection-related readmission. In multivariate analysis, XDR P. aeruginosa was independently associated with clinical failure on day 7 of treatment (OR 4.34, 95% CI 1.71–11.04) but not at EOT, or with mortality. Regarding hospital resource consumption, no significant differences were observed between groups. XDR P. aeruginosa cUTI was associated with worse early clinical cures and more antibiotic side effects than ESBL-K. pneumoniae infections. However, no differences in mortality or in hospitalization costs were observed. Full article

Doxorubicin (DOX) is a well-known and effective antineoplastic agent of the anthracycline family. But, multiple organ toxicities compromise its invaluable therapeutic usage. Among many toxicity types, nephrotoxicity is one of the major concerns. In recent years many approaches, including bioactive agents of natural origin, have been explored to provide protective effects against chemotherapy-related complications. α-Bisabolol is a naturally occurring monocyclic sesquiterpene alcohol identified in the essential oils of various aromatic plants and possesses a wide range of pharmacological properties such as antioxidant, anti-inflammatory, analgesic, cardioprotective, antibiotic, anti-irritant, and anticancer activities. The present study aimed to evaluate the effects of α-Bisabolol on DOX-induced nephrotoxicity in Wistar male albino rats. Nephrotoxicity was induced in rats by injecting a single dose of DOX (12.5 mg/kg, i.p.), and the test compound, α-Bisabolol (25 mg/kg) was administered intraperitoneally along with DOX as a co-treatment daily for 5 days. DOX-injected rats showed reduction in body weight along with a concomitant fall in antioxidants and increased lipid peroxidation in the kidney. DOX-injection also increased levels/expressions of proinflammatory cytokines namely tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and inflammatory mediators like inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and activated nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinases (MAPK) signaling in the kidney tissues. DOX also triggered apoptotic cell death, evidenced by the increased expression of pro-apoptotic markers like BCL2-Associated X Protein (Bax), cleaved caspase-3, caspase- 9, and cytochrome-C) and a decrease in the expressions of anti-apoptotic markers namely B-cell lymphoma 2 (Bcl2) and B-cell lymphoma-extra large (Bcl-xL) in the kidney. These biochemical alterations were additionally supported by light microscopic findings, which revealed structural alterations in the kidney. However, treatment with α-Bisabolol prevented body weight loss, restored antioxidants, mitigated lipid peroxidation, and inhibited the rise in proinflammatory cytokines, as well as favorably modulated the expressions of NF-κB/MAPK signaling and apoptosis markers in DOX-induced nephrotoxicity. Based on the results observed, it can be concluded that α-Bisabolol has potential to attenuate DOX-induced nephrotoxicity by inhibiting oxidative stress and inflammation mediated activation of NF-κB/MAPK signaling alongwith intrinsic pathway of apoptosis in rats. The study findings are suggestive of protective potential of α-Bisabolol in DOX associated nephrotoxicity and this could be potentially useful in minimizing the adverse effects of DOX and may be a potential agent or adjuvant for renal protection. Full article

Infective endocarditis (IE) is increasingly prevalent in the elderly, particularly due to the rising frequency of invasive procedures and intracardiac devices placed on these individuals. Several investigations have highlighted the unique clinical and echocardiographic characteristics, the microorganisms implicated, and the prognosis of IE in the elderly. In addition, the old population seems to be fairly diverse, ranging from healthy individuals with no medical history to patients with many ailments and those who are immobile. Furthermore, the therapy of IE in this group has not been well investigated, and worldwide recommendations do not propose tailoring the treatment approach to the patient’s functional state and comorbid conditions. A multicenter research study was designed as a retrospective study of hospitalized patients with infective endocarditis, aiming to examine the characteristics of elderly patients over 65 years old with infective endocarditis in relation to the antibiotic and antifungal treatments administered, as well as to quantify the incidence of treatment resistance, adverse effects, and mortality in comparison to patients younger than 65. Based on a convenience sampling method, we included in the analysis a total of 78 patients younger than 65 and 131 patients older than 65 years. A total of 140 patients had endocarditis on native valves and 69 patients had endocarditis on prosthetic valves. A significantly higher proportion of elderly patients had signs of heart failure on admission, and the mortality rate was significantly higher in the elderly population. A majority of infections had a vascular cause, followed by dental, maxillo-facial, and ENT interventions. The most common complications of IE were systemic sepsis (48.1% of patients older than 65 years vs. 30.8% in the younger group). The most frequent bacterium involved was Staphylococcus aureus, followed by Streptococcus spp. in a total of more than 50% of all patients. The most commonly used antibiotics were cephalosporins in 33.5% of cases, followed by penicillin in 31.2% and glycopeptides in 28.7%, while Fluconazole was the initial option of treatment for fungal endocarditis in 24.9% of cases. Heart failure at admission (OR = 4.07), the development of septic shock (OR = 6.19), treatment nephrotoxicity (OR = 3.14), severe treatment complications (OR = 4.65), and antibiotic resistance (OR = 3.24) were significant independent risk factors for mortality in the elderly patients. Even though therapeutic management was initiated sooner in the older patients, the associated complications and mortality rate remained significantly greater than those in the patients under 65 years old. Full article

The kidneys are often involved in adverse effects and toxicity caused by exposure to foreign compounds, chemicals, and drugs. Early predictions of these influences are essential to facilitate new, safe drugs to enter the market. However, in current drug treatments, drug-induced nephrotoxicity accounts for 1/4 of reported serious adverse reactions, and 1/3 of them are attributable to antibiotics. Drug-induced nephrotoxicity is driven by multiple mechanisms, including altered glomerular hemodynamics, renal tubular cytotoxicity, inflammation, crystal nephropathy, and thrombotic microangiopathy. Although the functional proteins expressed by renal tubules that mediate drug sensitivity are well known, current in vitro 2D cell models do not faithfully replicate the morphology and intact renal tubule function, and therefore, they do not replicate in vivo nephrotoxicity. The kidney is delicate and complex, consisting of a filter unit and a tubular part, which together contain more than 20 different cell types. The tubular epithelium is highly polarized, and maintaining cellular polarity is essential for the optimal function and response to environmental signals. Cell polarity depends on the communication between cells, including paracrine and autocrine signals, as well as biomechanical and chemotaxis processes. These processes affect kidney cell proliferation, migration, and differentiation. For drug disposal research, the microenvironment is essential for predicting toxic reactions. This article reviews the mechanism of drug-induced kidney injury, the types of nephrotoxicity models (in vivo and in vitro models), and the research progress related to drug-induced nephrotoxicity in three-dimensional (3D) cellular culture models. Full article

Urinary tract infections (UTIs) represent a health problem of the first magnitude since they affect large segments of the population, cause increased mortality and comorbidity, and have a high incidence of relapse. Therefore, UTIs cause a major socioeconomic concern. Current antibiotic treatments have various limitations such as the appearance of resistance to antibiotics, nephrotoxicity, and side effects such as gastrointestinal problems including microbiota alterations that contribute to increasing antibiotic resistance. In this context, Itxasol© has emerged, approved as an adjuvant for the treatment of UTIs. Designed with biomimetic principles, it is composed of arbutin, umbelliferon, and N-acetyl cysteine. In this work, we review the activities of these three compounds concerning the changes they produce in the expression of bacterial genes and those related to inflammation as well as assess how they are capable of affecting the DNA of bacteria and fungi. Full article

Background: Evaluating the options for antibiotic treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB)-associated pneumonia remains crucial. We compared the therapeutic efficacy and nephrotoxicity of two combination therapies, namely, colistin + carbapenem (CC) versus colistin + tigecycline (CT), for treating CR-GNB-related nosocomial pneumonia in critically ill patients. Methods: In this multicenter, retrospective, and cohort study, we recruited patients admitted to intensive care units and diagnosed with CR-GNB-associated nosocomial pneumonia. We divided the enrolled patients into CC (n = 62) and CT (n = 59) groups. After propensity score matching (n = 39), we compared the therapeutic efficacy by mortality, favorable outcome, and microbiological eradication and compared nephrotoxicity by acute kidney injury between groups. Results: There was no significant difference between the CC and CT groups regarding demographic characteristics and disease severities as assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and other organ dysfunction variables. Therapeutic efficacy was non-significantly different between groups in all-cause mortality, favorable outcomes, and microbiological eradication at days 7, 14, and 28; as was the Kaplan-Meier analysis of 28-day survival. For nephrotoxicity, both groups had similar risks of developing acute kidney injury, evaluated using the Kidney Disease Improving Global Outcomes criteria (p = 1.000). Conclusions: Combination therapy with CC or CT had similar therapeutic efficacy and risk of developing acute kidney injury for treating CR-GNB-associated nosocomial pneumonia in critically ill patients. Full article