Human-Derived collagen hydrogel as an antibiotic vehicle for topical treatment of bacterial biofilms.

The complexity of chronic wounds creates difficulty in effective treatments, leading to prolonged care and significant morbidity. Additionally, these wounds are incredibly prone to bacterial biofilm development, further complicating treatment. The current standard treatment of colonized superficial wounds, debridement with intermittent systemic antibiotics, can lead to systemic side-effects and often fails to directly target the bacterial biofilm. Furthermore, standard of care dressings do not directly provide adequate antimicrobial properties. This study aims to assess the capacity of human-derived collagen hydrogel to provide sustained antibiotic release to disrupt bacterial biofilms and decrease bacterial load while maintaining host cell viability and scaffold integrity. Human collagen harvested from flexor tendons underwent processing to yield a gellable liquid, and subsequently was combined with varying concentrations of gentamicin (50-500 mg/L) or clindamycin (10-100 mg/L). The elution kinetics of antibiotics from the hydrogel were analyzed using liquid chromatography-mass spectrometry. The gel was used to topically treat Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium perfringens in established Kirby-Bauer and Crystal Violet models to assess the efficacy of bacterial inhibition. 2D mammalian cell monolayers were topically treated, and cell death was quantified to assess cytotoxicity. Bacteria-enhanced in vitro scratch assays were treated with antibiotic-embedded hydrogel and imaged over time to assess cell death and mobility. Collagen hydrogel embedded with antibiotics (cHG+abx) demonstrated sustained antibiotic release for up to 48 hours with successful inhibition of both MRSA and C. perfringens biofilms, while remaining bioactive up to 72 hours. Administration of cHG+abx with antibiotic concentrations up to 100X minimum inhibitory concentration was found to be non-toxic and facilitated mammalian cell migration in an in vitro scratch model. Collagen hydrogel is a promising pharmaceutical delivery vehicle that allows for safe, precise bacterial targeting for effective bacterial inhibition in a pro-regenerative scaffold.

Regional antibiotic delivery for sternal wound infection prophylaxis a systematic review and meta-analysis of randomized controlled trials.

Despite evidence suggesting the benefit of prophylactic regional antibiotic delivery (RAD) to sternal edges during cardiac surgery, it is seldom performed in clinical practice. The value of topical vancomycin and gentamicin for sternal wound infections (SWI) prophylaxis was further questioned by recent studies including randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to comprehensively assess the safety and effectiveness of RAD to reduce the risk of SWI.We screened multiple databases for RCTs assessing the effectiveness of RAD (vancomycin, gentamicin) in SWI prophylaxis. Random effects meta-analysis was performed. The primary endpoint was any SWI; other wound complications were also analysed. Odds Ratios served as the primary statistical analyses. Trial sequential analysis (TSA) was performed.Thirteen RCTs (N = 7,719 patients) were included. The odds of any SWI were significantly reduced by over 50% with any RAD: OR (95%CIs): 0.49 (0.35-0.68); p < 0.001 and consistently reduced in vancomycin (0.34 [0.18-0.64]; p < 0.001) and gentamicin (0.58 [0.39-0.86]; p = 0.007) groups (psubgroup = 0.15). Similarly, RAD reduced the odds of SWI in diabetic and non-diabetic patients (0.46 [0.32-0.65]; p < 0.001 and 0.60 [0.44-0.83]; p = 0.002 respectively). Cumulative Z-curve passed the TSA-adjusted boundary for SWIs suggesting adequate power has been met and no further trials are needed. RAD significantly reduced deep (0.60 [0.43-0.83]; p = 0.003) and superficial SWIs (0.54 [0.32-0.91]; p = 0.02). No differences were seen in mediastinitis and mortality, however, limited number of studies assessed these endpoints. There was no evidence of systemic toxicity, sternal dehiscence and resistant strains emergence. Both vancomycin and gentamicin reduced the odds of cultures outside their respective serum concentrations' activity: vancomycin against gram-negative strains: 0.20 (0.01-4.18) and gentamicin against gram-positive strains: 0.42 (0.28-0.62); P < 0.001. Regional antibiotic delivery is safe and effectively reduces the risk of SWI in cardiac surgery patients.

Hierarchical antibiotic delivery system based on calcium phosphate cement/montmorillonite-gentamicin sulfate with drug release pathways.

Antibiotic-loaded calcium phosphate cement (CPC) has emerged as a promising biomaterial for drug delivery in orthopedics. However, there are problems such as the burst release of antibiotics, low cumulative release ratio, inappropriate release cycle, inferior mechanical strength, and poor anti-collapse properties. In this research, montmorillonite-gentamicin (MMT-GS) was fabricated by solution intercalation method and served as the drug release pathways in CPC to avoid burst release of GS, achieving promoted cumulative release ratios and a release cycle matched the time of inflammatory response. The results indicated that the highest cumulative release ratio and release concentration of GS in CPC/MMT-GS was 94.1 ± 2.8 % and 1183.05 µg/mL, and the release cycle was up to 504 h. In addition, the hierarchical GS delivery system was divided into three stages, and the kinetics followed the Korsmeyer-Peppas model, the zero-order model, and the diffusion-dissolution model, respectively. Meanwhile, the compressive strength of CPC/MMT-GS was up to 51.33 ± 3.62 MPa. Antibacterial results demonstrated that CPC/MMT-GS exhibited excellent in vitro long-lasting antibacterial properties to E. coli and S. aureus. Furthermore, CPC/MMT-GS promoted osteoblast proliferation and exhibited excellent in vivo histocompatibility. Therefore, CPC/MMT-GS has favorable application prospects in the treatment of bone defects with bacterial infections and inflammatory reactions.

Clinical safety and efficacy of a single-dose gentamicin, posaconazole and mometasone furoate otic suspension for treatment of canine otitis externa.

BACKGROUND: A single-dose, in-clinic, veterinary professional-administered treatment for canine otitis externa was developed to improve compliance and canine welfare. METHODS: This multicentre, controlled, examiner-masked, randomised field trial was conducted in 316 dogs over 42 days. Dogs were treated once, on day 0, with the investigational product containing gentamicin, posaconazole and mometasone furoate (Mometamax Ultra [MU]) or twice (days 0 and 7) with a control product containing florfenicol, terbinafine and betamethasone acetate (CP). The primary endpoint was a composite otitis index score of 4 or less (of 12) on day 14 and 3 or less (of 12) on day 28. RESULTS: On day 28, treatment success was recorded in 128 of 143 MU-treated dogs (89.5%), significantly non-inferior to 116 of 133 (87.2%) CP-treated dogs (Farrington-Manning test, Z = 4.1351, p < 0.0001). For mixed cultures of Staphylococcus pseudintermedius and Malassezia pachydermatis, there was 100% treatment success in MU-treated dogs (n = 33), significantly non-inferior to 90.2% (37 of 41) in CP-treated dogs (Farrington-Manning test, Z = 3.1954, p = 0.0007). LIMITATIONS: Efficacy in chronic otitis externa cases was not investigated. Cytology was not used to aid in diagnosis or for identification of secondary pathogens. CONCLUSION: This unique combination, single-dose product is safe and effective in dogs with otitis externa. It offers enhanced compliance, canine welfare and quality of life by eliminating the owner burden of treating this painful condition.

The Effect of 3-Dimensional-Printed Sequential Dual Drug-Releasing Patch on the Capsule Formation Around the Silicone Implant in a Rat Model.

BACKGROUND: Implant-based breast reconstruction is associated with increased risk of early infection and late-stage capsular contracture. OBJECTIVES: We evaluated the feasibility of a dual drug-releasing patch that enabled the controlled delivery of antibiotics and immunosuppressants in a temporally and spatially appropriate manner to the implant site. METHODS: The efficacy of a dual drug-releasing patch, which was 3-dimensional-printed (3D-printed) with tissue-derived biomaterial ink, was evaluated in rats with silicone implants. The groups included implant only (n = 10); implant plus bacterial inoculation (n = 14); implant, bacterial inoculation, and patch loaded with gentamycin placed on the ventral side of the implant (n = 10), and implant, bacterial inoculation, and patch loaded with gentamycin and triamcinolone acetonide (n = 9). Histologic and immunohistochemical analyses were performed 8 weeks after implantation. RESULTS: The 2 drugs were sequentially released from the dual drug-releasing patch and exhibited different release profiles. Compared to the animals with bacterial inoculation, those with the antibiotic-only and the dual drug-releasing patch exhibited thinner capsules and lower myofibroblast activity and inflammation, indicating better tissue integration and less foreign body response. These effects were more pronounced with the dual drug-releasing patch than with the antibiotic-only patch. CONCLUSIONS: The 3D-printed dual drug-releasing patch effectively reduced inflammation and capsule formation in a rat model of silicone breast reconstruction. The beneficial effect of the dual drug-releasing patch was better than that of the antibiotic-only patch, indicating its therapeutic potential as a novel approach to preventing capsular contracture while reducing concerns of systemic side effects.

Reducing the incidence of surgical site infection after ventral hernia repair: Outcomes from the RINSE randomized control trial.

BACKGROUND: The clinical and financial impact of surgical site infection after ventral hernia repair is significant. Here we investigate the impact of dual antibiotic irrigation on SSI after VHR. METHODS: This was a multicenter, prospective randomized control trial of open retromuscular VHR with mesh. Patients were randomized to gentamicin â€‹+ â€‹clindamycin (G â€‹+ â€‹C) (n â€‹= â€‹125) vs saline (n â€‹= â€‹125) irrigation at time of mesh placement. Primary outcome was 30-day SSI. RESULTS: No significant difference was seen in SSI between control and antibiotic irrigation (9.91 vs 9.09 â€‹%; p â€‹= â€‹0.836). No differences were seen in secondary outcomes: SSO (11.71 vs 13.64 â€‹%; p â€‹= â€‹0.667); 90-day SSO (11.1 vs 13.9 â€‹%; p â€‹= â€‹0.603); 90-day SSI (6.9 vs 3.8 â€‹%; p â€‹= â€‹0.389); SSIPI (7.21 vs 7.27 â€‹%, p â€‹= â€‹0.985); SSOPI (3.6 vs 3.64 â€‹%; p â€‹= â€‹0.990); 30-day readmission (9.91 vs 6.36 â€‹%; p â€‹= â€‹0.335); reoperation (5.41 vs 0.91 â€‹%; p â€‹= â€‹0.056). CONCLUSION: Dual antibiotic irrigation with G â€‹+ â€‹C did not reduce the risk of surgical site infection during open retromuscular ventral hernia repair.

Antibiotic cement-coated rigid locked nails in infected femoral and tibial nonunion. Reoperation rates of commercial versus custom-made nails.

INTRODUCTION: The objective of this study is to assess bone union, infection control, and reoperation rates in a series of patients with infected femoral or tibial nonunion treated with antibiotic-cement-coated rigid nails and to compare the results obtained with custom-made nails versus commercial nails. METHODS: We retrospectively analyzed a series of consecutive patients with infected nonunion of the femur or the tibia treated with antibiotic-cement-coated rigid nails between January 2010 and 2020. We assessed patients' distinctive characteristics, initial injury, type of nail used (custom-made nail with vancomycin or commercial nail with gentamicin), success rate (bone union + infection control), reoperation rate, and failure rate. Comparative analyses were conducted between reoperated and non-reoperated patients regarding the type of nail used. A multivariate regression analysis was performed to assess the risk variables that impacted reoperation rates. RESULTS: We included 54 patients with 22 (40.74%) infected femoral nonunions and 32 (59.25%) tibial nonunions, who were treated with 38 (70.37%) custom-made antibiotic-cement coated nails and 16 (29.62%) commercial nails. Bone union and infection control were achieved in 51 (94.44%) cases. The reoperation rate was 40.74% (n = 22), and the failure rate was 5.55% (n = 3). The use of custom-made nails was associated with a higher risk of reoperation (Odds Ratio 4.71; 95% Confidence Interval 1.10 - 20.17; p = 0.036). CONCLUSION: Antibiotic-cement-coated nails reached a 94.44% success rate. Nails manufactured in the OR coated with vancomycin cement were associated with a higher risk of reoperation than commercial nails loaded with gentamicin cement. LEVEL OF EVIDENCE: III comparative, observational, non-randomized.

Meningitis por Listeria: administración de gentamicina intraventricular y monitorización de concentraciones en líquido cefalorraquídeo / Listeria meningitis: administration of intraventricular gentamicin and monitoring of concentrations in cerebrospinal fluid

La Listeria continúa siendo una posible etiología de meningitis bacteriana en nuestro medio, siendo causa más frecuente en neonatos, ancianos o pacientes inmunodeprimidos. Debido a la gravedad y la mortalidad asociada, resulta de gran interés disponer de nuevas herramientas que permitan un manejo clínico y farmacológico más eficaz.Presentamos un caso de meningitis por Listeria que ingresa en la Unidad de Cuidados Intensivos. Dada la escasa penetración de la gentamicina en el sistema nervioso central y siendo ésta uno de los tratamientos de elección en las guías clínicas de referencia, se decide la administración de gentamicina intraventricular llevando a cabo una monitorización de concentraciones de gentamicina en líquido cefalorraquídeo (LCR).Debido a la alta variabilidad farmacocinética del paciente crítico, la monitorización de concentraciones en LCR de gentamicina tras su administración intraventricular puede resultar de gran utilidad para asegurar el alcance de concentraciones de fármaco que permitan una mayor eficacia del tratamiento. (AU)

Listeria is currently a possible etiology of bacterial meningitis in our society, being one more frequent cause in neonates, elderly or immunosuppressed patients. Due to the severity and mortality associated, it is therefore very useful to have new tools that allow a more effective clinical and pharmacological management.We present a case of Listeria meningitis admitted to the Intensive Care Unit. Given the low penetration of gentamicin into the central nervous system and being one of the treatments of choice in the clinical reference guidelines, the administration of intraventricular gentamicin was decided by monitoring the concentrations of gentamicin in cerebrospinal fluid (CSF).Due to the high pharmacokinetic variability of the critically ill patient, monitoring CSF concentrations of gentamicin after intraventricular administration can be very useful to ensure the achievement of drug concentrations that allow greater treatment efficacy. (AU)

Antibacterial Activities and Synergistic Interaction of Citrus Essential Oils and Limonene with Gentamicin against Clinically Isolated Methicillin-Resistant Staphylococcus aureus.

Citrus reticulata Blanco and Citrus aurantifolia are the edible plants which contain several biological properties including antibacterial activity. The aims of the present study were to determine the chemical compositions and evaluate antibacterial activities of citrus essential oils extracted from the fruit peels of C. reticulata (CREO) and C. aurantifolia (CAEO), alone and in combination with gentamicin, against a panel of clinically isolated methicillin-resistant S. aureus (MRSA) (n = 40) and methicillin-susceptible S. aureus (MSSA) (n = 45). Gas chromatography-mass spectrometry analysis revealed that 12 and 25 compounds were identified in CREO and CAEO with the most predominant compound of limonene (62.9-72.5%). The antibacterial activities were determined by agar disk diffusion and resazurin-based microdilution methods. The results found that almost all MRSA isolates were resistant to ciprofloxacin, erythromycin, and clindamycin, and some isolates were resistant to gentamicin. CREO and CAEO exhibited inhibitory effects toward clinical isolates (MIC: 1.0-32.0 and 8.0-32.0 mg/mL, respectively), with a similar trend to limonene (MIC: 1.0-32.0 mg/mL). However, the higher antibacterial effects were found in CREO and limonene when compared to CAEO (p < 0.01). In combination effect, the results showed the synergistic interaction of gentamicin with CREO and limonene on the MRSA and MSSA isolates (FIC indexes: 0.012-0.258 and 0.012-0.375), but that interaction of gentamicin with CAEO was observed only on MRSA (FIC index: 0.012-0.016). These findings demonstrated the potential of these citrus essential oils as natural antibacterial agents that may contribute to reduce the emerging of antimicrobial-resistant bacteria.

Population Pharmacokinetics and Dosing Optimization of Gentamicin in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

PURPOSE: Appropriate gentamicin dosing in continuous renal replacement therapy (CRRT) patients remains undefined. This study aimed to develop a population pharmacokinetic (PK) model of gentamicin in CRRT patients and to infer the optimal dosing regimen for gentamicin. METHODS: Fourteen CRRT patients dosed with gentamicin were included to establish a population PK model to characterize the variabilities and influential covariates of gentamicin. The pharmacokinetic/pharmacodynamic (PK/PD) target attainment and risk of toxicity for different combinations of gentamicin regimens (3-7 mg/kg q24h) and CRRT effluent doses (30-50 mL/h/kg) were evaluated by Monte Carlo simulation. The probability of target attainment (PTA) was determined for the PK/PD indices of the ratio of drug peak concentration/minimum inhibitory concentration (Cmax/MIC > 10) and the ratio of area under the drug concentration-time curve/MIC over 24 h (AUC0-24h/MIC > 100), and the risk of toxicity was estimated by drug trough concentration thresholds (1 and 2 mg/L). RESULTS: A one-compartment model adequately described the PK characteristics of gentamicin. Covariates including body weight, age, gender, and CRRT modality did not influence the PK parameters of gentamicin based on our dataset. All studied gentamicin regimens failed to achieve satisfactory PTAs for pathogens with an MIC ≥2 mg/L. A good balance of PK/PD target attainment and risk of toxicity (>2 mg/L) was achieved under 7 mg/kg gentamicin q24h and 40 mL/kg/h CRRT dose for an MIC ≤1 mg/L. CRRT dose intensity had a significant impact on the target attainment of AUC0-24h/MIC >100 and risk of toxicity. CONCLUSION: A combination of 7 mg/kg gentamicin q24h and 40 mL/kg/h CRRT dose might be considered as a starting treatment option for CRRT patients, and drug monitoring is required to manage toxicity.

Differential Ubiquitination as an Effective Strategy Employed by the Blood-Brain Barrier for Prevention of Bacterial Transcytosis.

The protective mechanisms of blood-brain barrier (BBB) prohibiting entry of pathogens into central nervous system (CNS) are critical for maintenance of brain homeostasis. These include various intracellular defense mechanisms that are vital to block transcytosis of neurotropic pathogens into the CNS. However, mechanistic details of coordination between these defense pathways remain unexplored. In this study, we established that BBB-driven ubiquitination acts as a major intracellular defense mechanism for clearance of Streptococcus pneumoniae, a critical neurotropic pathogen, during transit through BBB. Our findings suggest that the BBB employs differential ubiquitination with either K48- or K63-ubiquitin (Ub) chain topologies as an effective strategy to target S. pneumoniae toward diverse killing pathways. While K63-Ub decoration triggers autophagic killing, K48-Ub directs S. pneumoniae exclusively toward proteasomes. Time-lapse fluorescence imaging involving proteasomal marker LMP2 revealed that in the BBB, the majority of the ubiquitinated S. pneumoniae was cleared by proteasome. Fittingly, inhibition of proteasome and autophagy pathway led to accumulation of K48-Ub- and K63-Ub-marked S. pneumoniae, respectively, and triggered significant increases in intracellular S. pneumoniae burden. Moreover, genetic impairment of either K48- or K63-Ub chain formation demonstrated that although both chain types are key in disposal of intracellular S. pneumoniae, K48-Ub chains and subsequent proteasomal degradation have more pronounced contributions to intracellular S. pneumoniae killing in the BBB. Collectively, these observations, for the first time, illustrated a pivotal role of differential ubiquitination deployed by BBB in orchestrating a symphony of intracellular defense mechanisms for interception and degradation of S. pneumoniae, blocking its entry into the brain, which could be exploited to prevent bacterial CNS infections. IMPORTANCE The blood-brain barrier (BBB) represents a unique cellular barrier that provides structural integrity and protection to the CNS from pathogen invasion. Recently, ubiquitination, which is key for cellular homeostasis, was shown to be involved in pathogen clearance. In this study, we deciphered that the BBB deploys differential ubiquitination as an effective strategy to prevent S. pneumoniae trafficking into the brain. The different ubiquitin chain topologies formed on S. pneumoniae dictated the selection of downstream degradative pathways, namely, autophagy and proteasomes, among which the contribution of the proteasomal system in S. pneumoniae killing is more pronounced. Overall our study revealed how the BBB deploys differential ubiquitination as a strategy for synchronization of various intracellular defense pathways, which work in tandem to ensure the brain's identity as an immunologically privileged site.

Gentamicin-Containing Collagen Implant May Reduce Surgical Site Infections After Open Infrainguinal Arterial Revascularization.

BACKGROUND: Deep-space surgical site infections carry significant morbidity and mortality. The evidence for gentamicin-containing collagen implants at reducing surgical site infections in open infrainguinal arterial surgery is limited. This study examined whether gentamicin-containing collagen implants reduces 30-day surgical site infections and their severity following open infrainguinal arterial surgery. METHODS: A retrospective observational cohort study that included all patients undergoing infrainguinal arterial bypass or endarterectomy between November 2015 and March 2019 at a single tertiary vascular unit. Patients with contaminated/infected surgical fields, surgical wounds treated with negative pressure therapy, or the usage of antimicrobial implants and dressings other than Collatamp GⓇ (Aralez Pharmaceuticals, Canada) were excluded. Patients with gentamicin-containing collagen implants placed abutting vasculature were compared against patients without gentamicin-containing collagen implants. Outcomes included the rate of surgical site infections and their severity within 30 days after the operation. RESULTS: In 159 procedures (mean age 67.7 years, 74.8% male, 33.3% diabetic, 16.4% chronic renal failure, 25.2% anticoagulated postoperatively, 32.7% with prosthetic implants), 55 (34.6%) procedures received gentamicin-containing collagen implants. There were significantly more males (85.5% vs. 69.2%; P = 0.025), higher rates of obesity (41.8% vs. 26.0%; P = 0.041), and hyperlipidemia (65.5% vs. 49.0%; P = 0.048) in the gentamicin-containing collagen implant group. In total, 6 (3.8%) procedures developed deep-space surgical site infections (1 with gentamicin-containing collagen implant, 5 without) and 13 (8.2%) had severe surgical site infections that required re-intervention (1 with gentamicin-containing collagen implant, 12 without). On logistic regression analysis, the absence of gentamicin-containing collagen implants statistically significantly increased the odds of overall surgical site infections (OR = 2.50; 95% CI 1.01 - 6.19; P = 0.047). There was no statistically significant difference in the odds of deep-space surgical site infections or the severity and need for reintervention of surgical site infections. CONCLUSIONS: This is the first study that examined the effect of gentamicin-containing collagen implants on the severity of surgical site infections in vascular surgery. Gentamicin-containing collagen implants may reduce the odds of overall surgical site infections. It did not reduce the odds of deep-space surgical site infections or the severity and reintervention rate of surgical site infections following infrainguinal arterial revascularization. Larger studies are required to achieve adequate power to assess for these outcomes.

Biomarkers in neonates receiving potential nephrotoxic drugs.

OBJECTIVE: Novel biomarkers, such as kidney injury molecule-1 (KIM-1), cystatin, and neutrophil gelatinase-associated lipocalin (NGAL) were shown to predict acute kidney injury (AKI) earlier than serum creatinine in critically ill. We carried out the present study to evaluate these biomarkers in addition to conventional in our neonates. PATIENTS AND METHODS: We recruited 70 neonates of various gestational age groups receiving one or more potential nephrotoxic drug/s. Daily urine samples were collected for estimating KIM-1, cystatin, and NGAL. Modified neonatal kidney disease improving global outcomes (mKDIGO) classification was used in defining AKI. RESULTS: A significant trend in increased urine concentrations of KIM-1, cystatin, and NGAL were observed as we proceed from term to preterm categories. Strong positive correlation was observed between urine albumin and urine albumin creatinine ratio (ACR), and strong negative correlations between urine creatinine and urine cystatin, and between urine creatinine with urine NGAL. A moderate positive correlation was observed between urine KIM-1 and urine cystatin, between urine KIM-1 and urine NGAL, and between urine cystatin and urine NGAL; and a moderate negative correlation was observed between urine creatinine and urine KIM-1. Seven neonates met the mKDIGO criteria for AKI and ROC plot revealed that baseline KIM-1 and NGAL can significantly predict possible drug-induced AKI in neonates. CONCLUSIONS: Urine KIM-1, cystatin, and NGAL are significantly correlated with several other conventional biomarkers that reflect renal function in critically ill neonates. Baseline urine KIM-1 and NGAL concentrations can predict the AKI following potential nephrotoxic drug use in this population.

Changes in the gut microbiota diversity of brown frogs (Rana dybowskii) after an antibiotic bath.

BACKGROUND: Captive amphibians frequently receive antibiotic baths to control bacterial diseases. The potential collateral effect of these antibiotics on the microbiota of frogs is largely unknown. To date, studies have mainly relied on oral administration to examine the effects of antibiotics on the gut microbiota; in contrast, little is known regarding the effects of bath-applied antibiotics on the gut microbiota. The gut microbiota compositions of the gentamicin, recovery, and control groups were compared by Illumina high-throughput sequencing, and the functional profiles were analysed using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Furthermore, the relationship between the structure and predicted functional composition of the gut microbiota was determined. RESULTS: The alpha diversity indices were significantly reduced by the gentamicin bath, illustrating that this treatment significantly changed the composition of the gut microbiota. After 7 days, the gut microbiota of the recovery group was not significantly different from that of the gentamicin group. Forty-four indicator taxa were selected at the genus level, comprising 42 indicators representing the control group and 2 indicators representing the gentamicin and recovery groups. Potential pathogenic bacteria of the genera Aeromonas, Citrobacter, and Chryseobacterium were significantly depleted after the gentamicin bath. There was no significant positive association between the community composition and functional composition of the gut microbiota in the gentamicin or control frogs, indicating that the functional redundancy of the gut bacterial community was high. CONCLUSIONS: Gentamicin significantly changed the structure of the gut microbiota of R. dybowskii, and the gut microbiota exhibited weak resilience. However, the gentamicin bath did not change the functional composition of the gut microbiota of R. dybowskii, and there was no significant correlation between the structural composition and the functional composition of the gut microbiota.

The therapeutic effect of Cilastatin on drug-induced nephrotoxicity: a new perspective.

OBJECTIVE: By creating nephrotoxicity models with cisplatin, vancomycin, and gentamicin in HK-2 (human renal proximal tubule cell) and HEK293T (human embryonic kidney epithelial cells) cell lines, we aimed to evaluate the effect of cilastatin on recovery of cell damage after toxicity had occurred. MATERIALS AND METHODS: In the first phase of the study, the doses of cisplatin, vancomycin, and gentamicin (50% inhibitive concentration; IC50) were determined. In the second phase, the effective dose of cilastatin against these drugs was determined, and IC50 doses of nephrotoxic agents were administered simultaneously. In the third phase of our study, to evaluate the possible therapeutic effect of cilastatin after toxicity had occurred, the analyses of cell viability, apoptosis, oxidative stress, expression of kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) were performed. RESULTS: In the second phase of the study, it was observed that cilastatin increased cell viability when treated simultaneously with a nephrotoxic agent. In the third phase, cilastatin provided a significant increase in cell viability. After treatment with each agent for 24 hours, we determined that adding cilastatin to the medium had an effect on the recovery of cell damage by increasing cell viability and reducing apoptosis and oxidative stress. The expression of KIM-1 and NGAL increased when nephrotoxicity occurred and decreased with the addition of cilastatin to the medium. CONCLUSIONS: The findings of the study suggest that cilastatin may have a healing effect after the development of nephrotoxicity.

Preparation of Cross-linked Chitosan Quaternary Ammonium Salt Hydrogel Films Loading Drug of Gentamicin Sulfate for Antibacterial Wound Dressing.

Hydrogels, possessing high biocompatibility and adaptability to biological tissue, show great usability in medical applications. In this research, a series of novel cross-linked chitosan quaternary ammonium salt loading with gentamicin sulfate (CTMCSG) hydrogel films with different cross-linking degrees were successfully obtained by the reaction of chitosan quaternary ammonium salt (TMCS) and epichlorohydrin. Fourier transform infrared spectroscopy (FTIR), thermal analysis, and scanning electron microscope (SEM) were used to characterize the chemical structure and surface morphology of CTMCSG hydrogel films. The physicochemical property, gentamicin sulphate release behavior, cytotoxicity, and antibacterial activity of the CTMCSG against Escherichia coli and Staphylococcus aureus were determined. Experimental results demonstrated that CTMCSG hydrogel films exhibited good water stability, thermal stability, drug release capacity, as well as antibacterial property. The inhibition zone of CTMCSG hydrogel films against Escherichia coli and Staphylococcus aureus could be up to about 30 mm. Specifically, the increases in maximum decomposition temperature, mechanical property, water content, swelling degree, and a reduction in water vapor permeability of the hydrogel films were observed as the amount of the cross-linking agent increased. The results indicated that the CTMCSG-4 hydrogel film with an interesting physicochemical property, admirable antibacterial activity, and slight cytotoxicity showed the potential value as excellent antibacterial wound dressing.

Dual Topical Antibiotic Application Prior to Sternotomy Closure Reduces Sternal Wound Infection Rates: A Simple Solution to a Grave Morbidity.

BACKGROUND: A significant cohort of patients who undergo cardiac surgery suffer from diabetes and atherosclerosis. These patients have impaired tissue perfusion, hence a reduction in antibiotic concentration in the subcutaneous tissues at the side of the mammary artery harvesting. Topical application of gentamicin and vancomycin before wound closure broadens the antibiotic spectrum and reduces the incidence of deep sternal wound infection. In this article, we compare the use of single versus dual application of vancomycin and/or gentamicin in sternotomy wounds in a single tertiary center. METHODS: An observational cohort analysis with three sequential patient groups (N = 2550) was performed at Ain Shams University Hospital in Cairo. A control group (N = 850), vancomycin only group (N = 850), and vancomycin plus gentamicin group (N = 850) were included in the study, during the three-year period from January 2017 to December 2019. Patients who had minimal access surgery were excluded from this study. The presence of an infected postoperative sternotomy wound was assessed in all patients. RESULTS: The presence of an infected sternotomy wound (El Oakley class 2B) was present in 38 patients (4.5%) in the control group, in 19 patients (2.2%) in the vancomycin group, and in nine patients (1.1%) in the dual antibiotic group, respectively (P < .001). In contrast to the usual, we had a proliferous growth of gram-negative organisms 29 (3.4%) in the control group, 10 (1.2%) in the vancomycin group, and five (0.6%) in the dual antibiotic group, respectively (P < .001). CONCLUSION: Deep sternal wound infection is a major cause of post-cardiac surgery morbidity and prolonged hospital stay. Adding the simple step of topical application of vancomycin and gentamicin to the sternotomy wound at the end of the procedure appeared to significantly reduce deep wound infection rates.

Facile surface functional polyetheretherketone with antibacterial and immunoregulatory activities for enhanced regeneration toward bacterium-infected bone destruction.

Existing biologically inert or unmodified implants to treat infectious bone defects or osteomyelitis still cannot effectively solve bacterial infection and osseointegration. In this work, a simple co-deposition strategy was developed to modify porous polyetheretherketone (PEEK) with improved antibacterial activity and controllable immunoregulatory ability. After PEEK was treated by H2SO4 to obtain porous PEEK (SPEEK), the self-polymerization of dopamine was operated on SPEEK in the solution of dopamine and gentamicin sulfate (GS) to prepare polydopamine (pDA) and GS layer-modified SPEEK (labeled as SPEEK-pDA-GS). The morphology, surface property, and molecular structure of SPEEK-pDA-GS were investigated. Besides the antibacterial property of SPEEK-pDA-GS ascribed to the successful immobilization of GS, SPEEK-pDA-GS exhibited promoted osseointegration through the results of mineralization, alkaline phosphatase (ALP) levels and osteogenic gene expression. Furthermore, the evaluation of the cell proliferation suggested that SPEEK-pDA-GS possessed the biocompatibility and the immunoregulatory ability that induced macrophages to anti-inflammatory M2 phenotype. Using rat as model, in vivo results containing X-ray, µ-CT, immunohistochemistry, and pathological analysis showed the excellent healing effect of SPEEK-pDA-GS on bone defect with infection with biological safety. This work illustrates a new insight into the simple and effective modification of PEEK and other implants with antibacterial, immunoregulatory, and osseointegration abilities for clinical requirement.

Gentamicin Dosing in Neonates with Normal Renal Function: Trough and Peak Levels.

BACKGROUND AND OBJECTIVE: Gentamicin is commonly used in neonates, and it requires drug concentration monitoring. The objective of this study was to determine the extent of high trough (≥ 2 mg/l) and therapeutic peak serum gentamicin concentrations (5-12 mg/l) using our current gentamicin regimen and to adjust the dosing regimen accordingly and reassess. METHODS: This was a prospective cohort study of neonates, with normal renal function, who were prescribed gentamicin. Group 1: March 2014-July 2017-gentamicin intravenous (IV) 2.5 mg/kg given every 36 h if < 30 weeks gestational age (GA) and every 24 h if ≥ 30 weeks GA; Group 2: August 2019-February 2020-gentamicin IV 3.5 mg/kg given every 36 h if < 30 weeks GA and every 24 h if ≥ 30 weeks GA. We assessed the number of neonates with aberrant trough and peak serum gentamicin concentrations. RESULTS: Forty-eight neonates < 30 weeks GA and 34 ≥ 30 weeks GA were given 2.5 mg/kg gentamicin. Eleven (23%) neonates < 30 weeks GA and four (13%) ≥ 30 weeks GA had subtherapeutic peak concentrations (< 5 mg/l); none had supratherapeutic (> 12 mg/l) or toxic trough concentrations (≥ 2 mg/l). Forty-four neonates < 30 weeks GA and 54 ≥ 30 weeks GA were given 3.5 mg/kg gentamicin. Eighty-four (86%) had non-toxic trough concentrations (< 2 mg/l). One (1%) < 30 weeks GA neonate had subtherapeutic (< 5 mg/l) and one (1%) neonate ≥ 30 weeks GA had supratherapeutic (> 12 mg/l) peak concentrations. CONCLUSIONS: Gentamicin regimen of 2.5 mg/kg given every 36 h for neonates < 30 weeks GA and every 24 h for neonates ≥ 30 weeks GA was suboptimal at achieving therapeutic gentamicin peak. Increasing the dosage to 3.5 mg/kg achieved therapeutic peak concentrations in 98% and non-toxic trough concentrations in 86% of all neonates (prior to dose interval adjustment).