A Case of Severe Acute Kidney Injury Due to an Antibiotic-Loaded Cement Spacer for Infected Knee Arthroplasty.

The treatment for periprosthetic joint infection frequently involves the placement of a high-dose antibiotic-loaded bone cement spacer (ALCS) into the debrided joint. Typical antibiotics in the spacer include aminoglycosides and vancomycin. It has been believed that systemic absorption of intraarticular antibiotics would be low and early experience suggested that the risk of acute kidney injury (AKI) from ALCS was minimal. However, recent case reports and case series have suggested a risk of acute kidney injury due to antibiotic absorption, though confounding factors are common. We report a case of severe AKI requiring hemodialysis with extremely high systemic tobramycin levels after the placement of an ALCS with increased dosing of antibiotics after previous failure to resolve a periprosthetic joint infection with a prior ALCS. There was no concomitant use of intravenous nephrotoxic antibiotics nor other confounding factors. Despite dialysis, the patient needed urgent removal of the ALCS to control tobramycin levels with subsequent resolution of the AKI. This case highlights the potentially serious nephrotoxicity of ALCS's, the importance of antibiotic type and dosing, and the value of close monitoring after ALCS placement, especially in a patient with chronic kidney disease.

The efficacy of tobramycin dexamethasone combined with pranoprofen in middle-aged and elderly post-cataract patients and the value of improving inflammatory factor levels.

OBJECTIVE: To analyze the effect of tobramycin dexamethasone combined with pranoprofen on middle-aged and elderly patients after cataract surgery. METHODS: In this retrospective study, the clinical data from 108 middle-aged and elderly patients who had cataract surgery in the Second Hospital of Longyan between January 2021 and December 2023 were collected. The patients were divided into two groups based on treatment methods, a control group (n=54) that received tobramycin dexamethasone treatment, and an observation group (n=54) that treated with additional pranoprofen. The treatment effects in the two groups were compared. RESULTS: Significant differences were observed between the groups at 1 day, 1 week, 3 weeks, and 5 weeks post-treatment in terms of ocular symptom scores, signs scores, and intraocular pressure levels (all P < 0.05). The observation group demonstrated lower levels of inflammatory markers post-treatment (P < 0.05). Additionally, at 1 week, 3 weeks and 5 weeks after treatment, significant differences were noted in anterior chamber flare value, best-corrected visual acuity (BCVA), macular center thickness, degree of corneal edema, and posterior lens capsular opacity grading scores (all P < 0.05). The incidence of increased intraocular pressure and conjunctival congestion was 3.7% in the observation group, slightly lower than 7.41% in the control group (P > 0.05). CONCLUSION: The combination of pranoprofen and tobramycin dexamethasone can improve the inflammatory reaction, ocular symptoms, anterior chamber flare value, macular center thickness, corneal oedema, and clarity of the posterior lens capsule in middle-aged and elderly cataract patients. This regimen also helps restore intraocular pressure and visual acuity of the patients, with relatively low adverse reactions, indicating an ideal clinical outcome.

Practice preference and evidence analysis on topical use of tobramycin powder in lumbar spine surgery: A Multi-National AO spine survey with systematic review of the literature.

Study design: Cross-sectional study with systematic review of literature. Objective: There is an increasing interest in the topical use of antibiotics to prevent infection following spine surgery. To extend the antibiotic coverage to the gram-negative spectrum, the usage of tobramycin powder is being considered. We surveyed to analyze the current practice preference on the use of topical tobramycin in lumbar spine surgery and also aimed to analyze the literature for current evidence on the same. Methods: A multinational cross-sectional survey was conducted among AO Spine members worldwide to understand the use of topical tobramycin in 1 or 2-level open lumbar fusion surgeries. Also, an independent systematic review of four scientific databases (PubMed, Scopus, clinicaltrials.gov, Web of Science) was performed by two authors to identify relevant articles in adherence to the preferred reporting in systematic reviews and meta-analysis (PRISMA) guidelines. Studies reporting the usage of tobramycin in lumbar spine surgeries were included for analysis. Results: Among the 231 participating surgeons, only 1.7 %(n = 4) reported utilizing tobramycin in 1 or 2-level open lumbar fusion surgery. Upon systematic review of the literature, two studies with 484 patients were included for analysis. With the usage of tobramycin as a topical antibiotic powder, both studies noted a reduction in the incidence of infection with change in the spectrum of infective organisms. Conclusion: Topical Tobramycin is not the commonly preferred topical antibiotic to prevent SSI among spine surgeons worldwide. There is a lack of sufficient evidence to support the routine use of topical tobramycin in lumbar spine surgery.

Efficacy of combination antibiotic therapy including inhaled tobramycin on Burkholderia cepacia pneumonia in a non-cystic fibrosis patient.

Burkholderia cepacia complex (BCC) has been recognized as a serious cause of pneumonia in patients with cystic fibrosis. BCC infection has also been reported in non-cystic fibrosis patients. Notably, the mortality rate of bacterial pneumonia caused by BCC is high. Nonetheless, therapeutic management of BCC infection remains to be established. Recent reports have indicated successful treatment of BCC pneumonia with combination antibiotic therapy. However, no reports have detailed the efficacy of combination antibiotic therapy for both initial and recurrent BCC pneumonia management. We herein describe a rare case of BCC pneumonia in a non-cystic fibrosis patient that was successfully treated with a combination of intravenous, inhalational and oral antibiotics. Furthermore, antibiotic therapy including inhaled tobramycin has been continued after discharge from hospital, and no side effects or recurrence of bacterial pneumonia has been observed, although BCC has been detected in sputum. The findings of the present case suggest that combination antibiotic therapy including inhaled tobramycin may be effective for recurrent bacterial pneumonia caused by BCC. In the management of BCC infection, early diagnosis should be made based on sputum culture results, and combination antibiotic therapy should be initiated promptly.

Detectable Concentrations With Inhaled Tobramycin in Critically Ill Infants and Children Following Implementation of Standardized Protocol.

BACKGROUND: A protocol was established for ventilator-associated tracheitis or pneumonia using inhaled tobramycin 300 mg every 12 hours in mechanically ventilated children via a vibrating mesh nebulizer, 30 cm from the endotracheal tube in the inspiratory loop of the mechanical ventilator. OBJECTIVES: The primary objective was to determine the incidence of detectable tobramycin trough concentrations >0.5 µg/mL. Secondary objectives included a comparison of clinical characteristics between those with and without detectable concentrations and identification of patients with acute kidney injury (AKI) as defined by the Kidney Diseases Improving Global Outcomes (KDIGO) criteria. METHODS: This was a single-center retrospective study of critically ill children <18 years without cystic fibrosis receiving inhaled tobramycin between July 1, 2016, and August 31, 2021. Data collection included demographics, tobramycin regimen, and renal function. Analysis was performed using SAS 9.4, with a P-value <0.05, and a multivariable regression model was performed to identify factors for detectable concentrations and AKI. RESULTS: Forty-four patients (66 courses) were included, with an overall age of 0.83 years. Thirty (68%) patients had detectable concentrations and 9 (20.5%) developed AKI. No significant differences in demographics, diagnosis, mechanical ventilation settings, and number of nephrotoxins were noted between those with and without detectable concentrations or AKI. Multivariable regressions did not identify factors associated with detectable concentrations or AKI. CONCLUSION AND RELEVANCE: Detectable concentrations occurred with the majority of courses, with AKI associated with approximately one-fourth of courses. Clinicians should consider utilizing trough monitoring for all mechanically ventilated critically ill children receiving inhaled tobramycin.

A sensitive tobramycin electrochemical aptasensor based on multiple signal amplification cascades.

The residue of tobramycin, a broad spectrum antibiotic commonly used in animal husbandry, has evitable impact on human health, which may cause kidney damage, respiratory paralysis, neuromuscular blockade and cross-allergy in humans. Sensitive monitoring of tobramycin in animal-derived food products is therefore of great importance. Herein, a new aptamer electrochemical biosensor for sensing tobramycin with high sensitivity is demonstrated via exonuclease III (Exo III) and metal ion-dependent DNAzyme recycling and hybridization chain reaction (HCR) signal amplification cascades. Tobramycin analyte binds aptamer-containing hairpin probe to switch its conformation to expose the toehold sequence, which triggers Exo III-based catalytic digestion of the secondary hairpin to release many DNAzyme strands. The substrate hairpins immobilized on the Au electrode (AuE) are then cyclically cleaved by the DNAzymes to form ssDNAs, which further initiate HCR formation of lots of long methylene blue (MB)-tagged dsDNA polymers on the AuE. Subsequently electro-oxidation of these MB labels thus exhibit highly enhanced currents for sensing tobramycin within the 5-1000 nM concentration range with an impressive detection limit of 3.51 nM. Furthermore, this strategy has high selectivity for detecting tobramycin in milk and shows promising potential for detect other antibiotics for food safety monitoring.

A universal optical aptasensor for antibiotics determination based on a new high-efficiency Förster resonance energy transfer pair.

A novel "turn-on" aptasensor for kanamycin (Kana) detection based on a new Förster resonance energy transfer (FRET) pair is reported. A new organic small molecule was employed as a high-efficiency quencher for fluorophore. Based on specific interactions between ssDNA and the quencher, an ingenious and amplified strategy was designed. In the absence of the target, the fluorescence of the fluorophore labeled at the end of the aptamer was quenched. After the binding of the aptamer to the target, the fluorescence was recovered and amplified. The proposed aptasensor showed high specificity, selectivity, and stability in complicated systems. With the P3-based strategy, the limit of detection for Kana is estimated to be 10 nM, which is much lower than the maximum allowable concentration in milk. The recoveries of spiked Kana in milk were in the range 99.8 ~ 105.3% (n = 3). Fortunately, this novel method can be easily extended to other antibiotics such as tobramycin by simply replacing the aptamer, showing great potential as a universal platform for selective, sensitive, and rapid detection of hazardous analytes in food samples.

Design and application of an ultrasensitive and selective tobromycin electrochemiluminescence aptasensor using MXene /Ni/Sm-LDH-based nanocomposite.

Using a chemiluminescence reaction between luminol and H2O2 in basic solution, an ultrasensitive electrochemiluminescence (ECL) aptasensor was developed for the determination of tobramycin (TOB), as an aminoglycoside antibiotic. Ti3C2/Ni/Sm-LDH-based nanocomposite effectively catalyzes the oxidation of luminol and decomposition of H2O2, leading to the formation of different reactive oxygen species (ROSs), thus amplifying the ECL signal intensity of luminol, which can be used for the determination of TOB concentration. To evaluate the performance of the electrochemiluminescence aptasensor and synthesized nanocomposite, different methods such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) analyses were performed. The considerable specific area, large number of active sites, and enhanced electron transfer reaction on this nanocomposite led to the development of an ECL aptasensor with high sensitivity and electrocatalytic activity. After optimizing the preparation method and analysis conditions, the aptasensor revealed a wide linear response ranging from 1.0 pM to 1.0 µM with a detection limit of 18 pM, displaying outstanding accuracy, specificity, and response stability. The developed ECL sensor was found to be applicable to the determination of TOB in human serum samples and is anticipated to possess excellent clinical potentials for detecting other antibiotics, as well.

Mutations Affecting Cellular Levels of Cobalamin (Vitamin B12) Confer Tolerance to Bactericidal Antibiotics in Burkholderia cenocepacia.

The Burkholderia cepacia complex (Bcc) consists of opportunistic pathogens known to cause pneumonia in immunocompromised individuals, especially those with cystic fibrosis. Treating Bcc pneumonia is challenging due to the pathogens' high multidrug resistance. Therefore, inhalation therapy with tobramycin powder, which can achieve high antibiotic concentrations in the lungs, is a promising treatment option. In this study, we investigated potential mechanisms that could compromise the effectiveness of tobramycin therapy. By selecting for B. cenocepacia survivors against tobramycin, we identified three spontaneous mutations that disrupt a gene encoding a key enzyme in the biosynthesis of cobalamin (Vitamin B12). This disruption may affect the production of succinyl-CoA by methylmalonyl-CoA mutase, which requires adenosylcobalamin as a cofactor. The depletion of cellular succinyl-CoA may impact the tricarboxylic acid (TCA) cycle, which becomes metabolically overloaded upon exposure to tobramycin. Consequently, the mutants exhibited significantly reduced reactive oxygen species (ROS) production. Both the wild-type and mutants showed tolerance to tobramycin and various other bactericidal antibiotics under microaerobic conditions. This suggests that compromised ROS-mediated killing, due to the impacted TCA cycle, underlies the mutants' tolerance to bactericidal antibiotics. The importance of ROS-mediated killing and the potential emergence of mutants that evade it through the depletion of cobalamin (Vitamin B12) provide valuable insights for developing strategies to enhance antibiotic treatments of Bcc pneumonia.

"All-in-one" self-healing and injectable cationic guar gum hydrogel dressing functionalized by bioactive complexes composed of natural small molecules.

Reducing the risk of wound infection is an urgent issue health priority. Antibacterial polysaccharide-based hydrogels have attracted great attention for infectious wounds, attributed to their safe antimicrobial performance and natural non-toxicity and biodegradability advantages. In this study, the "all-in-one" self-adaptive and injectable cationic guar gum (CG)-based polysaccharide hydrogels (FA-TOB/CG) loaded with bioactive complexes were developed for infectious wound healing. The constructed antioxidant and antibacterial ferulic acid (FA)-tobramycin (TOB) bioactive complexes (FA-TOB) were used as the cross-linking agent and introduced into the CG matrix to construct the FA-TOB/CG hydrogel with a three-dimensional porous structure. The sterilization rates of FA-TOB/CG hydrogel against S. aureus and E. coli reached 98 % and 80 % respectively. In addition, the FA-TOB/CG also exhibits enhanced antioxidant performances (DPPH: > 40 %; ABTS: > 90 %; ·OH: > 50 %). More importantly, FA-TOB/CG hydrogel also showed the ability to sustain the release of FA and TOB. These superiorities of the FA-TOB/CG hydrogel enabled it to provide a moist wound environment and promote wound healing by eliminating bacteria, modulating the local inflammatory response, and accelerating collagen deposition and vascular regeneration. Thus, this study may enlarge a new sight for developing multifunctional dressings by incorporating bioactive complexes into polysaccharide hydrogels for infected wounds.

Implementation of green-assessed nanotechnology and quality by design approach for development of optical sensor for determination of tobramycin in ophthalmic formulations and spiked human plasma.

A fast eco-friendly colorimetric method was developed for the determination of Tobramycin in drug substance, ophthalmic formulations, and spiked human plasma using silver nanoparticles optical sensor. Even though tobramycin is non-UV-visible absorbing, the developed method is based on measuring the absorbance quenching of silver nanoparticles resulting from the interaction with tobramycin. Different factors affecting the absorbance intensity were studied as; silver nanoparticle concentration, pH, buffer type, and reaction time using quality by design approach. Validation of the proposed method was performed according to ICH guidelines and was found to be accurate, precise, and sensitive. The linearity range of tobramycin was 0.35-4.0 µg/mL. The optical sensor was successfully applied for the determination of Tobramycin in ophthalmic formulations and spiked human plasma without pre-treatment. Additionally, the binding between Tobramycin and PVP- capped silver nanoparticles was studied using molecular docking software. The method was assessed and compared to colorimetric reported methods for the green character using Green Analytical Procedure Index (GAPI) and Analytical GREEnness calculator (AGREE) tools and found to be greener.

Effect of L-arginine on cystic fibrosis Pseudomonas aeruginosa biofilms.

Cystic fibrosis (CF) airways are L-arginine deficient which may affect susceptibility to infection with certain pathogens. The potential impact of L-arginine supplementation on Pseudomonas aeruginosa, a common CF airway pathogen, is unclear. This study investigated the effects of L-arginine on P. aeruginosa biofilm cultures, using the laboratory strain PAO1 and multi-drug resistant CF clinical isolates. P. aeruginosa biofilms were grown in a chambered cover-glass slide model for 24 h, then exposed to either L-arginine alone or combined with tobramycin for an additional 24 h. Biofilms were visualized using confocal microscopy, and viable cells were measured via plating for colony-forming units. Increasing concentrations of L-arginine in bacterial culture medium reduced the biovolume of P. aeruginosa in a dose-dependent manner. Notably, L-arginine concentrations within the physiological range (50 mM and 100 mM) in combination with tobramycin promoted biofilm growth, while higher concentrations (600 mM and 1200 mM) inhibited growth. These findings demonstrate the potential of L-arginine as an adjuvant therapy to inhaled tobramycin in treating P. aeruginosa infections in people with CF.

Monitoring cystic fibrosis airway infections with Pseudomonas aeruginosa with anti-OprF serum antibodies.

BACKGROUND: The management of cystic fibrosis (CF) requires knowledge of the patient's microbiological status. The serology of anti-Pseudomonas aeruginosa antibodies against exoenzymes or water-soluble antigens has gained diagnostic value, particularly to detect the onset of colonization with P. aeruginosa. However, the diversity and variable expression of these antigens, which was unknown when the ELISAs became common diagnostic procedures at CF clinics, prohibits the quantitative evaluation of bacterial antigen load during intermittent and chronic infection. METHODS: An ELISA was developed to measure the serum IgG antibody levels against P. aeruginosa porin OprF, a species-specific, conserved, immunogenic and constitutively expressed protein present in the outer membrane and extracellular vesicles. RESULTS: Serial serum samples were collected from 310 people with CF (pwCF) over a period of up to 15 years. Compared to a reference of P. aeruginosa - negative CF sera set to 1, OprF antibody titers ranged from 0.3 to 13.2 (median: 1.7) in 56 intermittently colonized patients and from 0.5 to 51.2 (median: 11.8) in 176 chronically colonized pwCF showing higher anti-OprF antibody levels during chronic than during intermittent colonization with P. aeruginosa (P = 0, Z = - 21.7, effect size 0.62). Inhalation with twice daily 80 mg tobramycin decreased OprF antibody titers (P = 5 × 10-5), particularly during the third and fourth year of chronic colonization. CONCLUSION: The OprF ELISA should be an appropriate tool to monitor Pseudomonas serology at all stages of infection and disease severity and to study the impact of short- and long-term therapeutic interventions.

A New Class of Polyion Complex Vesicles (PIC-somes) to Improve Antimicrobial Activity of Tobramycin in Pseudomonas Aeruginosa Biofilms.

Pseudomonas aeruginosa (PA) is a major healthcare concern due to its tolerance to antibiotics when enclosed in biofilms. Tobramycin (Tob), an effective cationic aminoglycoside antibiotic against planktonic PA, loses potency within PA biofilms due to hindered diffusion caused by interactions with anionic biofilm components. Loading Tob into nano-carriers can enhance its biofilm efficacy by shielding its charge. Polyion complex vesicles (PIC-somes) are promising nano-carriers for charged drugs, allowing higher drug loadings than liposomes and polymersomes. In this study, a new class of nano-sized PIC-somes, formed by Tob-diblock copolymer complexation is presented. This approach replaces conventional linear PEG with brush-like poly[ethylene glycol (methyl ether methacrylate)] (PEGMA) in the shell-forming block, distinguishing it from past methods. Tob paired with a block copolymer containing hydrophilic PEGMA induces micelle formation (PIC-micelles), while incorporating hydrophobic pyridyldisulfide ethyl methacrylate (PDSMA) monomer into PEGMA chains reduces shell hydrophilicity, leads to the formation of vesicles (PIC-somes). PDSMA unit incorporation enables unprecedented dynamic disulfide bond-based shell cross-linking, significantly enhancing stability under saline conditions. Neither PIC-somes nor PIC-micelles show any relevant cytotoxicity on A549, Calu-3, and dTHP-1 cells. Tob's antimicrobial efficacy against planktonic PA remains unaffected after encapsulation into PIC-somes and PIC-micelles, but its potency within PA biofilms significantly increases.

Intravenous Tobramycin Inhalation for Patients With Advanced Bronchiectasis With Pseudomonas aeruginosa Infection in Home Medical Care: A Report of Two Cases.

Home medical care faces limitations in the number of doctor and nurse visits, availability of medical devices, and economic factors, making daily injections difficult for in-home patients. We describe two cases of advanced bronchiectasis with Pseudomonas aeruginosa infection treated with inhaled tobramycin in a home setting, demonstrating clinical effectiveness. Using commercially available empty eye drop containers to prepare an aseptic inhalation solution and nebulizers easily usable at home, our experience suggests that this could be a viable therapeutic alternative in home medical care.

Impact of pH modification of the empirically used tobramycin ophthalmic solution on MIC90 concentration in tears and aqueous humor of donkeys (Equus asinus).

BACKGROUND: Commercial tobramycin ophthalmic solution is frequently used empirically to treat ocular disorders in equines, despite being primarily formulated for use in humans. It has been noted that tobramycin MIC90 concentration (minimal inhibitory concentration to 90% of microbial growth) rapidly declined following topical administration. It is hypothesized that adjustment of the pH of the empirically used tobramycin ophthalmic solution -prepared for human use- with the pH of the tears of donkeys, could increase the bioavailability of the drug and subsequently improve its penetration to the aqueous humor. Therefore, this study aimed to evaluate the impact of pH adjustment of the empirically used tobramycin ophthalmic solution on MIC90 concentration in tears and aqueous humor of donkeys (Equus asinus). The study was conducted on six (n = 6) clinically healthy donkeys. In each donkey, one eye was randomly selected to receive 210 µg tobramycin of the commercial tobramycin (CT) and used as a positive control (C group, n = 6). The other eye (treated eye) received 210 µg of the modified tobramycin ophthalmic solution (MT) (T group, n = 6). Tears and aqueous humor samples were collected 5-, 10-, 15-, 30- min, and 1-, 2-, 4-, and 6 h post-instillation. RESULTS: Modifying the pH of the empirically used commercial tobramycin ophthalmic solution in donkeys at a pH of 8.26 enhanced the drug's bioavailability. The MIC90 of the most hazardous bacteria isolated from equines' eyes such as Pseudomonas aeruginosa (MIC90 = 128 µg/ml) and Staphylococcus aureus (MIC90 = 256 µg/ml) was covered early (5 min post-instillation) and over a longer period in donkey tears (239-342 min) and aqueous humor (238-330 min) with the modified tobramycin solution. CONCLUSIONS: Adjustment of the pH of the commercial tobramycin ophthalmic solution, empirically used by veterinarians to treat donkeys' ophthalmic infections at a pH of 8.26, isotonic with the donkeys' tears pH, resulting in higher concentrations of tobramycin in tears and aqueous humor for a longer time.

Possible impact of revisions in disc diffusion breakpoints for aminoglycosides and piperacillin/tazobactam in the 33rd edition of CLSI M100 document on clinical reporting and use in Indian settings with low susceptibility.

PURPOSE: The study explores the impact of significant interpretative breakpoint changes for aminoglycosides and piperacillin-tazobactam in Enterobacterales and Pseudomonas aeruginosa, considering PK/PD, clinical data, and susceptibility on clinical reporting and use. PROCEDURE: Between January 2021 and June 2023, a total of 189,583 samples were processed for bacterial pathogens and antimicrobial susceptibility testing was performed using disc diffusion method/VITEK® 2 Compact system/broth microdilution. WHONET software was utilised to capture and analyse the changes in the interpretation of disc diffusion method, following updates to CLSI M100 documents in comparison to previous editions. Antimicrobial consumption data was collected and interpreted as DDD/100 bed days using AMC tool software. Here, we present data for 13,615 members of Order Enterobacterales and 1793 Pseudomonas aeruginosa isolates. FINDING: Enterobacterales exhibited a significant susceptibility drop of 14.7% for gentamicin and 21.7% for amikacin. Pseudomonas aeruginosa showed an increase in isolates with intermediate tobramycin susceptibility, from 0.6% to 29.7%, with relatively minor changes in piperacillin-tazobactam interpretation. CONCLUSION: The changes indicate a shift toward increased 'resistance' and 'intermediate susceptibility' for these antibiotics, emphasizing the need for cautious use and leveraging PK/PD knowledge for improved antibiotic utilization, patient outcomes, and antimicrobial stewardship.

Development of a tobramycin-loaded calcium alginate microsphere/chitosan composite sponge with antibacterial effects as a wound dressing.

Traditional dressings exhibit several disadvantages, as they frequently lead to bacterial infections, cause severe tissue adhesion and perform a relatively single function. Therefore, in this study, a composite sponge dressing with antibacterial properties and excellent physicochemical properties was developed. Six groups of tobramycin-loaded calcium alginate microspheres were prepared by changing the amount of tobramycin added, and the optimal group was selected. Then, seven groups of tobramycin-loaded calcium alginate microsphere/chitosan composite sponges were fabricated via a solvent blending process and a freeze-drying method. The surface morphology, physicochemical properties,in vitrodegradation properties,in vitrodrug release properties, antibacterial properties and cytotoxicity of the composite sponges were examined. Group 3.0 contained the best microspheres with the largest drug loading capacity, good swelling performance and cumulative drug release rate, obvious and sustained antibacterial activity, and good cytocompatibility. The tobramycin-loaded calcium alginate microsphere/chitosan composite sponges exhibited three-dimensional porous structures, and their porosity, swelling rate, water absorption and water retention rates and water vapor transmission rate met the standards needed for an ideal dressing. The comprehensive performance of the sponge was best when 20 mg of drug-loaded microspheres was added (i.e. group 20). The cumulative drug release rate of the sponge was 29.67 ± 4.14% at 7 d, the diameters of the inhibition zones against the three bacteria were greater than 15 mm, and L929 cell proliferation was promoted. These results demonstrated that the tobramycin-loaded calcium alginate microsphere/chitosan composite sponge with 20 mg of tobramycin-loaded microspheres shows promise as a dressing for infected wounds.

Evaluation of Target Attainment for Tobramycin in Children and Adults with Cystic Fibrosis.

Introduction: Patients with cystic fibrosis (CF) commonly experience pulmonary exacerbations, and it is recommended by the TOPIC study to treat this with tobramycin at a dose of 10 mg/kg once daily. The aim of this study was to evaluate the target attainment of the current dosing regimen. Methods: A single-center retrospective cohort study of child and adult patients with CF who received tobramycin between 2019 and 2022 was conducted. Descriptive statistics and linear mixed models were used to assess target attainment for tobramycin. Results: In total, 25 patients (53 courses), of which 10 were children (12 courses) and 15 were adults (41 courses), were included. Those 25 patients all received 10 mg/kg/day. The tobramycin peak concentrations were supratherapeutic in 82.9% and therapeutic in 100.0% of adults and children, respectively. The trough concentrations were outside the target range in 0% and 5.1% of children and adults, respectively. We found lower tobramycin concentrations with the same dose in children compared to adults. Conclusions: This study illustrates the need to validate dosing advice in a real-world setting, as supratherapeutic concentrations of tobramycin were prevalent in adults with CF.