Gentamicin Levels Research Articles

Blood concentration monitoring and renal function changes during gentamicin administration for infective endocarditis: a retrospective observational study

BackgroundEstablished guidelines for monitoring gentamicin blood concentration are lacking; therefore, we focused on improving pharmacological interventions and ensuring their safety. We aimed to optimize gentamicin administration for infective endocarditis (IE) treatment.MethodsThe study involved adult patients diagnosed with IE and treated with gentamicin from January 2014 to December 2022. Clinical presentation and drug therapy regimen were comprehensively evaluated. We performed a retrospective chart review of the frequency of gentamicin dose adjustments and changes in renal function while on gentamicin. In addition, we attempted to extract risk factors for renal impairment using univariate analysis.ResultsOn average, a 7.1% decline [changed to − 6.7 ± 20.4 (standard deviation) mL/min/1.73 m2] in the estimated glomerular filtration rate was observed after gentamicin administration, but it was statistically insignificant. Notably, 58% of patients required dosage adjustments, with a subset requiring multiple adjustments. Among the cases in which dosage adjustments were made, 61% were within the first week of treatment. There were no patients with gentamicin levels below the target peak concentration. Furthermore, no independent risk factors were identified in patients requiring dose reduction.ConclusionsDose adjustment was necessary in many cases after treatment initiation. The time to dose adjustment varied widely. These findings highlight the importance of consistent blood concentration monitoring in patients of all demographics, at least weekly, and underscore that routine peak concentration assessments may not be essential when a 3 μg/mL target is maintained. This study provides information on monitoring gentamicin blood level, which can improve IE treatment safety.

Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance.

Aminoglycoside antibiotics target ribosomes and are effective against a wide range of bacteria. Here, we demonstrated that knockout strains related to energy metabolism in Escherichia coli showed increased tolerance to aminoglycosides during the mid-exponential growth phase. Contrary to expectations, these mutations did not reduce the proton motive force or aminoglycoside uptake, as there were no significant changes in metabolic indicators or intracellular gentamicin levels between wild-type and mutant strains. Our comprehensive proteomics analysis unveiled a noteworthy upregulation of proteins linked to the tricarboxylic acid (TCA) cycle in the mutant strains during the mid-exponential growth phase, suggesting that these strains compensate for the perturbation in their energy metabolism by increasing TCA cycle activity to maintain their membrane potential and ATP levels. Furthermore, our pathway enrichment analysis shed light on local network clusters displaying downregulation across all mutant strains, which were associated with both large and small ribosomal binding proteins, ribosome biogenesis, translation factor activity, and the biosynthesis of ribonucleoside monophosphates. These findings offer a plausible explanation for the observed tolerance of aminoglycosides in the mutant strains. Altogether, this research provides valuable insights into the mechanisms of aminoglycoside tolerance, paving the way for novel strategies to combat such cells.

In Vitro Elution of Gentamicin from CERAMENT® G Has an Antimicrobial Effect on Bacteria With Various Levels of Gentamicin Resistance Found in Fracture-related Infection.

Fracture-related infection is a serious complication after trauma. CERAMENT® G combines dead-space management with local release of gentamicin in a single-stage procedure. Bacterial resistance against antibiotics is increasing. The local effect of CERAMENT® G on bacteria resistant to systemically administered gentamicin is unknown. (1) What is the in vitro elution pattern of gentamicin from CERAMENT® G using a full washout model? (2) What is the in vitro antimicrobial activity (zone of inhibition) of CERAMENT® G against bacterial isolates found in fracture-related infection with different susceptibility levels toward gentamicin? Elution of gentamicin from CERAMENT® G was determined in vitro over a period of 2 months. Elution experiments were performed in fivefold, with gentamicin being sampled in threefold at 19 different timepoints within 2 months. Antimicrobial activity was determined using the four most-frequently cultured bacterial species found in fracture-related infection: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Enterobacter cloacae . For each of the species, four different isolates with a different susceptibility to gentamicin were used. According to the European Committee on Antimicrobial Susceptibility Testing, the susceptibility of each isolate was classified into four different groups: fully susceptible (minimum inhibitory concentration 0.064 to 4 mg/L), minimally resistant (minimum inhibitory concentration 4 to 16 mg/L), moderately resistant (minimum inhibitory concentration 8 to 96 mg/L), and highly resistant (minimum inhibitory concentration 24 to 1024 mg/L), depending on each organism. The antimicrobial activity of CERAMENT® G was determined according to the European Committee on Antimicrobial Susceptibility Testing disk protocol. The experiment was performed in fivefold for each isolate. The zone of inhibition was compared between each bacterial isolate and within each of the four separate species. Nonlinear regression statistics were calculated between the zone of interest and logarithmic minimum inhibitory concentration for each bacterial species. After 24 hours, 95% of all available gentamicin was eluted, and gentamicin was still detectable after 2 months. CERAMENT® G showed antimicrobial activity against all bacterial species; only S taphylococcus aureus (with a minimum inhibitory concentration > 1024 mg/L) was not susceptible. The zone of interest of the different bacterial isolates was correlated with the logarithmic minimum inhibitory concentration. CERAMENT® G offers a bone substitute capable of releasing high levels of gentamicin within a short period of time. This study shows that CERAMENT® G has antimicrobial activity against bacterial isolates that are resistant to gentamicin when systemically administered. This finding raises the question of whether European Committee on Antimicrobial Susceptibility Testing cutoff points for systemic application are useful for the use of local CERAMENT® G. Standardized experiments to determine local antibiotic antimicrobial activity in fracture-related infection treatment are needed to form guidelines for the use of local antibiotics and ultimately improve fracture-related infection treatment. Local concentrations of gentamicin with CERAMENT® G are much higher than when systemically administered. It seems effective against certain bacterial strains that are not affected by systemically reachable concentrations of gentamicin. CERAMENT® G might still be effective when bacteria that are resistant to systemically administered concentrations of gentamicin are occulated from patients with fracture-related infection.

Enterococcus Species and Their Antimicrobial Resistance in an Urban Watershed Affected by Different Anthropogenic Sources

Different anthropogenic sources can have a significant influence on bacterial populations and their antimicrobial activities. In this study, the impact of anthropogenic activities on Enterococcus species was studied in an urban watershed in southern California affected by concentrated animal feeding operations (CAFOs), recreational activities, wastewater treatment plants (WWTPs), urban runoff, and control sites. Water samples were collected quarterly for two years for the enumeration of Enterococcus species based on the Enterolert most probable-number (MPN) assay. Concentrations of enterococci were higher in the sediment compared to surface water (4.5 × 106 CFU/g of sediment vs. 2.3 × 105 MPN/100 mL of water). The species diversity was dominated by E. mundtii (32%), E. faecalis (27%), and E. faecium (25%). E. faecium exhibited the highest antibiotic-resistant phenotype. Resistances were mostly to ciprofloxacin, erythromycin, and tetracycline. Tetracycline and erythromycin resistance genes, encoded by tet (C, K, O, S) and ermB, respectively, were more common in isolates from sediment (42.9%) compared to water (12.7%). E. mundtii was sensitive to ampicillin, chloramphenicol, gentamicin, and high levels of vancomycin. A significant percentage of E. faecalis were also resistant to these antibiotics. E. faecium and E. faecalis exhibited resistance to multiple antibiotics. Our data suggest that resistant Enterococcus species within the watershed might provide some useful data to determine pollutant types and sources in that watershed. Therefore, the widespread occurrence and abundance of E. faecium and E. faecalis, and their resistance genes associated with multiple antibiotics may potentially pose risks to the local populations exposed to these water sources during recreational activities.

Pharmacokinetics of Locally Applied Antibiotic Prophylaxis for Implant-Based Breast Reconstruction

Antibiotic irrigation of breast implants is widely used internationally, but no clinical study has investigated the pharmacokinetics of antibiotic prophylaxis in the breast implant pocket. To evaluate how long locally applied gentamicin, cefazolin, and vancomycin concentrations in the implant pocket remain above the minimum inhibitory concentration (MIC) for the most common bacterial infections and to measure systemic uptake. This prospective cohort study was performed at the Department of Plastic Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark, between October 25, 2021, and September 22, 2022, among 40 patients undergoing implant-based breast reconstruction who were part of the ongoing BREAST-AB trial (Prophylactic Treatment of Breast Implants With a Solution of Gentamicin, Vancomycin and Cefazolin Antibiotics for Women Undergoing Breast Reconstructive Surgery: a Randomized Controlled Trial). Patients were randomized to receive locally applied gentamicin, cefazolin, and vancomycin or placebo. Samples were obtained from the surgical breast drain and blood up to 10 days postoperatively. The breast implant and the implant pocket were irrigated with 160 μg/mL of gentamicin, 2000 μg/mL of cefazolin, and 2000 μg/mL of vancomycin in a 200-mL saline solution. The primary outcome was the duration of antibiotic concentrations above the MIC breakpoint for Staphylococcus aureus according to the Clinical and Laboratory Standards Institute: gentamicin, 4 μg/mL; cefazolin, 2 μg/mL; and vancomycin, 2 μg/mL. Secondary outcomes included the time above the MIC for Pseudomonas aeruginosa and other relevant bacteria, as well as systemic uptake. The study included 40 patients (median age, 44.6 years [IQR, 38.3-51.4 years]; median body mass index, 23.9 [IQR, 21.7-25.9]) with a median number of 3 drain samples (range, 1-10 drain samples) and 2 blood samples (range, 0-6 blood samples). Vancomycin and cefazolin remained above the MIC for S aureus significantly longer than gentamicin (gentamicin, 0.9 days [95% CI, 0.5-1.2 days] for blood samples vs 6.9 days [95% CI, 2.9 to 10.9 days] for vancomycin [P = .02] vs 3.7 days [95% CI, 2.2-5.2 days] for cefazolin [P = .002]). The gentamicin level remained above the MIC for P aeruginosa for 1.3 days (95% CI, 1.0-1.5 days). Only cefazolin was detectable in blood samples, albeit in very low concentrations (median concentration, 0.04 μg/mL [range, 0.007-0.1 μg/mL]). This study suggests that patients treated with triple-antibiotic implant irrigation during breast reconstruction receive adequate prophylaxis for S aureus and other common implant-associated, gram-positive bacteria. However, the protection against P aeruginosa may be inadequate.

Intra-soft tissue and intramedullary antibiotic perfusion in combination with negative pressure wound therapy.

Intra-soft tissue and intramedullary antibiotic perfusion (iSAP and iMAP), which combine continuous administration of antibiotic solution to the wound and negative pressure wound therapy (NPWT), have been reported to be a useful management approach for hard-to-heal ulcers in the field of orthopaedic surgery. We report the efficacy of this treatment and discuss the key points. The recipients of this treatment had contaminated fresh severe trauma with a high risk of infection, or hard-to-heal ulcers which were expected to be difficult to manage with conventional NPWT alone. Continuous administration of 1200µg/ml of gentamicin (GM) solution to the wound was performed along with NPWT. The GM solution was administered subcutaneously using a small catheter for iSAP, while intramedullary administration used a bone marrow needle for iMAP. iSAP was employed in all 10 patients who took part, and iMAP in three of these patients. The average treatment time was 13.6 days with iSAP and 9.3 days with iMAP. The mean serum GM level during the therapy was 1.02µg/ml. Moderate GM-induced acute kidney injury was suspected in one case, but resolved spontaneously after GM administration was stopped. Favourable wound bed preparation was achieved in all cases without recurrence of infection. Combination with continuous suction by NPWT is able to keep the local concentration of antibiotic above the minimum inhibitory concentration of biofilm-coated bacteria within the wound. We have referred to this treatment as continuous local antibiotic perfusion. Further investigation of local pharmacodynamics in the wound and side-effects of this treatment are warranted.

Assessing the Risk of Nephrotoxicity Associated with Aminoglycosides in Brucellosis Patients: A Cross-sectional Study.

The purpose of this study was to investigate renal function in patients with brucellosis before and at the end of gentamicin therapy. To ensure the safety of therapeutic doses of gentamicin, renal functions in brucellosis patients were monitored regarding drug serum levels and check for early detection biomarkers of nephrotoxicity. In this cross-sectional study, 41 patients (25 men and 16 women, aged over 15 years) were included, with confirmed acute brucellosis that referred to Brucellosis Research Center in Hamadan, west of Iran between March 2018 to February 2019. At baseline before treatment (first step) and 7 days after gentamicin administration (second step), serum uric acid, blood urea nitrogen (BUN), serum and urine creatinine, erythrocyte sedimentation rate (ESR), quantitative C-reactive protein (CRP) and urinary β2-microglobulin (β2M) were measured. Gentamycin serum level due to the highest risk of nephrotoxicity with this drug in aminoglycoside class was also checked by HPLC method. The data were analyzed using SPSS version 22. The mean urinary β 2M level, serum and urinary creatinine, uric acid, BUN, and quantitative CRP levels in the first step and second step, there were no statistical differences between the two steps. There was a correlation between urinary creatinine and ESR. In addition, a positive correlation was found between urinary β2M and serum gentamicin level. ESR levels have been significantly reduced in the patients after the treatment compared to before it. Our findings confirm that gentamicin is safe at the dose of 5 mg/kg/day for one week intravenously in brucellosis patients.

P34 Gentamicin labels: improving the timing of gentamicin levels and reducing delay in dose administrations

Abstract Background Due to its narrow therapeutic index and significant risks of ototoxicity and nephrotoxicity, gentamicin requires meticulous prescribing, administration and monitoring. Despite readily available guidelines, gentamicin use continues to be associated with errors, with recent Datix reports within NHS Lothian recording incidents such as incorrectly prescribed doses or frequencies, missed levels, and delayed or omitted doses. In response to this, an audit was undertaken to investigate errors in gentamicin use within the Acute Medical Unit (AMU) at the Royal Infirmary of Edinburgh and evaluate the barriers to adherence to guidelines to unearth possible areas for improvement. Methods The initial audit studied patients prescribed gentamicin in AMU within a 3-week period, excluding those who received prophylactic or single one-off doses of gentamicin. The following parameters were examined both on their paper and electronic prescribing charts: (i) dose, (ii) dosing interval/frequency, (iii) time of level sampling, and (iv) administration times of the first and second gentamicin doses. After identifying issues with delayed gentamicin levels and subsequent dose administration times, we introduced the use of gentamicin labels in each AMU bay, in hopes of increasing staff awareness towards patients on gentamicin, thereby promoting timely level sampling and dose administration. The aforementioned parameters were re-audited for a further 3 weeks following this intervention. Results The baseline audit highlighted that only 23/31 (74%) patients had levels taken within the recommended window, and 23/31 (74%) received their second gentamicin doses at the right time. Following the introduction of the gentamicin labels, the second audit observed a slight improvement, with 31/40 (78%) patients having their levels taken within the recommended window, and 30/40 (75%) patients receiving their subsequent doses at the right interval. Noteworthily, in both the pre- and post-intervention groups, the majority of patients who had their second doses delayed received their first doses in the emergency department (ED) prior to admission to AMU. Conclusions In addition to improving staff awareness towards patients on gentamicin, a further overarching issue needs to be addressed: the delays in gentamicin administration which more commonly occurs for patients who transition from ED into AMU. Further interventions should therefore target improving the handover of time-critical medicines between ED and AMU.

Plasma concentration and eGFR in preterm and term neonates receiving gentamicin or successive amikacin therapy

BackgroundGentamicin and amikacin are aminoglycoside antibiotics which are renally excreted and known to be nephrotoxic. Estimate of glomerular filtration rate (eGFR) per body surface area is lower in neonates than in adults and exposure to these drugs could lead to more suppression in kidney function. The aim of this study was to determine maximum and minimum plasma concentrations (Cmax and Cmin), time to reach Cmin levels of gentamicin and amikacin, and to assess eGFR in preterm and term neonates.MethodsTwo groups of patients were recruited, 44 neonates receiving gentamicin (5 mg/kg/24 h) and 35 neonates receiving amikacin (15 mg/kg/24 h) by slow intravenous injection. Patients on amikacin had been on gentamicin before being switched to amikacin. Two blood samples were drawn for the determination of the maximum and minimum plasma concentration. Primary outcomes were determination of Cmax, Cmin, and the time it took to clear the aminoglycoside to a plasma concentration below the toxicity threshold (gentamicin: < 1 mcg/mL; amikacin: < 5 mcg/mL.ResultsTherapeutic range for Cmax of gentamicin (15–25 mcg/mL) or amikacin (30–40 mcg/mL) was achieved in only 27.3 and 2.9% of neonates, respectively. Percentage of neonates reaching plasma concentrations below the toxicity threshold within the 24-hour dosing interval was 72.7% for gentamicin and 97.1% for amikacin. Positive correlation between gentamicin clearance and postnatal age borderline statistical significance (p = 0.007), while the correlation between amikacin clearance and postnatal age was poor and not statistically significant (r2 = − 0.30, p = 0.971).ConclusionAlthough eGFR decreased significantly as a function of postnatal age in neonates receiving amikacin, the majority (91.4%) of these neonates were able to clear the drug to < 5 mcg/mL within a 24-hour dosing interval.

A selective dual quenching sensor (EY/BG@CDs) for simultaneous monitoring of gentamicin and ketorolac levels in plasma: a highly efficient platform that caters to the needs of therapeutic drug monitoring.

This research work introduces a novel sensor that utilizes two fluorophores to enable simultaneous monitoring of gentamicin sulphate (GNT) and ketorolac tromethamine (KET). The innovative sensor is composed of carbon dots (CDs) derived from black grapes (BG) and eosin Y (EY) dye. The interaction between the studied drugs and EY/BG@CDs sensor components allows for their simultaneous detection where GNT quenches the fluorescence of EY at 535 nm without affecting the fluorescence of CDs, while KET quenches the fluorescence of BG@CDs at 385 nm without impacting EY fluorescence. The BG@CDs probe was successfully characterized using various techniques such as absorption spectrophotometry, spectrofluorimetry, TEM imaging, infrared spectroscopic analysis, and XRD analysis. The suggested methodology was observed to be highly sensitive for the simultaneous determination of GNT and KET in their spiked rabbit plasma samples, with wide linear ranges and low limit of detection (LOD) values. The studied drugs were extracted using a highly selective extraction method involving protein precipitation followed by mixed mode solid phase extraction using an Oasis WCX cartridge. The simultaneous determination of GNT and KET is essential due to the potential interactions between the studied drugs. Therefore, this analysis can be used to evaluate the necessity of dose monitoring and the potential adverse effects of co-administration of these drugs.

Intravesical gentamicin treatment for recurrent urinary tract infections: A systematic review over the last two decades

Objectives: Recurrent urinary tract infections (rUTIs) have a significant effect on a patient’s quality of life and frequent use of antibiotics increases multi-drug resistance. Previous research on intravesical antibiotics suggests that this has a local effect on bacteria with reduced systemic absorption and associated side effects. We conducted a systematic review to assess the effectiveness and adverse effects of intravesical gentamicin treatment. Methods: Systematic review of all English published articles from January 2001 to October 2021 according to the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Results: A total of 139 studies were identified, 20 full-text articles were screened and 6 subsequently included totalling 166 patients. All studies reported a decrease in the mean number of urinary tract infections (UTIs) with a significant reduction ( p = 0.0025 and p &lt; 0.004) in two studies. When the number of breakthrough UTIs on prophylactic gentamicin installations was assessed, 65% ( n = 86/133) remained UTI free. Throughout treatment, 99% of serum gentamicin levels were &lt;0.3 ng/dL, and reported instances of increased creatinine were low (2%). A decrease in the growth of multi-drug-resistant bacteria was reported in two papers ( p = 0.065 and p = 0.04). Conclusion: Intravesical gentamicin seems to be an effective treatment in patients with symptomatic rUTIs. The evidence suggests it also reduces UTIs caused by multi-drug-resistant bacteria with no systemic absorption and minimal renal toxicity. Level of evidence: 2a

Caracterización filogenética y determinación de la susceptibilidad a los antibióticos de cepas patógenas de Escherichia coli aviar aisladas de órganos viscerales de pollos de engorde

The study aims to identify phylogenetic groups and antibiotic susceptibility of poultry Escherichia coli (APEC) isolates. E. coli was phenotypically and biochemically characterized. Isolates from 8/30 (26.66%) liver, 7/30 (23.33%) heart, and 4/30 (13.33%) spleen of 37-42 days old vaccinated broiler chickens were assessed. Then the E. coli isolates (19/90; 21.11%) were phylogrouped by quadruplex genotyping based on the presence or absence of arpA, chuA, yjaA genes, and TspE4.C2 DNA fragment.The majority of APEC strains belonged to phylogenetic group C, followed by groups A, E, and F. Phylogroup C was observed in the liver, phylogroup A in both liver and heart samples, phylogroup E in the heart and spleen, and phylogroup F in the liver. The highest antibiotic resistance was observed in Amoxicillin-Clavulanic acid and Ampicillin (100%) predominantly in groups A and E according to antibacterial susceptibility tests. Multiple antibiotic resistance (MDR) for APEC strains was also found at 68.42% (13/19). Of the 19 isolates tested, only 13 (68%) were susceptible to high levels of gentamicin. APEC strains belonging to phylogroups C, A, and E are of epidemiological importance for broilers. It would be beneficial to investigate new phylogroups by performing more detailed genotypic analyzes in APEC strains.

394 Gentamicin Guidelines – Available but Are They Followed? a Retrospective Audit

Abstract Introduction Many hospitals include gentamicin as part of prescribing protocols for clinical situations such as bacterial septicemia and urinary tract infections. High doses of gentamicin can lead to nephrotoxicity and/or auditory dysfunction. To prevent this, most hospital guidelines advise to adjust dosing according to age, renal function and if the patient is overweight. With therefore quite a complex prescribing protocol, an audit of the prescribing practices at the trust was deemed necessary to determine if clinical protocol was being followed for inpatient gentamicin dosing. Method A retrospective audit of all patients prescribed gentamicin as an inpatient between 1st of August and 31st of October 2020 was performed. Data was collected from two separate electronic record systems and combined. Results 2224 doses of Gentamicin (to 1224 patients) were given in the study period. Gentamicin dosing was not adjusted for obesity in either the &amp;lt;70 or &amp;gt;70 age group (p&amp;lt;0.05 for both). Dosing was not adjusted for Creatine clearance (p&amp;lt;0.05). 86% of patients that needed a gentamicin level had one taken but 15% had it taken too early. Of those who had a Gentamicin level &amp;gt;1, 100% had their next dose held. Conclusions Although gentamicin levels are taken and acted on effectively in most cases, a large proportion of patients are not being dosed as per protocol and therefore at risk of the side effects of overdosing or being clinically under treated. With such a complex prescribing protocol, electronic tools need to be implemented to improve compliance across the trust.

In vitro investigations of Staphylococcus aureus biofilms in physiological fluids suggest that current antibiotic delivery systems may be limited.

Orthopaedic surgical site infections, especially when a hardware is involved, are associated with biofilm formation. Clinical strategies for biofilm eradication still fall short. The present study used a novel animal model of long-bone fixation with vancomycin- or gentamicin-controlled release and measured the levels of antibiotic achieved at the site of release and in the surrounding tissue. Then, using fluids that contain serum proteins (synovial fluid or diluted serum), the levels of vancomycin or gentamicin required to substantially reduce colonising bacteria were measured in a model representative of either prophylaxis or established biofilms. In the in vivo model, while the levels immediately adjacent to the antibiotic release system were up to 50× the minimal inhibitory concentration in the first 24 h, they rapidly dropped. At peripheral sites, values never reached these levels. In the in vitro experiments, Staphylococcus aureus biofilms formed in serum or in synovial fluid showed a 5-10 fold increase in antibiotic tolerance. Importantly, concentrations required were much higher than those achieved in the local delivery systems. Finally, the study determined that the staged addition of vancomycin and gentamicin was not more efficacious than simultaneous vancomycin and gentamicin administration when using planktonic bacteria. On the other hand, for biofilms, the staged addition seemed more efficacious than adding the antibiotics simultaneously. Overall, data showed that the antibiotics' concentrations near the implant in the animal model fall short of the concentrations required to eradicate biofilms formed in either synovial fluid or serum.

Evaluation of Renal Biomarkers, Including Symmetric Dimethylarginine, following Gentamicin-Induced Proximal Tubular Injury in the Rat.

Symmetric dimethylarginine (SDMA) is an excretory renal function biomarker shown to correlate well with glomerular filtration rate in dogs, cats, humans, and rats. The objectives of this study were to determine utility of serum SDMA as a renal biomarker in a rat model of gentamicin-induced renal injury and to provide validation of a commercially available SDMA immunoassay for rat serum. Rats were randomly assigned to one of three dose levels of gentamicin (20, 50, or 100 mg/kg) or a vehicle control group and dosed once daily by subcutaneous injection for either four or ten days. Serum and urine renal biomarker evaluation, including serum SDMA, hematologic and serum biochemical analysis, urinalysis, and histologic examination of kidney, were performed. Before biologic validation, analytic validation of the SDMA immunoassay for rat serum was performed, including assessment of assay accuracy, precision, analytical sensitivity, linearity, analyte stability, and interference testing. Among markers of excretory renal function, SDMA and serum creatinine increased earliest and at the lowest gentamicin concentrations and were significantly increased in both the 50- and 100- mg/kg dose levels in the four- and ten-dose treatment groups compared with controls. Time- and dose-dependent increases were noted for all urinary biomarkers investigated in this study, with microalbumin being most responsive and osteopontin least responsive for detection of gentamicin-induced injury across dose levels and schedules investigated. The SDMA immunoassay met all set quality requirements assessed in analytical validation. This study is the first to investigate performance of serum SDMA compared with other excretory renal function markers in a rat gentamicin acute toxicity model. In this study, serum SDMA was an earlier biomarker for detection of gentamicin-induced toxicity than serum cystatin C, BUN, and creatinine clearance. The SDMA immunoassay provides a reliable commercially available assay for future renal investigations in rat models.

Prevalence and Antimicrobial Resistance of Enterococcus Species: A Retrospective Cohort Study in Italy

Antimicrobial resistance represents one of the main threats to healthy ecosystems. In recent years, among the multidrug-resistant microorganisms responsible for nosocomial infections, the Enterococcus species have received much attention. Indeed, Enterococcus have peculiar skills in their ability to acquire resistance genes and to cause severe diseases, such as endocarditis. This study showed the prevalence and antimicrobial resistance rate of Enterococcus spp. isolated from clinical samples, from January 2015 to December 2019 at the University Hospital “San Giovanni di Dio e Ruggi d’Aragona” in Salerno, Italy. A total of 3236 isolates of Enterococcus faecalis (82.2%) and Enterococcus faecium (17.8%) were collected from urine cultures, blood cultures, catheters, respiratory tract, and other samples. Bacterial identification and antibiotic susceptibility were performed with VITEK 2. E. faecium showed a high resistance rate against ampicillin (84.5%), ampicillin/sulbactam (82.7%), and imipenem (86.7%), while E. faecalis showed the highest resistance rate against gentamicin and streptomycin high level, but both were highly sensitive to such antibiotics as tigecycline and vancomycin. Studies of surveillance are an important tool to detect changes in the resistance profiles of the main pathogens. These antimicrobial susceptibility patterns are necessary to improve the empirical treatment guideline of infections.

Saliva as a sampling matrix for therapeutic drug monitoring of gentamicin in neonates: A prospective population pharmacokinetic and simulation study.

AimsTherapeutic drug monitoring (TDM) of gentamicin in neonates is recommended for safe and effective dosing and is currently performed by plasma sampling, which is an invasive and painful procedure. In this study, feasibility of a non‐invasive gentamicin TDM strategy using saliva was investigated.MethodsThis was a multicentre, prospective, observational cohort study including 54 neonates. Any neonate treated with intravenous gentamicin was eligible for the study. Up to eight saliva samples were collected per patient at different time‐points. Gentamicin levels in saliva were determined with liquid chromatography tandem mass‐spectrometry (LC–MS/MS). A population pharmacokinetic (PK) model was developed using nonlinear mixed‐effects modelling (NONMEM) to describe the relation between gentamicin concentrations in saliva and plasma. Monte Carlo simulations with a representative virtual cohort (n = 3000) were performed to evaluate the probability of target attainment with saliva versus plasma TDM.ResultsPlasma PK was adequately described with an earlier published model. An additional saliva compartment describing the salivary gentamicin concentrations was appended to the model with first‐order input (k13 0.023 h−1) and first‐order elimination (k30 0.169 h−1). Inter‐individual variability of k30 was 38%. Postmenstrual age (PMA) correlated negatively with both k13 and k30. Simulations demonstrated that TDM with four saliva samples was accurate in 81% of the simulated cases versus 94% when performed with two plasma samples and 87% when performed with one plasma sample.ConclusionTDM of gentamicin using saliva is feasible and the difference in precision between saliva and plasma TDM may not be clinically relevant, especially for premature neonates.

Fate of bacterial community, antibiotic resistance genes and gentamicin residues in soil after three-year amendment using gentamicin fermentation waste

Over a three-year field trial, the impacts of composted and raw gentamicin fermentation waste (GFW) application to land on residual soil gentamicin levels, physicochemical properties, bacterial community composition, and antibiotic resistance genes (ARGs) were assessed. In the saline-alkali soil tested, GFW application decreased electrical conductivity (EC) and pH. Importantly, there was no measurable long-term accumulation of gentamicin as a result of GFW addition. Changes in the abundance of Bacillus was primarily associated with degradation of gentamicin in soil, whereas wider (i.e. more general) shifts in bacterial communities over the treatments was linked to alteration of soil physicochemical properties, particularly pH, total nitrogen, dissolved organic carbon, EC, NO3−-N and NH4+-N. Compared with other treatments, soils receiving composted GFW harbored more types of ARGs and significantly higher (P < 0.05) abundances of mobile genes elements (MGEs) (especially IncQ and Int1) and aminoglycoside ARGs (especially aminoglycoside phosphotransferases genes, APH). Finally, the abundances of ARGs in soils receiving raw and composted GFW were 59.60% and 50.26% higher than that in soils only receiving chemical fertilizer, respectively. Specifically, the abundances of APH, especially strB, were significantly higher than other kinds of ARGs (P < 0.05). The results of linear regression and partial least squares path model showed that MGEs, including plasmids, integrons, and transposons, along with soil properties (EC and NH4+-N) were the main factors associated with change in ARGs. Furthermore, different MGEs were involved in different transfer mechanisms of specific ARGs. Our findings demonstrated the potential risks of using raw and composted GFW as fertilizer, and suggest potential solutions to this problem.

Optimizing gentamicin dosing in different pediatric age groups using population pharmacokinetics and Monte Carlo simulation

IntroductionThe use of once daily dosing of aminoglycosides in pediatrics is increasing but studies on dose optimization targeting the pediatric population are limited. This study aimed to derive a population pharmacokinetic model of gentamicin and apply it to design optimal dosing regimens in pediatrics.MethodsPopulation pharmacokinetics of gentamicin in pediatrics was described from a retrospective chart review of plasma gentamicin concentration data (peak/ trough levels) of pediatric patients (1 month − 12 years), admitted to non-critically ill pediatrics. Monte Carlo simulations were performed on the resulting pharmacokinetic model to assess the probability of achieving a Cmax/MIC target of 10 mg/L over a range of gentamicin MICs of 0.5–2 mg/L and once daily gentamicin dosing regimens. Results: A two-compartment model with additive residual error best described the model with weight incorporated as a significant covariate for both clearance and volume of distribution. Monte Carlo simulations demonstrated a good probability of target attainment even at a MIC of 2 mg/L, where neonates required doses of 6-7 mg/kg/day and older pediatrics required lower daily doses of 4–5 mg/kg/day while maintaining trough gentamicin concentration below the toxicity limit of 1 mg/L. Conclusion: Once daily dosing is a reasonable option in pediatrics that allows target attainment while maintaining trough gentamicin level below the limits of toxicity.

1. The Sensitivity Level Of Gentamicine, Cholramphenicol and Penicillin Inhibiting The Growth Of Pseudomonas Aeruginosa Bacteria Isolate From Aceh Bull Prepunce

This study aims to determine the sensitivity level of gentamicin, chloramphenicol and penicillin antibiotics to inhibit the bacterial growth of P. aeruginosa taken from preputium isolate of Aceh cattle. This Stock of Pseudomonas aeruginosa isolate from Microbiology Laboratory of FKH USK, re-identified its purity through: indole test, methyl red test, sugar test and as well as on Nutrient Broth (NB) media; incubated at 37ºC for 24 hours; observed the turbidity level of 0.5 Mc Farland solution. Then, the antibiotic sensitivity test was carried out using the method of Mueller Hinton Agar (MHA). The observations were made by measure the inhibition zone using the calipers in millimeters (mm) against antibiotics. The results of the observation of the inhibition zone on the gentamicin antibiotic was averaged of 25.5 mm, 23.7 mm chloramphenicol, and 12.1 mm penicillin. This study concluded that the gentamicin, chloramphenicol, and penicillin antibiotic were still effective against P. aeruginosa bacteria with the highest level of sensitivity seen in gentamicin antibiotic.