Dose Of Gentamicin Research Articles

Once versus thrice daily dose regimen of gentamicin in abdominal surgery

Objectives: The objectives of the study are to compare the effectiveness and likelihood of toxicity of 7.5 mg/kg single high dose and 80 mg thrice daily doses of intravenous gentamicin. Material and Methods: A total of 88 patients who had abdominal surgeries on account of acute abdomen infectious etiologies in a private hospital in Lagos, Nigeria, between August 2002 and July 2004 were studied. They were randomized into two groups (A and B), with each group comprising of 44 patients. Group A had 7.5 mg single high-dose gentamicin alongside cefuroxime for 5 days. Group B had 80 mg thrice daily of gentamicin for 5 days alongside cefuroxime. Renal function tests were carried out preoperatively and postoperatively. The surgical site infection rate was compared between Groups A and B. Results: There was statistically no significant difference in effectiveness and toxicity between the two groups except for severe infections in which 7.5 mg/kg body weight single high dose gentamicin was superior to 80 mg thrice daily doses. The infection rate was similar for both groups, and the organisms isolated in both groups were resistant to gentamicin. There was no difference in renal complication rate and ototoxicity. We also found that a single high dose was more convenient for nurses to administer, cost effective, decreased personnel time and had more patient comfort. Conclusion: A single high dose of gentamicin of 7.5 mg/kg daily is comparatively effective as 80 mg thrice daily dose. The infection rate was the same in both groups, with a single high dose much better in severe infection.

Gentamicin Pharmacokinetics in Neonates Undergoing Therapeutic Hypothermia for Hypoxic Ischemic Encephalopathy.

The purpose of this study was to review the pharmacokinetic profile of gentamicin among neonates with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) treatment. This was a retrospective study of neonates with HIE undergoing TH in the neonatal intensive care unit who received gentamicin between 2009 and 2014. Demographic information, diagnoses, laboratory test results, and medication administration and monitoring information were collected, and data were analyzed using SciPy. A total of 57 neonates were analyzed. The median birth weight was 3.25 kg (interquartile range [IQR] 2.8-3.68), and median gestational age was 39 weeks (IQR 38-40). An elevated gentamicin trough level (defined as > 2 mg/L) was observed in 61% (35/57) of neonates. Half of the neonates (49%) had multiple gentamicin trough levels obtained, and 4% of the neonates were switched to an alternate agent. There was a significant difference in the number of dosing interval changes in neonates with elevated gentamicin trough levels compared with those with therapeutic gentamicin trough levels (P < 0.001). Of the neonates with elevated gentamicin trough levels, 14% (5/35) failed their hearing screen (P = 0.389). Neonates with HIE undergoing TH may have an altered pharmacokinetic profile, requiring multiple blood draws so medication levels can be monitored and doses adjusted.Traditional gentamicin dosing regimens may not be ideal for this patient population, and further guidance is required for alternative treatment regimens.

Association between adjunctive rifampin and gentamicin use and outcomes for patients with staphylococcal prosthetic valve endocarditis: a propensity-score adjusted retrospective cohort study.

Although guidelines recommend adjunctive rifampin and gentamicin use for patients with staphylococcal prosthetic valve endocarditis (PVE), evidence behind the recommendation is limited and conflicting. We performed a retrospective cohort study of all patients with staphylococcal PVE within the Veterans Health Administration during 2003-2021. Patients were identified with diagnostic codes for prosthetic valves and positive blood cultures for Staphylococcus species and confirmed via manual chart reviews. The primary outcome was the composite of all-cause mortality or recurrence of staphylococcal PVE within one year from diagnosis. Inverse probability of treatment weighting (IPTW) was used to estimate the probability of individuals receiving rifampin using propensity scores. IPTW-adjusted multivariable Cox regression analysis was used to compare outcomes between patients who received rifampin and gentamicin, and those did not. Among 373 patients with staphylococcal PVE, 275 (73.7%) and 225 (60.3%) received at least one dose of rifampin and gentamicin, respectively. The incidence of staphylococcal PVE increased from 0.47 (2003-11) to 0.77 (2012-21) per 10,000 hospitalizations. Gentamicin use declined over time (70.1% in 2003-2011 to 54.8% in 2012-2021, p = 0.04) while rifampin use did not change significantly (76.1% in 2003-2011 to 72.4% in 2012-2021, p = 0.43). The composite outcome was observed in 209 (56.0%). Neither rifampin use (adjusted hazard ratio [HR] 0.77, 95% CI 0.48-1.24) and gentamicin use (adjusted HR 1.11, 95% CI 0.71-1.74) was associated with the composite outcome. No significant association was observed between adjunctive rifampin or gentamicin use and improved outcomes.

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.

Enhancing Gentamicin Antibacterial Activity by Co-Encapsulation with Thymoquinone in Liposomal Formulation

Background and Purpose. Gentamicin (GEN) is a broad-spectrum antibiotic that cannot be prescribed freely because of its toxicity. Thymoquinone (THQ), a phytochemical, has antibacterial, antioxidant, and toxicity-reducing properties. However, its hydrophobicity and light sensitivity make it challenging to utilize. This incited the idea of co-encapsulating GEN and THQ in liposomes (Lipo-GEN-THQ). Method. Lipo-GEN-THQ were characterized using the zeta-potential, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscope (TEM). The liposomes’ stability was evaluated under different storage and biological conditions. Lipo-GEN-THQ’s efficacy was investigated by the minimum inhibitory/bactericidal concentrations (MICs-MBCs), time–kill curves, and antibiofilm and antiadhesion assays. Bacterial interactions with the empty and GEN-THQ-loaded liposomes were evaluated using TEM. Results. The Lipo-GEN-THQ were spherical, monodispersed, and negatively charged. The Lipo-GEN-THQ were relatively stable and released GEN sustainably over 24 h. The liposomes exhibited significantly higher antibacterial activity than free GEN, as evidenced by the four-fold lower MIC and biofilm eradication in resistant E. coli strain (EC-219). TEM images display how the empty liposomes fused closely to the tested bacteria and how the loaded liposomes caused ultrastructure damage and intracellular component release. An antiadhesion assay showed that the Lipo-GEN-THQ and free GEN (0.125 mg/L) similarly inhibited Escherichia coli (EC-157) adhesion to the A549 cells (68% vs. 64%). Conclusions. The Lipo-THQ-GEN enhanced GEN by combining it with THQ within the liposomes, reducing the effective dose. The reduction in the GEN dose after adding THQ may indirectly reduce the toxicity and aid in developing an enhanced and safer form of GEN.

Combinatorial protection of cochlear hair cells: not too little but not too much.

A number of drugs are toxic to the cochlear sensory cells known as hair cells (HCs), resulting in hearing loss. Treatment with survival-promoting growth factors, antioxidants, and inhibitors of cell death pathways or proteinases have been shown to reduce HC damage in in vivo and/or in vitro animal models. Conversely, translation to humans has often been disappointing. This may be due to the complexity of intracellular damage processes. We hypothesized that combining treatments targeting different cellular processes would be more effective. Using an in vitro model of gentamicin ototoxicity for murine cochlear hair cells, we screened all 56 possible combinations of inhibitors targeting five different cell damage mechanisms, plus the activator of one cell survival pathway, each of which have been shown to be singly effective in preventing HC loss in experimental studies. A high dose of gentamicin (200 μM) was used over three days in culture. All compounds were added at a dosage below that required for significant protection in the assay, and only this single dose was then employed. This was done so that we could more easily detect interactive, as opposed to additive, effects. Increasing protection of hair cells was observed as combinations of compounds were increased from two to four factors, although not all combinations were equally protective. The optimal combination of four compounds consisted of an anti-oxidant, an apoptosis inhibitor, an autophagy inhibitor and a protective growth factor. Increasing the number of factors to five or six resulted in decreased protection. The results support the hypothesis that targeting multiple cellular damage or survival pathways provides more an effective hair cell protection approach. The results help to identify critical interactions among the cellular processes that operate in gentamicin ototoxicity. They also suggest that inhibiting too many biological processes impairs functions critical to HC survival, resulting in decreased protection.

THE EFFECT OF THE ANTIBIOTIC GENTAMICIN ON THE STAGES OF ONTOGENESIS IN CHICKEN EGGS

Introduction: Various studies have shown that the effects of the action of drugs, in addition to having positive effects, they can also provoke negative effects in different organs of the body, where by giving more doses in some cases it can exceed the therapeutic limit and become toxic and produce pathological effects in both experimental animals and humans. Uncontrolled use and drug overdose can lead to macroscopic histopathological changes and give teratogenic, mutagenic and carcinogenic effects. Purpose of the paper: This paper aims to study the effects of some drugs at different stages of embryonic development in chicken eggs. The research of this paper will consist of the toxic effect of drugs and macroscopic and microscopic histopathological changes in certain stages of embryonic development of chicken eggs. Material and method: In the study, fertilized chicken eggs were taken and incubated in the incubator for 21 days of incubation. The eggs were treated with the antibiotic gentamicin at certain stages of embryonic development. The eggs hatched on day thirteen, day fifteen, eighteen and day twentyone. Using the stereomicroscope with the macroscopic and microscopic method were analyzed ontogenetic changes in certain stages of embryonic development. Results: The given dose of the antibiotic gentamicin can have negative effects in certain stages of embryonic development in chicken eggs. The dose given in ampullary form in certain quantities to chicken eggs has inhibited and stagnated the processes of embryonic development at different stages compared to control eggs. Conclusion: The given dose of gentamicin can stagnate embryonic development in certain stages and can provoke changes in certain stages of embryonic development. This phenomenon encourages us to do even more detailed research in this direction to see the effect of the given dose and to analyze what consequences it can provoke overdoses at different stages of embryonic development and within the organism. The lethal dose applied at certain stages of ontogenesis may have lethal consequences for the chick embryo at certain stages of embryonic development.

Using PKPD Modeling to Optimize Gentamicin Dosing in Saudi Neonates

The intricate interplay between pharmacokinetics and pharmacodynamics is pivotal in optimizing gentamicin therapy for neonates, a population characterized by unique physiological developmental considerations and pathophysiological changes in critically ill neonates. Rapid growth, Altered body composition, the immature renal function and premature immune system, significantly influence pharmacokinetic parameters Cl and Vd which aggravate complexities to achieve targets attainment and therapeutic drug monitoring compared to adults, necessitating individualized dosing strategies. The primary aim of this review, highlights the importance of PKPD modeling to optimizing gentamicin dosing in neonates Emerging trends in pediatric pharmacotherapy underscore the urgency for advancing pharmacokinetic-pharmacodynamic (PKPD) modeling to enhance therapeutic efficacy. Future research should focus on integrating real-world data from diverse neonatal populations. Genetic variations may influence the outcomes of PKPD studies, and subsequent dosing recommendations. Conducting PKPD studies in diverse populations is crucial for obtaining more robust and reliable results, which would allow for more representative models that account for physiological variations. Incorporating advanced computational techniques such as machine learning may further refine predictive accuracy, enabling personalized dosing strategies that minimize toxicity while maximizing therapeutic benefits As research evolves, the role of pediatric-specific biomarkers in PKPD modeling warrants closer investigation, potentially leading to breakthroughs that redefine dosing paradigms. By addressing these critical areas, the field can advance toward more effective and individualized pharmacotherapy, reducing adverse outcomes and improving clinical care for vulnerable neonates.

Repetitive combined doses of bacteriophages and gentamicin protect against Staphylococcus aureus implant-related infections in Galleria mellonella.

Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella. For the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses. In the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant reduction in number of bacteria was observed in the larvae after receiving repetitive doses of phages and/or gentamicin in both infection models. Based on our results, a single dose of the combination of phages and gentamicin is sufficient to prevent a haematogenous S. aureus implant-related infection, whereas gentamicin needs to be administered daily for the same effect. To treat early-stage S. aureus implant-related infection, repetitive doses of the combination of phages and gentamicin are required.

Confirming the Suitability of a Gentamicin Dosing Strategy in Neonates Using the Population Pharmacokinetic Approach with Truncated Sampling Duration.

(1) Background: Gentamicin is known to be nephrotoxic and ototoxic. Although gentamicin dosage guidelines have been established for preterm and term neonates, reports do show attainment of recommended peak concentrations but toxic gentamicin concentrations are common in this age group. (2) Methods: This was a prospective, observational study conducted in Namibia with 52 neonates. A dose of 5 mg/kg gentamicin was administered over 3-5 s every 24 h in combination with benzylpenicillin 100,000 IU/kg/12 h or ampicillin 50 mg/kg/8 h. Two blood samples were collected from each participant using a truncated pharmacokinetic sampling schedule. (3) Results: The one-compartment linear pharmacokinetic model best described the data. Birthweight, postnatal age, and white blood cell count were predictive of clearance (CL), while birthweight was predictive of volume (V). For the typical neonate (median weight 1.57 kg, median postnatal age 4 days (0.011 years), median log-transformed WBC of 2.39), predicted CL and V were 0.069 L/h and 0.417 L, respectively-similar to literature values. Simulated gentamicin concentrations varied with respect to postnatal age and bodyweight. (4) Conclusions: A 5 mg/kg/24 h dosage regimen yielded simulated gentamicin concentrations with respect to age and birthweight similar to those previously reported in the literature to be safe and efficacious, confirming its appropriateness.

Impact of once-daily versus multiple-daily dosing of gentamicin on the incidence of acute kidney injury in patients treated with synergistic combinations of antibiotics

BackgroundGentamicin is a commonly used antibiotic with synergistic effects that is administered once or multiple times daily. However, the influence of the daily administration frequency on renal function has not yet been identified. This study aimed to investigate the effect of the daily dosing frequency on worsening renal function in patients receiving gentamicin.MethodsThis study included 35 patients undergoing gentamicin treatment who had at least one serum trough level measured and underwent therapeutic drug monitoring (TDM). We evaluated the influence of daily dosing frequency on gentamicin trough concentration and the risk of acute kidney injury (AKI).ResultsCompared to patients who received gentamicin once-daily dosing (n = 22), patients who received multiple-daily dosing (n = 13) had significantly higher initial and minimum trough concentrations after TDM. The proportion of patients with trough concentrations lower than 1.0 µg/mL was significantly higher in the once-daily dosing group at the initial trough concentration, whereas there was no significant difference at the minimum trough concentration after TDM. AKI developed in nine patients; however, there was no significant difference in the incidence of AKI according to the frequency of daily gentamicin dosing. In contrast, a higher minimum trough concentration after TDM was found to be a risk factor for AKI development with an odds ratio of 9.2 (95% confidence intervals; 1.3–65.5).ConclusionA higher trough concentration of gentamicin correlated with a higher incidence of AKI. The risk of developing AKI may be reduced by choosing a once-daily dosing regimen or implementing TDM.

Do High Doses of Multiple Antibiotics Loaded into Bone Cement Spacers Improve the Success Rate in Staphylococcal Periprosthetic Joint Infection When Rifampicin Cannot Be Employed?

Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10-147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment.

A Randomised Controlled Trial Comparing Intratympanic Gentamicin with Methylprednisolone in Meniere's Disease with Good Hearing.

Randomised prospective parallel group trial. Tertiary care centre in South India. Forty patients with unilateral Meniere's disease and serviceable hearing with vertigo following 6months of conservative therapy were enrolled between November 2018 and March 2020. Twenty patients were administered with one dose of intratympanic Gentamicin (40mg/ml) and the other half were given intratympanic Methylprednisolone (40mg/ml, 4 injections given on alternate days). Pure tone audiogram, speech discrimination score, number of vertigo episodes, dizziness handicap inventory, tinnitus handicap inventory and functional scores were compared before treatment, 3months later and up to 24months. There was no significant difference between the two treatments with regard to short term as well as long term DHI scores, THI scores, Functional level score and average pure tone audiogram of patients. In patients with unilateral Meniere's disease who have good hearing, one dose of Gentamicin had equivalent effect to that of four doses of Methylprednisolone in vertigo and tinnitus control, hearing preservation and quality of life.

Gentamicin concentration and acute kidney injury in term neonates treated for neonatal sepsis with gentamicin and ampicillin-cloxacillin combination.

Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit. Participants were started on intravenous gentamicin 5 mg/kg once a day in combination with ampicilin-cloxacillin. Blood samples for serum gentamicin concentration were taken at 0.25, 0.5, 1, 2, 3, 5, 6, 8, 10, 12, 14, 16, 18, 20, 23, and 24 hours after the initial dose, each participant contributing two samples to the 24 hour sampling schedule. An additional sample for trough concentration was taken from each participant just before the third gentamicin dose while serum creatinine concentration was measured before and after treatment. Twenty-four participants were enrolled into the study and included in the final analysis. Mean (SD) peak and trough serum gentamicin concentrations were 16.66 (0.64) µg/mL and 3.28 (0.70) µg/mL, respectively. Gentamicin clearance (CL) was 0.40 mL min-1 kg-1 and volume of distribution (VD) was 0.31 L kg-1. Mean (SD) serum creatinine level after treatment was 209.7 (70.4) µmol/L compared to 103.3 (23.6) µmol/L before treatment [mean difference (106.4 ± 67.1; 95% confidence interval (CI): 78.1; 134.7 µmol/L; t (23) = 7.77; P < 0.001]. All participants fulfilled the Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury after treatment. Treatment of neonatal infection with antimicrobial regimen containing gentamicin, without renal function and gentamicin concentration monitoring, carries a significant risk for drug-induced acute kidney injury.

Strategy for the Optimization of Read-Through Therapy for Junctional Epidermolysis Bullosa with COL17A1 Nonsense Mutation

The read-through therapy suppresses premature termination codons and induces read-through activity consequently restoring missing proteins. Aminoglycosides are widely studied as read-through drugs in different human genetic disorders including hereditary skin diseases. Our previous work revealed that aminoglycosides have effect on COL17A1 nonsense mutations and represent a therapeutic option to alleviate disease severity. However, the amount of restored type XVII collagen (C17) in C17 deficient junctional epidermolysis bullosa (JEB-C17) keratinocytes was less than 1% relative to normal keratinocytes and was achieved only after high dose gentamicin treatment, which induced deep transcriptional changes. Therefore, in this study, we designed a strategy for the read-through therapy to challenge with aminoglycosides limitation factors in clinical use and the chronic inflammation in JEB-C17 patients. We developed TRID-C5 containing low dosage of aminoglycosides, CC-90009, NMDI-14, melatonin and apocynin that was able to induce about 20% of missing C17 without cell toxicity and effect on in vitro wound closure. TRID-C5 significantly induced COL17A1 expression and reverted the proinflammatory phenotype of JEB-C17 keratinocytes. Evaluation of this drug cocktail regarding its stability, penetration and efficacy as a topical treatment remains to be determined. TRID-C5 might represent an improved therapeutic strategy for JEB and for other genetic skin disorders.

Nlmixr2 Versus NONMEM: An Evaluation of Maximum A Posteriori Bayesian Estimates Following External Evaluation of Gentamicin and Tobramycin Population Pharmacokinetic Models.

The objective of this project is to compare the results of the same study carried out on NONMEM and nlmixr2. This analysis consists of evaluating previously published population pharmacokinetic models of gentamicin and tobramycin in our population of interest with sparse concentrations. A literature review was performed to determine the gentamicin and tobramycin models in critically ill adult patients. In parallel, gentamicin and tobramycin dosing data, information on the treatment, the patient, and the bacteria were collected retrospectively in 2 Quebec establishments. The external evaluations were previously performed using NONMEM Version 7.5. Model equations were rewritten with R, and external evaluations were performed using nlmixr2. Predictive performance was assessed based on the estimation of bias and imprecision of the prediction error for maximum a posteriori (MAP) Bayesian PK parameter and observed concentrations. Comparison between nlmixr2 and NONMEM was performed on 4 gentamicin and 3 tobramycin population pharmacokinetic models. Compared to NONMEM, for gentamicin and tobramycin clearance and central volume of distribution, nlmixr2 produced individual pharmacokinetic parameters with bias values ranging from -32.5% to 5.67% and imprecision values ranging from 6.33% to 32.5%. Despite these differences, population bias and imprecision for sparse concentrations were low and ranged from 0% to 5.3% and 0.2% to 6.5%, respectively. The external evaluations performed with both software packages resulted in the same interpretation in terms of population predictive performance for all 7 models. Nlmxir2 showed comparable predictive performance with NONMEM with sparse concentrations that are, at most, sampled twice within a single dose administration (peak and trough).

Characterisation of the urinary microbiome of a frog, and the effect of antibiotics on bacterial abundance and sperm viability during refrigerated storage

Reproductive technologies are increasingly being adopted to improve the conservation management of threatened species. The storage and transport of sperm is a vital aspect of the practical implementation of reproductive technologies, however, bacterial contamination during the storage and transport of sperm samples presents a biosecurity risk and can contribute to a reduction in sperm longevity during storage. The present study: 1) characterised the urinary microbiome (bacterial species composition and abundance) using culture-independent 16S rRNA sequencing; 2) quantified the effect of various doses of gentamicin and streptomycin-penicillin on bacterial abundance (colony-forming units; CFUs) and; 3) quantified the effect of antibiotic supplementation on the sperm viability (proportion live/dead) of spermic urine during a 12-day cold-storage period, using the common eastern froglet, Crinia signifera. Overall, urine samples were found to host a diverse array of bacteria, dominated by the phyla Proteobacteria, Firmicutes, and Bacteroidetes. Bacterial abundance was significantly reduced in all antibiotic treatment groups compared to the control group. Antibiotic supplementation had no effect on sperm viability between day 0 and day 6 of storage, however both antibiotic treatments significantly improved sperm viability from days 9 to 12 of storage compared to the control group. Overall, the results of this study provide novel insight into the urinary microbiome, being the first to use a metagenomics approach to characterise the bacterial community present in the urine of an amphibian. Importantly, this study provides evidence that antibiotic supplementation with either gentamicin or streptomycin-penicillin, minimises bacterial proliferation and improves sperm viability during cold storage. These findings will contribute to the development of biosecurity protocols aimed at reducing the risk of disease transmission and cross-infection from unwanted bacteria and infectious agents in amphibian captive breeding programs.

Assessment of gentamicin dosing and monitoring in neonates: A single center experience.

Gentamicin is a commonly used medication in NICUs. It is known to have ototoxic & nephrotoxic side effects. To date there is no consensus about dosing regimen in different institutions. Our study aims to evaluate the Neofax® dosing regimen for gentamicin in neonatal early onset sepsis in relation to trough level before the second dose and its association with the incidence of gentamicin side effects, namely hearing impairment/loss and acute kidney injury. Retrospective chart review of newborns admitted to Tawam hospital NICU (June 2019-May 2020) who received gentamicin for early onset sepsis (≤72 hours old). Trough levels before the second dose at 24,36 and 48 hours were reviewed (≥1 mg/L is high). Excluded patients with renal risk factors. Side effects (hearing impairment, acute renal injury) were also assessed. Total of 265 infants were included, among whom 149 patients received gentamicin at 24 hours interval, 99 at 36 and 17 at 48 hours interval. Trough level was high in 76% (P = 0.022), 65% (P = 0.127), and 53% (P = 0.108) of patients who received gentamicin at 24, 36, and 48 hours, respectively. Hearing screening was normal in 99.2% of patients, while 2 patients failed the test (Both with normal trough levels). No patients in our study developed renal injury related to gentamicin use. Neofax® gentamicin dosing often results in high trough levels, especially in late preterm/term infants. This study found no correlation between high trough levels and hearing impairment upon discharge or acute kidney injury. Further studies with larger sample size are recommended.

Antibiotic prophylaxis with urodynamic studies in spinal cord injury: Assessing practice patterns and outcomes to guide future practice in a single center

Context/Objective Despite urinary tract infections (UTIs) being a common problem in patients with spinal cord injuries (SCIs), and a well-known complication of invasive urologic procedures, little consensus exists regarding the standard of care for peri-procedural antibiotic use for SCI patients undergoing urodynamics studies (UDS). Our research seeks to evaluate local antibiotic prophylaxis pattern in SCI patients undergoing UDS, assess incidence of post-procedural UTI, describe local antibiotic resistance trends, and provide antibiotic stewardship considerations to guide future practice. Design/Setting/Participants Retrospective cohort study of SCI patients undergoing UDS from January 2010 to January 2020 at a Veterans Affairs SCI Center. Data on patient demographics, UTI risk factors, pre-procedural urinalysis and culture, and peri-procedural antibiotics was extracted. Incidence of post-procedural UTI was tabulated. Findings were summarized using descriptive statistics. Results 331 patients were studied. Pre-procedural urine culture was done in 73% of cases, with positive results in 49%. E. coli was the most commonly isolated organism (19%). Antibiotics were used in 86% of cases, 26% of which had a negative culture. A onetime dose of intramuscular gentamicin given immediately pre-procedure was the most common practice (53%; N = 152). No cases of post-procedural UTIs were identified during the study period. Conclusion No post-UDS UTIs occurred under current local practice where most patients received a one-time dose of intramuscular gentamicin as prophylaxis. Though routine gentamicin prophylaxis may play a role in reducing UTI incidence, the low rate of post-UDS UTI in this population, including patients with positive cultures who received no antibiotics, suggests the possibility of refining practice patterns to improve antibiotic stewardship.

In vitro susceptibility of Neisseria gonorrhoeae to netilmicin and etimicin in comparison to gentamicin and other aminoglycosides

PurposeSingle doses of gentamicin have demonstrated clinical efficacy in the treatment of urogenital gonorrhea, but lower cure rates for oropharyngeal and anorectal gonorrhea. Formulations selectively enriched in specific gentamicin C congeners have been proposed as a less toxic alternative to gentamicin, potentially permitting higher dosing to result in increased plasma exposures at the extragenital sites of infection. The purpose of the present study was to compare the antibacterial activity of individual gentamicin C congeners against Neisseria gonorrhoeae to that of other aminoglycoside antibiotics.MethodsAntimicrobial susceptibility of three N. gonorrhoeae reference strains and 152 clinical isolates was assessed using standard disk diffusion, agar dilution, and epsilometer tests.ResultsGentamicin C1, C2, C1a, and C2a demonstrated similar activity against N. gonorrhoeae. Interestingly, susceptibility to the 1-N-ethylated aminoglycosides etimicin and netilmicin was significantly higher than the susceptibility to their parent compounds gentamicin C1a and sisomicin, and to any other of the 25 aminoglycosides assessed in this study. Propylamycin, a 4’-propylated paromomycin analogue, was significantly more active against N. gonorrhoeae than its parent compound, too.ConclusionSelectively enriched gentamicin formulations hold promise for a less toxic but equally efficacious alternative to gentamicin. Our study warrants additional consideration of the clinically established netilmicin and etimicin for treatment of genital and perhaps extragenital gonorrhea. Additional studies are required to elucidate the mechanism behind the advantage of alkylated aminoglycosides.