Gentamicin Levels Research Articles

Trend of Bacterial Uropathogens and Their Susceptibility Pattern: Study of Single Academic High-Volume Center in Italy (2015-2019).

Urinary tract infections (UTIs) are a very widespread infection that can occur in disparate age range, in both sexes and in pregnancy/menopause state. Treatment of UTIs is difficult due to the emergence of antibiotic-resistant bacterial strains. The present study shows five years of data collected on patients admitted at the University Hospital “San Giovann di Dio e Ruggi d'Aragona” in Salerno, Italy. The investigation exhibits the incidence of the infection, of the gender, and of the age group affected, identifying the most representative bacteria involved, drawing their profile of antimicrobial resistance. Bacterial identification and antibiotic susceptibility testing were performed using the VITEK 2 system. Among the 46382 studied patients, 9896 (21.34%) and 36486 (78.66%) were positive and negative for microorganism growth, respectively. Of 9896 positive patients, 6158 (62.23%) females and 3738 (37.77%) males were identified. The highest incidence of positive subjects (56.66%) was recorded in the elderly (>61 years). 8431 (85.20%) uropathogens were Gram-negative, 1367 (13.81%) were Gram-positive, and 98 (0.99%) were Candida species (Candida spp.). Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis) were the most representative Gram-negative and Gram-positive strains, respectively. The Gram-negative bacteria most representative were highly resistant to ampicillin, whereas among the Gram-positive bacteria, E. faecalis was highly resistant to gentamicin and streptomycin high level synergy, and Enterococcus faecium (E. faecium) to ampicillin, ampicillin/sulbactam, and imipenem. This retrospective work investigates the local epidemiological trend in our university hospital in order to induce an increasingly targeted empirical therapeutic approach for the treatment of UTIs.

In vitro elution characteristics of gentamicin- and teicoplanin-loaded CMW1 and Palacos R bone cement

PurposeTo compare the in vitro elution characteristics of CMW1 and Palacos R bone cement loaded with gentamicin, teicoplanin, or in combination. MethodsFour bone cement discs were prepared for each cement type. Disc 1 contained no antibiotics; disc 2 contained 0.5 g gentamicin; disc 3 contained 2 g teicoplanin; disc 4 contained 0.5 g gentamicin and 2 g teicoplanin. Elution studies were conducted using a fluorescence polarisation immunoassay technique and performed at intervals of 6 weeks. ResultsFor CMW1, gentamicin and teicoplanin elution levels in combination discs were higher than those in the single antibiotic discs (p < 0.001 & p < 0.06). For Palacos R, gentamicin elution levels in combination discs were higher than those in the single antibiotic discs (p < 0.001), but teicoplanin elution levels in combination discs were lesser than that from the single antibiotic discs (p < 0.02). In single and combination discs, gentamicin elution levels in Palacos R were higher than those in CMW1 (p < 0.001 & p < 0.001). Palacos R eluted more teicoplanin than CMW1, except in combined disc with gentamicin, when less teicoplanin was eluted. ConclusionAntibiotic elution is higher in Palacos R than CMW1. Antibiotic combination in both cement types has the synergistic effect of increasing antibiotic elution, except for teicoplanin from Palacos R. When high elution of gentamicin is required, Palacos R is preferable. When high elution of teicoplanin is required, Palacos R with only teicoplanin is superior to CMW1.

The antimicrobial activity and biocompatibility of a controlled gentamicin-releasing single-layer sol-gel coating on hydroxyapatite-coated titanium.

AimsThe aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses.MethodsCoatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods.ResultsThe coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface.ConclusionIn this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection.Cite this article: Bone Joint J 2021;103-B(3):522–529.

In vitro elution characteristics of gentamicin-impregnated Polymethylmethacrylate: premixed with a second powder vs. liquid Lyophilization

BackgroundAntibiotic-loaded bone cement, or antibiotic-impregnated polymethylmethacrylate (PMMA), were developed to prevent and treat bone and joint infections. Gentamicin is an antibiotic that is commonly used in combination with PMMA; however, gentamicin powder is hard to obtain in many countries. This study aimed to evaluate the elution characteristics of gentamicin-impregnated PMMA made with lyophilized liquid gentamicin, compared with PMMA; which is made from commercial gentamicin powder.MethodsThe experimental sample was divided into 2 groups: the gentamicin power group (PG-PMMA) and the lyophilized liquid gentamicin group (LG-PMMA). Ten cement spacers were prepared in each group. These were produced by mixing gentamicin powder, or lyophilized liquid gentamicin, with a powder polymer before adding the liquid monomer (2 g of gentamicin and 40 g of PMMA). The volume and surface area of the antibiotic-impregnated cement spacers were 50 cm3 and 110 cm2, respectively. Each spacer was immersed in phosphate-buffered saline, which was changed daily under sterile conditions. The solutions were collected to measure the level of gentamicin using the enzyme multiplied immunoassay technique (EMIT), at days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28, 35 and 42.ResultsThe collections from both groups had high concentrations of gentamicin on day 1 (113.63 ± 23.42 mg/dL in LG-PMMA and 61.7 ±8.37 mg/dL in PG-PMMA), but experienced a continuous decrease over time. The PMMA spacers from both groups could release gentamicin for up to 6 weeks (3.28 ± 1.17 mg/dL in LG-PMMA and 1.21 ± 0.28 mg/dL in PG-PMMA). However, there were significantly higher levels of gentamicin concentrations in the LG-PMMA group compared to the PG-PMMA group at all time points (P< 0.05).ConclusionGentamicin-impregnated PMMA made with lyophilized liquid gentamicin had approximately a two times higher rate of antibiotic elution in preliminary in vitro studies, as compared with PMMA made with premixed gentamicin powder.

Abstract 15682: A Novel Antibiotic Delivery Approach Enhances Salvage of Infected Cardiovascular-implantable Electronic Devices

Introduction: Infection of cardiovascular-implantable electronic devices (CIED) is a serious complication. Systemic antibiotic therapy is considered ineffective, justifying the current guidelines proposing total CEID and lead extraction. Objective: To evaluate the safety and efficacy of continuous in-situ-targeted, ultra-high concentration of antibiotics (CITA) in CIED infections limited to the subcutaneous pocket. Methods: Infected CIED were treated with CITA, delivered to the CIED pocket following minimally invasive surgery (MIS). The CIED were submerged in a 10 2 -10 3 minimal inhibition concentration (MIC) solution of vancomycin and/or gentamicin as per daily conventional dosing. Serum antibiotic levels were regulated by adjusting the concentration and flow of pocket irrigation. CIED salvage rate was assessed. Results: A total of 937 and 481serum assays of vancomycin and gentamicin, respectively, from 83 infected CIED was evaluated (Figure). Target antibiotic serum levels were obtained at 12-48 hours. Median treatment was 8 days (IQR 5,12). Parallel intravenous (IV) vancomycin treatment was applied in 6 (7%) infections. Vancomycin serum levels exceeded a trough limit of 20μg/ml in 20 (2.1%) assays, of which 19/20 received parallel IV treatment. No peak gentamicin levels were recorded. Gentamicin exceeded trough serum level reaching 2-3μg/ml in 80 (16.6%), reached potentially toxic levels of 3-5μg/ml in 33 (6.9%), and exceeded 5μg/ml in 10 (2.1%) assays. CITA resulted in a 1-year salvage of 71 (86%) CIED. Treatment failed in 12 infections, resulting in 8 uneventful total CIED extractions. The 30-day mortality rate was 2.4%. Conclusions: CITA provided ultra-high pocket antibiotic levels, with its safety confirmed by systemic level assays. CITA combined with MIS enabled salvage of 86% of infected CIED. The CITA-MIS approach may serve as an initial therapeutic option prior to the extraction of locally infected CIED, especially in high-risk patients.

Nano-strategies in pursuit of efflux pump activeness in Acinetobacter baumannii and Pseudomonas aeruginosa

Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are the two bacteria notorious for nosocomial infections and threats in healthcare settings. Efflux pump is an important mechanism of the antibiotic resistant phenomenon. The emergence of antibiotic-resistant bacteria demands the development of either new antibacterial agents to overcome the distressing situation. The aim of this study was to evaluate the efficacy of chitosan and silver (Ag) nanoparticles (NPs) and their combination with antibiotics to alter the expression level of efflux pumps and any increase in the inhibitory capacity of antibiotics against clinical A.baumannii and P.aeruginosa isolates. To conduct the experiments, initially antibiotic resistant A. baumannii and P. aeruginosa (PAO1) strains were exposed to chitosan and AgNPs with and without ciprofloxacin and gentamicin in their sub inhibitory levels. RNA was then extracted to study the antibacterial effects of the nanoparticles in relation to the expression of the efflux pump using real-time PCR. The present investigation found expression levels of abeM efflux pumps in A.baumannii and mexY efflux pumps in P.aeruginosa decreased after exposing the bacteria to sub-inhibitory concentrations of chitosan, chitosan NPs, and their combination with ciprofloxacin and gentamicin. Conversely, the minimum inhibitory concentration (MIC) levels of ciprofloxacin and gentamicin were found to have increased after exposure to the synthetic substances. Though nanoparticles have found their place in the modern scientific therapeutic world however, before they step into treatment strategies it is necessary to determine their effects either alone or with antibiotics in lowering antibiotic resistance.

Comparative osteoconductivity of bone void fillers with antibiotics in a critical size bone defect model

The study aimed to evaluate the comparative osteoconductivity of three commercially available bone void fillers containing gentamicin with respect to new bone, growth, host tissue response and resorption of the implant material. Defects were created in the cancellous bone of the distal femur and proximal tibia of 12-skeletally mature sheep and filled with three commercially available bone void fillers containing gentamicin (Stimulan-G, Cerament-G, Herafill-G). Peripheral blood was taken pre-operatively and at the time of implantation, as well as at intermittent timepoints following surgery to determine systemic gentamicin levels (5-,15- and 30- minutes, 1, 2, 3, 6, 12, 24, 48- and 72-hours, 3-, 6- and 12-weeks). Decalcified, embedded samples were stained with haematoxylin and eosin (H&E) and used to assess the host tissue response and the formation of new bone in the presence of test implant materials. No adverse reactions were noted at harvest at any time points for any cancellous implantation sites with the various implant materials. Comparative microCT analysis of the Stimulan-G, Cerament-G and Herafill-G test materials revealed a similar increase in bone surface area and volume between animals implanted with Stimulan-G or Cerament-G test materials. Animals implanted with Herafill-G test materials demonstrated the lowest increases in bone volume and surface area of the test materials tested, at levels similar to the negative control sites. By 12-weeks, Stimulan-G defects were completely closed with mature bone and bone marrow whilst the Cerament-G material was still present after 12 weeks by histological examination. In conclusion, this study demonstrated differences in the bone regenerative capacity of a range of bone void fillers in an in vivo setting.

Drug Utilization in Critically Ill Adults with Augmented Renal Clearance Compared to Normal Renal Clearance: Implications for use of Antimicrobials with Predominant Renal Excretion.

Critically ill adults have Augmented Renal Clearance, (ARC) decreasing the systemic circulation of drugs with predominant renal elimination. The phenomenon of ARC is crucial for antimicrobial drugs as it hinders the therapeutic response and aids the development of antimicrobial resistance. The present study was conducted to assess the impact of ARC on an Intensive Care Unit (ICU) of a tertiary care hospital. This was a prospective observational study carried out in critically ill patients with normal serum creatinine without any history of renal disease. Details on their demographic characteristics, clinical diagnoses, laboratory parameters including trough levels of vancomycin and gentamicin, ICU length of stay, and clinical outcomes (discharged alive/death) were obtained. Creatinine clearance (Crcl) was estimated from 24-hour urine creatinine. Monte Carlo simulation test with 100000 iterations was used for predicting serum vancomycin trough levels with the observed Crcl. Eighty patients were recruited in the study of which 52.5% had ARC. Patients in younger age and body weight were observed with a trend to have ARC. No significant differences were observed in any of the drug classes prescribed between patients with and without ARC, including the systemic antimicrobials. Although the observed serum trough levels of vancomycin in patients with ARC did not differ significantly from those without ARC, Monte Carlo simulation predicted that 90% of patients with ARC were likely to have trough levels between 5.63 and 7.85 mg/dl, while those without ARC may have it between 7.75 to 9.82 mg/dl. A significant proportion of critically ill adults exhibit ARC and such patients are more likely to achieve lower trough concentrations of vancomycin than recommended. All critically ill adults with normal serum creatinine have to be screened for ARC using urine creatinine as soon as possible for appropriate adjustment in the dosage regimen of antimicrobials with predominant renal elimination.

Reduction of gentamicin standard dose combined with phytochemicals against Enterobacter cloacae DSM 3264 BRB using response surface methodology

Antibiotic-phytochemicals combinations are used for enhancing the antibacterial efficiency against pathogens aiming to prevent microbial resistance development. This study was conducted at the Faculty of Agriculture, Ain Shams University in Cairo, Egypt, to study the in-vitro inhibitory activities of gentamicin antibiotic and phytochemical combinations of Cinnamomum zeylanicum (cinnamon), Syzygium aromaticum (clove) and Mentha piperita (mint) against Enterobacter cloacae DSM 3264 BRB by Minimal inhibitory concentrations (MICs) and Bactericidal inhibitory concentrations (MBCs) of the agents. Inhibitory activity of four recommended antibiotics (ciproflaxacin, cefepime, meropenem and gentamicin) and three oil plant extracts of the selected plants (cinnamon, clove, mint) were tested against E. cloacae DSM 3264 using well diffusion method on Muller-Hinton agar plates by studying MIC and MBC tests. Gentamicin was selected among the four tested antibiotics based on its high potential against Enterobacter cloacae DSM 3264 BRB. For the reduction of gentamicin standard dose, a synergism experiment between gentamicin and the three phytochemicals under investigation (cinnamon, mint and clove) was carried out using a new statistical approach of mixture drug design of response surface methodology against E. cloacae DSM 3264 growth. A mixture design of twenty mixture combination runs using different concentration levels of gentamicin and the three oil plants extracts was performed against Enterobacter cloacae DSM 3264 growth. The software “Design Expert® 12” Stat-Ease was used to analyze the experimental mixture design. Results showed that the standard recommended gentamicin dose 10 µg/100ml may be substituted by oil extract of Cinnamomum zeylanicum 4.75 % (v/v), Syzygium aromaticum 5.0% (v/v), Mentha piperita 5.0%(v/v) and gentamicin 0.25%(w/v) as an antibacterial agents. Analysis of clove, cinnamon and mint oils by GC-MS proved that the major components were 3-allyl-6-methoxyphenol (46.4%) followed by propylene glycol (53.59%), whereas cinnamon contains cinnamic acid and phenethyl ester being 41.79% while Mint contains menthol (32.9%) followed by menthone (27.7 %).

Exploring the Relationship between FEV1 Loss and Recovery and Aminoglycoside Pharmacokinetics in Adult Patients with Cystic Fibrosis: Implications for Clinical Dosing Strategies.

Systemic aminoglycosides remain a cornerstone of treatment for cystic fibrosis (CF) pulmonary exacerbations (PEx); however, the impact of aminoglycoside pharmacokinetics (PK) on outcomes is not well defined in adult CF patients. Our objective was to assess the impact of increasing PK exposures on the clinical outcomes of PEx treatment in adult CF patients receiving high-dose and standard-dose extended-interval aminoglycosides. We conducted a retrospective study of adult CF patients treated with an intravenous aminoglycoside for a PEx. Serum amikacin, gentamicin, and tobramycin levels and forced expiratory volume over 1 second (FEV1 ) data were used to evaluate exposure-response relationships. PK parameters were estimated using a Bayesian approach to obtain area under the curve (AUC)0-24 hr , maximum concentration (Cmax0-24 hr ), and minimum concentration (Cmin0-24 hr ) estimates. The primary efficacy end point was a 90% recovery of baseline FEV1 by 30days posttreatment. Toxicity included signs or symptoms of ototoxicity, vestibular toxicity, or renal toxicity. Multivariate linear mixed-effects models of FEV1 were used for exposure-response analysis. The study included 51 patients who contributed 188 FEV1 observations. There were 3.0±1.7 (mean±SD) aminoglycoside concentrations per patient. The mean AUC0-24 hr , Cmax0-24 hr , and Cmin0-24 hr across all agents and patients were 156±96mg*hr/L, 29.9±12.7mg/L, and 0.35±0.66mg/L, respectively. A total of 42 amikacin-, gentamicin-, or tobramycin-treated patients contributed to the efficacy analysis, of whom 85.7% experienced recovery posttreatment. Of the 51 included patients, 6 (11.8%) experienced seven toxicity events. In exploratory exposure-response analyses, neither AUC0-24 hr nor Cmax0-24 hr was associated with FEV1 values after adjusting for clinical covariates and baseline FEV1 . Increasing aminoglycoside AUC0-24 hr and Cmax0-24 hr were not associated with FEV1 during PEx treatment. Although individualizing aminoglycoside dosing in adult CF patients is necessary to minimize toxicity risk, more work is needed to define optimally safe and effective dosing strategies for this population.

Preclinical evaluation of efficacy and pharmacokinetics of gentamicin containing extracellular-matrix envelope.

BackgroundUsing synthetic antibiotic‐eluting envelope (ABE) is an effective intervention for prevention of cardiovascular implantable electronic device (CIED) infection. The biologic extracellular‐matrix envelope (ECME), may offer potential advantages over the synthetic ABE. To further minimize the risk of infection, the ECME can be hydrated in gentamicin prior to CIED implantation. We aimed to evaluate the efficacy and pharmacokinetics (PK) of gentamicin containing ECME in an animal model.MethodsFor all experiments, the ECME was hydrated in gentamicin (40 mg/Ml) (treatment) for 2 min. In vitro antimicrobial efficacy against six different bacterial species was assessed. In vivo experiments were conducted using a rabbit model of CIED pocket infection. Serum and ECM gentamicin concentrations were measured. Five different organisms were inoculated into the device pocket of control (ECME hydrated in 0.9% saline) and treatment groups. Macroscopic appearance and colony forming units from CIED, ECME, and tissue were determined.ResultsNo bacteria were recovered from any culture after 12 h of exposure to the gentamicin containing ECME. Serum gentamicin levels dropped below the limit of quantification at 15 h after implant. Gentamicin concentration in the ECME remained relatively stable for up to 7 days. Signs of clinical infection were observed in the control but not in the treatment group. In the presence of gentamicin, statistically significant reduction was demonstrated across all tested bacterial species.ConclusionsIn this preclinical animal infection model, gentamicin containing ECME was highly effective in reducing bacterial burden in the implant pocket, while systemic exposure after implantation remained low.

Susceptibility of monomicrobial or polymicrobial biofilms derived from infected diabetic foot ulcers to topical or systemic antibiotics in vitro.

Diabetic foot ulcers can become chronic and non-healing despite systemic antibiotic treatment. The penetration of systematically-administered antibiotics to the site of infection is uncertain, as is the effectiveness of such levels against polymicrobial biofilms. We have developed an in vitro model to study the effectiveness of different treatments for infected diabetic foot ulcers in a wound-like environment and compared the activity of systemic levels of antibiotics with that for topically applied antibiotics released from calcium sulfate beads. This is the first study that has harvested bacteria from diabetic foot infections and recreated similar polymicrobial biofilms to those present in vivo for individual subjects. After treatment with levels of gentamicin attained in serum after systemic administration (higher than corresponding tissues concentrations) we measured a 0–2 log reduction in bacterial viability of P. aeruginosa, S. aureus or a polymicrobial biofilm. Conversely, addition of gentamicin loaded calcium sulfate beads resulted in 5–9 log reductions in P. aeruginosa, S aureus and polymicrobial biofilms derived from three subjects. We conclude that systemically administered antibiotics are likely to be inadequate for successfully treating these infections, especially given the vastly increased concentrations required to inhibit cells in a biofilm, and that topical antibiotics provide a more effective alternative.

Experience of adopting a standardised nomogram for gentamicin monitoring- an audit

Background: Gentamicin, an aminoglycoside antibiotic, requires therapeutic drug monitoring to decrease the risk of nephrotoxicity and ototoxicity. We audited compliance with our dosing and monitoring guidelines since adoption of the Barnes-Jewish Nomogram for once daily 5mg/kg dosing in September 2018. Methods: We retrospectively reviewed 62 patients who received 171 gentamicin doses with 173 accompanying levels taken between 1/11/18 and 31/1/19. Results: The audit demonstrated overall poor adherence to guidelines. Only 50% of patients received the correctly calculated dose. 40% of gentamicin levels were taken between 6-14 hours resulting in a large number of uninterpretable levels requiring additional actions e.g. repeat levels. 50% of follow up doses were given in the correct time frame. For patients with normal renal function twice weekly monitoring is recommended. In all cases (n=35) where this applied levels were monitored more frequently that indicated. U&amp;Es were regularly monitored for all patients and we did not identify any acute kidney injury. Conclusion: The Barnes-Jewish nomogram was adopted to provide a standardised evidence based monitoring system for gentamicin. However our audit demonstrates the guidance was not well executed clinically. There appeared to be a lack of appreciation and responsibility for monitoring and interpretation of levels. This resulted in erratic sampling, unnecessary levels, and delayed doses. As a result of this audit we intend to adopt a simpler trough level system based on the gentamicin SPC. Our audit demonstrates the need to evaluate service improvement implementations since theoretical benefits do not always translate in to clinical practice

Developing a quality assurance system for the use of stimulan beads in a diabetic foot clinic

Background Diabetic foot infections are an increasing healthcare issue and managing these infections can be difficult. A recent innovation in the way they are managed in the Hull clinic is the use of antibiotic impregnated (generally Gentamicin and Vancomycin) STIMULAN beads. Often only a couple of beads can be used in a foot wound making it a very uneconomical strategy if the beads can’t be stored and used on other wounds. There is no recommended quality assurance method provided by the manufacturers to validate this practice leading to this study. Methods Five beads were removed from a batch; at 1, 4, 8 and 12 week intervals for testing: Bacterial Challenge: a 10mL spot of bead suspension was placed on Mueller Hinton seeded with Staphylococcus aureus ATCC 29213 and E. coli ATCC 25922 and incubated in Air, at 35±1ºC for 18±2hrs; zones of inhibition were read and recorded. TDM: Vancomycin and Gentamicin levels present in each bead was established by analysing 50mL of suspension (1:5 DF) using a therapeutic drug monitoring assay. Results Beads were microbiologically active for 12 weeks with no notable loss of potency. Bacterial challenge: Staphylococcus aureus range 17-23mm, av. 20.4mm and E. coli range 11-20mm, av. 17.5mm. TDM Assay: Vancomycin range 62.01 – 110.18 Av. 88.88mg/L, Gentamicin range 20.38 – 27.41 Av.23.20mg/L. Conclusion Quality assurance of the STIMULAN beads can be established using standard TDM assays and microbiological activity, enabling a kit to be used for up to 12 weeks with clinical confidence.

Comparison of plasma and intra-articular gentamicin levels after intravenous administration in healthy horses

Septic arthritis is considered one of the most severe disorders that affect horses’ joints. Therapy is intended to eliminate the microorganisms that cause this infection. The intravenous administration of antibiotics is an easily performed technique, but there is no guarantee that the antibiotics will reach the joint milieu at high concentrations and remain elevated for a certain period of time. This study aimed to determine and compare the levels of gentamicin in the plasma and synovial fluid of healthy horses after intravenous administration for seven days. Five horses received 6.6 mg/kg intravenous gentamicin every 24 h for seven consecutive days. Blood and synovial fluid samples were collected from the right metacarpal-phalangeal joint before the start of the treatment (T0) and after 6 h (T6), 12 h (T12), and every 24 h during antibiotic therapy for seven days (D1 to D7). The levels of gentamicin in serum and synovial fluid were quantified by Enzyme-Linked Immunosorbent Assay (ELISA). The intravenous administration of 6.6 mg/kg of gentamicin, in horses, after a period of 24 h, promotes synovial fluid concentrations below the MIC of the drug, in spite of reaching high plasma concentrations of gentamicin, daily mean serum concentration which was 29-fold higher than the minimum inhibitory concentration (MIC) of the drug. The intravenous administration every 24 h during seven consecutive days did not cause systemic side effects, such as hepatic or renal injury.

Estimated glomerular filtration rate in patients overdosed with gentamicin

Abstract Background The aim of this study was to compare the estimated glomerular filtration rate (eGFR) from serum creatinine (eGFRcrea) and cystatin C (eGFRcys) in patients with elevated serum trough levels of gentamicin before the next planned dose during treatment in the intensive care unit (ICU). Methods This was a retrospective observational study. Patients who stayed in an ICU, received a once-daily dose of gentamicin, and who had results from all serum gentamicin trough levels, eGFRcrea and eGFRcys analyses were included in the study. Overdosed patients were defined as those with serum gentamicin trough levels above 1 mg/L before the next dose. Gentamicin was measured by a particle-enhanced turbidimetric immunoassay (PETIA). Creatinine and cystatin C were measured by standardized methods. Results The median age (range) was lower in all patients with gentamicin concentration measurements than in overdosed patients (67 [19–96] vs. 75 [48–99] years, respectively; p &lt; 0.0001). The median interquartile range (IQR) of the eGFRcrea was higher than that of the eGFRcys in overdosed patients (60 [44–79] mL/min/1.73 m2 vs. 41 [29–58] mL/min/1.73 m2, respectively; p &lt; 0.0001). The median IQR of the eGFRcrea was higher than that of the eGFRcys in controls (87 [78–98] mL/min/1.73 m2 vs. 66 [54–93] mL/min/1.73 m2, respectively; p &lt; 0.0001). Conclusions Overdosed patients had both a lower eGFRcrea and eGFRcys than controls. Elderly patients are the most commonly overdosed patients. We recommend measuring cystatin C and calculating the eGFRcys and combined equation (eGFRcrea + cys) in ICU patients over 65 years of age, which would enable improved gentamicin dosage adjustments.

The evaluation of the appropriate gentamicin use for preterm infants.

Gentamicin (GM) is used for neonates as the initial treatment for neonatal bacterial infection. An association between high trough GM levels and the elevation of the serum creatinine (sCr) level and hearing loss has been reported, although there have been no reports investigating the serial changes in the sCr level in preterm neonates treated with GM. The present study evaluated the serial changes in the sCr level and the incidence of hearing loss in preterm neonates treated with GM. This study included 56 neonates born at a gestational age of 32-36weeks. Fifteen (group 1) and 20 (group 2) neonates were treated with 2.5mg/kg of GM every 12h and 4mg/kg of GM every 36h, respectively. Group 3 included 21 neonates without GM therapy. Serum GM levels, serial changes in the sCr levels, and the incidence of hearing loss were then compared among the three groups. The serum trough GM level in group 2 was significantly lower than that in group 1 (P < 0.001), whereas the serum peak GM levels in these groups were almost the same. The ratio of the sCr level at birth to that at the 5th day of life in group 1 was the lowest among the 3 groups. No neonates had hearing loss. GM therapy worsened the sCr level in late preterm neonates, especially those with multiple doses per day. The appropriate use of GM is needed in order to prevent the occurrence of nephrotoxicity.

Is gentamicin administered to individual patients in optimal doses already at the beginning of therapy?

Abstract Introduction A gentamicin dose, which the physicians select, frequently does not take any pharmacokinetic parameters into consideration. Aim To analyse the results of therapeutic drug monitoring (TDM) of gentamicin for those patients who have not had the gentamicin dose adjusted at the beginning of therapy (first group) and for those patients who had the gentamicin dose adjusted at the beginning of therapy (second group). Methods We acquired the basic data about patients from the requests for laboratory examination of levels of gentamicin. We measured all the gentamicin concentrations mentioned in this work using the FPIA method. Results The monitored set included 379 hospitalized patients during a 4-year period. We divided the monitored set into 2 groups. First group was composed of patients without dose adjustment of gentamicin at the beginning of therapy, and the second group was composed of patients with dose adjustment of gentamicin by the clinical pharmacist at the beginning of therapy. In addition, the patients in each group were divided according to the body mass index (BMI). In the first group of patients, a low percentage of patients had both optimal levels (trough, peak levels). As for patients with BMI &gt; 25 m2/kg, there were only 17 % such cases, and the patients with BMI ≤ 25 m2/kg were only 18.8 %. In the second group, the patients had all trough and peak levels in optimal therapeutic range at obese patients, overweight patients and also at patients with normal weight (p &lt; 0.001). Conclusion Adjustment of dosage regimens immediately at the beginning of therapy will provide for administering sufficient doses of antibiotics at the beginning of therapy, which is a pre-condition for a successful anti-infective therapy. Therapeutic monitoring of levels allows for administration of sufficient dose of gentamicin without fear of any undesirable effects.

Safety and efficacy of current gentamicin dosing schedules used in neonates in Sri Lanka

Introduction: Gentamicin is the first line antibiotic for early onset neonatal sepsis. Yet the problem with gentamicin is the low therapeutic index. It is known that high trough levels correlate with ototoxicity and nephrotoxicity while the peak levels decide the therapeutic effect. Once daily dose (ODD) and twice daily dose (TDD) schedules are practised in neonatal units in Sri Lanka. Objectives: To assess whether the ODD and TDD schedules of gentamicin used in neonates are effective in avoiding high serum trough levels and in achieving peak serum levels in the therapeutic range. Method: A prospective study was conducted from April to August 2017 in four neonatal units on term neonates less than one week old, in whom gentamicin was started (TDD regime= 2.5 mg/kg 12 hourly and ODD regime= 5mg /kg 24 hourly) during the study period. Trough and peak serum gentamicin levels (SGLs) were assessed before and after the third dose in the TDD regime and after the second dose in the ODD regime. Serum creatinine (SCr) was measured in all the neonates and neonates with high trough levels were referred for hearing assessment. Results: A total of 50 neonates of clinical maturity 37-41 weeks and birth weight 1.8-4.1 kg was included. High trough levels (>2 mg/dl) were seen in 48% of the TDD group and in 12% of the ODD group (p=0.005) Mean trough value in the ODD group was 1.15 mg/dl (SD 0.87) and in the TDD group was 2.14 mg/dl (SD 1.72). (T=-2.564, df=35, p = 0.015). Peak SGL in the therapeutic range (5-10 mg/dl) was seen in 92% of ODD regime and in 80% of the TDD regime. Mean peak values in the ODD and TDD regimes were 9.42 (SD 2.37) mg/dl and 7.12 (SD 2.18) mg/dl respectively (T= 3.56, df=48, p = 0.001). SCr and the hearing assessment were within normal limits in all neonates. Conclusions: The ODD gentamicin schedule of 5 mg/kg achieves a significantly higher peak serum gentamicin level and safer trough levels than the TDD schedule of 2.5 mg/kg.

Individual Control Optimization of Drug Dosage Using Individual Bayesian Pharmacokinetics Model Approach

Giving the right dose of medicine is very important in the healing process from a disease. Improper dosing may worsen the disease or even can cause death. Drug dosing should not only be done based on the population because each individual has different body characteristics. Therefore, the drug dosage was carried out individually using the individual Bayesian pharmacokinetics modeling approach. This case evokes problems regarding how to obtain the estimated population and individual parameters and then determine the optimal dose. The purpose of this analysis is to get the parameters estimation of both population and individual and determine their optimal dose. The data used in this study is patient data who received gentamicin injection. Variables used is gentamicin levels in serum as response variables and sampling times and initial doses as predictor variables. The results obtained are individual pharmacokinetic models with 100% prediction accuracy and dose ranges that can still be tolerated for each individual.