Serum Gentamicin Concentrations Research Articles

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.

Three-minute nebulization of gentamicin in healthy dogs results in therapeutic concentrations in bronchoalveolar lavage fluid while remaining below the toxic range values in blood.

To determine and compare the concentration of gentamicin in the lower airways and serum of healthy spontaneously breathing dogs after nebulization with 5% undiluted gentamicin during 3 versus 10 minutes. 10 healthy experimental Beagles. This was a prospective crossover study. A standardized bronchoalveolar lavage (BAL) procedure was performed in each dog after 1 week of administration of each of 2 different gentamicin nebulization protocols separated by a 1-week washout period. The 2 protocols consisted of nebulization of 5% undiluted gentamicin (50 mg/mL) twice daily either during 10 minutes per session (± 95 mg; 10-minute protocol) or 3 minutes per session (± 28 mg; 3-minute protocol). BAL fluid (BALF) was obtained under general anesthesia using a bronchoscope within 15 minutes after administration of the last nebulization. Blood was collected within 5 minutes after BALF collection. BALF and serum gentamicin concentrations were determined by particle-enhanced turbidimetric inhibition immunoassay. Concentrations between protocols were compared using a paired t test. Both BALF and serum gentamicin concentrations were higher after the 10-minute protocol compared with the 3-minute protocol (mean ± SD: 2.41 ± 0.87 mg/L vs 1.25 ± 0.31 mg/L, P = .001; and 1.02 ± 0.59 mg/L vs 0.31 ± 0.24 mg/L, P < .0001 in BALF and serum, respectively), while the BALF-to-serum ratio did not differ between the protocols (3.75 [1.37 to 5.75] (median [IQR]) in the 3-minute protocol vs 2.48 [2.02 to 2.67] in the 10-minute protocol; P = .754). A 3-minute nebulization of gentamicin seems to achieve sufficient concentrations of gentamicin in the BALF to have good efficacy against aminoglycoside-sensitive bacteria while remaining below the toxic range values in blood.

Neonatal Serum Gentamicin Concentrations and Outcomes Following Maternal Once-Daily Gentamicin Dosing.

This study evaluated newborn gentamicin serum concentrations after birth and the effects on the newborn after extended interval gentamicin dosing in peripartum mothers. This was a single-center, retrospective chart review of neonates born to mothers that received peripartum once-daily gentamicin dosing of approximately 5 mg/kg within 12 hours of delivery. A gentamicin serum concentration was obtained immediately after birth in the newborn. The primary outcome was initial neonatal gentamicin serum concentration after birth. Several secondary outcomes were evaluated including nephrotoxicity and ototoxicity. A subgroup analysis comparing baseline demographics of mother-newborn dyads with birth neonatal serum concentrations of less than 2 mcg/mL versus 2 mcg/mL or greater was performed. A total of 32 mother-newborn dyads were included. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.4 kg. The mean initial gentamicin serum concentration was elevated at 3.1 ± 1.9 mcg/mL among all newborns. The median maternal dose based on actual body weight in newborns with gentamicin serum concentrations less than 2 mcg/mL was 3.5 (IQR, 3.3-4.8) mg/kg versus 4.8 (IQR, 4.3-5.2) mg/kg in those that had serum concentrations of 2 mcg/mL or greater (p = 0.025). All newborn gentamicin serum concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n = 8). There were no significant differences in nephrotoxicity or ototoxicity. Peripartum once daily dosing of gentamicin administered between 1 to 12 hours of birth may lead to clinically significant serum concentrations in newborns.

Intranasal and Serum Gentamicin Concentration: Comparison of Three Topical Administration Protocols in Dogs.

Antimicrobials' topical administration efficacy has not been assessed in dogs with upper respiratory tract disease. The aim was to compare the concentration of gentamicin in nasal lavage fluid (NALF) and in serum after three topical protocols. This was a prospective crossover study of ten healthy dogs. Gentamicin was nebulized for a duration of 1 week, twice a day, for 10 min in the first protocol (10-min protocol) and for 3 min in the second protocol (3-min protocol), while the third protocol consisted of the administration of 0.25 mL of gentamicin in each nostril (drop protocol). Median concentrations of gentamicin in NALF were 9.39 µg/mL (8.12-19.97 interquartile range), 4.96 µg/mL (4.60-6.43) and 137.00 µg/mL (110.5-162.00) in the 10-min protocol, 3-min protocol and drop protocol, respectively. The result for the drop protocol was significantly higher than those of both nebulization protocols in NALF (p = 0.039). In serum, the gentamicin concentration was 0.98 µg/mL (0.65-1.53) and 0.25 µg/mL (0.25-0.44) in the 10-min and 3-min protocols, respectively. Gentamicin was not detected in the serum of seven out of ten dogs in the drop protocol, and gentamicin was significantly higher in the 10-min protocol compared to the drop protocol (p = 0.001). This study found that the 10-min, 3-min and drop protocols achieved superior concentrations in NALF compared to the minimum inhibitory concentration for gentamicin-sensitive bacteria, while remaining below the toxic values in blood.

Gentamicin serum concentration measurement in children.

Gentamicin is often used to treat serious paediatric infections. It has been standard practice in Norway to measure the serum concentration of gentamicin immediately prior to the second or third dose (pre-dose [trough] concentration) to assess the risk of toxicity. The clinical significance of such measurements in children has not previously been evaluated in Norway. This is a retrospective study of routine pre-dose samples obtained for the measurement of serum gentamicin in paediatric patients aged 1 month to 17 years at four hospitals in Norway. Clinical data were extracted from electronic medical records from two of the hospitals. All children received treatment with intravenous gentamicin at a dose of 7mg/kg once daily in accordance with Norwegian guidelines. The most common indications for treatment were febrile urinary tract infection, febrile neutropenia, and suspected or confirmed sepsis. The median (interquartile range) duration of treatment in 353 episodes at two of the hospitals was 4 (3-5) days. Serum gentamicin pre-dose samples were analysed for 1,288 treatment episodes across four hospitals. In 1,223 episodes (95%), the pre-dose sample showed a serum gentamicin concentration of less than 0.6mg/L. In 7 episodes (0.5%), the pre-dose sample showed an elevated gentamicin concentration, defined as greater than 1.0mg/L. An in most cases mildly elevated serum gentamicin concentration was found in the pre-dose sample in 7 of 1,288 treatment episodes. Routine measurement of serum gentamicin via a pre-dose sample should in future be reserved for children receiving long-term gentamicin treatment, those with impaired kidney function, or those who are also receiving nephro- or ototoxic drugs.

An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection.

Local antibiotic therapy is increasingly being recognised for its role in preventing and treating orthopaedic device-related infection (ODRI). A bioresorbable, injectable gentamicin-loaded hydrogel has been developed to deliver local antibiotics at the time of surgery with potential for both prevention and treatment of ODRI. In a prophylaxis model, the antibiotic hydrogel was compared with systemic perioperative antibiotic prophylaxis alone in twelve sheep (six per group) at the time of intramedullary (IM) nail insertion to the tibia, which was inoculated with methicillin-sensitive Staphylococcus aureus (MSSA). In a treatment model of single-stage revision surgery, adjunctive antibiotic-loaded hydrogel was compared with systemic antibiotics alone in a single stage revision of MSSA infection associated with a tibia intramedullary nail in eleven sheep (five/six per group). The primary endpoint was quantitative microbiological results of soft tissue, bone and sonicate fluid from explanted hardware at the time of euthanasia. At euthanasia, the control sheep that received no local antibiotics in the prophylaxis model were all culture-positive (median 1x108, range 7x106-3x108 colony forming units, CFU) while only two of six sheep receiving local gentamicin had any culture positive biopsies (median 1x101, range 0 - 1x105 CFU). For the treatment model, sheep receiving only systemic antibiotics were all culture-positive (median 8x105, range 2x103- 9x106 CFU) while only two of six sheep treated with gentamicin-loaded hydrogel had any culture positive biopsies (median 3x102, range 0 - 7x104 CFU). Local gentamicin concentrations measured in extracellular fluid in the tibial canal show a burst release of gentamicin from the hydrogel. Serum gentamicin concentrations peaked in both models at one day post application and were below detection limit thereafter. This study has demonstrated the effective use of a locally delivered antibiotic hydrogel for both the prevention and treatment of ODRI that is superior to that of systemic antibiotics alone. Future studies will endeavour to translate from preclinical to clinical research trials.

La concentration sérique de gentamicine est-elle modifiée par une autotransfusion sanguine par cell-saver après une arthroplastie totale du genou avec de l’acide tranexamique ? Un essai contrôlé randomisé

BackgroundSelf-transfusion has been proven as an effective management of blood loss after total knee arthroplasty (TKA). Considering that the high local concentration of antibiotic from bone cement is delivered intravenously through the self-transfusion process, systematic toxicity has never been evaluated. In addition, the effectiveness of self-transfusion with the routine concomitant use of other modern blood-salvage strategies, like tranexamic acid, should also be assessed. Therefore we performed a randomized study to assess: (1) the safety of self-transfusion in TKA by comparing the gentamicin concentrations resulting from the use or not of autologous blood transfusion; (2) the efficacy of self-transfusion in TKA, with the concomitant administration of tranexamic acid. HypothesisSelf-transfusion in TKA elevates the serum gentamicin concentration and the potential risk of nephrotoxicity. MethodsThe serum concentration of aminoglycosides was measured in two groups of 20 patients each, after TKA, according to the use of self-transfusion. Hemoglobin, renal function and calculated blood loss were compared at several points in time between groups. ResultsThe only time where there was a statistically significant difference in serum gentamicin, was at 48h postoperatively between groups [0.3 ug/ml±0.21, range: 0.15 to 0.72 vs. 0.14ug/ml±0.1, range: 0 to 0.35 (p=0.02)]. There were no significant differences in total blood loss [1341ml±501, range: 830 to 2230 vs. 1263ml±459 range: 840 to 2480 (p=0.67)] and need of allogeneic blood transfusion [3 units vs. 2 units] between groups. ConclusionThe use of autologous blood transfusion was found to be safe, in terms of nephrotoxicity of aminoglycosides after TKA, but it seemed to be ineffective as a blood salvage strategy, when used concomitantly with the administration of tranexamic acid. Level of EvidenceII; low powered randomized study. ClinicalTrials.gov registration numberNCT04505748.

1314. Neonatal Serum Gentamicin Concentrations following Maternal Once-daily Gentamicin Dosing

BackgroundGentamicin is commonly used for peripartum infections. Given literature supporting efficacy of once-daily dosing (ODD) of 5 mg/kg for chorioamnionitis, University of Chicago Medicine made the change from three times daily dosing (TIDD) to ODD. As gentamicin readily cross the placenta, it would be expected that maternal ODD would result in higher gentamicin neonatal serum concentrations following birth.MethodsThis was a single-center, retrospective chart review of all neonates born to mothers receiving peripartum ODD gentamicin within 12 hours of delivery between October 2019 and March 2020. A STAT random gentamicin serum concentration was obtained upon admission in neonates when initiation of antibiotics was desired. Specific dosing recommendations (Table 1) were developed utilizing neonatal population-based pharmacokinetics. The primary outcome was initial neonatal gentamicin serum concentration at birth. Other outcomes were also evaluated. Results were evaluated in two groups based on neonatal serum concentrations of less than 2 mcg/mL (Group 1) versus 2 mcg/mL or greater (Group 2).Table 1: Neonatal gentamicin dosing algorithm ResultsThirty-two mother-newborn dyads were included in this study. Baseline demographics are shown in Table 2. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.39 kilograms. The mean initial gentamicin concentration was supratherapeutic at 3.06 + 1.92 mcg/mL among all newborns (Table 3). The mean maternal dose in Group 1 (n=11) was 3.52 mg/kg (3.34, 4.77) based on actual body weight and 4.78 mg/kg (4.34, 5.18) in Group 2 (n=21) (p=0.025). The median time between maternal gentamicin administration and time of delivery varied between the groups at 0.5 hours versus 2.63 hours, respectively (p=0.005). All newborn gentamicin concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n=8) (Figure 1). Overall protocol compliance rate was 81.3%. There were no significant differences in nephrotoxicity or ototoxicity between groups.Table 2. Baseline Demographics Table 3. Outcomes Figure 1. Comparison of maternal gentamicin time from administration to delivery and neonatal serum gentamicin concentrations ConclusionThis study suggests peripartum ODD of gentamicin may lead to clinically significant serum concentrations in neonates if administered between 1 to 12 hours of birth. Further studies are warranted to evaluate the effects of maternal ODD of gentamicin on newborns.Disclosures All Authors: No reported disclosures

Is serum gentamicin concentration modified with autologous cell-saved blood transfusion after total knee arthroplasty using tranexamic acid? A randomised control trial

BackgroundSelf-transfusion has been proven as an effective management of blood loss after total knee arthroplasty (TKA). Considering that the high local concentration of antibiotic from bone cement is delivered intravenously through the self-transfusion process, systematic toxicity has never been evaluated. In addition, the effectiveness of self-transfusion with the routine concomitant use of other modern blood-salvage strategies, like tranexamic acid, should also be assessed. Therefore, we performed a randomised study to assess: 1) the safety of self-transfusion in TKA by comparing the gentamicin concentrations resulting from the use or not of autologous blood transfusion; 2) the efficacy of self-transfusion in TKA, with the concomitant administration of tranexamic acid. HypothesisSelf-transfusion in TKA elevates the serum gentamicin concentration and the potential risk of nephrotoxicity. MethodsThe serum concentration of aminoglycosides was measured in two groups of 20 patients each, after TKA, according to the use of self-transfusion. Hemoglobin, renal function and calculated blood loss were compared at several points in time between groups. ResultsThe only time where there was a statistically significant difference in serum gentamicin, was at 48h postoperatively between groups [0.3 ug/mL±0.21, range: 0.15 to 0.72 vs. 0.14ug/mL±0.1, range: 0 to 0.35 (p=0.02)]. There were no significant differences in total blood loss [1341mL±501, range: 830 to 2230 vs. 1263mL±459 range: 840 to 2480 (p=0.67)] and need of allogeneic blood transfusion [3 units vs. 2 units] between groups. ConclusionThe use of autologous blood transfusion was found to be safe, in terms of nephrotoxicity of aminoglycosides after TKA, but it seemed to be ineffective as a blood salvage strategy, when used concomitantly with the administration of tranexamic acid. Level of evidenceII; low-powered randomised study. ClinicalTrials.gov registration numberNCT04505748.

Acute kidney failure after total knee arthroplasty revision with antibiotic-impregnated cement spacer.

Gentamicin-impregnated cement beads and spacers are frequently used in case of infective complications after Total Knee Arthroplasty (TKA). A great number of studies in the literature demonstrated that the local administration of gentamicin produces high local antibiotic levels but low serum and urine gentamicin concentrations. Gentamicin-impregnated cement spacer can induce nephrotoxicity in patients presenting major renal impairment susceptibility. We report a case of acute renal failure using a gentamicin-impregnated block spacer. An 83-year-old woman underwent a gentamicinimpregnated bone–cement spacer implant because of an infected TKA removal. Three days later patient clinical status got worse reporting a decreased urine output and increasing C-reactive protein (CRP), Serum Creatinine (SCr) and Blood Urea Nitrogen (BUN). Because the symptoms could be related to the knee spacer lead us to the decision of gentamicin-impregnated cement spacer removal. The day following the removal procedure showed progressive improvement of general condition with evidence of SCr and BUN normalization. Gentamicin-impregnated cement spacer can induce nephrotoxicity in patients presenting major renal impairment susceptibility.

Gentamicin serum concentrations after reinfusion of blood in patients undergoing arthroplasty with gentamicin-loaded bone cement.

Gentamicin serum concentrations after reinfusion of blood in patients undergoing arthroplasty with gentamicin-loaded bone cement.

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.

Clinical audit of gentamicin use by Bayesian pharmacokinetic approach in critically ill children

IntroductionCritically ill children tend to have altered gentamicin pharmacokinetics (PK); and so we carried out an audit of gentamicin use using the estimated peak concentrations (Cmax), trough concentrations (Cmin) and area-under-the-concentration-time curve (AUCs) by Bayesian approach. MethodsCritically ill children with at least one serum gentamicin concentrations available were recruited. We used multiple models Bayesian adaptive control to estimate Cmax, and AUC0-t following each dose. Pediatric risk, injury, failure, loss, end stage renal disease (pRIFLE) criteria was used to identify the incidence of acute kidney injury (AKI). ResultsSeventy-three children (961 doses and 143 concentrations) were analysed. AUC0-24 was observed to be higher in earlier age groups with a steady decline in older children. Similar changes were observed in Cmax, Cmin and AUC0-24 at steady state. Significantly higher proportions of children in the other age groups were estimated to have Cmax between 5 and 10 mg/L compared to neonates. Neonates had a higher risk of Cmax above 10 mg/L. Patients with augmented renal clearance exhibited lower AUC0-24 and reduced proportion achieving the target AUC0-24 levels. Nearly one-third of children were observed to meet the pRIFLE criteria for AKI. ConclusionWe observed higher initial doses and peak concentrations of gentamicin in neonates and infants compared to older age groups in critically ill children. Uniformity in the paediatric-specific standard treatment guidelines for gentamicin is the need of the hour.

Gentamicin Alone Is Inadequate to Eradicate Neisseria Gonorrhoeae From the Pharynx.

Centers for Disease Control and Prevention (CDC) guidelines recommend 240 mg gentamicin plus 2 g azithromycin for the treatment of gonorrhea in cephalosporin-allergic patients. The efficacy of gentamicin alone in the treatment of pharyngeal gonorrhea is uncertain. Between September 2018 and March 2019, we enrolled men who have sex with men with nucleic acid amplification test-diagnosed pharyngeal gonorrhea in a single-arm, unblinded clinical trial. Men received a single 360-mg intramuscular dose of gentamicin and underwent test of cure by culture 4-7 days later. The study measured creatinine at enrollment and test of cure, serum gentamicin concentration postdose to establish peak concentration (Cmax), and standard antimicrobial minimum inhibitory concentrations (MICs) by agar dilution. The trial was designed to establish a point estimate for gentamicin's efficacy for pharyngeal gonorrhea. We planned to enroll 50 evaluable participants; assuming gentamicin was 80% efficacious, the trial would establish a 95% confidence interval (CI) of 66%-90%. We planned interim analyses at n = 10 and n = 25. The study was stopped early due to poor efficacy. Of 13 enrolled men, 10 were evaluable, and only 2 (20% [95% CI, 2.5%-55.6%]) were cured. Efficacy was not associated with gentamicin Cmax or MIC. No participants experienced renal insufficiency. The mean creatinine percentage change was +5.2% (range, -6.7% to 21.3%). Six (46%) participants experienced headache, all deemed unrelated to treatment. Gentamicin alone failed to eradicate Neisseria gonorrhoeae from the pharynx. Clinicians should use caution when treating gonorrhea with the CDC's current alternative regimen (gentamicin 240 mg plus azithromycin 2 g) given increases in azithromycin resistance and gentamicin's poor efficacy at the pharynx. NCT03632109.

A review of population pharmacokinetic models of gentamicin in paediatric patients.

Gentamicin is often used for the treatment of Gram-negative infections. Due to pharmacokinetic variability in paediatric patients, appropriate dosing of gentamicin in the paediatric population is challenging. This article reviews published population pharmacokinetic models of gentamicin in paediatric patients, identifies covariates that significantly influence gentamicin pharmacokinetics, and determines whether there is a consensus on proposed dosing for intravenous gentamicin in this population. The PubMed database was searched for articles published until the end of 2017. If the articles described population pharmacokinetic models of gentamicin in the paediatric population (after intravenous administration of gentamicin), the following data were extracted: type of study, year of publication, population characteristics and number of patients, gentamicin dosing, total number of gentamicin (serum and/or plasma) concentrations, type of population modelling approach, developed model with pharmacokinetic parameters and covariates included. In most of the studies, one- or two-compartment modelling was applied. The mean estimated gentamicin clearance for newborns, infants and the complete paediatric population was 0.048, 0.13 and 0.067L/h/kg, respectively, and the mean predicted volume of distribution was 0.475, 0.35 and 0.33L/kg, respectively. The values reflect differences in body composition and kidney maturation within the different paediatric populations. Gentamicin pharmacokinetics were most influenced by age, body size and renal function. Based on our review, the authors agree on a prolonged dosing interval for preterm and term newborns (up to 48hours). However, there was no agreement on proposed dosing with respect to gestational age. In general, the proposed daily doses were lower compared to those initially applied for preterm newborns and comparable to those for term newborns. For infants and children, the dosing interval remained unchanged (24hours), but the proposed daily doses were higher than actually applied. When differences in the paediatric population are considered and an appropriate population PK model with applicable covariates is applied, dosing can be individualized. In the future, studies of gentamicin pharmacokinetics in paediatric patients should focus on currently underestimated covariates, such as fat-free mass, concomitantly administered drugs, body temperature and critical illness because these can change gentamicin PK considerably. Consequently, different dosing is required and TDM becomes even more important.

Individualization of treatment with gentamicin in neonates based on drug concentration in the blood serum.

AimTo evaluate how useful it is to make measurements of gentamicin concentrations in newborns' b/ood in order to optimize antibiotic therapy.Material and methods73 newborns empirically treated with gentamicin, in doses consistent with the Neofax® guidelines. There were 152 measurements of maximum and minimum serum gentamicin concentrations. Samples were determined based on the chemiluminescence technique on the Siemens Advia Centaur analyzer. The concentrations of gentamicin that were measured were compared with various therapeutic ranges used in the literature.ResultsAccording to the standards adopted in the University Hospital in Wrocław, the maximum concentration was reached in 38.16% of all the chi/dren, white the minimum in 26.32%. In other chi/dren the concentrations were below or above the therapeutic range. According to the Neofax® guidelines, the intended maximum concentration was observed in 71.05% of the newborns, and the minimum in 32.89%. The minimum concentration of <2 mg/L was found in 93.42% of the newborns, white >2 mg/L was determined in 33.33%, despite a 48-hour dosing interval. These were premature ba bies (<28th week of gestational age) and 55.56% of them reached a maximum concentration of 5-12 mg/L.There was no significant correlation between maximum or minimum concentration and gestational age or body weight.Conclusions1. The dosage of gentamicin in newborns according to the Neofax® recommendations does not ensure achieving the intended serum antibiotic concentrations. 2. In order to optimize gentamicin therapy in newborns it is necessary to individualize the dose based on measurements of drug concentrations in the blood and pharmacokinetic calculations.

Concentrations of Gentamicin In Serum, Intrauterine Fluid, and Endometrial Tissue After Intravenous Administration in Healthy Mares

In all eutherian mammals, there are two modes for supplying nutrients to the conceptus, histotrophic and hemotrophic nutrition. In general, these modes are sequential; although in some species, the two operate in parallel throughout the entire pregnancy. Although hemotrophic nutrition is the most important for proper growth of the fetus as assessed by birth weight, there is growing evidence that the phase of histotrophic nutrition is critical for initial development of the placenta. Evidence from animal species has revealed the existence of a signaling dialog between the trophoblast of the placenta and the endometrial glands, whereby the secretion of nutrients, collectively known as uterine milk proteins, and growth factors is upregulated during early pregnancy. In this way, the placenta is able to stimulate its own development. Circumstantial evidence suggests that an equivalent dialog occurs in the human and that deficiencies in endometrial function in early pregnancy may underpin complications of later pregnancy. The conservation of the trophoblast-endometrial dialog across species, with such differences in placental types as the horse and the human, suggests that it is of fundamental importance in placentation. The implication is that attempts should be made to ensure the endometrium is in optimal condition before conception.

The "Ideal" Body Weight for Pediatric Gentamicin Dosing in the Era of Obesity: A Population Pharmacokinetic Analysis.

Obese pediatric patients often require dose reductions when initiating gentamicin therapy. An appropriate method for calculating ideal body weight for dosing gentamicin in pediatric patients has not been validated. A retrospective population pharmacokinetic study was designed and included non-intensive care pediatric patients who received gentamicin and had serum gentamicin concentrations sampled. Actual body weight (ABW), adjusted body weight, and fat-free mass (FFM) were used to describe the pharmacokinetic variables. Descriptive statistical methods were used for the population, and pharmacokinetic analysis occurred with NONMEM (ICON Plc, Dublin, Ireland). Simulation was performed to estimate dosing based on adjustments in body weight. A total of 520 patients met inclusion criteria (male 57.3%, mean age 9.6 ± 4.9 years, ABW 38.0 ± 24.3 kg). Obesity was present in 21.3% of the patients and overweight in 15.8%. Gentamicin was administered at 2.17 ± 0.86 mg/kg per dose. A median of 2 (interquartile range, 1-3) gentamicin serum concentrations were sampled at a median 1.8 (interquartile range, 1.1-7.8) hours after a dose. Population pharmacokinetic analysis demonstrated a 2-compartment model with allometrically scaled FFM providing the best fit. Other significant covariates included serum creatinine and age. Simulation demonstrated increased doses per body weight for traditional and once-daily dosing when using FFM for gentamicin dosing. FFM should be used to adjust ABW for empirically dosing gentamicin in pediatric patients aged 2-18 years.

Cement mantle thickness does not influence serum or local gentamicin concentrations in hybrid total hip arthroplasty: a randomised controlled trial.

We investigated the in vivo gentamicin elution kinetics of Hi-Fatigue Gentamicin Bone Cement (AAP Biomaterials GmbH) in serum and drain fluid after hybrid hip arthroplasty and the relationship with cement mantle thickness. We compared in a randomised, non-blinded prospective study, the local and systemic gentamicin concentrations in 2 groups. The thin cement mantle group ( n = 16) received a stem implanted line-to-line with the broach, whereas the thick group ( n = 14) had an undersized stem. Gentamicin concentrations were measured in drain fluid and serum at set intervals for 3 days postoperatively. In both groups, local gentamicin concentrations were similar. After a high initial burst above the minimal inhibitory concentration (thin: 57.2 mg/L (SD 34.4), thick: 54.9 mg/L (SD 19.9), p = 0.823) local gentamicin concentrations declined rapidly. In both groups, serum concentrations never exceeded toxic levels (maximum 1.08 mg/L). In hybrid total hip arthroplasty, Hi-Fatigue Gentamicin Bone Cement resulted in effective and safe gentamicin concentrations. Clinical trial protocol number: PMCI 12/02.

Monitoring of gentamicin serum concentrations in obstetrics and gynaecology patients in Namibia.

Background Therapeutic drug monitoring is frequently used to optimize the gentamicin dose. Objective The study investigated whether a 240mg once daily standard dose achieves the recommended target serum gentamicin concentrations. Setting The prospective, observational study took place in the 2 major public hospitals in Namibia. Method Twenty-nine female patients receiving a standard dose (240mg gentamicin once daily) participated in the study. Two blood samples were withdrawn to estimate gentamicin pharmacokinetic parameters. Serum creatinine was used to calculate creatinine clearance with the Cockcroft-Gault formula (CLcr), and estimate glomerular filtration rate (eGFR) by the Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Main outcome measure The outcome measure was the proportion of patients receiving 240mg gentamicin once daily having Cmax values above 15mg/L. Results Total body weight (TBW) and body mass index were highly variable: 43-115kg, and 17.3-41.3kg/m2, respectively. The gentamicin dose normalized for TBW (adjusted body weight for obese patients) was relatively low, i.e. 4.2 ± 0.8mg/kg (mean SD). Gentamicin Cmax was 14.4 ± 4.7mg/L; only 9 patients (31%) had a Cmax > 15g/mL. eGFR (MDRD-4) correlated well with CLcr, but eGFR (EPI-CKD) formula showed systematic deviations from CLcr. Conclusions (1) a standard 240mg dose results in gentamicin Cmax values below 15mg/L in the majority of the patients, (2) eGFR formulas to estimate kidney function will have to be evaluated for their usefulness in the Namibian patient population.