Dose Of Gentamicin Research Articles

Renal safety of short-term empiric gentamicin therapy in aged patients.

To determine the incidence of acute kidney injury (AKI) in aged patients receiving empiric gentamicin therapy. Patients aged ≥65 years receiving gentamicin upon admission between 2013 and 2015 at two Australian hospitals were retrospectively studied. AKI was defined as a rise in creatinine by ≥50% and/or ≥26.5 μmol/L. Most patients (95%) received a single dose of gentamicin. The incidence of AKI was 15% (36/242 patients). A composite outcome of persistent kidney injury, requirement for renal replacement therapy or inpatient death in a patient with AKI occurred in 10 (4%) patients. Patients who developed AKI were older (median 80.5 vs 78 years, P = 0.03), had higher Charlson Co-morbidity Index (median 7 vs 5, P = 0.0004) and had more advanced chronic kidney disease at baseline (Stages IV and V) (OR 4.38, 95% confidence interval 1.45-13.2, P = 0.01). Empiric gentamicin use in patients with advancing age is associated with low rates of predominantly transient renal impairment.

Antimicrobial labelling in Australia: a threat to antimicrobial stewardship?

Antimicrobial resistance is a public health emergency, placing veterinary antimicrobial use under growing scrutiny. Antimicrobial stewardship, through appropriate use of antimicrobials, is a response to this threat. The need for antimicrobial stewardship in Australian veterinary practices has had limited investigation. A 2016 survey undertaken to investigate antimicrobial usage patterns by Australian veterinarians found that antimicrobial dose rates were varied and often inappropriate. Doses of procaine penicillin in horses and cattle were often low, with 68% and 90% of respondents, respectively, reporting doses that were unlikely to result in plasma concentrations above minimum inhibitory concentrations for common equine and bovine pathogens. Frequency of penicillin administration was also often inappropriate. Gentamicin doses in horses were largely appropriate (89% of dose rates appropriate), but 9% of respondents reported twice daily dosing. Amoxycillin and amoxycillin-clavulanate were administered at the appropriate doses, or above, to dogs and cats by 54% and 70% of respondents, respectively. Here, we explore the potential reasons for inappropriate antimicrobial dose regimens and report that antimicrobial labels often recommend incorrect dose rates and thus may be contributing to poor prescribing practices. Changes to legislation are needed to ensure that antimicrobial drug labels are regularly updated to reflect the dose needed to effectively and safely treat common veterinary pathogens. This will be especially true if changes in legislation restrict antimicrobial use by veterinarians to the uses and doses specified on the label, thus hampering the current momentum towards improved antimicrobial stewardship.

A Randomized Controlled Trial of Preoperative Prophylactic Antibiotics Prior to Percutaneous Nephrolithotomy in a Low Infectious Risk Population: A Report from the EDGE Consortium

Single institution studies suggest a benefit of a week of preoperative antibiotics prior to percutaneous nephrolithotomy. These studies are limited by lower quality methodology, such as the inclusion of heterogeneous populations or nonstandard definitions of sepsis. The AUA (American Urological Association) Best Practice Statement recommends less than 24 hours of intravenous antibiotics but to our knowledge no other data exist on the duration or benefit of preoperative antibiotics. Using CONSORT (Consolidated Reporting of Trials) guidelines we sought to perform a rigorous multi-institutional trial to assess preoperative antibiotics in patients in whom percutaneous nephrolithotomy was planned and who were at low risk for infection. This randomized controlled trial enrolled patients undergoing percutaneous nephrolithotomy who were at low risk, defined as negative preoperative urine cultures and no urinary drain. Of the subjects 43 were randomized to nitrofurantoin 100 mg twice daily for 7 days preoperatively while a control arm of 43 received no oral antibiotics. All subjects received perioperative doses of ampicillin and gentamicin. Prone percutaneous nephrolithotomy was performed by urologists blinded to randomization. The primary outcome was the development of sepsis. A total of 86 subjects were enrolled. Preoperative patient characteristics were similar in the treatment and control cohorts with a stone size of 19 and 17 mm, respectively (p = 0.47). Intraoperative characteristics also did not differ. The sepsis rate was not statistically different between the treatment and control groups (12% and 14%, respectively, 95% CI -0.163-0.122, p = 1.0). Other infectious parameters and complications were similar, including intensive care admission, fever, hypotension and leukocytosis. Our study demonstrated no advantage to providing 1 week of preoperative oral antibiotics in patients at low risk for infectious complications who undergo percutaneous nephrolithotomy. Perioperative antibiotics according to the AUA Best Practice Statement appear sufficient.

Daily gentamicin using ideal body weight demonstrates lower risk of postpartum endometritis and increased chance of successful outcome compared with traditional 8-hour dosing for the treatment of intrapartum chorioamnionitis

Background: Clinical chorioamnionitis complicates approximately 1–4% of pregnancies overall. Although universal agreement does not exist regarding the antibiotic regimen of choice, most studies have evaluated intravenous ampicillin dosed at 2 g every 6 hours plus gentamicin dosed every 8 hours. Only three studies have examined daily gentamicin for the treatment of intrapartum chorioamnionitis and thus is insufficiently investigated.Objective: This study seeks to determine whether daily dosing of gentamicin using ideal body weight for the treatment of intrapartum chorioamnionitis is more or equivalently efficacious when compared to traditional 8-hour dosing regimens.Materials and methods: We conducted a retrospective cohort study and reviewed charts on all women receiving treatment for intrapartum chorioamnionitis, which included intravenous gentamicin daily dosing calculated using 5 mg/kg ideal body weight or receiving traditional every 8 hours dosing of gentamicin at two large academic centers. Our primary outcomes were resolution of infection following delivery without the development of maternal endometritis and/or neonatal sepsis. Baseline characteristics were compared between dosing groups using Welch two-sample t-tests for continuous variables, uncorrected X2 test and exact binomial 95% confidence intervals. We calculated the risk ratios of each outcome in the ideal versus traditional dosing groups using modified Poisson regression, both crude and adjusted. Adjusted models were controlled for variables determined to be potential confounders, which included BMI, diabetes mellitus, gestational blood pressure >140/90, group β-Streptococcus status, race, advanced maternal age (>34 y), and parity.Results: The study included 500 patients with 255 patients receiving daily dosing of gentamicin and 245 receiving traditional dosing of gentamicin. Of the patients receiving daily gentamicin compared to traditional dosing, 95.7% (95% CI 94.9–96.6%) achieved the primary outcome versus 92% (95% CI 90.8 − 93.2%), 2.4% (95% CI 1.8–3%) developed endometritis versus 5.6% (4.5–6.7%), 1.6% (95% CI 1.1–2.1%) delivered neonates with sepsis versus 3.3% (CI 2.5–4.1%), and 36.9% required cesarean delivery versus 41.4%. In crude analysis, compared to traditional dosing, IDW daily dosing was associated with a lower risk of postpartum endometritis (RR 0.42, 95% CI 0.16–1.10, p = .032). After adjusting for BMI, diabetes mellitus, gestational blood pressure >140/90, group β-Streptococcus status, race, advanced maternal age (>34 y), and parity, the IDW daily dosing group had a 5% greater chance of successful outcome (RR 1.05, 95% CI 1.00–1.10, p = .046) and a 64% lower risk of endometritis (RR 0.35, 95% CI 0.15–0.83, p = .017).Conclusion: Daily dosing of gentamicin using ideal body weight is associated with a lower risk of postpartum endometritis and high chance of a successful outcome in the treatment of intrapartum chorioamnionitis compared with traditional 8-hour dosing in our ethnically diverse, urban population and thus may be considered a superior option to every 8 hours dosing regimens.

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.

Quantitative Analysis of Gentamicin Exposure in Neonates and Infants Calls into Question Its Current Dosing Recommendations.

Optimal dosing of gentamicin in neonates is still a matter of debate despite its common use. We identified gentamicin dosing regimens from eight international guidelines and seven Swiss neonatal intensive care units. The dose per administration, the dosing interval, the total daily dose, and the demographic characteristics between guidelines were compared. There was considerable variability with respect to dose (4 to 6 mg/kg), dosing interval (24 h to 48 h), total daily dose (2.5 to 6 mg/kg/day), and patient demographic characteristics that were used to calculate individualized dosing regimens. A model-based simulation study in 1071 neonates was performed to determine the achievement of efficacious peak gentamicin concentrations according to predefined MICs (Cmax/MIC ≥ 10) and safe trough concentrations (Cmin ≤ 2 mg/liter) with recommended dosing regimens. MIC targets of 0.5 and 1 mg/liter were used. Dosing optimization was performed giving priority to the first day of treatment and with the goal of simplifying dosing. Current gentamicin neonatal guidelines allow to achieve effective peak concentrations for MICs ≤ 0.5 mg/liter but not higher. Model-based simulations indicate that to attain peak gentamicin concentrations of ≥10 mg/liter, a dose of 7.5 mg/kg should be administered using an extended dosing interval regimen. Trough concentrations of ≤2 mg/liter can be maintained with a dosing interval of 36 to 48 h in neonates according to gestational and postnatal age. For treatment beyond 3 days, therapeutic drug monitoring is advised to maintain adequate serum concentrations.

An evaluation of serum gentamicin concentrations and bacterial susceptibility to gentamicin in equine practice.

BackgroundTherapeutic drug monitoring and minimum inhibitory concentration (MIC) data allow more informed use of gentamicin.Hypothesis/ObjectivesTo measure peak and trough serum gentamicin concentrations in horses after a 6.6 mg/kg dose of gentamicin given IV and the MIC of gentamicin of bacteria for which gentamicin might be selected.MethodsRetrospective analysis of hospital records. Peak and trough plasma gentamicin concentrations were measured after 6.6 mg/kg gentamicin IV in 339 hospitalized horses. The MIC of gentamicin was measured for 503 isolates from ambulatory practice and 33 from hospital practice. The distribution of gentamicin concentrations and MIC results were compared to current recommendations for MIC breakpoints.ResultsThe median serum gentamicin concentration at 60 minutes after administration (C 60min) was 21.4 μg/mL with a distribution indicating that bacteria with MIC ≥2 μg/mL were unlikely to be exposed to sufficient gentamicin for effective killing. Approximately 90% of isolates from ambulatory practice and 36% of hospital isolates had MICs at or below breakpoints for susceptibility with most of the remainder unlikely to be responsive, even to higher IV doses.Conclusions and Clinical ImportanceGentamicin at a dosage of 6.6 mg/kg IV is likely to be effective against the majority of infections encountered in ambulatory practice, but less effective in an equine hospital. Because there was a dichotomy of most bacteria as being clearly susceptible or clearly resistant to gentamicin, it appears unlikely that higher doses would have been more efficacious, especially in the hospitalized population in our study.

Evaluation of Low-Dose Gentamicin Once Daily Dosing Regimen at A General Hospital in Malaysia

Objective: Once daily dosing (ODD) aminoglycoside is gaining wide acceptance as an alternative way of dosing. In our setting it is the regimen of choice whenever gentamicin is indicated. The objective of this study was to evaluate the practice of gentamicin ODD in a public hospital in Malaysia. Methods: We conducted a retrospective review of medical records of patients on gentamicin ODD who were admitted to Hospital Melaka during January 2002 until March 2010. All adult patients who were on ODD gentamicin with various level of renal function were included in the study. Patients on gentamicin less than 72 hours and pregnant women were excluded. Results: From 110 patients, 75 (68.2%) were male and 35 (31.8%) were female. Indications for ODD gentamicin included pneumonia, 34 (31.0%) neutropenic sepsis, 27 (24.5%) and sepsis, 11 (10.0%). The mean dose and duration of gentamicin was 3.2 mg/kg/day and 7 days, respectively. Almost all patients were on gentamicin combined with other antibiotics. Clinical cure based on fever resolution was found in 89.1% of patients treated with ODD. Resolution of fever took an average of 48 hours after initiation of therapy. The evaluation for bacteriologic cure could not be performed because of insufficient data on culture and sensitivity. Out of 38 patients with analyzable serum creatinine data, four patients might have developed nephrotoxicity. Conclusion: In our setting, lower dosages of ODD gentamicin when used in combination with other antibiotics seemed to be effective and safe in treating most gram negative infections.

Neonatal Gentamicin Dosing ‐ Experience with Extending the Dose Interval to 60 Hours and Simplifying Monitoring

Neonatal Gentamicin Dosing ‐ Experience with Extending the Dose Interval to 60 Hours and Simplifying Monitoring

Gentamicin in Newborn Sepsis: Once Daily Dose versus Twice Daily Dose

Gentamicin is commonly used as first line drug in neonatal sepsis. It is usually used in combination with other drugs. It is a nephrotoxic and an ototoxic drug. Long term use causes renal failure and hearing impairment. Its efficacy depends on the peak concentration, and its toxicity is related to the trough concentration. There is no set protocol of using gentamicin in neonate in Bangladesh, whether it should be used once daily or twice, it is till debatable in this perspective. In daily practice, it is not followed up trough and peak concentration of gentamicin, so it is not known the renal and hearing status of the baby treated with aminoglycosides. In this regard, primary objectives were to measure the peak level (to observe efficacy) and trough (to observe toxicity) level of gentamicin in once-daily dose (ODD) and in twice-daily dose (TDD) of gentamicin in neonates treated for suspected or culture proven sepsis and finally to assess the renal status and hearing status. This was an open label clinical trial, conducted in the Neonatal Intensive Care Unit, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, during the period of March, 2012 to November, 2012. A total of 50 neonates were included in the study, 25 in ODD group and 25 in TDD group of gentamicin. Serum gentamicin peak and trough were measured in both groups. Mean gestational age were 38.85±1.21Wk and 38.83±1.16Wk in ODD and TDD respectively, and their corresponding mean weights were 2341.66±377 gram and 2307±363 gram. Only a fraction (12 % in ODD group 20% in TDD group) of patients had culture positive sepsis. The mean peak concentration of gentamicin was significantly higher (p value < 0.001) among neonates who received once-daily dose (7.19±1.7 microgram/ml) compare to patients who received the twice-daily dose (4.81±1.8 microgram/ml). The mean trough concentration of gentamicin was significantly lower (p value = 0.04) among neonates who received once-daily dose (1.5±0.78) compared to patients who received the twice-daily dose (2.00±0.9). Serum creatinine concentration raise was statistically non-significant in both group. Only 4% in ODD and 8% in TDD had ototoxicity which was non-significant finding. It may be concluded that ODD of gentamicin had significant higher concentration of peak and lower trough concentration, but no significant difference was in serum creatinine concentration and ototoxicity.

Preoperative measures to prevent/minimize risk of surgical site infection in spinal surgery.

Background:Multiple measures prior to spine surgery may reduce the risks of postoperative surgical site infections (SSIs).Methods:The incidence of SSI following spinal surgery (including reoperations and readmissions) may be markedly reduced by performing less extensive procedures and avoiding fusion where feasible. Preoperative testing up to 3 weeks postoperatively should include other studies to limit the perioperative SSI risk; cardiac stress tests (e.g., older patients/cardiac comorbidities), starting tamsulosin in males over 60 (e.g. avoid urinary retention due to benign prostatic hypertrophy), albumin/prealbumin levels (e.g., low levels increase SSI risk), and HBA1C levels to identify new/treat known diabetics (normalize/reduce preoperative levels).Results:Other measures include the timely administration of preoperative antibiotics (e.g., cefazolin 2 g nonpenicillin allergic), one dose of gentamicin (adjusted dose/weight), nasal cultures for methicillin-resistant Staphylococcus aureus (patients/health-care workers), and bathing 2 weeks preoperatively with chlorhexidine gluconate 4% (not just night before/morning of surgery). Additionally, prior to surgery, the following medications that increase the bleeding risk should be stopped (e.g. for varying periods); anticoagulants, antiplatelet therapies (e.g., aspirin for at least 7–10 days), nonsteroidal anti-inflammatories (NSAIDS: timing depends on the drug), vitamin E, and herbal supplements. Additionally, avoiding elective spinal surgery in morbidly obese patients and recognizing other major medical contraindications to spinal surgery should help reduce infection, morbidity, and mortality rates.Conclusions:Appropriate preoperative and intraoperative prophylactic maneuvers may reduce the risk of postoperative spinal SSI. Specific attention to these details may avoid infections and improve outcomes.

Protective Role of Pomegranate and Sodium bicarbonate on Acute Renal Failure Induced by Gentamicin In Rabbits Model

Acute renal failure ARF is common condition can be categorized as prerenal, intrinsic or postrenal causes in which the glomerular filtration rate decreases GFR over days to weeks . The aim of this study was to test whether the administration of pomegranate and sodium bicarbonate minimize the adverse health effect of acute renal failure. Methods : twenty female rabbits were assessed in to five groups ( n = 4 ) ,Group 1 : control group (C) .Group 2 : Gentamicin group ( G ): animals were injected with a single dose of Gentamicin ( 80 mg / Kg / bw ) intramuscular , daily for 10 days to induce renal failure. Group 3 : sodium bicarbonate group ( G+S ),animals were treated as in group 2 plus they received sodium bicarbonate ( 1 ml / Kg / bw ) of 8.4% by gavage daily for 10 days .Group 4 : pomegranate group ( G+P ),animals were treated as in group 2 plus they received pomegranate 500 ( mg / Kg / bw ) by gavage. Group 5 : combination group ( G+S+P ),animals were treated as in group 2 plus group 3 and group 4 for 10 days. Results : serum creatinine and blood urea levels were decreased in both groups (G+P) and (( G+S+P ) , p < 0.05 . while in group ( G+S ) they increased more effectively than the ( G) group .Serum electrolytes concentrations and serum ( pH ) shows different response , they were improved mostly in the ( G+S+P ) group, and they fluctuated in (G+S) group showing significant decreasing in serum ( Cl and Ca ) , p < 0.05 . Although the results for the hematological parameters were also improved in the combination group ( G+S+P ) but the differences were non significant between all others measured parameters and control group. Conclusions : the administration of sodium bicarbonate in Gentamicin model to induced acute renal failure inducement has adverse biological effects . but those effects were minimized by the ameliorative effects of the pomegranate administration which was helpful in speeding recovery

Potential of allogeneic bone grafts as antibiotic carriers : Effect of different preparation processes on efficacy

The rising number of primary joint replacements worldwide is causing an increase of endoprosthetic revision surgery due bacterial infection. Revision surgery using non-cemented implants seems beneficial for the long-term outcome, and the use of antibiotic-impregnated bone grafts might control the infection and provide agood support for the implant. In this study, we evaluated the release of antibiotics from fresh-frozen and lyophilized allogeneic bone grafts. Heat-treated, lyophilized and fresh frozen cryopreserved bone chips were impregnated with gentamicin sulphate, gentamicin palmitate and vancomycin, and calcium carbonate/calcium sulphate treated with antibiotics. The efficacy of each preparation was measured by drug release tests and bacterial susceptibility using B.subtilis, S.aureus and methicillin-resistant Staphylococcus aureus. The release of gentamicin from lyophilized bone was similar to the release rate from fresh frozen bone during the entire experiment. This might be related to the similar porosity and microstructure of the bone chips. The release of gentamicin from lyophilized and fresh frozen bone was high on the first and second days, then decreased and stayed at alow rate until the end of the second week. Depending on the surgical strategy, either polymethylmethacrylate or allogeneic bone are able to deliver sufficient concentrations of gentamicin to achieve bacterial inhibition within 2 weeks after surgery. In the case of uncemented revision of joint replacements, allogeneic bone can deliver therapeutic doses of gentamicin and peak levels immediately and afortnight after implantation.

Balancing Antibacterial Efficacy and Reduction in Renal Function to Optimise Initial Gentamicin Dosing in Paediatric Oncology Patients.

This study aimed to determine the optimal starting dose of gentamicin in paediatric oncology patients. A population pharmacokinetic model describing drug exposure, a semi-mechanistic model describing bacterial killing and an Emax model describing renal cortex accumulation were linked in a utility function using NONMEM®. The optimal gentamicin starting dose was estimated in patients aged from 0.1 to 18.2years, by balancing the probability of efficacy on day 1 against relative renal function reduction on day 7 with continued dosing. Using achievement of a gentamicin area under the concentration time curve to bacterial minimum inhibitor concentration (MIC) ratio of ≥ 100 and maximum concentration to MIC ratio of ≥ 10 as the efficacy endpoints, a starting dose of 7.1, 9.5, 10.8 and 14.6mg/kg/q24h was optimal at a MIC of 0.5, 1, 2 and 4mg/L respectively, with ≥ 75% probability of obtainment. Using achievement of a 2-log10 bacterial count reduction at 24-h post-dose as the efficacy endpoint, a starting dose of 12.8mg/kg/q24h was optimal, with 85.6% probability of obtainment. Under these different dosing scenarios, relative reduction in renal function ranged on average from 6.9 to 14.5% on day 7. The current recommended starting dose of gentamicin of 7.5mg/kg/q24h may not be sufficient to achieve efficacy on day 1 if bacterial MIC is > 0.5mg/L. A higher initial dose (up to 14.6mg/kg/q24h), in less sensitive microorganisms, would likely cause only a relatively small reduction in renal function at day 7. Close monitoring is crucial if high doses are given, especially for longer than 7days.

Listeria monocytogenes switches from dissemination to persistence by adopting a vacuolar lifestyle in epithelial cells.

Listeria monocytogenes causes listeriosis, a foodborne disease that poses serious risks to fetuses, newborns and immunocompromised adults. This intracellular bacterial pathogen proliferates in the host cytosol and exploits the host actin polymerization machinery to spread from cell-to-cell and disseminate in the host. Here, we report that during several days of infection in human hepatocytes or trophoblast cells, L. monocytogenes switches from this active motile lifestyle to a stage of persistence in vacuoles. Upon intercellular spread, bacteria gradually stopped producing the actin-nucleating protein ActA and became trapped in lysosome-like vacuoles termed Listeria-Containing Vacuoles (LisCVs). Subpopulations of bacteria resisted degradation in LisCVs and entered a slow/non-replicative state. During the subculture of host cells harboring LisCVs, bacteria showed a capacity to cycle between the vacuolar and the actin-based motility stages. When ActA was absent, such as in ΔactA mutants, vacuolar bacteria parasitized host cells in the so-called “viable but non-culturable” state (VBNC), preventing their detection by conventional colony counting methods. The exposure of infected cells to high doses of gentamicin did not trigger the formation of LisCVs, but selected for vacuolar and VBNC bacteria. Together, these results reveal the ability of L. monocytogenes to enter a persistent state in a subset of epithelial cells, which may favor the asymptomatic carriage of this pathogen, lengthen the incubation period of listeriosis, and promote bacterial survival during antibiotic therapy.

Adverse effects of a single dose of gentamicin in adults: a systematic review.

To systematically review the frequency and type of adverse events associated with a single dose of intravenous or intramuscular gentamicin in adults, for any indication, in studies where a comparator was available. A review protocol was developed and registered (PROSPERO: CRD42013003229). Studies were eligible for review if they: recruited participants aged ≥16years; used gentamicin intramuscularly or intravenously as a single one-off dose; compared gentamicin to another medication or placebo; and monitored adverse events. MEDLINE, EMBASE, Cochrane Library, trial registries, conference proceedings and other relevant databases were searched up to November 2016. Risk of bias was assessed on all included studies. In total, 15 522 records were identified. After removal of duplicates, screening of title/abstracts for relevance and independent selection of full texts by two reviewers, 36 studies were included. Across all the included studies, 24 107 participants received a single one-off dose of gentamicin (doses ranged from 1mgkg-1 to 480mg per dose). Acute kidney injury was described in 2520 participants receiving gentamicin. The large majority of cases were reversible. There were no cases of ototoxicity reported in patients receiving gentamicin. A meta-analysis was not performed due to study heterogeneity. A significant number of patients saw a transient rise in creatinine after a single dose of gentamicin at doses up to 480mg. Persistent renal impairment and other adverse events were relatively rare.

Antibiotics Reduce Retinal Cell Survival In Vitro.

Antibiotics such as gentamicin (an aminoglycoside) and penicillin (a beta-lactam antibiotic) are routinely used in retinal cell and explant cultures. In many cases, these in vitro systems are testing parameters regarding photoreceptor transplantation or preparing cells for transplantation. In vivo, milligram doses of gentamicin are neurotoxic to the retina. However, little is known about the effects of antibiotics to retina in vitro and whether smaller doses of gentamicin are toxic to retinal cells. To test toxicity, retinal cells were dissociated from tiger salamander, placed in culture, and treated with either 20μg/ml gentamicin, 100μg/ml streptomycin, 100U/ml antibiotic/antimycotic, 0.25μg/ml amphotericin B, or 100U/ml penicillin G. All dosages were within manufacturer's recommended levels. Control cultures had defined medium only. Cells were fixed at 2h or 7days. Three criteria were used to assess toxicity: (1) survival of retinal neurons, (2) neuritic growth of photoreceptors assessed by the development of presynaptic varicosities, and (3) survival and morphology of Mueller cells. Rod cells were immunolabeled for rod opsin, Mueller cells for glial fibrillary acidic protein, and varicosities for synaptophysin. Neuronal cell density was reduced with all pharmacological treatments. The number of presynaptic varicosities was also significantly lower in both rod and cone photoreceptors in treated compared to control cultures; further, rods were more sensitive to gentamicin than cones. Penicillin G (100U/ml) was overall the least inhibitory and amphotericin B the most toxic of all the agents to photoreceptors. Mueller cell survival was reduced with all treatments; reduced survival was accompanied by the appearance of proportionally fewer stellate and more rounded glial morphologies. These findings suggest that even microgram doses of antibiotic and antimycotic drugs can be neurotoxic to retinal cells and reduce neuritic regeneration in cell culture systems.

Survey on Single Dose Gentamicin in Treatment of UTI in Children from 1 Month to 1313 Years in Jahrom during 2015

Survey on Single Dose Gentamicin in Treatment of UTI in Children from 1 Month to 1313 Years in Jahrom during 2015

Partial Aminoglycoside Lesions in Vestibular Epithelia Reveal Broad Sensory Dysfunction Associated with Modest Hair Cell Loss and Afferent Calyx Retraction.

Although the effects of aminoglycoside antibiotics on hair cells have been investigated for decades, their influences on the dendrites of primary afferent neurons have not been widely studied. This is undoubtedly due to the difficulty in disassociating pathology to dendritic processes from that resulting from loss of the presynaptic hair cell. This was overcome in the present investigation through development of a preparation using Chinchilla laniger that enabled direct perilymphatic infusion. Through this strategy we unmasked gentamicin’s potential effects on afferent calyces. The pathophysiology of the vestibular neuroepithelia after post-administration durations of 0.5 through 6 months was assessed using single-neuron electrophysiology, immunohistochemistry, and confocal microscopy. Hair cell densities within cristae central zones (0.5-, 1-, 2-, and 6-months) and utricle peri- and extrastriola (6-months) regions were determined, and damage to calretinin-immunoreactive calyces was quantified. Gentamicin-induced hair cell loss exhibited a profile that reflected elimination of a most-sensitive group by 0.5-months post-administration (18.2%), followed by loss of a second group (20.6%) over the subsequent 5.5 months. The total hair cell loss with this gentamicin dose (approximately 38.8%) was less than the estimated fraction of type I hair cells in the chinchilla’s crista central zone (approximately 60%), indicating that viable type I hair cells remained. Extensive lesions to afferent calyces were observed at 0.5-months, though stimulus-evoked modulation was intact at this post-administration time. Widespread compromise to calyx morphology and severe attenuation of stimulus-evoked afferent discharge modulation was found at 1 month post-administration, a condition that persisted in preparations examined through the 6-month post-administration interval. Spontaneous discharge was robust at all post-administration intervals. All calretinin-positive calyces had retracted at 2 and 6 months post-administration. We found no evidence of morphologic or physiologic recovery. These results indicate that gentamicin-induced partial lesions to vestibular epithelia include hair cell loss (ostensibly reflecting an apoptotic effect) that is far less extensive than the compromise to stimulus-evoked afferent discharge modulation and retraction of afferent calyces (reflecting non-apoptotic effects). Additionally, calyx retraction cannot be completely accounted for by loss of type I hair cells, supporting the possibility for direct action of gentamicin on the afferent dendrite.

Therapeutic Drug Monitoring of Gentamicin Peak Concentrations in Critically Ill Patients.

Adequate gentamicin peak concentrations (Cmax) are important for optimal clinical efficacy. Within a critically ill patient, substantial variability in Cmax can occur over time, hampering the usefulness of therapeutic drug monitoring (TDM). The aim of this study was to evaluate the effect of gentamicin dosing based on Cmax after the first dose on gentamicin target attainment in critically ill patients. From gentamicin-treated critically ill patients, dosing information, clinical parameters, and serum concentrations were collected prospectively. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling to estimate Cmax after each dose. To evaluate the usefulness of routine TDM, percentages of Cmax within (%Cther, 15-20 mg/L), above (>20 mg/L), and below (%Csubther, <15 mg/L) the therapeutic range after the first and second doses were compared. In addition, simulations were performed to evaluate the impact of TDM. Four hundred sixteen measurements from 59 patients receiving 130 gentamicin doses were included. In the 30 patients who received >1 dose, TDM increased %Cther from 40% after a first median dose of 5.0 mg/kg to 50% after the second dose, and decreased %Csubther from 47% to 30%. Simulations using a 5 mg/kg starting dose revealed %Cther after the second dose of 28.4% without and 36.8% with TDM and %Csubther of 56.9% and 29.3%, respectively. Increasing the simulated starting dose to 6 mg/kg increased %Cther after the first dose from 27.7% to 33.5% and decreased %Csubther from 58.6% to 35.6%. TDM after a first dose of 6 mg/kg had no substantial effect on %Cther or %Csubther after the second dose. Gentamicin dosing based on Cmax after the first dose increased %Cther and decreased %Csubther, but did not result in therapeutic Cmax in half of the patients. When simulating a higher starting dose, %Csubther after the first dose decreased, and TDM showed no additional influence. These data suggest that a starting dose of 6 mg/kg should be considered and that repeated Cmax measurements are not of added value.