Gentamicin Levels Research Articles

NaCl promotes antibiotic resistance by reducing redox states in Vibrio alginolyticus.

The development of antibiotic resistance in Vibrio alginolyticus represents a threat to human health and fish farming. Environmental NaCl regulation of bacterial physiology is well documented, but whether the regulation contributes to antibiotic resistance remains unknown. To explore this, we compared minimum inhibitory concentration (MIC) of V. alginolyticus cultured in different media with 0.5%-10% NaCl, and found that the MIC increased as the NaCl concentration increased, especially for aminoglycoside antibiotics. Consistent with this finding, internal NaCl also increased, while intracellular gentamicin level decreased. GC-MS-based metabolomics showed different distributions of pyruvate cycle intermediates among 0.5%, 4% and 10% NaCl. Differential activity of enzymes in the pyruvate cycle and altered expression of Na(+)-NQR led to a reducing redox state, characterized by decreased levels of NADH, proton motive force (PMF) and ATP. Meanwhile, NaCl negatively regulated PMF as a consequence of the reducing redox state. These together are responsible for the decreased intracellular gentamicin level with the increased external level of NaCl. Our study reveals a previously unknown redox state-dependent mechanism regulated by NaCl in V. alginolyticus that impacts antibiotic resistance.

Antibiotic Containing Bone Substitute in Major Hip Surgery: A Long Term Gentamicin Elution Study.

Objectives: The objective is to present the antibiotic elution from a locally implanted gentamicin containing hydroxyapatite and calcium sulphate bone substitute with an extended follow up of 30 days.We also compare the pharmacokinetics of the ceramic bone substitute with a published study on gentamicin containing poly (methyl methacrylate) (PMMA) bone cement used in primary total hip arthroplasty.Methods: Gentamicin release was measured in the urine for a month and the serum for 4 days in 10 patients operated for trochanteric hip fractures and 10 patients in uncemented hip revisions. 17 patients were followed up at one year and 3 patients at 6 months.Results and Discussion: The gentamicin concentrations measured in serum were low and approximately 100 times less than in urine during the first days, indicating high local concentrations at the implant site. The elution from the biphasic bone substitute showed a stronger burst and higher gentamicin concentrations for the first week compared to that reported for PMMA used in hip arthroplasty. Also, for the bone substitute a complete gentamicin elution was obtained after 30 days, while for the PMMA cement sub-inhibitory MIC levels of gentamicin were still present in urine 60 days past surgery. No infections were detected.Conclusions: A new biphasic bone substitute containing antibiotics could potentially be used to prevent infection in patients treated for trochanteric hip fractures or uncemented hip revisions. The gentamicin elution from the bone substitute is efficient with high initial local gentamicin concentrations and complete release at 30 days.

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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.

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.

Antibiotic residues in different chicken Carcass parts in Menufyia and Cairo governorates

A grand total of 120 freshly slaughtered broiler chickens (50 each of breast and thigh and 5 each of thigh skin, breast skin, liver and kidney) were collected from dfferent small slaughter houses at both Menufiya and Cairo governorates for detection of the residual level of streptomycin, gentamicin, florfenicol, lincospectin and enrofloxacin. The detection and estimation of such antibiotics were applied by Micrbiological Inhibiotion Test & HPLC. The overall incidence of antibiotic residues positive samples resulted from microbiological inhibition test was 40% each of liver and kidney, it was also 40% for each of thigh skin and breast skin and 36% and 20% for thigh and breast from highest to the lowest incidence. The mean concentrations (mean value of positive samples only) of antibiotic residues at Menufiya governorate was higher than those in Cairo governorate. Using HPLC, the arrangement of mean concentration from the highest to the lowest at Menufiya governorate was streptomycin residues in examined samples by ppb were 1588.8± 488.92 for thigh and 1048.75± 290.46 for breast followed by the only lincospectin sample (259.4± 0 for thigh) then gentamycin (142.05±84.75 for thigh and 103.5±0 for breast) and after that florfenicol (26.34±7.52 for thigh and 11.24±3.06 for breast). Enrofloxacin failed to be detected in any of examined samples. At Cairo governorate, there wasn’t any lincospectin nor enrofloxacin residues in examined samples. The arrangement from the highest to the lowest will be streptomycin (1572±237 for thigh and 543±82 for breast), gentamicin (97.65±58.55 for thigh and 61.7±0 for breast), florfenicol (18.95±4.88 for thigh and 5.53±0.64 for breast), and finally lincospectin and enrofloxacin with zero value.

Systemic Absorption of Antibiotics From Antibiotic-Loaded Cement Spacers for the Treatment of Periprosthetic Joint Infection

BackgroundTwo-stage treatment of periprosthetic joint infections involves placement of high-dose antibiotic-loaded cement spacers (ACSs). Reports of ACS-induced nephrotoxicity have raised concern regarding systemic absorption of antibiotics after ACS placement. We sought to characterize the serum concentrations of antibiotics that occur after ACS placement. MethodsWe performed a prospective study of patients with an infected primary total hip (THA) or knee arthroplasty (TKA) treated with standardized ACSs with vancomycin, gentamicin, and tobramycin. Serum antibiotic levels were collected weekly for 8 weeks. ResultsTwenty-one patients (10 THA, 11 TKA) were included. Mean serum gentamicin levels ranged between 0.275±0.046 and 0.364±0.163 mg/L; mean serum tobramycin levels ranged from 0.313±0.207 to 0.527±0.424 mg/L; and mean serum vancomycin levels ranged from 5.46±6.6 to 15.34±9.6 mg/L. Serum antibiotic levels were detectable throughout the 8-week duration of ACS treatment. Regression analysis found that diabetes (coefficient 6.73, 95% CI 0.92-12.54, P < .05), blood urea nitrogen (coefficient 0.83, 95% CI 0.45-1.22, P < .001), number of cement doses (coefficient 3.71, 95% CI 0.76-6.66, P < .05), and use of systemic vancomycin (coefficient 6.24, 95% CI 2.72-9.75, P < .001) correlated with serum vancomycin levels. Patient age (coefficient −0.01, 95% CI −0.02 to 0, P < .01) and male sex (coefficient 0.20, 95% CI 0-0.41, P < .05) correlated with serum aminoglycoside level. ConclusionSystemic absorption of antibiotics from high-dose ACS persists for at least 8 weeks. Patients should be monitored closely for complications related to systemic absorption of antibiotics from ACS treatment.

The Efficacy of a Novel Surgical Device in Preventing Intraoperative Wound Contamination in an In Vivo Porcine Model.

Surgical site infections (SSIs) remain a morbid and costly complication in abdominal surgery. Topical antibiotic delivery via intraoperative irrigation and barrier wound protection are strategies for preventing SSI. We tested the safety and efficacy of a novel wound protector device with an integrated fluid irrigation platform in a porcine model. A simulated colorectal resection model was designed and performed on adult female pigs with a standardized concentration of 109 colony-forming units (CFU) of Escherichia coli administered to the wound site in 10 mL of normal saline (n = 7). The device was tested intraoperatively with and without irrigation with gentamicin-containing irrigant solution. Swab and tissue samples were obtained in addition to peripheral blood samples. Quantitative culture analysis was performed in addition to histological and immunohistochemical analysis and gentamicin concentration measurements. There were no adverse events observed in the animals. Tissue protected by the device yielded exponentially lower levels of E. coli growth compared to exposed tissue, with a mean 1 × 102 CFU/swab. Use of the device, both with and without irrigation, was associated with an exponential reduction in quantitative bacterial load compared to the control wounds with no device, with limited growth after wound closure in the pigs receiving irrigation. Histology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining analysis revealed no significant damage to tissue. Serum gentamicin levels remained below the clinical threshold and decreased over time. This in vivo study suggests safety and efficacy of a novel device for the prevention of intraoperative wound contamination.

Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis

Neonatal infections are a leading cause of childhood mortality in low-resource settings. World Health Organization guidelines for outpatient treatment of possible serious bacterial infection (PSBI) in neonates and young infants when referral for hospital treatment is not feasible include intramuscular gentamicin (GEN) and oral amoxicillin. GEN is supplied as an aqueous solution of gentamicin sulphate in vials or ampoules and requires health care workers to be trained in dose calculation or selection of an appropriate dose based on the patient's weight band and to have access to safe injection supplies and appropriate sharps disposal. A simplified formulation, packaging, and delivery method to treat PSBI in low-resource settings could decrease user error and expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period. We developed dissolving polymeric microneedles (MN) arrays to deliver GEN transdermally. MN arrays were produced from aqueous blends containing 30% (w/w) of GEN and two polymers approved by the US Food and Drug Administration: sodium hyaluronate and poly(vinylpyrrolidone). The arrays (19×19 needles and 500μm height) were mechanically strong and were able to penetrate a skin simulant to a depth of 378μm. The MN arrays were tested in vitro using a Franz Cell setup delivering approximately 4.45mg of GEN over 6h. Finally, three different doses (low, medium, and high) of GEN delivered by MN arrays were tested in an animal model. Maximum plasma levels of GEN were dose-dependent and ranged between 2 and 5μg/mL. The time required to reach these levels post-MN array application ranged between 1 and 6h. This work demonstrated the potential of dissolving MN arrays to deliver GEN transdermally at therapeutic levels in vivo.

Exposure to sub-inhibitory concentrations of gentamicin, ciprofloxacin and cefotaxime induces multidrug resistance and reactive oxygen species generation in meticillin-sensitive Staphylococcus aureus.

The role of antibiotics below their MIC in the development of bacterial drug resistance is becoming increasingly important. We investigated the effect of sub-MICs of bactericidal antibiotics on the susceptibility pattern of Staphylococcus aureus and evaluated the role of free radicals. A total of 12 S. aureus strains were recovered from pus samples and their antibiograms determined. The test isolates were treated with sub-MIC levels of tetracycline, gentamicin, ciprofloxacin and cefotaxime. Alterations in their respective breakpoints were observed along with measurements of free radical generation by nitro blue tetrazolium test.Results/Key findings. Gentamicin, ciprofloxacin and cefotaxime exposure significantly altered the breakpoints of exposed isolates against several tested antibiotics and higher levels of free radicals were generated after antibiotic exposure. Our study demonstrates that sub-MIC levels of antimicrobials can lead to resistance and cross-resistance across several classes of antibiotics in wild strains of S. aureus, possibly by free radical production. The molecular mechanisms behind the acquisition of drug resistance at low antibiotic concentrations and the specific target genes of reactive oxygen speciesneed to be explored further.

The use of intravesical gentamicin to treat recurrent urinary tract infections in lower urinary tract dysfunction

To assess the use of intravesical gentamicin to treat intractable recurrent urinary tract infections in lower urinary tract dysfunction. A two-center retrospective cohort study of 27 patients treated with intravesical gentamicin was performed over a 2-year period. A treatment protocol was developed, reviewed, and accepted by the clinical effectiveness committee of both hospitals. Patients were taught to instill the gentamicin into the bladder on a nightly basis. Inclusion criteria included failure to respond to standard therapy, having six or more cultured confirmed UTIs over a 12-month period, or at least one hospital admission with sepsis. Serum gentamicin levels were taken after 7 days and the treatment was discontinued if the level was >1 mg/L. Patients were counseled about the limited evidence base for this treatment. Twenty-seven patients have been treated with intravesical gentamicin for an average of 26 months. Seventeen were performing ISC, five had suprapubic catheters, three were voiding, and two had ileal conduits at the time of instituting treatment. All patients started on daily 80 mg gentamicin. Twenty two patients had less frequently occurring infections after starting intravesical gentamicin treatment. Six stopped the treatment and none had side effects as a result of the instillations. This study has shown that in a small group of adult patients who have multiple symptomatic UTIs refractory to conventional treatment, intravesical gentamicin is effective in reducing the frequency of infections. The treatment is well tolerated with no evidence of systemic absorption.

Empirical gentamicin dosing based on serum creatinine levels in premature and term neonates.

Empirical gentamicin dosing based on serum creatinine (SCr) levels in premature and term neonates was evaluated. This single-center, retrospective cohort study was conducted in a standalone children's hospital with a level IIIB, 44-bed neonatal intensive care unit (NICU). Data were abstracted and collected for all neonates admitted to the NICU from March 5, 2012, through March 5, 2014. Patients were included in the study if gentamicin was administered within the first 7 days of life, a trough gentamicin level was measured, and the neonate had a baseline SCr level measured within the first 24 hours of life. A series of logistic regressions was conducted to determine if gentamicin trough levels were influenced by gestational age (≤29 weeks [group 1], 30 weeks to 34 weeks and 6 days [group 2], and ≥35 weeks [group 3]) and SCr level (0.81-0.99 mg/dL [mildly elevated] and ≥1 mg/dL [elevated]). Of the 577 neonates reviewed during the study period, 507 met the inclusion criteria. Mildly elevated and elevated SCr levels were significantly associated with the presence of an elevated gentamicin trough (p < 0.001). When the effect of gestational age was evaluated, the data suggested that SCr is a strong predictor of elevated gentamicin troughs. Neonates with a gestational age of ≥30 weeks who had an SCr level of ≥1 mg/dL within the first 12-24 hours of life were more likely to have an elevated gentamicin trough level than their counterparts with normal SCr levels.

Effect of gentamicin and levels of ambient sound on hearing screening outcomes in the neonatal intensive care unit: A pilot study

ObjectiveHearing loss rates in infants admitted to neonatal intensive care units (NICU) run at 2–15%, compared to 0.3% in full-term births. The etiology of this difference remains poorly understood. We examined whether the level of ambient sound and/or cumulative gentamicin (an aminoglycoside) exposure affect NICU hearing screening results, as either exposure can cause acquired, permanent hearing loss. We hypothesized that higher levels of ambient sound in the NICU, and/or gentamicin dosing, increase the risk of referral on the distortion product otoacoustic emission (DPOAE) assessments and/or automated auditory brainstem response (AABR) screens. MethodsThis was a prospective pilot outcomes study of 82 infants (<37 weeks gestational age) admitted to the NICU at Oregon Health & Science University. An ER-200D sound pressure level dosimeter was used to collect daily sound exposure in the NICU for each neonate. Gentamicin dosing was also calculated for each infant, including the total daily dose based on body mass (mg/kg/day), as well as the total number of treatment days. DPOAE and AABR assessments were conducted prior to discharge to evaluate hearing status. Exclusion criteria included congenital infections associated with hearing loss, and congenital craniofacial or otologic abnormalities. ResultsThe mean level of ambient sound was 62.9 dBA (range 51.8–70.6 dBA), greatly exceeding American Academy of Pediatrics (AAP) recommendation of <45.0 dBA. More than 80% of subjects received gentamicin treatment. The referral rate for (i) AABRs, (frequency range: ∼1000–4000 Hz), was 5%; (ii) DPOAEs with a broad F2 frequency range (2063–10031 Hz) was 39%; (iii) DPOAEs with a low-frequency F2 range (<4172 Hz) was 29%, and (iv) DPOAEs with a high-frequency F2 range (>4172 Hz) was 44%. DPOAE referrals were significantly greater for infants receiving >2 days of gentamicin dosing compared to fewer doses (p = 0.004). The effect of sound exposure and gentamicin treatment on hearing could not be determined due to the low number of NICU infants without gentamicin exposure (for control comparisons). ConclusionAll infants were exposed to higher levels of ambient sound that substantially exceed AAP guidelines. More referrals were generated by DPOAE assessments than with AABR screens, with significantly more DPOAE referrals with a high-frequency F2 range, consistent with sound- and/or gentamicin-induced cochlear dysfunction. Adding higher frequency DPOAE assessments to existing NICU hearing screening protocols could better identify infants at-risk for ototoxicity.

The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.

Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by <3-logs. A combination of 0.05 mg PlySs2 + 0.05 mg gentamicin reduced S. suis by >5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans.

Determinants of gentamicin concentrations in critically ill patients: a population pharmacokinetic analysis

When treating critically ill patients with gentamicin for severe infection, peak concentrations (Cmax) determine clinical efficacy and trough concentrations (Cmin) determine toxicity. Despite administration of body weight-standardised starting doses, a wide range of Cmax is generally observed. Furthermore, in therapeutic drug monitoring, several measures of renal function are used to predict appropriate Cmin and gentamicin dosing intervals, but the most accurate predictor is not known. This study aimed to quantify the impact of several patient parameters on gentamicin Cmax values and to determine which measure of renal function best predicts gentamicin clearance (CL). Clinical data and serum gentamicin levels were retrospectively collected from all critically ill patients treated with gentamicin at our intensive care unit between 1 January and 30 June 2011. Data were analysed using non-linear mixed-effects modelling (NONMEM v.7.1.2). A two-compartmental model was developed based on 303 gentamicin concentration–time data from 44 critically ill patients. Serum albumin levels explained 25% of interindividual variability in the volume of distribution (Vd). Creatinine clearance calculated from the creatinine concentration in a 6-h urine portion (CalcCLCr) resulted in acceptable estimation of gentamicin CL, whilst serum creatinine (SCr) and creatinine clearance estimated by the Cockcroft–Gault formula (CGCLCr) overestimated gentamicin CL and therefore underestimated Cmin. In conclusion, low albumin concentrations resulted in a larger Vd and lower Cmax of gentamicin. These results suggest that use of a higher gentamicin starting dose in critically ill patients with hypoalbuminaemia may prevent underdosing. Urinary CalcCLCr is a better predictor of Cmin than SCr or CGCLCr.

Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig

Intratympanic gentamicin therapy is widely used clinically to suppress the vestibular symptoms of Meniere's disease. Dosing in humans was empirically established and we still know remarkably little about where gentamicin enters the inner ear, where it reaches in the inner ear and what time course it follows after local applications. In this study, gentamicin was applied to the round window niche as a 20 μL bolus of 40 mg/ml solution. Ten 2 μL samples of perilymph were collected sequentially from the lateral semi-circular canal (LSCC) at times from 1 to 4 h after application. Gentamicin concentration was typically highest in samples originating from the vestibule and was lower in samples originating from scala tympani. To interpret these results, perilymph elimination kinetics for gentamicin was quantified by loading the entire perilymph space by injection at the LSCC with a 500 μg/ml gentamicin solution followed by sequential perilymph sampling from the LSCC after different delay times. This allowed concentration decline in perilymph to be followed with time. Gentamicin was retained well in scala vestibuli and the vestibule but declined rapidly at the base of scala tympani, dominated by interactions of perilymph with CSF, as reported for other substances. Quantitative analysis, taking into account perilymph kinetics for gentamicin, showed that more gentamicin entered at the round window membrane (57%) than at the stapes (35%) but the lower concentrations found in scala tympani were due to greater losses there. The gentamicin levels found in perilymph of the vestibule, which are higher than would be expected from round window entry alone, undoubtedly contribute to the vestibulotoxic effects of the drug. Furthermore, calculations of gentamicin distribution following targeted applications to the RW or stapes are more consistent with cochleotoxicity depending on the gentamicin concentration in scala vestibuli rather than that in scala tympani.

Lyophilized allogeneic bone tissue as an antibiotic carrier.

The rising number of primary joint replacements worldwide causes an increase of revision surgery of endoprostheses 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 give a good support for the implant. In this study we evaluated the release of antibiotics from fresh-frozen and lyophilized allogeneic bone grafts. Lyophilized bone chips and fresh frozen bone chips were mixed with gentamicin sulphate, gentamicin palmitate, vancomycin, calcium carbonate/calcium sulphate impregnated with gentamicin sulphate, and calcium carbonate/calcium sulphate bone substitute material impregnated with vancomycin. 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 all the experimental time. That fact 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 in the first and second day, decreasing and keeping a low 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 two weeks after surgery. In case of uncemented revision of joint replacements allogeneic bone is able to deliver therapeutic doses of gentamicin and peak levels immediately after implantation during a fortnight. The use of lyophilized and fresh frozen bone allografts as antibiotic carriers is recommended for prophylaxis of bone infection.

Patients' safety: is there a systemic release of gentamicin by gentamicin-coated tibia nails in clinical use?

IntroductionOsteitis is one of the most serious complications in orthopedic surgery. Expert Tibia Nail (ETN) PROtect™ coated with a biodegradable layer of gentamicin-laden polymer was developed for prophylaxis of osteomyelitis. In systemic administration, gentamicin has only a small therapeutic index and serious side effects; it is potentially nephrotoxic as well as ototoxic. It is not yet known if relevant gentamicin concentrations are released into the systemic circulation after implantation of gentamicin-coated nails. In order to evaluate the patients’ risks profiles and increase patient safety, we measured gentamicin levels in pre- and postoperative serum samples of patients undergoing implantation of ETN PROtect.MethodsTwenty-five patients who received ETN PROtect between March 2012 and August 2014 were included in this study. Collection of blood samples occurred before the operation, at weeks 1–4, 3 and 6 months, and up to 1 year after the implantation. Measurement of gentamicin levels in serum samples was performed at the central laboratory of Heidelberg University Hospital. Additionally, laboratory parameters, C-reactive protein, leukocyte number, urea and creatinine concentrations were analyzed in routine controls before and after operating and assessed for systemic side effects.ResultsOver the course of this prospective observational study, we were able to determine that gentamicin-coated nails do not release gentamicin into the systemic circulation above the lowest detectable level of 0.2 mg/dL. There were slight increases in the mean inflammation and renal retention markers, but no gentamicin-associated side effects could be linked to implantation. Furthermore, no allergic reactions could be detected during our study.ConclusionOur findings suggest that there is no relevant release of gentamicin into the systemic circulation causing a systemic effect, and serious side effects due to gentamicin-coated tibia nails should not be feared. Postoperative monitoring of renal function does not seem necessary because of the implantation of ETN PROtect.

DEVELOPMENT OF A ONCE DAILY GENTAMICIN REGIMEN FOR PAEDIATRIC SURGERY PATIENTS

AimIntravenous gentamicin is given as a 5 day course to paediatric patients who have undergone abdominal surgery. There was an impression that the multiple daily dosing regimen in use at...

IMPLEMENTATION OF AN ELECTRONIC PRESCRIPTION CHART FOR GENTAMICIN FOR NEONATAL UNITS AND POSTNATAL WARDS

AimSince the introduction of NICE guidance for Early Onset Neonatal Sepsis (EONS)1 in August 2012, the number of locally reported prescribing and administration errors involving gentamicin has increased. This guideline...