Regimen Of Gentamicin Research Articles

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.

PP-45 Gentamicin exposure in neonates according to swiss neo-natal intensive care dosing regi-mens and international guidelines

Background To assess the achievement of adequate gentamicin exposure for dosing regimens used across Swiss neonatal intensive care units (NICUs) and interna-tional guidelines. Methods Gentamicin dosing regimens were collected from 7 Swiss level III NICUs and 8 international guidelines (Frank Shann`s, BNF for children, Nelson Textbook of Pedi-atrics, Neonatal Formulary 7th edition, The Blue Book, Lex-icomp Paediatric and Neonatal Dosage Handbook, The Red Book and Neofax). Variables used for selection of individ-ualized dosing regimen (single dose, dosing interval, total daily dose and demographic characteristics) from each guideline were assessed. Model-based simulations were performed to compare the various dosing regimens with respect to their ability to achieve effective peak drug con-centrations according to predefined minimum inhibitory concentrations (MICs), peak concentrations (Cmax/MIC >10) and safe trough concentration (Cmin Results Gentamicin dosing regimens based on Swiss NICUs and international guidelines showed consider-able variability with respect to dose, dosing interval and demographic variables (weight, gestational age, post-menstrual age and postnatal age) to determine a priori individual dosing regimens. Doss and dosing intervals ranged from 4 mg/kg to 6 mg/kg and from 24 hours to 48 hours, respectively. Overall, this resulted in seven possible dosing regimens for gentamicin in neonates, which can vary between neonatal subgroups when neonates were categorised based on demographic variables. Based on demographic variables, six different alternatives could be distinguished for the determination of individualised dos-ing regimens of gentamicin; either based on one patient characteristic (GA: n=1; PNA: n=1), a combination of characteristics (WT and PNA: n=3; GA and PNA: n=5; PMA and PNA: n=2) or no characteristics at all (n=2). Model-based simulations suggested that for a MIC breakpoint of 0.5 mg/L (i.e. target Cmax >5 mg/L), a high proportion of neonates [range: 26%–36%] did not reach the target af-ter the first dose according to current dosing approaches. Assuming a target MIC breakpoint of 2 mg/L, an effective. Cmax is not achieved with any evaluated dosing recom-mendation. On the safety side, potential toxic trough con-centrations (≥2 mg/L) were observed in less than 5% of neonates. Conclusion Current neonatal dosing approaches for gentamicin are associated with subtherapeutic drug ex-posures in a considerable portion of neonates. These sub-therapeutic exposures are associated with increasing MIC breakpoint. Therefore, there is a clear need for harmoniza-tion and simplification of dosing regimen for gentamicin in the neonatal patient population, based on quantitative rationale to achieve the effective and safe exposure.

Extended-interval Dosing of Gentamicin in Premature Neonates Born at 7 Days of age

PurposeExtended-interval dosing (EID) regimens of gentamicin have been validated for treating confirmed or suspected early- and late-onset sepsis in preterm infants in the first week of life. Despite the marked changes in volume of distribution and renal clearance in preterm infants after the first few days of life, few studies have validated EID regimens of gentamicin in this population. The objective of the study was to evaluate an EID regimen of gentamicin in infants born at <32 weeks’ gestational age and aged >7 days. MethodsThis observational study of an EID regimen was conducted in 39 infants. Dosing interval was based on the serum drug concentration at 22 hours after the administration of the first dose of 5 mg/kg. Gentamicin peak (5–12 µg/mL) and trough (<2 µg/mL) levels were compared to those in a historical control group of 39 infants who received traditional-interval dosing (TID) of 2.5 mg/kg of gentamicin with dosing intervals of 8, 12, or 24 hours. FindingsThere were no differences in birthweight, gestational age at birth, postmenstrual age, weight at the start of gentamicin administration, postnatal age, small for gestational age status, antenatal corticosteroid use, or postnatal indomethacin exposure between the 2 groups. In the EID group, dosing intervals were 24 hours in 30 infants, 36 hours in 6 infants, and 48 hours in 3 infants. Compared with the TID group (n = 39), the EID group had a significantly higher peak level (median, 9.0 vs 4.7 µg/mL) and a significantly lower trough level (median, 0.7 vs 1.1 µg/mL) (both, P < 0.001). On regression analysis, the postmenstrual age was correlated significantly with trough levels in the EID group. There was no adverse effect on renal function in either group. On follow-up, 1 infant in the EID group and 2 infants in the TID group had evidence of sensorineural hearing loss. ImplicationsIn infants born at <32 weeks’ gestation and >7 days of age, an EID gentamicin regimen, with a dosing interval based on a single concentration measurement at 22 hours after the administration of the first dose, achieved therapeutic peak and trough levels and performed significantly better than did a TID regimen in reaching target peak and trough levels. Larger-scale trials are needed for assessing the clinical efficacy (treatment failure/success) of these regimens.

Estimating drug-free period using a graphical method: an alternative way to monitor extended-interval dosing of gentamicin therapy.

Published nomograms to monitor extended-interval dosing (EID) gentamicin therapy were based on a fixed dose of 5 or 7mg/kg. However, the average dose used for EID gentamicin regimen in our setting was about 3mg/kg per day. We developed a new method of monitoring based on the duration of drug-free period (DFP) in a 24-h dosing interval. Hospitalised adult patients on EID gentamicin were selected. We considered a DFP of between 2 and 8h as appropriate. Data from two blood samples (2 and 6h postdose) from each patient were used to estimate the duration of DFP (i.e. DFP method 1). DFP was also calculated for the same patient using an empirically estimated elimination rate constant (Ke ) and the same 6h postdose concentration value (DFP method 2). Correlation between the two methods was made. An alternative graphical method to estimate DFP was attempted. Correlation between Ke and age was favourable (r=-0.453; P=0.001). Ke derived from this empirical relationship was used to estimate DFP method 2. DFP method 1 correlated well with DFP method 2 (r=0.742; P<0.001). On this basis, two curves representing minimum and maximum DFPs of 2 and 8h, respectively, were constructed. The final coordinates, which were plotted from an empirically estimated Ke and a 6h postdose concentration, were used to determine whether the DFP was within the targeted range. We have proposed using DFP to monitor EID of gentamicin therapy. A graphical method offers a convenient way to estimate this parameter.

One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates.

Animal studies and trials in older children and adults suggest that a 'one dose per day' regimen of gentamicin is superior to a 'multiple doses per day' regimen. To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates. Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3) in the Cochrane Library (searched 8 April 2016), MEDLINE (1966 to 8 April 2016), Embase (1980 to 8 April 2016), and CINAHL (December 1982 to 8 April 2016). All randomised or quasi-randomised controlled trials comparing one dose per day ('once a day') compared to multiple doses per day ('multiple doses a day') of gentamicin to newborn infants. Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group. Eleven RCTs were included (N = 574) and 28 excluded. All except one study enrolled infants of more than 32 weeks' gestation. Limited information suggested that infants in both 'once a day' as well as 'multiple doses a day' regimens showed adequate clearance of sepsis (typical RR 1.00, 95% CI 0.84 to 1.19; typical RD 0.00, 95% CI -0.19 to 0.19; 3 trials; N = 37). 'Once a day' gentamicin regimen was associated with fewer failures to attain peak level of at least 5 µg/ml (typical RR 0.22, 95% CI 0.11 to 0.47; typical RD -0.13, 95% CI -0.19 to -0.08; number needed to treat for an additional beneficial outcome (NNTB) = 8; 9 trials; N = 422); and fewer failures to achieve trough levels of 2 µg/ml or less (typical RR 0.38, 95% CI 0.27 to 0.55; typical RD -0.22, 95% CI -0.29 to -0.15; NNTB = 4; 11 trials; N = 503). 'Once a day' gentamicin achieved higher peak levels (MD 2.58, 95% CI 2.26 to 2.89; 10 trials; N = 440) and lower trough levels (MD -0.57, 95% CI -0.69 to -0.44; 10 trials; N = 440) than 'multiple doses a day' regimen. There was no significant difference in ototoxicity between two groups (typical RR 1.69, 95% CI 0.18 to 16.25; typical RD 0.01, 95% CI -0.04 to 0.05; 5 trials; N = 214). Nephrotoxicity was not noted with either of the treatment regimens. Overall, the quality of evidence was considered to be moderate on GRADE analysis, given the small sample size and unclear/high risk of bias in some of the domains in a few of the included studies. There is insufficient evidence from the currently available RCTs to conclude whether a 'once a day' or a 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However, data suggest that pharmacokinetic properties of a 'once a day' gentamicin regimen are superior to a 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There was no change in nephrotoxicity or auditory toxicity. Based on the assessment of pharmacokinetics, a 'once a day regimen' may be superior in treating sepsis in neonates of more than 32 weeks' gestation.

ONCE DAILY GENTAMICIN DOSE BANDING IN NEWBORNS WITH SIGNS OF EARLY ONSET OF NEONATAL SEPSIS (EONS), BASED ON INITIAL BIRTH WEIGHT AND GESTATIONAL AGE

AimProspective assessment of safety of dose banding of once daily gentamicin in newborns with signs of EONS in their first days of life.MethodAll neonates admitted on the level-3 neonatal unit,...

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...

Reduction in post-operative acute kidney injury following a change in antibiotic prophylaxis policy for orthopaedic surgery: an observational study.

Evidence has shown that a prophylactic antibiotic regimen of flucloxacillin and gentamicin for orthopaedic surgery was associated with increased rates of post-operative acute kidney injury (AKI). This resulted in changes in the national antibiotic policy recommendation for orthopaedic surgical prophylaxis. This study aimed to assess whether this change from flucloxacillin and gentamicin to co-amoxiclav was associated with changes in the rates of AKI and Clostridium difficile infection (CDI). An observational study and interrupted time series analyses were used to assess rates of post-operative AKI separately in patients undergoing neck of femur (NOF) repair and other orthopaedic operations that required antibiotic prophylaxis. Incidence rate ratios were used to evaluate changes in CDI rates. Following the change in policy, from flucloxacillin and gentamicin to co-amoxiclav, there was a relative change in rates of post-operative AKI of -63% (95% CI -77% to -49%) at 18 months in the other orthopaedic operations group. In the NOF repair group, there was no change in the rate of post-operative AKI [-10% (95% CI -35%-15%)] at 18 months. The incident rate ratio for CDI in the other orthopaedic operations group was 0.29 (95% CI 0.09-0.96) and in the NOF repair group was 0.76 (95% CI 0.28-2.08). The use of co-amoxiclav for antibiotic prophylaxis in orthopaedic surgery was associated with a decreased rate of post-operative AKI compared with flucloxacillin and gentamicin and was not associated with increased rates of CDI.

Gentamicin dosing strategy in patients with end-stage renal disease receiving haemodialysis: evaluation using a semi-mechanistic pharmacokinetic/pharmacodynamic model.

Gentamicin is widely used in end-stage renal disease (ESRD) patients for the treatment of infections. The goal of this study was to find the most reasonable dosing regimen for gentamicin in ESRD patients receiving haemodialysis. The in vitro antimicrobial activity of gentamicin was evaluated by static and dynamic time-kill experiments against three bacterial strains of MSSA, MRSA and Pseudomonas aeruginosa. A semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model was established afterwards, allowing the characterization of the antibacterial effect of gentamicin in the human body. The model was utilized to assess dosing regimens of gentamicin in ESRD patients receiving haemodialysis, taking both efficacy and safety into account. The PK/PD model was capable of describing the bacterial response to gentamicin exposure in all three strains. Simulation based on the PK/PD model showed that pre-dialysis and post-dialysis dosing would bring comparable benefit to the ESRD patient regardless of whether the PK/PD target (fCmax/MIC >8-fold) was achieved, while the post-dialysis dosing resulted in a significantly lower trough concentration. The result of simulated dose fractionation demonstrated that both fCmax/MIC and fAUC(0-24)/MIC are strong predictors of drug effectiveness, but the PK/PD model would provide a more precise prediction of antibacterial activity as well as valuable information on dose selection in ESRD patients receiving haemodialysis. Our study supports the original FDA label with regard to the dosing regimen of gentamicin in ESRD patients, which offers adequate clinical benefit as well as an acceptable safety profile.

Pharmacoepidemiology of Gentamicin Prescription in Dogs by some Practicing Veterinarians in Nigeria

The objective of this study was to evaluate the prescribing trend of gentamicin in dogs by veterinarians in Nigeria. A retrospective and cross-sectional survey was done in six geopolitical zones of Nigeria. About 150 questionnaires were administered to practicing licensed veterinarians within the study areas addressing issues such as prescribing pattern, indications, dosage regimen, therapeutic monitoring, efficacy and adverse effects of gentamicin in dogs. Data obtained was checked for its completeness and analyzed using Microsoft office Excel 2007. Gentamicin had the highest prescription rate (32%), closely followed by streptomycin (31%) and neomycin (22%). A greater percentage (59 %) of the respondents affirmed that they don’t often prescribe gentamicin. However, it is mostly prescribed for dogs with signs of gastroenteritis at a common dose of 4-5 mg/kg intramuscularly, where by 94 % of the respondents attested to its effectiveness. But 52 % of the respondents were not sure of the gentamicin dose they administer in dogs. Very few monitored their patients after treatment hence a small number of adverse effects, predominantly nephrotoxicity were observed by the respondents. Prescription pattern of gentamicin in dogs and patient monitoring is generally poor suggesting inadequate knowledge and application of pharmacology consequently the need for proper education in this subject.

Effect of rifampicin and gentamicin on Shiga toxin 2 expression level and the SOS response in Escherichia coli O104:H4.

A novel pathotype, Shiga toxin-producing Escherichia coli O104:H4, was the cause of a severe outbreak that affected European countries, mainly Germany, in 2011. The effect of different regimens of rifampicin and gentamicin were evaluated to determine possible treatment modes for the novel strain, and to evaluate the SOS response and its effect on toxin release. Pulsed-field gel electrophoresis (PFGE) was performed on the novel E. coli O104:H4 pathotype and two pre-outbreak E. coli O104:H4 CDC strains. Transcript levels of the stx2 and recA gene (SOS response inducer) were evaluated using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in the novel E. coli O104:H4 samples subjected to different regimens of rifampicin and gentamicin. Consequently, reverse passive latex agglutination (RPLA) was used to determine the Stx2 titers in these samples. Western blot was performed to determine the LexA levels (SOS response repressor) in E. coli O104:H4. The efficacy of treatment with antimicrobial agents was assessed in BALB/c mice. The outbreak and pre-outbreak strains are closely related as shown by PFGE, which demonstrated slight genomic differences between the three strains. The transcription level of the stx2 gene in the new pathotype was 1.41- and 1.75-fold that of the 2009 EL-2050 and 2009 EL-2071 pre-outbreak strains, respectively. Moreover, the transcription level of the stx2 gene in the new pathotype was substantially decreased as a result of treatment with the different concentrations of the antimicrobial agents, but was enhanced when the antibiotics were administered at two subinhibitory levels. RPLA data were in accordance with the qRT-PCR results. E. coli O104:H4 exposed to gentamicin at both sub-minimum inhibitory concentration (MIC) levels led to high transcription levels of the recA gene and lack of expression of the LexA protein, implying that the SOS response was activated. Rifampicin at both sub-MIC levels resulted in low transcript levels of the recA gene, indicating that the SOS response was not induced. In vivo, the highest survival rate in BALB/c mice was observed in the group that was treated with the minimum bactericidal concentration (MBC) of gentamicin. The use of antimicrobial agents in E. coli O104:H4 infection seems to be effective at the MIC and MBC levels. This provides a promising ground for treatment of E. coli O104:H4.

Intratympanic gentamicin treatment for Ménière’s disease: a randomized, double-blind, placebo-controlled trial on dose efficacy - results of a prematurely ended study

BackgroundGentamicin is used as a therapeutic agent for Ménière’s disease because of its vestibulotoxicity causing chemo-ablation of the vestibular sensory epithelia. Its use has increased in recent years. However, there is still no consensus about the dose regimen of gentamicin in the treatment of Ménière’s disease. In this study two different dose regimen treatment protocols are compared in a placebo controlled study design. The primary objective is to quantify the treatment effect on dizziness, the secondary objective is hearing evaluation.MethodsWe performed a randomized, double-blind, placebo-controlled study in adults with unilateral Ménière’s disease according to the AAO-HNS guidelines resistant to conservative medication. Three groups received four injections, administered weekly (four intratympanic injections with 40 mg/mL gentamicin solution, two injections gentamicin solution and two injections of placebo in random order, or four injections with placebo). Outcome measures were the score on the Dizziness Handicap Inventory and pure tone audiometry (PTA). Intended follow-up was 2 years.ResultsDuring follow-up one patient exceeded the accepted amount of hearing loss. Further, enrollment was very slow (until 12 months between two patients) and new insights showed an apparent benefit of intratympanic gentamicin treatment (ITG). Therefore we performed an unscheduled interim analysis which showed that PTA threshold shifts reached the stopping criteria in two more patients. Because of this, this study was ended. Of the three patients with the significant PTA threshold shift two were enrolled in the gentamicin group.ConclusionNo conclusions can be drawn concerning doses regimens. Now that new publications have shown that ITG treatment can be an effective and safe treatment, a placebo-controlled randomized controlled trial may not pass the ethical committee because of these recent reports in literature. Still, a dose regimen study (without placebo) on ITG treatment needs to be performed.Trial registrationThis trial was registered in The University Medical Center Utrecht/ Gelre hospital Apeldoorn. Protocol ID: 07/343, EudraCT number 2006-005913-37.

Dose Derivation of Once-Daily Dosing Guidelines for Gentamicin in Critically Ill Pediatric Patients

To determine dose and eligibility criteria for once-daily dosing (ODD) of gentamicin in critically ill pediatric patients. Retrospective chart review of patients admitted to the Pediatric Intensive Care Unit or Cardiac Critical Care Unit at The Hospital for Sick Children (SickKids) who received traditionally dosed intravenous (IV) gentamicin (January 2008 to June 2010). Statistically significant patient characteristics associated with gentamicin pharmacokinetic (PK) parameters were determined by multiple linear regression. Binary partitioning was used to set critical values for these characteristics to derive dose for ODD of gentamicin. Feasibility of implementing ODD of gentamicin in critically ill children was assessed using individualized PK parameters to simulate area under the concentration-time curves and drug-free intervals while targeting a maximum concentration (C(max)) of 16-20 mg/L. Eligibility criteria were determined by patient characteristics that had a statistically significant impact on gentamicin PK. Volume of distribution (V(d)) and elimination rate constant (k(e)) were calculated for 140 patients. Weight and admission unit were significantly associated with weight-normalized V(d) (Vd/kg), whereas age and serum creatinine (SCr) were significantly associated with k(e). Weight <5 kg and SCr ≥20% over age-specific upper normal limit before gentamicin initiation were associated with prolonged gentamicin elimination. Gentamicin 6 mg/kg IV every 24 hours, the dose at which the highest percentage of patients achieved C(max), area under the curve, and drug-free interval within target ranges simultaneously, was selected as the proposed ODD regimen. A regimen of gentamicin 6 mg/kg IV every 24 hours for Pediatric Intensive Care Unit/Cardiac Critical Care Unit patients at SickKids weighing ≥5 kg with SCr <20% above age-specific upper normal limit before initiation of gentamicin is proposed.

Optimization of Dosage Regimen of Gentamicin against Pasteurella multocida in Bovines: Old Drug, New Approach

Background: Gentamicin is commonly used to treat Haemorrhagic Septicemia (HS) and other respiratory tract infections in bovines. But no data on its doses and schedules optimized for therapeutic success against P. multocida using pharmacokinetics (PK) - pharmacodynamic (PD) integration and modeling is available in farm animals. We investigated PD of gentamicin against P. multocida isolates and optimized the dosage schedules in buffalo species using novel approach of PK-PD modeling. Results: The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of gentamicin against P. multocida in Mueller Hinton Broth (MHB) and serum were similar. The MBC:MIC ratios were 1.23 and 1.27, respectively, for MHB and calf serum.. The mutant prevention concentration (MPC) =6 μg/mL of gentamicin was higher than MIC (0.75 μg/mL) and MBC (0.95 μg/mL). In vitro growth inhibition curves of gentamicin in MHB and serum were characteristic of bactericidal activity against P. multocida. Time kill kinetics demonstrated that killing activity of gentamicin is concentration andtime dependent.. The values of PK-PD indicators, Cmax/MIC and AUC24h /MIC were 21 and 61 h, respectively. Based on MPC, PK-PD indices, Cmax/MPC and AUC24h /MPC were 2.60 and 7.62 h, respectively. Using PK-PD modelling, the predicted gentamicin values of AUC24h/MIC for bacteriostatic bactericidal action and bacterial eradication were 32.13, 47.15 and 60.96 h, respectively. Conclusions: The PK-PD indicespredicted therapeutic success of the gentamicin against P. multocida. Based on PK-PD modeling, optimum daily dosage of gentamicin was 2-2.5 mg/kg for treating infections caused by P. multocida (MIC90 ≤1.0 μg/mL) in buffalo calves. However, in difficult clinical infections associated with pathogens of MIC90≤4.0 μg/mL, a higher dosage of 7.5 mg/kg is recommended. Low MPC of gentamicin against P. multocida suggested low selection pressure for emergence and amplification of resistant subpopulation during treatment.

Antibiotic Prophylaxis for Hip Fracture Surgery: Three-Dose Cefuroxime versus Single-Dose Gentamicin and Amoxicillin

To compare a 3-dose cefuroxime regimen with a single-dose gentamicin and amoxicillin regimen as antibiotic prophylaxis for hip hemiarthroplasty in terms of microbiological outcome. Records of 2 matched groups of patients who underwent hip hemiarthroplasty for femoral neck fractures were reviewed. 29 men and 84 women (mean age, 82 years) who received a 3-dose cefuroxime regimen in 2006 were compared with 23 men and 84 women (mean age, 83 years) who received a single-dose gentamicin and amoxicillin regimen in 2008. Patient demographics, antibiotics prescribed in the peri- and immediate postoperative period, microbiological evidence for Clostridium difficile 'infection', length of hospital stay, mortality, as well as biochemical and haematological findings were reviewed. The 3-dose cefuroxime group was significantly higher in terms of the mean length of hospital stay (17 vs. 13 days, p=0.043) and the percentage of patients receiving postoperative antibiotics (88% vs. 68%, p<0.001) and having C difficile 'infection' (6% vs. 0%, p=0.016). If patients with C difficile 'infection' were excluded, there was no significant difference in the length of hospital stay. The single-dose gentamicin and amoxicillin regimen was associated with a lower C difficile 'infection' rate.

High-dose gentamicin in newborn infants: is it safe?

Dosing regimens often recommend lower gentamicin doses in neonates (3-5mg/kg) than in older children (7mg/kg or more) despite the higher volume of distribution in neonates. We studied an extended-interval high-dose (6mg/kg) gentamicin regimen in a single tertiary neonatal unit from 2004-2012. During the first week of life, dosing interval was 24h for term infants, 36h for preterm infants with gestational age (GA) 29-36weeks and 48h for preterm infants with GA <29weeks. After the first week of life, dosing interval was 24h if corrected age (GA + postnatal age) ≥29weeks and 36h if corrected age <29weeks. Outcome measures were trough plasma concentration (TPC), ototoxicity and prescription errors. In 546 treatment episodes, TPC was measured prior to the third gentamicin dose. There were 37 episodes (6.7%) of prescription errors, mainly a too long dosing interval. We included 509 treatment episodes (440 infants) in the final analysis. Mean (standard deviation) gentamicin TPC during the first week of life was 1.1 (0.5) mg/L and after the first week of life 0.8 (0.6) mg/L. In 31 (6%) episodes, TPC was ≥2.0mg/L, predominantly among term infants with renal impairment. Thirty-eight patients failed the neonatal hearing screening, but only four of these 38 had permanent hearing loss. All four had a TPC <2.0mg/L. Conclusions: This extended-interval high-dose gentamicin regimen was associated with low numbers of elevated TPCs, low numbers of prescription errors and no evidence for ototoxicity.

Safety and Efficacy of Simplified Antibiotic Regimens for Outpatient Treatment of Serious Infection in Neonates and Young Infants 0–59 Days of Age in Bangladesh

Background:Because access to care is limited in settings with high mortality, exclusive reliance on the current recommendation of 7–10 days of parenteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections.Methods:We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural surveillance site in Bangladesh. The reference regimen of intramuscular procaine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular gentamicin once daily and oral amoxicillin twice daily for 7 days and (2) intramuscular penicillin and gentamicin once daily for 2 days followed by oral amoxicillin twice daily for additional 5 days. All regimens are provided in the infant’s home. The primary outcome is treatment failure (death or lack of clinical improvement) within 7 days of enrolment. The sample size is 750 evaluable infants enrolled per treatment group, and results will be reported at the end of 2013.Discussion:The trial builds upon previous studies of community case management of clinical severe infections in young infants conducted by our research team in Bangladesh. The approach although effective was not widely accepted in part because of feasibility concerns about the large number of injections. The proposed research that includes fewer doses of parenteral antibiotics if shown efficacious will address this concern.

Recurrent Vertigo after Intratympanic Gentamicin for Ménière's Disease: Long‐term Follow‐up of Two Regimens

Objectives: 1) Analyze the recurrence rate of vertigo and the need for repeated injections of two different regimens of intratympanic gentamicin (ITG) (low dose and multiple daily dose). 2) Evaluate the efficacy of retreatment after long-term recurrence of vertigo attacks. Methods: We retrospectively analyzed 2 series of patients suffering from unilateral Ménière’s disease treated with low dose ITG (42) and multiple daily dose ITG (35) in a tertiary referral center. The mean period of follow-up was 4.8 years, and the outcome measurements were a) control of vertigo attacks, b) need of repeated treatment for recurrent vertigo evaluated using the Kaplan-Meyer method, and c) incidence of side effects (post-treatment dizziness, hearing loss). Results: At 2-year follow-up, complete control of vertigo was obtained with only 1 round of treatment in 30 (71%) low dose patients and 28 (80%) multiple daily dose patients. Side effects of ITG were significantly higher in the multiple daily dose group. At long-term follow-up (&gt; 4 years), the complete control vertigo rate decreased significantly, especially in the low dose group. 13 (31%) patients in the low dose group and 9 (25%) in the multiple daily dose group needed multiple rounds of treatment. Conclusions: Both regimen of ITG offered an excellent rate of vertigo control at 2-year follow-up. At long-term follow-up, the probability of recurrent vertigo attacks progressively increases, especially in the low dose group. The patients who experienced late recurrences of vertigo had less chance of achieving good results with additional rounds of ITG.

Antibiotic susceptibility profiles of neonatal invasive isolates of Escherichia coli from a 2-year nationwide surveillance study in Germany, 2009–2010

A nationwide 2-year surveillance study on invasive neonatal Escherichia coli infections in Germany was conducted. A total of 158 isolates were tested for antibiotic susceptibility. The empirical treatment regimen of ampicillin plus gentamicin for neonatal sepsis appears to remain effective, but emerging resistance needs to be closely monitored.

Gentamicin in Hemodialyzed Critical Care Patients: Early Dialysis after Administration of a High Dose Should Be Considered

Gentamicin is a widely used antibiotic in the intensive care unit (ICU). Its dosage is difficult to adapt to hemodialyzed ICU patients. The FDA-approved regimen consists of the administration of 1 to 1.7 mg/kg of gentamicin at the end of each dialysis session. Better pharmacokinetic management could be obtained if gentamicin were administered just before the dialysis session. We performed Monte Carlo simulations (MCS) to determine the best gentamicin pharmacokinetic profile (high peak and low trough concentrations). Then, 6 mg/kg of gentamicin was infused into 10 ICU patients over a period of 30 min. A 4-h-long hemodialysis session was started 30 min after the end of the infusion. Pharmacokinetic samples were regularly collected over 24 h. A one-compartment model with zero-order input and first-order elimination was developed in Nonmem version VI to analyze patients' measured gentamicin concentration-versus-time profiles. Finally, additional MCS were performed to compare the regimen chosen with the FDA-approved gentamicin regimen. High peak concentrations (C(max), 31.8 ± 16.8 mg/liter) were achieved. The estimated C(24) and C(48) values (concentrations 24 and 48 h, respectively, after the beginning of the infusion) were 4.1 ± 2.3 and 1.8 ± 1.2 mg/liter, respectively. The volume of distribution was 0.21 ± 0.06 liter/kg. MCS confirmed that the dosing regimen chosen achieved the target C(max) whereas the FDA-approved regimen did not (31.0 ± 10.9 versus 8.8 ± 3.1 mg · liter(-1)). Moreover, the C(24) values were similar while the AUC(0-24) values were moderately increased (190.8 ± 65.0 versus 135 ± 42.2 mg · h · liter(-1)). Therefore, administration of 6 mg/kg of gentamicin before hemodialysis to critically ill patients achieves a high C(max) and an acceptable AUC, maximizing pharmacokinetic/pharmacodynamic endpoints.