Use Of Tobramycin Research Articles

Enhanced sensitivity in tobramycin monitoring using a surfactant-aligned liquid crystal aptasensor with a ternary hybrid aptamer

Determining pharmaceutical residues in foodstuffs is of great importance worldwide. The improper use of tobramycin (TOB) with abroad spectrum antibacterial activity results in its accumulation in the food chain and human body. Given its detrimental effects on human health, the careful surveillance of TOB concentrations is essential to ensure food safety. Presented here is a highly sensitive aptasensing array designed to measure the TOB concentration by disrupting the alignment of liquid crystal (LC) molecules induced by surfactants. For the first time, a ternary hybrid of the aptamer strands was incorporated onto the surfactant-designed LC-aqueous interface instead of a single strand of aptamer, causing a significant disruption in the customary orientation of LCs. This changed the brightness quantity from 35.06 to 69.54, due to higher interaction with the positively charged section of the surfactant than that for one aptamer strand. The presence of TOB caused the ternary aptamer hybrid to break apart by creating the complex between the aptamer and TOB, separating the aptamer strands from the LC-aqueous interface. Subsequently, the TOB presence was specified by inducing a color change in the polarized vision of the aptasensor platform, resulting in a shift from colorful to murky. The aptasensor could monitor TOB in the linear concentration range of 1 fM-10 nM, with an impressively low detection limit of 0.217 fM. With the capability to determine TOB in beef, chicken egg, and low-fat milk, the LC-decorated aptasensor is proficient in food quality control. The aptasensor possesses characteristics such as simplicity, high sensitivity, ease of use, and affordability. As a result, it has the potential to be marketed as a portable testing kit that is convenient and cost-effective.

Antibiotic Use in Adult Spine Deformity Surgery: Results From the AO Spine Surveillance of the Management of Patients With Adult Spine Deformity.

Cross-sectional international survey with literature review. To evaluate the evidence for these strategies and to understand the current trends in prophylactic antibiotic use during ASD surgery through an international survey. An online survey was conducted among international AO Spine members regarding the peri-operative management of patients with ASD. The details of perioperative systemic and topical antibiotic use were solicited. Descriptive data were summarized for the responding surgeons who perform at least 10 long-segment fusions of >5 levels extending to the pelvis annually. The literature supports the use of prophylactic antibiotic effective against gram positive organisms. The use of topical vancomycin remains debated, and there is limited evidence for topical tobramycin use. A total of 116 responses were received. 74 (64%) surgeons use topical vancomycin, most usually deep to the fascia only 45 (61%). The most usual dose used is 1-2g. 4 (3%) surgeons use topical tobramycin deep to fascia. Following surgery, 90 (78%) surgeons use prophylactic cephalosporin with 3 (3%) using cloxacillin, 5 (4%) using ciprofloxacin and 9 (8%) using vancomycin and 6 (5%) using clindamycin either in addition or alone. The present survey identifies a trend towards systemic and topical antibiotic prophylaxis primarily targeted at gram positive pathogens. The use of topical tobramycin, proposedly effective against gram negative infections, remains uncommon. There is a lack of consensus in the selection of perioperative antibiotic prophylaxis, thus a prospective study of the rates of infection with each strategy would be useful to inform guidelines.

Efficacy and Safety of Dry Powder Antibiotics: A Narrative Review.

The use of inhaled antibiotics was initially almost exclusively confined to patients with cystic fibrosis (CF). However, it has been extended in recent decades to patients with non-CF bronchiectasis or chronic obstructive pulmonary disease who present with chronic bronchial infection by potentially pathogenic microorganisms. Inhaled antibiotics reach high concentrations in the area of infection, which enhances their effect and enables their long-term administration to defeat the most resistant infections, while minimizing possible adverse effects. New formulations of inhaled dry powder antibiotics have been developed, providing, among other advantages, faster preparation and administration of the drug, as well as avoiding the requirement to clean nebulization equipment. In this review, we analyze the advantages and disadvantages of the different types of devices that allow the inhalation of antibiotics, especially dry powder inhalers. We describe their general characteristics, the different inhalers on the market and the proper way to use them. We analyze the factors that influence the way in which the dry powder drug reaches the lower airways, as well as aspects of microbiological effectiveness and risks of resistance development. We review the scientific evidence on the use of colistin and tobramycin with this type of device, both in patients with CF and with non-CF bronchiectasis. Finally, we discuss the literature on the development of new dry powder antibiotics.

Clinical cases of Pseudomonas aeruginosa eradication in patients with cystic fibrosis

Pseudomonas aeruginosa is the most common highly pathogenic flora in patients with cystic fibrosis. It is associated with severe lung damage and affects life expectancy. According to the register of patients with cystic fibrosis in the Russian Federation (2019), the incidence of P. aeruginosa pulmonary infection among them is 34.3%. Inhaled tobramycin is the drug of choice for the eradication of P. aeruginosa in patients with cystic fibrosis according to European and Russian recommendations. Clinical studies showed that Bramitob is highly effective against P. aeruginosa infection in patients with cystic fibrosis.The aim of the study: to demonstrate the effectiveness and safety of eradication therapy with inhaled tobramycin in several clinical cases of children with cystic fibrosis.Methods. The article analyzes 6 clinical cases of effective eradication of P. aeruginosa in patients with cystic fibrosis, including 1 clinical case that involved a new approach to assessing the resistance of P. aeruginosa. Positive culture of P. aeruginosa was confirmed in all patients in specialized laboratories (State Budgetary Healthcare Institution “Morozov Children’s City Clinical Hospital of the Department of Health of the City of Moscow”, Federal State Budgetary Institution “N.F.Gamaleya National Research Center for Epidemiology and Microbiology”, Ministry of Health of the Russian Federation). All patients received inhaled tobramycin 300 mg 2 times a day for 1 – 3 courses (a course of 28 days of inhalations/28 days – a break).Results. All children tolerated tobramycin well, and two of them were younger than 6 years old. The effectiveness of eradication was confirmed by negative cultures of P. aeruginosa during 1-year follow-up that included quarterly microbiological control. The clinical case that involved assessment of resistance to inhaled tobramycin is especially important because of polyresistance of the pathogen.Conclusion. The presented clinical cases of eradication of P. aeruginosa with the use of tobramycin confirm its clinical efficacy and wider application possibilities.

154. Antibiotic Use During Three Separate Waves of the COVID-19 Pandemic at a Large Academic Medical Center in Detroit, MI

BackgroundInpatient antibiotic use early on in the COVID-19 pandemic may have increased due to the inability to distinguish between bacterial and COVID-19 pneumonia. The purpose of this study was to determine the impact of COVID-19 on antimicrobial usage during three separate waves of the COVID-19 pandemic.MethodsWe conducted a retrospective review of patients admitted to Detroit Medical Center between 3/10/19 to 4/24/21. Median days of therapy per 1000 adjusted patient days (DOT/1000 pt days) was evaluated for all administered antibiotics included in our pneumonia guidelines during 4 separate time periods: pre-COVID (3/3/19-4/27/19); 1st wave (3/8/20-5/2/20); 2nd wave (12/6/21-1/30/21); and 3rd wave (3/7/21-4/24/21). Antibiotics included in our pneumonia guidelines include: amoxicillin, azithromycin, aztreonam, ceftriaxone, cefepime, ciprofloxacin, doxycycline, linezolid, meropenem, moxifloxacin, piperacillin-tazobactam, tobramycin, and vancomycin. The percent change in antibiotic use between the separate time periods was also evaluated.ResultsAn increase in antibiotics was seen during the 1st wave compared to the pre-COVID period (2639 [IQR 2339-3439] DOT/1000 pt days vs. 2432 [IQR 2291-2499] DOT/1000 pt days, p=0.08). This corresponded to an increase of 8.5% during the 1st wave. This increase did not persist during the 2nd and 3rd waves of the pandemic, and the use decreased by 8% and 16%, respectively, compared to the pre-COVID period. There was an increased use of ceftriaxone (+6.5%, p=0.23), doxycycline (+46%, p=0.13), linezolid (+61%, p=0.014), cefepime (+50%, p=0.001), and meropenem (+29%, p=0.25) during the 1st wave compared to the pre-COVID period. Linezolid (+39%, p=0.013), cefepime (+47%, p=0.08) and tobramycin (+47%, p=0.05) use remained high during the 3rd wave compared to the pre-COVID period, but the use was lower when compared to the 1st and 2nd waves.Figure 1. Antibiotic Use 01/2019 to 04/2019 ConclusionAntibiotics used to treat bacterial pneumonia during the 1st wave of the pandemic increased and there was a shift to broader spectrum agents during that period. The increased use was not sustained during the 2nd and 3rd waves of the pandemic, possibly due to the increased awareness of the differences between patients who present with COVID-19 pneumonia and bacterial pneumonia.Disclosures All Authors: No reported disclosures

Characterizations of the viability and gene expression of dispersal cells from Pseudomonas aeruginosa biofilms released by alginate lyase and tobramycin.

Biofilm infections are hard to manage using conventional antibiotic treatment regimens because biofilm structures discourage antibiotics from reaching the entire bacterial community and allow pathogen cells to persistently colonize and develop a plethora of tolerance mechanisms towards antibiotics. Moreover, the dispersed cells from biofilms can cause further complications by colonizing different sites and establishing new cycles of biofilms. Previously, we showed that alginate lyase enzyme (AlyP1400), purified from a marine Pseudoalteromonas bacterium, reduced Pseudomonas aeruginosa biofilm biomass and boosted bactericidal activity of tobramycin by degrading alginate within the biofilm extracellular polymeric substances matrix. In this work, we used a flow cytometry-based assay to analyze collected dispersal cells and demonstrated the synergy between tobramycin with AlyP1400 in enhancing the release of both live and dead biofilm cells from a mucoid P. aeruginosa strain CF27, which is a clinical isolate from cystic fibrosis (CF) patients. Interestingly, this enhanced dispersal was only observed when AlyP1400 was combined with tobramycin and administered simultaneously but not when AlyP1400 was added in advance of tobramycin in a sequential manner. Moreover, neither the combined nor sequential treatment altered the dispersal of the biofilms from a non-mucoid P. aeruginosa laboratory strain PAK. We then carried out the gene expression and tobramycin survival analyses to further characterize the impacts of the combined treatment on the CF27 dispersal cells. Gene expression analysis indicated that CF27 dispersal cells had increased expression in virulence- and antibiotic resistance-related genes, including algR, bdlA, lasB, mexF, mexY, and ndvB. In the CF27 dispersal cell population, the combinational treatment of AlyP1400 with tobramycin further induced bdlA, mexF, mexY, and ndvB genes more than non-treated and tobramycin-treated dispersal cells, suggesting an exacerbated bacterial stress response to the combinational treatment. Simultaneous to the gene expression analysis, the survival ability of the same batch of biofilm dispersal cells to a subsequent tobramycin challenge displayed a significantly higher tobramycin tolerant fraction of cells (~60%) upon the combinational treatment of AlyP1400 and tobramycin than non-treated and tobramycin-treated dispersal cells, as well as the planktonic cells (all below 10%). These results generate new knowledge about the gene expression and antibiotic resistance profiles of dispersed cells from biofilm. This information can guide the design of safer and more efficient therapeutic strategies for the combinational use of alginate lyase and tobramycin to treat P. aeruginosa biofilm-related infections in CF lungs.

Evaluation of Antibiotic Tolerance in Pseudomonas aeruginosa for Aminoglycosides and Its Predicted Gene Regulations through In-Silico Transcriptomic Analysis

Pseudomonas aeruginosa causes chronic infections, such as cystic fibrosis, endocarditis, bacteremia, and sepsis, which are life-threatening and difficult to treat. The lack of antibiotic response in P. aeruginosa is due to adaptive resistance mechanism, which prevents the entry of antibiotics into the cytosol of the cell to achieve tolerance. Among the different groups of antibiotics, aminoglycosides are used as a parenteral antibiotic for the treatment of P. aeruginosa. This study aimed to determine the kinetics of antibiotic tolerance and gene expression changes in P. aeruginosa exposed to amikacin, gentamicin, and tobramycin. These antibiotics were exposed to P. aeruginosa at their MICs and the experimental setup was monitored for 72 h, followed by the measurement of optical density every 12 h. The growth of P. aeruginosa in the MICs of antibiotics represented the kinetics of antibiotic tolerance in amikacin, gentamicin, and tobramycin. The transcriptomic profile of antibiotic exposed P. aeruginosa PA14 was taken from the Gene Expression Omnibus (GEO), NCBI as microarray datasets. The gene expressions of two datasets were compared by test versus control. Tobramycin-exposed P. aeruginosa failed to develop tolerance in MICs of 0.5 µg/mL, 1 µg/mL, and 1.5 µg/mL, whereas amikacin- and gentamicin-treated P. aeruginosa developed tolerance. This illustrated the superior in vitro response of tobramycin over gentamicin and amikacin. Further, in silico transcriptomic analysis of tobramycin-treated P. aeruginosa resulted in differentially expressed genes (DEGs), enriched in 16s rRNA methyltransferase E, B, and L, alginate biosynthesis genes, and several proteins of the type II secretion system (T2SS) and type III secretion system (T3SS). The regulation of mucA in alginate biosynthesis, and gidB in RNA methyltransferases, suggested an increased antibiotic response and a low probability of developing resistance during tobramycin treatment. The use of tobramycin as a parenteral antibiotic with its synergistic combination might combat P. aeruginosa with increased response.

Subgroup causal effect identification and estimation via matching tree

Inferring causal effect from observational studies is a central topic in many scientific fields, including social science, health and medicine. The statistical methodology for estimating population average causal effect has been well established. However, the methods for identifying and estimating subpopulation causal effects are relatively less developed. Part of the challenge is that the subgroup structure is usually unknown, therefore, methods working well for population level effect need to be modified to address this. A tree method based on a matched design is proposed to identify subgroups with differential treatment effects. To remove observed confounding, propensity-score-matched pairs are first created. Then the classification and regression tree is applied to the within-pair outcome differences to identify the subgroup structure. This nonparametric approach is robust to model misspecification, which is important because it becomes much harder to specify a parametric outcome model in the presence of subgroup effects. In addition to describing assumptions under which our matching estimator is unbiased, algorithms for identifying subgroup structures are provided. Simulation results indicate that the proposed approach compares favorably, in terms of the percentage of correctly identifying true tree structure, with other competing tree-based methods, including causal trees, causal inference trees and the virtual twins approach. Finally the proposed method is implemented to examine the potential subgroup effect of the timing of Tobramycin use on chronic infection among pediatric Cystic Fibrosis patients.

Активность тобрамицина в отношении штаммов Pseudomonas aeruginosa, выделенных у пациентов с муковисцидозом

Study Objective: To determine in vitro activity of Tobramycin for Pseudomonas aeruginosa spp. isolated in children with cystic fibrosis (CF); to retrospectively study the efficiency dynamics of inhalative Tobramycin in management of bronchopulmonary process exacerbation in children with CF aged 9 years old (2009–2018). Study Design: retrospective analysis. Materials and Methods. The study included 173 children with cystic fibrosis aged 3 to 17 years old; the median age in the general group was 11 [8; 15] years. Subjects were divided into two comparison groups, depending on various 14-day combined antipseudomonal therapy: 42 children were treated with Cefepime 150 mg/kg + Amikacin 20 mg/kg IV drop infusion; 48 subjects — with Meropenem 100 mg/kg + Amikacin 20 mg/kg IV drop infusion; 83 patients — with Ceftazidime 200 mg/kg IV + Tobramycin (Bramitob) 300 mg twice daily, inhalation + Ciprofloxacin per os 30–40 mg/kg. Study Results. After the two-week therapy of 83 children with Tobramycin inhalations plus oral Ciprofloxacin and Ceftazidime IV, 123 (82%) out of 150 pathogenic P. aeruginosa and Staphylococcus aureus spp. were eliminated (p < 0.001 when compared to bacteriologic test results of pre-therapy bronchial mucus). Comparison groups demonstrated statistically significantly lower number of such subjects: in Cefepime + Amikacin group, 32 (43.8%) out of 73 pathogenic P. aeruginosa and S. aureus spp. were eliminated; whereas in Meropenem + Amikacin group, only 28 (35.4%) pathogens were eliminated out of 79 species. Upon admission in 2013, 50 followed up children underwent antimicrobial therapy with inhalative Tobramycin using the same regimen as in 2009; the P. aeruginosa elimination was the same: 11 (18%) out of 61 pathogenic species remained viable, 50 (82%) species were eliminated, as demonstrated by control sputum. The difference between the number of P. aeruginosa and S. aureus colonies before and after therapy was statistically significant (p < 0.001). Practically the same result after the use of inhalative Tobramycin was observed in 2018: 14 (70%) out 20 children with P. aeruginosa spp. had their control sputum samples sanitised (p < 0.001). Conclusion. Despite a 20-year history of using in patients with cystic fibrosis, inhalative Tobramycin is still clinically efficient and potent for isolated P. aeruginosa as a component of primary eradication and management of chronic Pseudomonal lung infections. Keywords: cystic fibrosis, Pseudomonas aeruginosa, inhalative Tobramycin.

330. Risk Factors for Acute Kidney Injury after the Use of Antibiotic Loaded Bone Cement in Orthopedic Surgery – a Retrospective Case-control Study

BackgroundAs the number of joint replacement surgeries continues to rise, so does the number of joint infections. Many patients end up needing the implantation of antibiotic loaded bone cement (ALBC) to treat their infection. The use of localized high dose vancomycin, tobramycin, and gentamicin may be linked to acute kidney injury (AKI) in certain patients. Our hypothesis is that patients who developed AKI after receiving a joint spacer had a predisposition to AKI due to other comorbidities, high antibiotic doses in ALBC, immunosuppression, or the use of other nephrotoxic drugs pre-op. These patients may need close monitoring of their renal function and serum antibiotic levels after surgery.MethodsWe performed a chart review of 428 patients who underwent an orthopedic surgery that involved insertion of ALBC at our institution between 2015 and 2018. We excluded patients under age 18, those who had antibiotic irrigation only, trauma patients, non-arthroplasty surgeries (such as fractures and debridement of deep wounds), and patients with missing data for 30 days after the surgery. We identified 57 patients who fit our inclusion criteria and received a bone cement spacer or beads to treat an infection of the hip, knee, shoulder, or ankle. We matched patients who had AKI to 2 patients who did not have AKI. Matching was based on age (± 5 years), joint operated on, and antibiotics used.Results15 patients showed an elevated serum creatinine level of over 1.2 within 30 days of surgery. 86.7% of these patients were male, their average age was 64.1 ± 6.2 years old, 40% had hip surgery, 46.7% knee surgery, 6.7% ankle, and 6.7% shoulder. All received vancomycin and tobramycin in Palacos bone cement. Compared to their case-control matches, these patients had more frequent use of immunosuppressive medication, a history of malignancy, a history of previous kidney disease, and obesity. The use of combined intravenous vancomycin and piperacillin-tazobactam post-operatively may also be linked to higher rates of AKI.ConclusionImmunosuppression, obesity, male gender, and history of kidney injury and cancer are factors associated with AKI after ALBC spacer implantation. Further analysis and study are needed to identify potential causation between ALBC use and AKI.Disclosures All Authors: No reported disclosures

Effect of Concomitant Azithromycin and Tobramycin Use on Cystic Fibrosis Pulmonary Exacerbation Treatment.

Rationale: Pulmonary exacerbations (PExs) are associated with significant morbidity in people with cystic fibrosis (CF). Severe PExs are treated with intravenous antibiotics, including tobramycin. CF care guidelines recommend continuing chronic maintenance medications during PEx treatment. Azithromycin (AZM) is one of the most widely prescribed chronic medications for CF in the United States. Recent evidence has identified a potential antagonistic relationship between AZM and tobramycin.Objectives: To determine whether, among PEx treated with intravenous tobramycin, concomitant AZM use is associated with worse clinical outcomes.Methods: Retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System (CFFPR-PHIS)-linked dataset. People with CF age 6-21 years were included if they were hospitalized between 2006 and 2016 for a PEx. Inverse probability of treatment weighing was used to minimize the effects of confounders, including indication bias. Associations of concomitant treatment with AZM and lung function outcomes were determined using linear mixed-effect models and generalized estimating equations. Cox proportional hazard regression models were used to evaluate associations with time to next PEx.Results: Among the 10,660 people with CF included in the CFFPR-PHIS-linked dataset, 2,294 children and adolescents with 5,022 PExs that had intravenous tobramycin use were identified. A little less than half (n = 2,247; 45%) of all PExs were treated concomitantly with AZM and intravenous tobramycin. AZM use both at the most recent outpatient clinic encounter and during PEx treatment in combination with intravenous tobramycin was associated with a significantly lower absolute improvement in percentage-predicted forced expiratory volume in 1 second (ppFEV1) (-0.93%; 95% confidence interval [CI], -1.78 to -0.07; P = 0.033), a lesser odds of returning to 90% or more of baseline ppFEV1 (odds ratio, 0.79; 95% CI, 0.68-0.93; P = 0.003), and a shorter time to next PEx requiring intravenous antibiotics (hazard ratio, 1.22; 95% CI, 1.14-1.31; P < 0.001) compared with intravenous tobramycin use without concomitant AZM.Conclusions: Concomitant AZM and intravenous tobramycin use for in-hospital PEx treatment was associated with poorer clinical outcomes than treatment with intravenous tobramycin without AZM. These results support the hypothesis that an antagonistic relationship between these two medications might exist.

Tobramycin Promotes Melanogenesis by Upregulating p38 MAPK Protein Phosphorylation in B16F10 Melanoma Cells.

Tobramycin is an aminoglycoside-based natural antibiotic derived from Streptomyces tenebrarius, which is primarily used for Gram-negative bacterial infection treatment. Although tobramycin has been utilized in clinical practice for a long time, it has exhibited several side effects, leading to the introduction of more effective antibiotics. Therefore, we conducted our experiments focusing on new possibilities for the clinical use of tobramycin. How tobramycin affects skin melanin formation is unknown. This study used B16F10 melanoma cells to assess the effect of tobramycin on melanin production. After cytotoxicity was assessed by MTT assay, melanin content and tyrosinase activity analyses revealed that tobramycin induces melanin synthesis in B16F10 cells. Next, Western blot analyses were performed to elucidate the mechanism by which tobramycin increases melanin production; phosphorylated p38 protein expression was upregulated. Protein inhibitors have been used to elucidate the mechanism of tobramycin. Kanamycin A and B are structurally similar to tobramycin, and 2-DOS represents the central structure of these antibiotics. The effects of these substances on melanogenesis were evaluated. Kanamycin A reduced melanin production, whereas kanamycin B and 2-DOS had no effect. Overall, our data indicated that tobramycin increases melanin production by promoting p38 protein phosphorylation in B16F10 melanoma cells.

Topical antibiotic therapy in chronic rhinosinusitis: an update.

Topical antibiotic therapies have been investigated for their use in chronic rhinosinusitis (CRS). However, society guidelines and evidence-based medicine reviews have recommended against the use of topical antibiotic therapy based on randomized controlled trials (RCTs). The purpose of this article is to review recent clinical research published since the aforementioned guidelines were published. A structured literature review was performed on clinical studies published in the last 5 years investigating the use of topical antibiotic therapies. One double-blinded, randomized controlled trial (DB-RCT) supported the use of tobramycin using a vibrating aerosolizer; 1 non-blinded non-randomized controlled prospective trial lent support to use of topical ofloxacin for its anti-biofilm properties; and 1 meta-analysis found mupirocin irrigations to be beneficial in the short term. One Cochrane Review was unable to make a recommendation as no trial met the inclusion criteria. An additional systematic review found limited evidence to support the use of topical antibiotics with the exception of mupirocin irrigations that may be considered in Staphylococcus aureus infections. Two retrospective studies found that topical antibiotics change bacterial cultures of the sinuses. There is additional evidence to support continuing investigation of topical antibiotic therapies. Further, larger RCTs are required to establish the efficacy of topical antibiotic therapies.

Investigation of the effects of various antibiotics against Klebsiella pneumoniae biofilms on in vitro catheter model

Klebsiella pneumoniae continues to be an important cause of community-acquired and nosocomial infection. This bacterium can cause catheter related infections by forming biofilm on the surface of catheter. The aim of our study is to determine the in vitro stability and efficacy of colistin, ciprofloxacin, tobramycin, doripenem and tigecycline alone, or in combination with clarithromycin or esomeprazole, as 24-h lock solutions against biofilm-embedded K. pneumoniae strains. The efficacy of antibiotic lock solutions was tested in an in vitro catheter biofilm model against K. pneumoniae. In our study, we observed that the use of doripenem and tobramycin as a lock solution had potent bactericidal effects. When colistin was used in combination with clarithromycin or esomeprazole, the combinations had a synergistic effect. No antagonistic effect was observed. The findings of our study have important information for effectiveness of tested antibiotic lock solution in the catheter-related infections with K. pneumoniae.

Bacterial Keratitis in Toronto: A 16-Year Review of the Microorganisms Isolated and the Resistance Patterns Observed.

To review the incidence, distribution, current trends, and resistance patterns of bacterial keratitis isolates in Toronto over the past 16 years. Microbiology records of suspected bacterial keratitis that underwent a diagnostic corneal scraping and cultures from January 1, 2000, through December 31, 2015, were retrospectively reviewed. The distribution of the main isolated pathogens and in vitro laboratory minimum inhibitory concentration testing results were used to identify resistance patterns. A total of 2330 corneal scrapings were taken over 16 years. A pathogen was recovered in 1335 samples (57.3%), with bacterial keratitis accounting for 1189 of the positive cultures (86.0% of all isolates). The total number of gram-positive and gram-negative isolates was 963 and 324, respectively. Coagulase-negative Staphylococcus and Pseudomonas aeruginosa were the most common gram-positive and gram-negative bacteria isolates, respectively. A decreasing trend in the number of isolates in gram-positive bacteria (P = 0.01), specifically among Staphylococcus aureus (P < 0.0001) and Streptococcus species (P = 0.005), was identified. When analyzing the susceptibilities of gram-positive and gram-negative isolates, an increasing trend in antibiotic resistance was observed in erythromycin (P = 0.018), ceftazidime (P = 0.046), and piperacillin/tazobactam (P = 0.005). The susceptibility of tested gram-positive microorganisms to vancomycin was 99.6%. There has been a decreasing trend in the number of isolates in gram-positive microorganisms over the past 16 years. An increasing trend in resistance for various antibiotics against gram-negative and gram-positive isolates was identified. High susceptibility to vancomycin reinforced the empirical use of fortified tobramycin and vancomycin in the initial management of severe bacterial keratitis.

Reducing Second Gram-Negative Antibiotic Therapy on Pediatric Oncology and Hematopoietic Stem Cell Transplantation Services.

OBJECTIVE To evaluate interventions to reduce avoidable antibiotic use on pediatric oncology and hematopoietic stem cell transplantation (HSCT) services. DESIGN Interrupted time series. SETTING Academic pediatric hospital with separate oncology and HSCT services. PARTICIPANTS Children admitted to the services during baseline (October 2011-August 2013) and 2 intervention periods, September 2013-June 2015 and July 2015-June 2016, including 1,525 oncology hospitalizations and 301 HSCT hospitalizations. INTERVENTION In phase 1, we completed an update of the institutional febrile neutropenia (FN) guideline for the pediatric oncology service, recommending first-line β-lactam monotherapy rather than routine use of 2 gram-negative agents. Phase 2 included updating the HSCT service FN guideline and engagement with a new pediatric antimicrobial stewardship program. The use of target antibiotics (tobramycin and ciprofloxacin) was measured in days of therapy per 1,000 patient days collected from administrative data. Intervention effects were evaluated using interrupted time series with segmented regression. RESULTS Phase 1 had mixed effects-long-term reduction in tobramycin use (97% below projected at 18 months) but rebound with increasing slope in ciprofloxacin use (+18% per month). Following phase 2, tobramycin and ciprofloxacin use on the oncology service were both 99% below projected levels at 12 months. On the HSCT service, tobramycin use was 99% below the projected level and ciprofloxacin use was 96% below the projected level at 12 months. CONCLUSIONS Locally adapted guidelines can facilitate practice changes in oncology and HSCT settings. More comprehensive and ongoing interventions, including follow-up education, feedback, and engagement of companion services may be needed to sustain changes. Infect Control Hosp Epidemiol 2017;38:1039-1047.

Nebulized Gentamicin as an Alternative to Nebulized Tobramycin for Tracheitis in Pediatric Patients.

Tracheitis is an infection of the lower respiratory tract and is defined by the US Centers for Disease Control and Prevention (CDC) based on signs and symptoms with no radiographic evidence of pneumonia. One method of treatment involves the use of tobramycin given by nebulizer. The purpose of this study was to compare the safety and efficacy of nebulized gentamicin with nebulized tobramycin. This study was conducted in patients under 21 years of age who received greater than or equal to 1 day of gentamicin, 80 mg, or tobramycin, 300 mg, given twice a day by nebulization within the 14-month study period. The primary endpoint was amount of time until the patient no longer met the CDC definition of tracheitis. There were 19 patients who presented with 60 separate encounters. The average age of the patients within the gentamicin group was 7.2 and 5 years old within the tobramycin group. The average duration of time for the gentamicin treatment encounters to be free of the CDC definition of tracheitis was 3.36 days compared to 3.17 days with tobramycin. No adverse effects were observed that were attributable to aminoglycoside nebulization. No differences were detected between the safety and efficacy of intravenous gentamicin administered twice a day by nebulizer and that of tobramycin inhalation solution given twice daily in children without cystic fibrosis.

Previous aminoglycoside use and acute kidney injury risk in non-critically ill children.

Aminoglycosides (AG) are a group of bactericidal antibiotics with nephrotoxic effects that are commonly used in the treatment of hospitialized children. We have examined previous AG treatment as a risk factor for acute kidney injury (AKI) during current AG treatment. We performed a retrospective cohort study of children ranging in age from 1 month to 18 years who were treated with AG between October 2008 and April 2012 at Montreal's Children's Hospital. Children for whom no serum creatinine data (SCr) were available and those with baseline renal disease were excluded from the analysis. Main exposures were prior AG use (number and hours of prior treatments) and time since last AG treatment. The main outcome was AKI, defined on the basis of theKidney Disease: Improving Global Outcomes guidelines. Logistic regression was used to examine exposure-outcome associations. AG treatments episodes with Stage 1, 2, and 3 AKI, respectively, were associated with a median of 98 [interquartile range (IQR) 339], 231 (IQR 688), and 111 (IQR 505) h of prior AG treatment, respectively, versus non-AKI (median 0, IQR 54 h) (p < 0.0001). AKI episodes were associated with a mean (± standard deviation) of 1.5 ± 1.8 AG treatments in the previous 6months, versus 0.9 ± 1.6 AG treatments for non-AKI. The number of AG-treatment days during the preceding 6 months [adjusted odds ratio (adjOR) 1.04, 95% confidence interval (CI) 1.03-1.06; p < 0.001], younger age (adjOR 0.96, 95% CI 0.93-0.99; p = 0.009), admission to hematology-oncology department (adjOR 3.88, 95% CI 2.17-6.96; p < 0.001), and tobramycin use (adjOR 1.77, 95% CI 1.04-3.02; p = 0.04) were independently associated with AKI. Episodes with Stage 1 and 2 AKI were associated with fewer days since last treatment compared to non-AKI treatment (p < 0.02 and p < 0.005, respectively; Mann-Whitney test). Based on these results, priorAG treatment is a risk factor for AKI and should be considered when dosing and monitoring hospitalized children being treated with AG.

Prediction of inventory sustainability during a drug shortage.

A methodology for predicting how long the on-hand inventory of a given medication will last during a supply shortage is described; a practical example of application of the methodology is provided. Single-site data on consumption of i.v. tobramycin over an eight-month evaluation period were collected using commercial software that tabulates barcode-assisted medication administration (BCMA) events; administered doses were standardized as 1200-mg "vial-equivalents" and summed over the review period. The total number of vial-equivalents consumed was divided by the number of "non-zero weeks of consumption" (i.e., weeks during which any tobramycin use occurred) to obtain a mean ± S.D. weekly consumption rate; this rate was multiplied by the total i.v. tobramycin on-hand supply (in vial-equivalents) to determine the mean number of potentially sustainable weeks of therapy in the event a shortage were to restrict the future supply of the drug. Overall, 99.6 vial-equivalents of i.v. tobramycin were used during the evaluation period. The mean ± S.D. number of vial-equivalents used per non-zero week of consumption was 3.11 ± 1.26. A manual count of pharmacy inventory revealed that 102.9 vial-equivalents were available at the time of analysis. The mean predicted duration of supply was 33 weeks (95% confidence interval, -126 to 192 weeks). Available BCMA data on tobramycin consumption over eight months were used to calculate the mean number of weeks the on-hand supply of the drug could be expected to last during a persistent drug shortage.

Cost Reduction of Inhaled Tobramycin by Use of Preservative-Free Intravenous Tobramycin Given via Inhalation.

This study evaluates drug cost outcomes related to automatic therapeutic substitution of branded tobramycin solution for inhalation (TOBI®) with inhaled generic preservative-free intravenous tobramycin (PFIT). A retrospective single-center evaluation of inhaled tobramycin use from 2008 through 2012 was performed. Number of doses dispensed and acquisition costs were obtained. Hourly wage data was acquired, pharmacy production costs were estimated and total cost-savings calculated. Days of therapy (DOTs) were determined for each year. Quality assurance and safety data was collected. In 2008, TOBI® drug costs and doses dispensed were $118,665 and 1769, respectively. Following implementation of the interchange in May 2009, TOBI® utilization ceased. PFIT costs in 2010 through 2012 averaged $34,775 annually and TOBI® cost-avoidance exceeded $94,000 annually when accounting for pharmacy production costs, which were determined to be at most $5.28 per dose. The maximum estimated pharmacy production cost ranged from $8812 to $11,299 annually. PFIT doses dispensed exceeded 1650 each year and annual DOTs ranged from 815 to 1069. The 40-month savings were calculated to be $374,706. Quality assurance and safety data identified one patient who refused PFIT due to odor complaints and one patient who was inappropriately administered a dose orally. Therapeutic substitution of TOBI® with PFIT can produce immediate and sustained savings with an acceptable safety profile.