Therapeutic Antibiotics Research Articles

Reporter-Phage-Based Detection and Antibiotic Susceptibility Testing of Yersinia pestis for a Rapid Plague Outbreak Response

Pneumonic plague is a lethal infectious disease caused by Yersinia pestis, a Tier-1 biothreat agent. Antibiotic treatment can save infected patients; however, therapy should begin within 24 h of symptom onset. As some Y. pestis strains showed an antibiotic resistance phenotype, an antibiotic susceptibility test (AST) must be performed. Performing the Clinical and Laboratory Standards Institute (CLSI)-recommended standard process, which includes bacterial isolation, enumeration and microdilution testing, lasts several days. Thus, rapid AST must be developed. As previously published, the Y. pestis-specific reporter phage ϕA1122::luxAB can serve for rapid identification and AST (ID-AST). Herein, we demonstrate the ability to use ϕA1122::luxAB to determine minimal inhibitory concentration (MIC) values and antibiotic susceptibility categories for various Y. pestis therapeutic antibiotics. We confirmed the assay by testing several nonvirulent Y. pestis isolates with reduced susceptibility to doxycycline or ciprofloxacin. Moreover, the assay can be performed directly on positive human blood cultures. Furthermore, as Y. pestis may naturally or deliberately be spread in the environment, we demonstrate the compatibility of this direct method for this scenario. This direct phage-based ID-AST shortens the time needed for standard AST to less than a day, enabling rapid and correct treatment, which may also prevent the spread of the disease.

Application of Physiologically Based Pharmacokinetic-Pharmacodynamic Modeling in Preterm Neonates to Guide Gentamicin Dosing Decisions and Predict Antibacterial Effect.

Clinical studies in preterm neonates are rarely performed due to ethical concerns and difficulties associated with trials and recruitment. Consequently, dose selection in this population is primarily empirical. Scaling neonatal doses from adult doses does not account for developmental changes and may not accurately predict drug kinetics. This is especially important for gentamicin, a narrow therapeutic index aminoglycoside antibiotic. While gentamicin's bactericidal effect is associated with its peak plasma concentration, keeping trough concentrations below 1 µg/mL prevents toxicity and also helps to counteract adaptive resistance in bacteria such as Escherichia coli. In this study, physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) modeling was used to support and/or guide dosing decisions and to predict the antibacterial effect in preterm neonates. A gentamicin PBPK model was successfully verified in healthy adults and preterm neonates across all gestational ages. Clinical data from a neonatal intensive care unit at NYU Langone Hospital-Long Island was used to identify dosing regimens associated with increased incidence of elevated gentamicin trough concentrations in different preterm patient cohorts. Model predictions demonstrated that a higher dose with an extended-dosing interval (every 36 hours) in neonates with a postmenstrual age of 30 to 34 weeks and ≥35 weeks, with postnatal age 8 to 28 days and 0 to 7 days, respectively, were more likely to have a trough <1 µg/mL when compared with once-daily (every 24 hours) dosing. PBPK-PD modeling suggested that a higher dose administered every 36 hours may provide effective antibacterial therapy.

Impact assessment of the reduction or removal of ionophores used for controlling coccidiosis in the UK broiler industry.

Coccidiosis is a complex parasitic disease ubiquitous in all types of poultry production. It can have both a direct effect on bird health and welfare with significant negative impacts on the production parameters and indirect effect as it predisposes to other pathogens. Ionophore coccidiostats have been used safely for over 45 years by poultry producers. Concerns have been raised that their use in livestock production could promote the development of antibiotic resistance, but their unique mode of action makes it unlikely. Conversely their removal can result in increased use of therapeutic antibiotics to treat disease posing a greater risk of antibiotic resistance development. Economic and environmental models examining the impact of the removal of ionophore coccidiostats from UK production suggest the annual cost to the broiler sector would be between £68.02-£109.95 million and result in an additional 84,000 tonnes CO2 e being produced per annum. Any cost increase would make this wholesome and affordable animal protein less affordable to poorer sectors of society. Increased greenhouse gas production, demand for water and land as a result of less efficient production will impact on climate change targets.

An Investigation on Spray-Granulated, Macroporous, Bioactive Glass Microspheres for a Controlled Drug Delivery System.

Bioactive glass (BG) has been regarded as an excellent candidate for biomedical applications due to its superior properties of bioactivity, biocompatibility, osteoconductivity and biodegradability. Thus, in this study, we aimed to fabricate drug carriers that were capable of loading therapeutic antibiotics while promoting bone regeneration using macroporous BG microspheres, prepared by a spray drying method. Characterizations of particle morphology and specific surface area were carried out via scanning electron microscopy and nitrogen adsorption/desorption isotherm. Evaluations of in vitro bioactivity were performed based on Kokubo’s simulated body fluid to confirm the formation of the hydroxyapatite (HA) layer after immersion. In addition, the in vitro drug release behaviors were examined, using tetracycline as the therapeutic antibiotic in pH 7.4 and 5.0 environments. Finally, the results showed that BG microspheres of up to 33 μm could be mass-produced, targeting various therapeutic situations and their resulting bioactivities and drug release behaviors, and related properties were discussed.

Dissemination of IncFII plasmids carrying fosA3 and blaCTX-M-55 in clinical isolates of Salmonella enteritidis.

Multidrug-resistant Salmonella Enteritidis (S. Enteritidis) isolates have become a significant threat to public health, and fosfomycin has been proposed as one of the therapeutic antibiotics for serious infections by resistant pathogens. In this study, a total of 501 clinical S. Enteritidis isolates were screened and 14 (2.8%) isolates exhibited resistance to fosfomycin (MIC≥1,024μg/mL) as well as ceftriaxone (MIC≥128μg/mL). The fosA3 gene was identified in these 14 isolates. The fosA3 gene that co-transferred with blaCTX-M-55 was observed on the IncFII plasmids with sizes of~78 (n=7) or~111 (n=2) kbp in 9 transconjugants. The fosA3-bearing plasmid p12367A is 111,764bp in length and possessed a typical IncFII backbone. A 7.6-kbp multidrug resistance region (MRR) was identified in p12367A, which was comprised of fosA3 and blaCTX-M-55 genes interspersed with ΔISEcp1 and three copies of IS26. Two typical antibiotic resistance determinants (IS26-orf3-orf2-orf1-fosA3-IS26 and IS26-orf477-blaCTX-M-55 -ΔISEcp1-IS26) shared one IS26 in the MRR. The genetic arrangement of the MRR may have resulted from the stepwise integration of IS26 mobile elements via homologous recombination. Horizontal transfer of IncFII plasmids might contribute to the dissemination of fosA3 and blaCTX-M-55 resistance genes in S. Enteritidis interspecies. These findings underline further challenges for the prevention and treatment of Enterobacteriaceae infections posed by epidemic IncFII plasmids bearing fosA3-blaCTX-M-55 .

ANTIBACTERIAL POTENTIAL OF ESSENTIAL OILS DERIVED FROM NATURAL, CALLUS AND IN-VITRO PROPAGATED SOURCES OF MELALEUCA ALTERNIFOLIA AGAINST COMMON BACTERIAL PATHOGENS

Objective: Melaleuca alternifolia (M. alternifolia) and its essential oil (EO) fractions have been used widely and traditionally in the treatment of various infectious diseases and hence its antibacterial potential is investigated in the present study.&#x0D; Methods: The antibacterial activity was studied through the agar disc diffusion method and broth dilution method, DNA fragmentation studies and confocal microscopy morphological studies were done. In-silico molecular interaction was studied against microbial target using docking software.&#x0D; Results: The inhibitory concentration of the EOs was recorded at 75% dilution with larger inhibition zones. The DNA fragmentation analyzed in the essential oil derived from in-vitro propagated leaves (EOIPL) of M. alternifolia treated bacterial cultures was compared with negative and positive controls. In Minimum Inhibitory Concentration (MIC) of EOIPL treated Staphylococcus aureus (S. aureus) showed time-dependent growth inhibition. The DNA content in the EOIPL treated bacterial cultures was comparatively less than in control cultures. The cell morphology changes of S. aureus cells were studied through confocal laser scanning microscopic analysis which showed a significant decrease in viable bacterial cells. The active component, terpinen-4-ol docked to autolysin receptor revealed stable interaction with the microbial target.&#x0D; Conclusion: Thus EOIPL was explored to possess bactericidal activity against common infectious bacteria and could in incorporated in therapeutic natural antibiotic formulations as with future studies.

268 In-feed Antibiotics Elicit Intestinal Integrity Modifications Early in Post-weaning Life

Abstract The physiological mechanisms by which in-feed antibiotics improve pig growth performance are largely unknown. One proposed mode of action is improvements in intestinal integrity and function. Therefore, the objective of this study was to test the hypothesis that in-feed therapeutic and sub-therapeutic antibiotics would improve intestinal integrity and function in nursery pigs. Twenty-four weaned pigs (6.1±1.1 kg BW) were randomly allotted to individual pens and assigned one of three dietary treatments as follows (n = 8 pigs/trt): 1) control, no antibiotics (CON), 2) CON + sub-therapeutic chlortetracycline [40 ppm in feed (sCTC)], and 3) CON + chlortetracycline-tiamulin [400 ppm + 35 ppm, respectively (CTCDen)]. The study consisted of two consecutive 14 d phases. Chlortetracycline-tiamulin was only fed in phase 1, sCTC was fed in both phases. Phase 1 and 2 ADG, ADFI, and G:F were determined. After 28 d, ileal and colonic ex vivo intestinal integrity was assessed via transepithelial resistance (TER) and macromolecule flux (FD4) in modified Ussing chambers. All data were analyzed for the fixed effects of treatment and start BW as a covariate. In phase 1, compared with CON and sCTC, CTCDen tended to have greater ADG (0.28, 0.31, and 0.33 kg/d, respectively, P = 0.10) and ADFI (0.28, 0.30, and 0.35 kg/d, respectively, P = 0.09). No differences in phase 1 G:F were observed (P = 0.11). Phase 2 ADG, ADFI, and G:F did not differ (P &amp;gt; 0.10). Further, ileal TER and FD4 did not differ (P &amp;gt; 0.10). Colonic TER tended to be increased in sCTC compared with CON and CTCDen (78, 56, and 59 Ω/cm2, respectively, P = 0.07). Compared with CON, colonic FD4 flux was decreased in sCTC and CTCDen by 35–40% (P = 0.03). Altogether, these data indicate that in-feed antibiotics improve colon integrity early in production which may contribute to improved growth performance.

103 The Role of Crude Protein in Reducing the Need for Antibiotics in the Post-weaning Period

Abstract For many decades, antimicrobial compounds such as antibiotics and some mineral compounds have been used in pork production to promote pig growth and survival after weaning through mitigation of subclinical and clinical diseases, such as enterotoxigenic strains of Escherichia coli. Bans and restrictions in the use of some antimicrobial compounds has led, often out of necessity, to the development of alternative feeding strategies to address these challenges. One tool to reduce the post-weaning malaise in the absence of specific antimicrobial compounds is manipulation of the protein content of diets offered to pigs. Numerous studies have shown that feeding higher crude protein diets in the post-weaning period, usually in the absence of specific antimicrobials, is generally related to decreased fecal consistency (looser stools) and an increased incidence of post-weaning diarrhea. In some cases, this causes more therapeutic antibiotic administrations, more animal care, and a greater mortality. Production indices are poorer as a consequence. Conversely, feeding diets of lower crude protein content after weaning has typically been associated with better health outcomes, but if diets are not correctly formulated with the addition of appropriate crystalline amino acids, then production outcomes can suffer. Increasing the quantity of fermentable protein entering the cecum and colon by feeding more dietary protein will stimulate changes in microbial composition, with the microbiota shifting to a more N-utilizing community resulting in greater protein catabolic activity and the increased production of products including ammonia, amines and branched-chain fatty acids. This, in turn, can be associated with increased diarrhea. Formulating starter diets that limit the flow of exogenous and endogenous proteinaceous compounds posteriorly to the ileo-caecal valve can be used to reduce the post-weaning malaise and may minimize the use of certain antimicrobial compounds. However, feeding lower-protein diets alone is not always the panacea to this production issue, and will likely need to be used in conjunction with other targeted nutritional and health measures specific to the farm in question.

Immuno protective potential of Sida schimperiana chloroform root extract against E. coli 018: K1 induced peritonitis in albino Wistar rats

Objective: The present study was aimed to evaluate the in vivo immune protective potential of chloroform root extract of Sida schimperiana on E.coli 018:K1 induced peritonitis in albino Wistar rats. Methods: Acute toxicity of was performed by oral administration of S. schimperiana chloroform root extract (SSRCH) 5, 50, 300 and 2000mg/kg body of male albino Wistar and mortality was monitored for 14 days. Based on LD50, 1/10th, 1/5th cut-off values of the (SSRCH) plant extract was selected as a dose for E. coli induced peritonitis in albino Wistar rats. Wistar rats were pre-treated with 200 and 400mg/kg/bwt of SSRCH and Standard antibiotic Ofloxacin 5mg/Kg body weight was given oraly for a period of 7 days. The dosing regimens were started on day -1,-2, -3, 0, 1, 2 and 3 relative to the day of challenge (day 0) with 2×104 CFU of E. coli CFU/ml (i.p.) and mortality was monitored for 14 days. After the monitoring the mortality, the treated (Groups I-IV) rats were sacrificed, and assess the in vivo antibacterial activity of S. schimperiana chloroform root extract by determination of CFU/ml in peritoneal lavage fluid. Further SSRCH extract (400mg /kg bw) was analyzed by the neutrophil adhesion in Wistar rats for evaluated immunomodulatory activity. Results: In acute toxicity studies no mortality was observed for 24-48 hours. SSRCH extract 400mg (Group-IV) showed protection against E. coli induced peritonitis in albino Wistar rats by showing 60% survivability and also exhibited significantly increased percentage of neutrophils adhesion. i.e (25.74±2.351and 36.14±5.609) at 200 and 400mg/kg respectively. Conclusion: The present study concluded that the chloroform root extract of S. schimperiana had a significant amount of polyphenolic compounds and could serve as a potential source of natural antibacterial and Immunomodulatory agents for the development of therapeutic antibiotics with immunostimulatory activity in the treatment of intraperitoneal infections.

The post-hematopoietic cell transplantation microbiome: relationships with transplant outcome and potential therapeutic targets.

Microbiota injury occurs in many patients undergoing allogeneic hematopoietic cell transplantation, likely as a consequence of conditioning regimens involving chemo- and radiotherapy, the widespread use of both prophylactic and therapeutic antibiotics, and profound dietary changes during the peri-transplant period. Peri-transplant dysbiosis is characterized by a decrease in bacterial diversity, loss of commensal bacteria and single-taxon domination (e.g., with Enterococcal strains). Clinically, deviation of the post-transplant microbiota from a normal, high-diversity, healthy state has been associated with increased risk of bacteremia, development of graft-versus-host disease and decreases in overall survival. A number of recent clinical trials have attempted to target the microbiota in allogeneic hematopoietic cell transplantation patients via dietary interventions, selection of therapeutic antibiotics, administration of pre- or pro-biotics, or by performing fecal microbiota transplantation. These strategies have yielded promising results but the mechanisms by which these interventions influence transplant-related complications remain largely unknown. In this review we summarize the current approaches to targeting the microbiota, discuss potential underlying mechanisms and highlight the key outstanding areas that require further investigation in order to advance microbiota-targeting therapies.

Limited efficacy with additional adverse effect of anti-adhesion barrier at primary cesarean section

In our experience, adhesion after the primary CS is generally minimal or nonexistent. However, adhesion barriers users have experienced more febrile episodes that may require therapeutic antibiotics during the postcesarean period. We evaluated clinical efficacy of HA-CMC and ORC to prevent adhesion at secondary CS and the post-operative outcome at primary and secondary CS. This retrospective study includes 199 Asian women undergoing primary and secondary cesarean section between January1, 2011, and September 31, 2019. We used linear and logistic regression to analyze risk factors of postcesarean fever. An interaction term analysis was performed to examine the effect of surgical site infection risk factors and use of adhesion barrier on postcesarean fever rates. We found that use of adhesion barrier at the primary cesarean section is associated with a significantly higher incidence of postcesarean fever (p=0.045), which is an independent risk factor of postcesarean fever (adjusted hazard ratio (Adj-HR)=3.53, 95% CI=1.03-10.24, p=0.045). The strongest risk factor for postcesarean fever is the use of anti-adhesion film during emergency cesarean section (p=0.041). In the subgroup of labor before operation and emergency cesarean section, adhesion barrier user had significant higher risk of postcesarean fever than nonuser (p=0.018, Adj-HR=12.12, 95% CI=1.53-95.78; emergency cesarean section: p=0.016, Adj-HR=12.71, 95% CI=1.62-99.62). Use of anti-adhesion films during emergency cases and with a significantly higher risk of postcesarean fever which potentially means increased risk of surgical site infection. Therefore, we do not suggest routine application of anti-adhesion films during cesarean deliveries especially in emergency cesarean section or in a woman having labor before operation.

Prophylactic antibiotic use in acellular dermal matrix-assisted implant-based breast reconstruction.

Prophylactic antibiotics are used in acellular dermal matrix-assisted implant-based breast reconstructions. However, there are no universally accepted guidelines regarding the best regimen. This retrospective, multicentre study was designed to compare the different prophylactic antibiotic regimens in these patients in three hospitals across two NHS trusts over a five-year period. Case notes and electronic records were reviewed for all patients undergoing acellular dermal matrix-assisted implant-based breast reconstructions between January 2010 and December 2014. Prophylactic antibiotic regimens, duration of use, wound infection, implant loss, seroma and therapeutic antibiotic use was recorded. Patients were divided into groups based on prophylactic antibiotic regimen and actual duration of use. Intergroup analysis was performed using Stata 13.0. Implant loss due to infection was the primary outcome measure. A total of 105 patients had 122 breast reconstructions performed over the study period. Four prophylactic antibiotic regimens were identified: single dose (n = 20), three doses (n = 17), antibiotics for five-seven days (n = 51) and antibiotics until drains removed (n = 32). There was no statistically significant difference (p > 0.05) between the various regimens in implant loss, wound infection, therapeutic antibiotic prescription or seroma rates. Based on the actual duration of prophylactic antibiotics usage, three groups were identified: prophylactic antibiotics given for one day (n = 26), antibiotics for up to one week (n = 76) and for more than one week (n = 13). Again, no statistically significant difference was observed in the groups for any outcome measure. The study demonstrated no difference in outcomes between different prophylactic antibiotic regimens in acellular dermal matrix-assisted implant-based breast reconstructions.

Recent Advances in the Heterologous Biosynthesis of Natural Products from Streptomyces

Streptomyces is a significant source of natural products that are used as therapeutic antibiotics, anticancer and antitumor agents, pesticides, and dyes. Recently, with the advances in metabolite analysis, many new secondary metabolites have been characterized. Moreover, genome mining approaches demonstrate that many silent and cryptic biosynthetic gene clusters (BGCs) and many secondary metabolites are produced in very low amounts under laboratory conditions. One strain many compounds (OSMAC), overexpression/deletion of regulatory genes, ribosome engineering, and promoter replacement have been utilized to activate or enhance the production titer of target compounds. Hence, the heterologous expression of BGCs by transferring to a suitable production platform has been successfully employed for the detection, characterization, and yield quantity production of many secondary metabolites. In this review, we introduce the systematic approach for the heterologous production of secondary metabolites from Streptomyces in Streptomyces and other hosts, the genome analysis tools, the host selection, and the development of genetic control elements for heterologous expression and the production of secondary metabolites.

Think Twice before Prescribing Antibiotics for That Swollen Knee: The Influence of Antibiotics on the Diagnosis of Periprosthetic Joint Infection.

Periprosthetic joint infection (PJI) is a rare but devastating complication after total joint arthroplasty. An estimated 7–12% of patients have negative cultures despite clear clinical evidence of infection. One oft-cited reason for this occurrence is the administration of antibiotics in the weeks prior to obtaining cultures. This article reviews the influence of antibiotics on the diagnosis of PJI. Specifically, we examine the effect of prophylactic and therapeutic antibiotic administration on the diagnostic accuracy of microbiological cultures as well as serum and synovial biomarkers. We also explore the potential of molecular techniques in overcoming these limitations in patients who have received antibiotics before specimen collection and propose areas for future research.

Antimicrobial Prophylaxis for Caesarean Delivery; A comparative study between different agents

Antimicrobial prophylaxis is commonly used for pre-intra and post-operative caesarean delivery. Caesarean delivery is still the single most important risk factor for puerperal infection. Post-caesarean infections include wound infections, endomyometritis, bacteraemia, septic shock, septic pelvic vein thrombophlebitis, necrotising fasciitis, pelvic abscess, dehiscence of the wound or evisceration. The goal of antimicrobial prophylaxis is to put a stop to postoperative infection of the surgical site, the use of therapeutic antibiotics, additional surgical interventions, longer duration of hospital stay, to decrease postoperative infectious morbidity and mortality and the cost of postoperative health care. A post-caesarean wound infection detected prior to hospital discharge will lead to prolongation of hospital stay and will increase the hospitalisation costs and need of readmission. Both the American College of Obstetricians and Gynaecologists and the American Society of Health-Care System Pharmacists have introduced single-dose prophylactic protocols using a heterogeneity of agents (penicillins, cephalosporins, clindamycin and azithromycin). Women undergoing caesarean delivery have a greater risk of developing infection compared to women who have a vaginal birth by 5 to 20-fold. The use of prophylaxis in patients undergoing a low-risk Caesarean Delivery remains controversial.

Overview of the actions to combat bacterial resistance in large hospitals

Objective:to analyze, in the clinical practice of large hospitals, how the adoption of measures to prevent and control the spread of bacterial resistance has occurred, and to propose a score for the institutions’ adherence.Method:a cross-sectional study carried out in 30 large hospitals of Minas Gerais, from February 2018 to April 2019, after approval by the Ethics and Research Committee. Interviews were conducted with hospital managers, with Hospital Infection Control Services coordinators, and with the care coordinators of the Inpatient Units and Intensive Care Center. In addition, observations were made of the adoption of preventive measures by the multidisciplinary team in the care units.Results:in the 30 participating hospitals, 93.3% (N=28) had protocols for prophylactic antibiotics, and 86.7% (N=26) performed their audit, 86.7% (N=26) for therapeutic antibiotics and 83.3% (N=25) their audit; 93.3% (N=56) used gloves and cloaks for patients in contact precautions, and 78.3% (N=47) of the professionals were unaware of or answered incompletely on the five moments for hand hygiene. In the score to identify the adoption of measures to control bacterial resistance, 83.3% (N=25) of the hospitals were classified as partially compliant, 13.3% (N=04) as deficient, and 3.4% (N=01) as non-adoption.Conclusion:it was found that the recommended measures to contain bacterial resistance are not consolidated in the clinical practice of the hospitals.

174. Shotgun Metagenomics and Colonization by Antibiotic-resistant Bacteria in Pediatric Hematopoietic Stem Cell Transplant Recipients

BackgroundBacteremia in hematopoietic stem cell transplant (HSCT) recipients most frequently arises from gut bacterial translocation and is associated with a higher mortality if the organism is antibiotic-resistant. We sought to determine the impact of prior antibiotic exposure on antibiotic resistance genes (ARGs) in the gut metagenomes of HSCT recipients to inform future infection prevention strategies.MethodsWe performed shotgun metagenomic sequencing of fecal samples collected during the transplant hospitalization from children (< 18 years of age) undergoing HSCT at Duke University between 2015 and 2018. Host-decontaminated sequencing reads were aligned to the Comprehensive Antibiotic Resistance Database. We used a negative binomial regression model to determine the impact of recent therapeutic antibiotic exposure on the number of ARGs prior to HSCT.ResultsMedian age of the 77 children included in these analyses was 4.8 years, and 58% were male. Hematological malignancy was the transplant indication for 42% of children, and 87% of transplants were allogeneic. In the 654 longitudinal samples, we identified 926 unique ARGs, conferring resistance to 31 classes of antibiotics. The median number of ARGs per sample was 24 (interquartile range: 13, 49). The most common ARGs detected were dfrF (conferring resistance to trimethoprim), tetO (tetracyclines), and tetW (tetracyclines), each detected in >65% of samples. Of the 66 children with fecal samples collected prior to HSCT, 70% of children received therapeutic antibiotics in the 2 weeks prior to enrollment. Accounting for transplant indication, sex, and age, the incidence of ARGs was 47% higher in children who received recent therapeutic antibiotics (incidence rate ratio 1.47; 95% CI (1.03–2.13); p=0.04).ConclusionARGs are commonly found in the gut metagenomes of pediatric HSCT recipients prior to HSCT and are associated with recent receipt of therapeutic antibiotics. Future directions for this dataset include determining the ability of ARGs in the metagenome to predict clinical outcomes, including mortality and infections. Understanding the colonization and acquisition of ARGs could inform infection prevention strategies and empiric therapies and lead to improved infectious outcomes in these high-risk patients.Disclosures All Authors: No reported disclosures

189. Risk Factors and Outcomes of Hematogenous Vertebral Osteomyelitis in Patients with staphylococcus Aureus Bacteremia: Results from a 20-year Prospective Cohort

BackgroundHematogenous vertebral osteomyelitis (HVOM) is a rare, but devastating complication of Staphylococcus aureus bacteremia (SAB). Risk factors and outcomes associated with HVOM among patients with SAB remain incompletely understood.MethodsAll adult, hospitalized, non-neutropenic patients with SAB were prospectively enrolled from 1995 to 2015. Additional data was subsequently collected on all patients with HVOM. Diagnosis of HVOM was made either radiographically or microbiologically by culture from the infection site. Patients who underwent lumbar puncture or spinal surgery within 30 days prior to the diagnosis of HVOM were excluded.ResultsOf 2,475 cases of prospectively enrolled patients with SAB, 90 (3.6%) developed HVOM. The most common site of involvement was the lumbar spine (65.6%). MRI was used in the diagnosis of 90% of patients and although only 28.9% underwent bone biopsy, 88.5% of these bone cultures grew S. aureus. Patients with HVOM were more likely to have community-acquired SAB (22.2% vs. 9.9%, P < 0.0001) and persistent bacteremia (47.8% vs. 20.5%, P < 0.0001). Patients with HVOM who required surgical intervention were more likely to have motor deficit (60.9% vs. 21.4%, P = 0.0013) and have associated epidural abscesses (69.6% vs. 44.8%, P = 0.0400). Prolonged antibiotic use for HVOM was common, with 13.3% remaining on therapeutic antibiotics and 16.6% on suppressive therapy at 6 months. This dropped to 2.2% on therapeutic and 15.5% on suppressive therapy at 12 months. All-cause mortality was high in the HVOM cohort at 14.4% at 90-days, increasing to a cumulative 18.9% and 20.0% at 6 and 12-months, respectively. Rates of readmission, recurrent bacteremia, paralysis, and mortality at 6 and 12-months were similar for those who required surgical intervention and those who did not.Demographics, comorbidities, and clinical characteristics of patients with and without hematogenous vertebral osteomyelitis (HVOM) ConclusionHVOM in patients with SAB was associated with high rates of all-cause mortality up to 12 months following date of diagnosis. Patients with community-acquired bacteremia and persistent bacteremia were more likely to develop HVOM.Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

A Implementation of Antibiotic Prophylaxis Program for Cesarean Section at Thai Nguyen National Hospital

This study aims to evaluate the effectiveness of the use of antibiotic prophylaxis in cesarean section at Thai Nguyen National Hospital as a first pilot activity of a surgical prophylaxis program. In the study, a randomized controlled trial was designed with two groups: intervention group and control group. Patients characteristics and effectiveness of prophylactic antibiotics for caesarean section were compared. The study results show that the patients’ ages ranged from 18 to 44 years; most of the patients had ASA score of 1; and mean hospital length of stay was statistically significant between the two groups (p&lt;0.05). Regarding the indication of caesarean section, the reason of genital tract abnormalities accounted for the highest proportion. The percentage of the patients switching from prophylactic antibiotic regimens to therapeutic antibiotics in the intervention group was 2%. There was no patient with superficial and/or deep incisional surgical site infections in both groups. The difference in mean number of injections in the two groups was statistically significant (p&lt;0.05). The average cost of antibiotics for each patient in the intervention group and control group were 267.720 VND and 543.871 VND, respectively. The study concludes that the effectiveness of antibiotics prophylaxis for caesarean section: 99% of the patients were without wound infection; hospital length of stay in the intervention group was shorter than the control group; and using prophylactic antibiotics was not only more economical but could also reduce the workload of medical staff, costs of antibiotics and medical supplies.&#x0D; Keywords&#x0D; Antibiotics prophylaxis, caesarean section, Thai Nguyen National Hospital.&#x0D; References&#x0D; [1] Viet Nam Ministry of Health, National guideline on prevention of surgical site infection, issued with Decision No. 3671/QD-BYT, September 27, 2012 of Viet Nam Ministry of Health, Ha Noi, 2012 (in Vietnamese).[2] Viet Nam Ministry of Health, National guideline on antibiotics use, issued with Decision No.708/QD-BYT, March 2, 2015 of Viet Nam Ministry of Health, Ha Noi, 2015 (in Vietnamese).[3] D.W. Bratzler, K.M. Olsen, et al., Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery, American Journal of Health-System Pharmacy 70 (2013) 195 – 283. https://doi.org/10.2146/ajhp120568.[4] R.F. Lamont, J.D. Sobel, et al., Current debate on the use of antibiotic prophylaxis for caesarean section, BJOG: An International Journal of Obstetrics &amp; Gynaecology 118 (2011) 193-201. https://doi.org/10.1111/j.14710528.2010.02729.x.[5] T.V. Khai, Infection rate of surgical incisions and associated factors on women after cesarean section at Dong Nai General Hospital, Scientific Research Project of Dong Nai Hospital, 2015 (in Vietnamese).[6] N.H. Tuan, Study on the use of cefazolin to prevent infection after cesarean section or uterine fibroids surgery at the Institute of maternal and neonatal protection, Master’s thesis, Hanoi University of Pharmacy, 2002 (in Vietnamese).[7] F.M. Smaill, R.M. Grivell, Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section, Cochrane Database Syst Rev 10 (2014) CD007482. https://doi.org/10.1002/14651858.cd007482.pub3.&#x0D; &#x0D;

Inhibition of the clinical isolates of Acinetobacter baumannii by Pseudomonas aeruginosa: Invitro assessment of a case-based study.

The global rise in nosocomial infections associated with gram-negative bacteria and the spread of multi-drug resistant Acinetobacter baumannii (MDR-AB) pose public health concerns. This study investigates the inhibitory effects and possible inhibitory mechanism of Pseudomonas aeruginosa (PA) on selected clinical strains of A. baumannii (AB) isolated from Taiwanese patients. Four and eight clinical strains of AB and PA, respectively, were randomly selected from the bacterial collection of Feng-Yuan Hospital, Taiwan. Antimicrobial-susceptibility was performed on the AB strains. Inhibition potential of the PA strains against AB was assessed by measuring the inhibition zones. Invitro analysis using phenazine-1-carboxamide (PCN) was conducted to assess the possible inhibitory mechanism of PA, which was later confirmed in the clinical isolates by liquid chromatography-mass spectrometry. All the clinical AB strains showed resistance to the eleven antibiotics and were classified as MDR-AB. The nine PA strains exert either a high (PA3596, PA3681, PA3772, and ATCC27853) or a low (PA3613, PA3625, PA3712, PA3715, and PA3744) degree of inhibition against AB strains. 0.25mg/ml PCN had a clearer inhibition zone than 0.05mg/ml PCN, suggesting a dose-dependent inhibition of PCN on the AB strains. The four PA strains that demonstrated a high degree of inhibition had a relatively high amount of PCN. Selected strains of PA exert inhibitory actions on MDR-AB with PCN being a possible inhibitory agent. This finding raises the possibility of developing effective therapeutic antibiotics and disinfectant from specific components of PA for the treatment and control of Acinetobacter-associated infections in hospital settings.