Systemic Antibiotic Exposure Research Articles

Advanced Antimicrobial and Anti-Infective Strategies to Manage Peri-Implant Infection: A Narrative Review.

Despite reductions in bacterial infection and enhanced success rate, the widespread use of systemic antibiotic prophylaxis in implant dentistry is controversial. This use has contributed to the growing problem of antimicrobial resistance, along with creating significant health and economic burdens. The basic mechanisms that cause implant infection can be targeted by new prevention and treatment methods which can also lead to the reduction of systemic antibiotic exposure and its associated adverse effects. This review aims to summarize advanced biomaterial strategies applied to implant components based on anti-pathogenic mechanisms and immune balance mechanisms. It emphasizes that modifying the dental implant surface and regulating the early immune response are promising strategies, which may further prevent or slow the development of peri-implant infection, and subsequent failure.

Safety Profile of Seven-Day Intra-articular Antibiotic Irrigation for the Treatment of Chronic Periprosthetic Joint Infection: A Prospective Randomized Phase II Comparative Study

BackgroundSystemic intravenous antimicrobials yield poor outcomes during treatment of periprosthetic joint infection due to the inability to obtain minimum biofilm eradication concentrations. This study evaluated the safety of a novel method of optimized local delivery of intra-articular antibiotics (IAAs). MethodsThis was a Phase II, multicenter, prospective randomized trial evaluating safety of a rapid (seven-day) two-stage exchange arthroplasty with IAA irrigation compared to standard two-stage exchange. The Experimental Group received irrigation using 80 mg tobramycin daily with a 2-hour soak, followed by hourly irrigation using 125 mg vancomycin with a 30-minute soak via an intramedullary irrigation device. The Control Group received an antibiotic-loaded cement spacer with vancomycin (average 8.4 g) and tobramycin (average 7.1 g, total 16 g antibiotics). Both groups received 12 weeks of systemic antibiotics following Stage 2. Safety measures included adverse events, peak vancomycin/tobramycin serum concentrations (Experimental Group), blood transfusion, and mortality. There were thirty-seven patients randomized to the Experimental Group and 39 to control. There was no difference in baseline demographics or comorbidities. ResultsThere were no antibiotic medication-related adverse events and 2 serious adverse events related to antibiotic instillation. Of 188 vancomycin peak measurements, 69% had detectable serum level concentrations, with all concentrations well below the maximum acceptable trough threshold of 20 μg/mL. Of the 103 tobramycin peak measurements, 45% had detectable levels, with all below the maximum acceptable peak threshold of 18 to 24 μg/mL. There was no difference in blood transfused per subject (Experimental: 655 mL versus Control: 792 mL; P = .4188). There were two (2) deaths in the Experimental Group and four (4) in the control. ConclusionsThe use of IAA is safe with minimal systemic antibiotic exposure. There was no difference in the rates or severity of serious adverse events between groups. Further research is being conducted to examine treatment efficacy.

Multidrug-Resistant Pathogens in Burn Wound, Prevention, Diagnosis, and Therapeutic Approaches (Conventional Antimicrobials and Nanoparticles).

Multidrug-resistant pathogens are one of the common causes of death in burn patients and have a high risk of nosocomial infections, especially pneumonia, urinary tract infections, and cellulitis. The role of prolonged hospitalization and empirical antibiotics administration in developing multidrug-resistant pathogens is undeniable. In the early days of admitting burn patients, Gram-positive bacteria were the dominant isolates with a more sensitive antibiotic pattern. However, the emergence of Gram-negative bacteria that are more resistant later occurs. Trustworthy guideline administration in burn wards is one of the strategies to prevent multidrug-resistant pathogens. Also, a multidisciplinary therapeutic approach is an effective way to avoid antibiotic resistance that involves infectious disease specialists, pharmacists, and burn surgeons. However, the emerging resistance to conventional antimicrobial approaches (such as systemic antibiotic exposure, traditional wound dressing, and topical antibiotic ointments) among burn patients has challenged the treatment of multidrug-resistant infections, and using nanoparticles is a suitable alternative. In this review article, we will discuss different aspects of multidrug-resistant pathogens in burn wounds, emphasizing the full role of these pathogens in burn wounds and discussing the application of nanotechnology in dealing with them. Also, some advances in various types of nanomaterials, including metallic nanoparticles, liposomes, hydrogels, carbon quantum dots, and solid lipid nanoparticles in burn wound healing, will be explained.

Exposure to systemic antibiotics in outpatient care and the risk of multiple sclerosis

Background: Infections, early life exposures and the microbiome have been associated with the aetiology of multiple sclerosis (MS). Data on any possible roles of antibiotics is scarce and conflicting. Objective: The objective of this study was to investigate associations between outpatient systemic antibiotic exposure and the risk of MS in a nationwide case-control setting. Methods: Patients with MS were identified from the nation MS registry and their exposure to antibiotics was compared with that of persons without MS, provided by the national census authority. Antibiotic exposure was investigated using the national prescription database and analyzed by Anatomical Therapeutic Chemical (ATC) category. Results: Among the 1830 patients with MS and 12765 control persons, there were no associations between exposure to antibiotics in childhood (5–9 years) or adolescence (10–19 years) and the subsequent risk of MS. There was also no association between antibiotic exposure 1–6 years before disease onset and the risk of MS, save for exposure to fluoroquinolones in women (odds ratio: 1.28; 95% confidence interval: 1.03, 1.60; p = 0.028) which is probably associated with the increased infection burden in the MS prodrome. Conclusion: Use of systemic prescription antibiotics was not associated with subsequent MS risk.

Clinical outcomes for Clostridioides difficile associated diarrhea in inflammatory bowel disease patients versus non-IBD population: A retrospective cohort study.

Patients with inflammatory bowel disease (IBD) have a higher incidence of Clostridioides difficile infection (CDI). Previous studies have demonstrated negative clinical outcomes in IBD patients with CDI compared to patients without CDI. The clinical presentation of CDI is indistinguishable from IBD exacerbation, thus posing a frequent clinical dilemma on the role of Clostridioides infection in the testing, diagnosis, and treatment of these patients. To compare clinical outcomes of CDI in patients with IBD to those without IBD. Retrospective cohort of adult patients admitted to Rabin Medical Center Israel between the years 2014 and 2020 with a concurrent diagnosis of IBD and CDI. Matching 1:2 was performed between the IBD patients and the non-IBD population with respect to age and sex. Sixty-seven patients with IBD and 134 patients without IBD were included in the study. The groups' median age was 40.6 (interquartile range [IQR] of 29.8-68.9), with 45.8% male and 54.2% female. The non-IBD group had a higher Charlson score with 2 (IQR 0; 5) versus 0 (IQR 0; 4) in the IBD group (P value <.01). Patients with IBD had more exposure to systemic antibiotics, 71.1% versus 26.3% (P value <.01). In a multivariable analysis we found no difference in 90-day mortality and rate of relapse between the 2 study groups with an odds ratio of 1.709 (95% confidence interval 0.321-9.905) and odds ratio of 0.209 (95% confidence interval 0.055-1.513) respectively. In our cohort patients with IBD who present with diarrhea and concomitant CDI have similar rates of relapse and mortality compared with patients without IBD.

On-demand synthesis of antiseptics at the site of infection for treatment of otitis media

Otitis media (OM) is the main reason for pediatric antibiotic prescriptions. The current treatment mandates a rigorous regimen of multidose antibiotics over 5–10 days. The systemic antibiotic exposure and often prematurely terminated treatment due to the challenge of drug administration to young patients are believed to breed antibiotic resistance. To address these challenges, we designed a local treatment that converted a metabolic product (H2O2) of an OM pathogen (Streptococcus pneumoniae) into a potent antiseptic (HOBr), a reaction catalyzed by locally administered vanadium pentoxide nanowires. The therapeutic, HOBr, was only synthesized in the presence of the pathogen, enabling on-demand generation of therapeutics for OM treatment. Hypohalous acids are broad-spectrum and have a long history in general disinfection applications without breeding substantial drug resistance. A single dose of the nanowire formulation eradicated OM in a standard chinchilla model in 7 days with no observable tissue toxicity or negative impact on hearing sensitivity.

Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case-control study.

Microbial dysbiosis has been implicated in the development of atopic dermatitis (AD). The risk of development of AD following early-life infections remains unclear. To investigate the impact of early-life infections on AD development. This population-based nested case-control study was conducted using the Taiwan's National Health Insurance Research Database. A total of 5454 AD patients and 16 362 control subjects without AD were identified, for the period 1997 to 2013. Demographic characteristics, comorbidities and maternal factors were compared. Adjusted odds ratio (aOR) was calculated to examine the associations between early-life infections and subsequent AD by conditional stepwise logistic regression analysis. Mean age was 2.6 ± 2.9 years in both groups. Overall infections (41.8% vs. 28.9%) before the diagnosis of AD were more common in AD patients than in control subjects (P < 0.001). Infectious diseases [aOR, 1.40; 95% confidence interval (CI), 1.29-1.51], skin infections (aOR, 1.55; 95% CI, 1.40-1.71) and systemic antibiotic exposure (aOR 1.67, 95% CI 1.55-1.79) before AD diagnosis were independently associated with AD development on multivariate analyses. These results were consistent across observation periods (0-1, 1-2 and >2 years after birth) and sensitivity analyses after redefining the index date as 3 or 6 months before the date of AD diagnosis. Other independent risk factors included asthma, allergic rhinitis, intussusception and neonatal hyperbilirubinemia. No association with subsequent AD was found for maternal age at delivery, Caesarean delivery or prenatal antibiotic exposure. Infections in early life are associated with AD development in infancy and early childhood.

Nebulized Antibiotics for Healthcare- and Ventilator-Associated Pneumonia.

Global emergence of multidrug-resistant and extensive drug-resistant gram-negative bacteria has increased the risk of treatment failure, especially for healthcare- or ventilator-associated pneumonia (HAP/VAP). Nebulization of antibiotics, by providing high intrapulmonary antibiotic concentrations, represents a promising approach to optimize the treatment of HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria, while limiting systemic antibiotic exposure. Aminoglycosides and colistin methanesulfonate are the most common nebulized antibiotics. Although optimal nebulized drug dosing regimen is not clearly established, high antibiotic doses should be administered using vibrating-mesh nebulizer with optimized ventilator settings to ensure safe and effective intrapulmonary concentrations. When used preventively, nebulized antibiotics reduced the incidence of VAP without any effect on mortality. This approach is not yet recommended and large randomized controlled trials should be conducted to confirm its benefit and explore the impact on antibiotic selection pressure. Compared with high-dose intravenous administration, high-dose nebulized colistin methanesulfonate seems to be more effective and safer in the treatment of ventilator-associated tracheobronchitis and VAP caused by multidrug resistant and extensive-drug resistant gram-negative bacteria. Adjunctive nebulized aminoglycosides could increase the clinical cure rate and bacteriological eradication in patients suffering from HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria. As nebulized aminoglycosides broadly diffuse in the systemic circulation of patients with extensive bronchopneumonia, monitoring of plasma trough concentrations is recommended during the period of nebulization. Large randomized controlled trials comparing high dose of nebulized colistin methanesulfonate to high dose of intravenous colistin methanesulfonate or to intravenous new β-lactams in HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria are urgently needed.

Infantile infection and antibiotic exposure in association with pediatric psoriasis development: A nationwide nested case-control study

Microbioldysbiosis and antibiotic exposure have been implicated in the pathogenesis of pediatric inflammatory diseases. To investigate the impacts of infantile infection and antibiotic exposure on pediatric psoriasis development. This is a nationwide nested case-control study. From the National Health Insurance Research Database of Taiwan, a total of 1527 patients with pediatric psoriasis were identified and matched with 15,270 reference individuals without psoriasis, for the period of 2000 to 2017. Demographic characteristics and comorbidities were compared. Conditional stepwise logistic regression analysis was conducted to examine the associations. The mean ages were 9.9±3.7years in both groups. Atopic dermatitis (adjusted odds ratio [aOR], 2.07; 95% confidence interval [CI], 1.84-2.32) and family history of psoriasis, especially of the mother (aOR, 9.86; 95% CI, 6.89-14.10) or other first-degree relatives (aOR, 5.49; 95% CI, 3.91-7.70), were independently associated with pediatric psoriasis on multivariate analyses. Skin viral and bacterial infections (aOR, 1.35; 95% CI, 1.13-1.62) and fungal infections (aOR, 1.71; 95% CI, 1.44-2.04) in the first 2years of life were significantly associated with pediatric psoriasis. Systemic antibiotic exposure was not. These results were consistent at different time periods across sensitivity analyses. Information about diet and lifestyle was not available. Skin infections at an early age were associated with pediatric psoriasis development.

Carbapenem-resistant Enterobacteriaceae carriage risk for parameterization of a regional healthcare network agent-based model

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly common in the United States and have the potential to spread widely across healthcare networks. Only a fraction of patients with CRE carriage (ie, infection or colonization) are identified by clinical cultures. Interventions to reduce CRE transmission can be explored with agent-based models (ABMs) comprised of unique agents (eg, patients) represented by a synthetic population or model-generated representation of the population. We used electronic health record data to determine CRE carriage risk, and we discuss how these results can inform CRE transmission parameters for hospitalized agents in a regional healthcare network ABM. Methods: We reviewed the laboratory data of patients admitted during July 1, 2016−June 30, 2017, to any of 7 short-term acute-care hospitals of a regional healthcare network in North Carolina (N = 118,022 admissions) to find clinically detected cases of CRE carriage. A case was defined as the first occurrence of Enterobacter spp, Escherichia coli, or Klebsiella spp resistant to any carbapenem isolated from a clinical specimen in an admitted patient. We used Poisson regression to estimate clinically detected CRE carriage risk according to variables common to data from both the electronic health records and the ABM synthetic population, including patient demographics, systemic antibiotic administration, intensive care unit stay, comorbidities, length of stay, and admitting hospital size. Results: We identified 58 (0.05%) cases of CRE carriage among all admissions. Among these cases, 30 (52%) were ≥65 years of age and 37 (64%) were female. During their admission, 47 cases (81%) were administered systemic antibiotics and 18 cases (31%) had an intensive care unit stay. Patients administered systemic antibiotics and those with an intensive care unit stay had CRE carriage risk 6.5 times (95% CI, 3.4–12.5) and 4.9 times (95% CI, 2.8–8.5) higher, respectively, than patients without these exposures (Fig. 1). Patients ≥50 years of age and those with a higher Elixhauser comorbidity index score and with longer length of stay also had increased CRE carriage risk. Conclusions: Among admissions in our dataset, CRE carriage risk was associated with systemic antibiotic exposure, intensive care unit stay, higher Elixhauser comorbidity index score, and longer length of stay. We will use these risk estimates in the ABM to inform agents’ CRE carriage status upon hospital admission and the CRE transmission parameters for short-term acute-care hospitals. We will explore CRE transmission interventions in the parameterized regional healthcare network ABM and assess the impact of CRE carriage underestimation.Funding: This work was supported by Centers for Disease Control and Prevention (CDC) Cooperative Agreement number U01CK000527. The conclusions, findings, and opinions expressed do not necessarily reflect the official position of CDC.Disclosures: None

Postnatal pediatric systemic antibiotic episodes during the first three years of life are not associated with mode of delivery.

BackgroundDelivery by cesarean section (C-section) is associated with adverse short-term and long-term infant outcomes. Given that antibiotics during early life are prescribed for infant outcomes that are more likely among c-section deliveries, we hypothesized that postnatal antibiotic exposure will be greater among c-section infants compared to vaginally delivered infants.ObjectiveThe aim of this paper was to evaluate if mode of infant delivery was associated with patterns of systemic antibiotic exposure in children during their first three years.MethodsPediatric electronic health records from UFHealth, 2011 to 2017 were reviewed. We included singleton, term infants (37–42 weeks gestation) with a birth weight ≥ 2500 grams, with documented mode of delivery and well visits on record. Infants with a neonatal intensive care unit stay were excluded. Both oral and intravenous antibiotics for a 10-day duration were classified as a single episode. The primary outcome was antibiotic episodes in the first three years of life, and a sub-analysis was performed to compare broad-spectrum versus narrow-spectrum antibiotic exposures.ResultsThe mean number of antibiotic episodes in 4,024 full-term infants was 0.34 (SD = 0.79) and 24.1% of infants had at least one antibiotic episode. Penicillins were the most prescribed antibiotic in children 0–1 years (66.9%) and cephalosporins were the most common antibiotic prescribed for children 1–3 years (56.2%). We did not detect a meaningful or significant rate ratio (RR) between mode of delivery and overall antibiotic episodes 1.14 (95% CI 0.99, 1.31), broad-spectrum episodes 1.19 (95% CI 0.93, 1.52, or narrow-spectrum episodes 1.14 (95% CI 0.97, 1.34).ConclusionOur results do not support the hypothesis that postnatal antibiotic exposure was greater among infants delivered by cesarean section compare to infants delivered vaginally during the first three years of life.

Real-world evidence of the impact of prior antibiotic exposure on immune checkpoint inhibitor outcomes in patients with metastatic urothelial cancer.

452 Background: Prior research suggests that systemic antibiotic (ABX) exposure may impact gut microbiome and potentially result in suboptimal immune checkpoint inhibitor (ICI) treatment outcomes. A recent real-world analysis demonstrated that cumulative ABX exposure was associated with poorer outcomes across multiple tumor types independent of known prognostic clinical factors. Given the paucity of real-world data, we set out to evaluate the association of prior ABX exposure with ICI treatment outcomes among patients with metastatic urothelial cancer (mUC). Methods: This was a retrospective analysis using Truven Health MarketScan Commercial, Medicare Supplemental, and Coordination of Benefits (Medicare) databases. Patients with mUC, ≥18 years old, who received first line (1L) ICI therapy between 1/1/2016 and 12/31/2018 were analyzed. Prior ABX exposure was defined as any use in the 90 days prior to 1L ICI therapy initiation. Time to treatment discontinuation was used as a proxy to quantify ICI treatment outcomes. Results: Among the 304 ICI treated patients, 128 (42%) had ABX exposure within 90 days prior to ICI initiation. Statistically significant differences in baseline co-morbidities and urinary tract infections (36% vs. 17%; p&lt;0.001) were observed between patients with vs. without ABX exposure. The median time to treatment discontinuation was shorter for patients with ABX exposure (7.9 months) vs. without (9.3 months). In adjusted regression analysis, there was no statistically significant difference in time to treatment discontinuation between patients with vs. without ABX exposure (p=0.95). These findings were consistent in a sensitivity analysis looking at ABX exposure 30 and 60 days prior to 1L ICI initiation. Conclusions: In this real-world analysis of patients with mUC, those with ABX exposure within 90 days prior to 1L ICI initiation demonstrated similar outcomes to those without ABX exposure. While there was a shorter time to treatment discontinuation in the patients with vs. without ABX exposure, findings were not statistically significant. Further research is warranted to investigate the impact of concomitant ABX use on ICI outcomes.

Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility-Onset Clostridioides difficile Infection in Targeted Patients During Systemic Antibiotic Exposure.

Limited retrospective data suggest prophylactic oral vancomycin may prevent Clostridioides difficile infection (CDI). We sought to evaluate the effectiveness of oral vancomycin for the prevention of healthcare facility-onset CDI (HCFO-CDI) in targeted patients. We conducted a randomized, prospective, open-label study at Novant Health Forsyth Medical Center in Winston-Salem, North Carolina, between October 2018 and April 2019. Included patients were randomized 1:1 to either oral vancomycin (dosed at 125 mg once daily while receiving systemic antibiotics and continued for 5 days postcompletion of systemic antibiotics [OVP]) or no prophylaxis. The primary endpoint was incidence of HCFO-CDI. Secondary endpoints included incidence of community-onset healthcare facility-associated CDI (CO-HCFA-CDI), incidence of vancomycin-resistant Enterococci (VRE) colonization after receiving OVP, adverse effects, and cost of OVP. A total of 100 patients were evaluated, 50 patients in each arm. Baseline and hospitalization characteristics were similar, except antibiotic exposure. No events of HCFO-CDI were noted in the OVP group compared with 6 (12%) in the no-prophylaxis group (P = .03). CO-HCFA-CDI was identified in 2 patients who were previously diagnosed with HCFO-CDI. No patients developed new VRE colonization, with only 1 patient reporting mild gastrointestinal side effects to OVP. A total of 600 doses of OVP were given during the study, with each patient receiving an average of 12 doses. Total acquisition cost of OVP was $1302, $26.04 per patient. OVP appears to protect against HCFO-CDI during in-patient stay in targeted patients during systemic antibiotic exposure. Further prospective investigation is warranted.

Risk factors for Clostridioides (Clostridium) difficile infection following solid organ transplantation in children.

Clostridioides (Clostridium) difficile infection (CDI) in pediatric solid organ transplant (SOT) recipients is a growing problem, though CDI risk factors in this population are poorly understood. Our objective was to characterize CDI risk factors in pediatric SOT recipients. This retrospective case-control study, performed at a single freestanding academic children's hospital, included all SOT recipients age 1-22years who were tested for C.difficile by toxin B gene PCR between August 2009 and August 2017. CDI risk factors were assessed by comparing PCR-positive and PCR-negative cases by generalized linear mixed models. Between August 2009 and August 2017, 409 SOTs were performed of which 138 (33.7%), 134 (32.8%), 131 (32.0%), and 6 (1.5%) were kidney, liver, heart, and small intestine transplants, respectively. Of 205 SOT recipients were tested for CDI, with 723 C.difficile PCR tests performed among these patients. 68/205 (33%) patients developed CDI at least once during the study period. Median (interquartile range) time to diagnosis of first CDI following SOT was 8.9 (1.2, 19.6) months. CDI was independently associated with calcineurin inhibitor use at time of C.difficile testing (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.08, 5.24, P=0.03) and systemic antibiotic exposure within 30days of C.difficile testing (OR 1.74, 95% CI 1.08, 2.79, P=0.02). CDI is a common, relatively late post-transplant complication and independently associated with calcineurin inhibitor and systemic antibiotic exposure. The potential impact of specific immunosuppressive drug and antibiotic selection on CDI risk reduction requires further investigation.

The Association Between the Developing Nasal Microbiota of Hospitalized Neonates and Staphylococcus aureus Colonization.

BackgroundHospitalized neonates are at high risk for invasive Staphylococcus aureus infections. S. aureus nasal colonization often precedes infection. The nasal microbiota may preclude or support colonization. We aimed to characterize and compare the nasal microbiota of hospitalized neonates who acquire S. aureus colonization (cases) and those who do not acquire S. aureus (controls).MethodsWe obtained residual nares samples from hospitalized neonates who were screened weekly for S. aureus nasal colonization and treated with intranasal mupirocin if colonized. Eight cases were matched based on chronologic age and systemic antibiotic exposure to 7 controls. We extracted DNA, sequenced the V3-V4 region of the 16s rRNA gene, and performed taxonomic assignments. The bacterial species richness, relative abundance, and in silico predicted gene content were compared between cases and controls at 7 days before S. aureus acquisition, at the time of acquisition, and 7 days after acquisition and treatment.ResultsCommon commensals including nondiphtheriae corynebacteria were more abundant in the nares of controls and Rothia mucilaginosa was more abundant in cases 7 days after intranasal mupirocin treatment than in cases 7 days before S. aureus acquisition. Controls and treated cases had a higher predicted abundance of genes contributing to the synthesis of certain antimicrobial compounds than in cases before S. aureus acquisition.ConclusionsNeonates without S. aureus nasal colonization had a higher abundance of bacterial species that antagonize S. aureus directly or by selecting for beneficial co-colonizers. These differences may inform novel S. aureus infection prevention strategies in high-risk infants.

Association of Staphylococcus aureus Colonization with the Evolving Neonatal Nasal Microbiome and the Impact of Intranasal Mupirocin

BackgroundLittle is known about the bacterial communities in the nares of critically ill neonates. Our objectives were to explore the evolving nasal microbiome in neonates who acquire Staphylococcus aureus (S. aureus) colonization and the impact of intranasal mupirocin on the nasal microbiome.MethodsIn the setting of a tertiary care neonatal intensive care unit S. aureus control program where neonates are screened weekly using chromogenic agar cultures and treated with intranasal mupirocin if found to acquire S. aureus colonization, we identified 15 neonates, 8 who acquired S. aureus colonization (cases) and 7 who did not acquire S. aureus colonization (controls). Cases and controls were matched on chronologic age and systemic antibiotic exposure. DNA was extracted for amplification of the 16S rRNA gene (V3V4 region), followed by next-generation sequencing using Illumina MiSeq. Sequences were merged into consensus fragments by FLASH and submitted for high-resolution taxonomic assignment using Resphera Insight. Differentially abundant taxa and alpha diversity measures were detected utilizing a nonparametric difference test with p-value correction using the False Discovery Rate.ResultsCompared with conventional bacterial culture results, sequencing identified S. aureus membership in residual culture samples of all neonates who acquired S. aureus colonization. Figure 1 illustrates statistically significant differences in abundant taxa comparing cases prior to S. aureus colonization and controls. Several species were more abundant in controls, including Corynebacterium propinquum and accolens and Rothia mucilaginosa. C. propinquum and accolens and Rothia mucilaginosa were also more abundant in neonates after treatment with intranasal mupirocin than before treatment.ConclusionThese data suggest that there are differences in bacterial taxa abundance in the nasal microbiome in neonates who do and do not acquire S. aureus colonization and in neonates before and after treatment with intranasal mupirocin. A single species may not provide sufficient resistance to S. aureus colonization, but a community of organisms may protect against colonization.Disclosures J. White, Resphera Biosciences: Shareholder, Equity

Management and Outcomes of Patients With Failed Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

Introduction: Fecal Microbiota Transplantation (FMT) is a safe and effective treatment for recurrent Clostridium difficile infection (rCDI) with success rates >85%. Data on management and clinical sequelae of patients who have rCDI after FMT are scarce. In this study, we report our single-center tertiary care experience on post-FMT treatment and outcomes of patients with failed FMT. Methods: All patients who underwent FMT for rCDI from August 2012 to April 2015 were included. Donor and recipient screening was performed using standard protocols and rCDI treatment was stopped 24 hours before FMT. Patients were followed using standardized questionnaires and instructed to call with recurrent diarrhea. FMT failure was defined as recurrent diarrhea with a positive C. difficile stool test. Clinical data including demographics, comorbid conditions, donor information, FMT route, post-FMT systemic antibiotic exposure and post-FMT CDI management were collected and analyzed. Results: After a median follow-up of 61.4 weeks (range 4-147 weeks), of the 238 rCDI patients who underwent FMT; 25 (10.5%; median age 63.5 years [range 18.2-89]; 56% female) had subsequent rCDI. Amongst these 25 patients, 8 (33%) had underlying IBD, 1 had chronic liver disease and 2 were hospitalized with severe-complicated CDI. Standard unrelated donors were used in 21 (84%) patients and colonoscopy was the most common instillation route (88%). Among FMT failures, post-FMT; 4 patients (16%) had minimal symptom improvement after FMT and were early failures. The median time to rCDI after FMT was 19.5 weeks (range 1.4-152 weeks) with 90% patients recurring within 68 weeks. Patients with rCDI after FMT, commonly were exposed to systemic antibiotics (15/25; 60%) leading to FMT failure and 33% had underlying IBD which appeared to be a risk factor in the absence of antibiotic exposure. Of the patients with rCDI after FMT, 4% were treated with metronidazole, 80% were treated with vancomycin and 16% with fidaxomicin. Overall, 5 patients (20%) who had further recurrences were successfully managed with repeat FMT. One patient elected comfort care and died in hospice, one died of non-rCDI related causes, one underwent colectomy for severe-complicated rCDI and one is on chronic low dose vancomycin therapy. Conclusion: CDI recurred in 10% patients after FMT and most common reasons include repeat antibiotic exposure and underlying IBD. Patients with FMT failure can be managed with repeat antibiotics or repeat FMT.

Assessment of risk factors for oxacillin-resistant ocular flora in eyes having cataract surgery

To assess the risk factors for eyes of cataract surgery patients harboring oxacillin-resistant Staphylococcus species on the ocular surface. Ambulatory surgical center, Saint Louis University, Saint Louis, Missouri, USA. Prospective in vitro laboratory study of a patient cohort. Conjunctival cultures were obtained on the day of surgery from eyes scheduled for cataract surgery. Patients answered a questionnaire about risk factors that might lead to having oxacillin-resistant Staphylococcus organisms in their eyes. The factors tested were age, sex, race, recent systemic and topical antibiotic usage, recent hospitalization, and exposure to healthcare and institutional settings. Logistic regression analysis was performed. Of the 183 eyes cultured, 128 (70.0%) tested positive for Staphylococcus organisms, of which 70 (54.7%) were oxacillin-resistant. Only recent antibiotic usage was statistically significantly associated with the presence of oxacillin-resistant organisms (odds ratio, 8.2; 95% confidence interval, 2.2-30.5; P=.002). The other risk factors were not statistically significantly associated: age (P=.06), sex (P=.33), race (P=.34), recent hospitalization (P=.94), and exposure to healthcare and institutional settings (P=.10). Although the nonophthalmic literature has reported various risk factors for the harboring of oxacillin-resistant organisms, in the eyes in this study, only antibiotic usage within 30 days preoperatively was significantly associated with the colonization of oxacillin-resistant organisms on the ocular surface. This finding is important to ophthalmic surgeons when considering perioperative antibiotic prophylaxis. No author has a financial or proprietary interest in any material or method mentioned.

Antibiotic lock solutions allow less systemic antibiotic exposure and less catheter malfunction without adversely affecting antimicrobial resistance patterns

There are current concerns that antibiotic lock solutions (ABL) can induce antimicrobial resistance in long-term hemodialysis patients. Retrospective chart review of 157 children on hemodialysis between January 1997 and June 2006 was performed. In ERA I, only systemic antibiotics were used. In ERA II, ABL were added to systemic antibiotics when needed. In ERA III, ABL were used for treatment of all cases of catheter-related bacteremia (CRB) and for CRB prophylaxis in high-risk patients. The study includes 111,325 catheter days. The CRB incidence was 3.9 CRB/1000 catheter days. There was significant decrease for the total systemic antibiotic exposure (P = 0.0484) and the percentage of catheters lost to malfunction (P = 0.001) in ERA III. Protocol ABL exposure was associated with a trend to increased tobramycin-gentamicin resistance for gram-positive CRBs (P = 0.2586) but with improved tobramycin-gentamicin resistance for gram-negative (P = 0.0949) and polymicrobial CRBs (P = 0.1776) and improved vancomycin resistance for gram-positive CRBs (P = 0.0985). This retrospective analysis does not support the premise that ABL use will promote antimicrobial resistance in the hemodialysis population. The decreased exposure to systemic antibiotics by vigorous ABL use may even improve the antimicrobial resistance patterns in this population in the long term.

In vivo ciprofloxacin release from hydroxyapatite-based bone implants in rabbit tibia: a preliminary study.

The present study deals with the preliminary evaluation of in vivo ciprofloxacin release from HAp-ciprofloxacin bone implants in rabbit tibia. The HAp-ciprofloxacin implants (2 × 2.5 mm) were prepared using various HAp-ciprofloxacin composites synthesized by precipitation technique and 1.5% w/v guar gum as a binder. 5 implants were implanted in artificial cortical bone window at the right proximal tibia of each rabbit. After 3- and 6-day intervals, the rabbits were euthanized. Bone marrow and serum concentrations of ciprofloxacin were determined from the harvested tibia using HPLC method. The results displayed the availability of elevated local antibiotic concentration at the implanted site with the limitation of systemic antibiotic exposure, which can be useful to minimize the risk of systemic toxicity-related side effects. This study is the preliminary investigation of the suitability of in vivo ciprofloxacin release from HAp-ciprofloxacin bone implants in rabbit tibia, after implantation, and these implants can be useful for the treatment of bacterial bone infections like osteomyelitis.