Enteral Antibiotics Research Articles

Assessment of Add-On Therapy of N-Acetylcysteine in the Management of Acute Pancreatitis

Abstract Background Acute pancreatitis (AP) is an inflammation of the pancreas. The conservative therapeutic options include enteral nutrition, antibiotics, and/or surgery. Oxidative stress in AP has been pathologically linked with the systemic inflammatory response. N-acetylcysteine (NAC), an antioxidant, attenuates oxidative stress-induced cell injury and other potential pathological events in AP. Objective This article evaluates the treatment outcome of NAC combined with conventional therapy in AP patients and assesses the difference in the duration of hospital stay between the NAC with conventional therapy group and the conventional therapy group. Materials and Methods This observational study was conducted in a tertiary care hospital with 65 AP patients above 18 years of age. The effect of adding NAC with conventional therapy (intravenous hydration 0.9% normal saline, pancreatin, optional antibiotics) was assessed in patients by comparing serum amylase, lipase, Acute Physiology and Chronic Health Examination (APACHE) II score, and Ranson's score, before and after therapy and the difference in duration of hospital stay was assessed using the independent t-test. Results Of the 65 AP patients, 62% (n = 40) were on conventional therapy and 38% (n = 25) were on NAC along with conventional therapy. The difference in mean values of reduced serum amylase between the two treatment groups indicates a significant difference (p = 0.01). However, the variance in mean serum lipase values was statistically insignificant (p = 0.1). The mean scores of Ranson's criteria showed no significant difference between both groups (p = 0.4). There was a significant difference in APACHE II severity scores after 24 (p = 0.04) and 48 hours (p = 0.01), respectively. Similarly, the mean duration of hospital stay in both treatment groups was found to be statistically insignificant (p = 0.4). Conclusion Both treatment options, conventional therapy and NAC combined with conventional therapy, resulted similar treatment outcomes for AP patients, with no additional benefits observed.

Increasing the Use of Enteral Antibiotics in Hospitalized Children With Uncomplicated Infections.

Route of administration is an important component of antimicrobial stewardship. Early transition from intravenous to enteral antibiotics in hospitalized children is associated with fewer catheter-related adverse events, as well as decreased costs and length of stay. Our aim was to increase the percentage of enteral antibiotic doses for hospital medicine patients with uncomplicated common bacterial infections (community-acquired pneumonia, skin and soft tissue infection, urinary tract infection, neck infection) from 50% to 80% in 6 months. We formed a multidisciplinary team to evaluate key drivers and design plan-do-study-act cycles. Interventions included provider education, structured discussion at existing team huddles, and pocket-sized printed information. Our primary measure was the percentage of antibiotic doses given enterally to patients receiving other enteral medications. Secondary measures included antibiotic cost, number of peripheral intravenous catheters, length of stay, and 7-day readmission. We used statistical process control charts to track our measures. Over a 6-month baseline period and 12 months of improvement work, we observed 3183 antibiotic doses (888 in the baseline period, 2295 doses during improvement work). We observed an increase in the percentage of antibiotic doses given enterally per week for eligible patients from 50% to 67%. We observed decreased antibiotic costs and fewer peripheral intravenous catheters per encounter after the interventions. There was no change in length of stay or readmissions. We observed increased enteral antibiotic doses for children hospitalized with common bacterial infections. Interventions targeting culture change and communication were associated with sustained improvement.

Post-COVID-19 and Irritable Bowel Syndrome: A Literature Review.

The emergence of post-COVID-19 syndrome (PCS), a complex and multifactorial condition that follows the acute COVID-19 infection, has raised serious concerns within the global medical community. Concurrently, Irritable Bowel Syndrome (IBS), a widespread chronic gastrointestinal (GI) dysfunction, is considered to be one of the most common disorders of gut-brain interaction (DGBI) that significantly affects the quality of life and social functioning of patients. PCS presents a wide range of symptoms and GI manifestations, including IBS. This review aims to analyze the GI involvement and the prolonged symptoms of COVID-19 infection as part of PCS, in order to explore the potential development of post-infection IBS (PI-IBS) in COVID-19 patients. Irritating factors such as enteric infection, psychosocial conditions, food antigens, and antibiotics may lead to abnormalities in the physiological function of the GI system and could be involved in the development of PI-IBS. Through the presentation of the pathophysiological mechanisms and epidemiological studies that assessed the prevalence of IBS as part of PCS, we attempted to provide a better understanding of the long-term consequences of COVID-19 and the pathogenesis of PI-IBS. Even though PI-IBS is becoming a global challenge, there are only a few studies about it and therefore limited knowledge. Currently, the majority of the existing treatment options are referred to non-COVID-19-associated DGBIs. Forthcoming studies may shed light on the mechanisms of PI-IBS that could be targeted for treatment development.

Antibiotic therapy and necrotizing enterocolitis

Antibiotic therapy remains a cornerstone of treatment of both medical and surgical presentations of necrotizing enterocolitis (NEC). However, guidelines regarding the administration of antibiotics for the treatment of NEC are lacking and practices vary amongst clinicians. Although the pathogenesis of NEC is unknown, there is consensus that the infant gastrointestinal microbiome contributes to the disease. The presumed connection between dysbiosis and NEC has prompted some to study whether early prophylactic enteral antibiotics can prevent NEC. Yet others have taken an opposing approach, studying whether perinatal antibiotic exposure increases the risk of NEC by inducing a state of dysbiosis. This narrative review summarizes what is known about antibiotics and their association with the infant microbiome and NEC, current antibiotic prescribing practices for infants with medical and surgical NEC, as well as potential strategies to further optimize the use of antibiotics in this population of infants.

Neonatal prophylactic antibiotics after preterm birth affect plasma proteome and immune development in pigs.

Most preterm infants receive antibiotics to prevent serious infections shortly after birth. However, prolonged antibiotic treatment predisposes to gut dysbiosis and late-onset sepsis. Using preterm pigs as model, we hypothesized that neonatal prophylactic antibiotics impair systemic immune development beyond the days of antibiotic treatment. Preterm pigs (90% gestation) were fed formula for 9 days, treated with sterile water (CON) or enteral antibiotics from day 1 to 4. On days 5 and 9, blood was collected for haematology, in vitro LPS stimulation, and plasma proteomics. Antibiotic treatment altered the abundance of 21 and 47 plasma proteins on days 5 and 9, representing 6.6% and 14.8% of the total annotated proteins, respectively. Most antibiotics-induced proteome changes related to complement cascade, neutrophil degranulation, and acute phase responses. Neutrophil and lymphocyte counts were higher in antibiotics-treated pigs on day 5 but did not change from days 5-9, in contrast to increasing cell counts in CON. The antibiotics treatment suppressed TNF-alpha and IL-10 responses to in vitro LPS challenge on day 5, 7 and 9. Few days of antibiotics treatment following preterm birth alter the plasma proteome and inhibit systemic immune development, even beyond the days of treatment. 1. Neonatal prophylactic antibiotics alter the plasma proteome and suppress systemic immune development in preterm pigs 2. The effects of prophylactic antibiotics last beyond the days of treatment. 3. Neonatal antibiotics treatment for compromised human newborns may predispose to longer-term risks of impaired immunity and infections.

564. Patient and Prescriber Characteristics Associated with Inappropriately Long Antibiotic Duration for Skin and Soft Tissue Infections

Abstract Background For common infections, previous studies suggest more seasoned prescribers more commonly use inappropriately long antibiotic durations however, there is a paucity of data regarding patient and provider factors associated with antibiotic prescription duration for pediatric skin and soft tissue (SSTI). Methods Retrospective analysis of patients age 0-21 years prescribed enteral antibiotics for cellulitis, abscess, impetigo, or other SSTI in one of 13 Nationwide Children’s Hospital’s primary care clinics in 2020. Encounters for paronychia, facial abscess, and immunocompromised patients were excluded. Based on national and local SSTI guidelines, antibiotic duration was considered inappropriately long if >5 days for cellulitis or drained abscess or >7 days for undrained abscess, impetigo, or other SSTI. Patient and prescriber factors were collected (Table 1) then univariate and multivariable analyses performed to determine which factors were associated with long antibiotic duration. Statistical analyses accounted for within prescriber correlation. Results From 1/1/2020 to 12/31/2020, we identified 1248 encounters for SSTI. After exclusions, 577 encounters with enteral prescriptions written by 89 prescribers were analyzed. Patient age ranged from 11 days to 20 years, 314 (54%) were female, and 497 (86%) had public insurance. The most common diagnosis was impetigo in 165 (29%). Similar rates of long duration were seen across patients of all ages and insurance categories. No difference in prescriber degree type was associated with antibiotic duration. Mean years since completion of medical training for prescribers of long vs guideline concordant prescriptions was 13 vs 10 in univariate analysis (p=.001). In the multivariable analysis, only diagnosis was associated with increased odds of long duration (Table 2). Compared to impetigo, the adjusted odds ratio for inappropriately long duration was 9.36 for cellulitis and 2.03 for abscess. Patient and Prescriber Characteristics for SSTI Antibiotic Prescriptions IQR, interquartile range, MD, Doctor of Medicine, DO, Doctor of Osteopathic Medicine, NP, Nurse Practitioner †Mann Whitney ‡Fisher’s exact *Chi-square ¶N=556 due to missing data for 21 encounters Multivariable Analysis of Patient and Provider Factors and Inappropriately Long Antibiotic Duration for SSTI Multivariable Analysis of Patient and Provider Factors and adjusted odds ratios for inappropriately long antibiotic duration. *Unknown insurance type for 24 encounters †Missing data for 21 encounters Conclusion In this study of antibiotic duration for SSTI, diagnosis of cellulitis was most strongly associated with inappropriately long duration- providing a focus for future stewardship efforts. Contrary to prior studies, no other patient or provider factor was associated with long duration in our pediatric primary care network. Disclosures Jack Stevens, PhD, Colgate Palmolive (although this abstract does not pertain to any products/services of that highly diversified company): Stocks/Bonds|Procter and Gamble (although this abstract does not pertain to any products/services of that highly diversiified company): Stocks/Bonds.

Neonatal Morbidities and Feeding Tolerance Outcomes in Very Preterm Infants, before and after Introduction of Probiotic Supplementation.

While probiotics are reported to reduce the risks of neonatal morbidities, less is known about probiotics and feeding tolerance. With this retrospective cohort study, we investigate whether introduction of probiotic supplementation as the standard of care was associated with fewer neonatal morbidities and improved feeding tolerance in very preterm infants. Using the Swedish Neonatal Quality Register, 345 live-born very preterm infants (28–31 weeks’ gestation), from January 2019–August 2021, in NICUs in Stockholm, Sweden, either received probiotic supplementation (Bifidobacterium infantis, Bifidobacterium lactis, Streptococcus thermophilus) (139) or no supplementation (206); they were compared regarding a primary composite outcome of death, sepsis, and/or necrotising enterocolitis and secondary outcomes: time to full enteral feeding and antibiotics use. Probiotics seemed associated with a reduced risk of the composite outcome (4.3% versus 9.2%, p = 0.08). In the subgroup of 320 infants without the primary outcome, probiotics were associated with shorter time to full enteral feeding (6.6 days versus 7.2 days) and less use of antibiotics (5.2 days versus 6.1 days). Our findings suggest that probiotics improve feeding tolerance and further support that very preterm infants may benefit from probiotic supplementation.

Jejunoileal mucosal growth in mice with a limited microbiome.

Previous work demonstrated enhanced enterocyte proliferation and mucosal growth in gnotobiotic mice, suggesting that intestinal flora participate in mucosal homeostasis. Furthermore, broad-spectrum enteral antibiotics are known to induce near germ-free (GF) conditions in mice with conventional flora (CONV). We hypothesized that inducing near GF conditions with broad-spectrum enteral antibiotics would cause ordered small intestinal mucosal growth in CONV mice but would have no effect in GF mice with no inherent microbiome. C57BL/6J CONV and GF mice received either an antibiotic solution (Ampicillin, Ciprofloxacin, Metronidazole, Vancomycin, Meropenem) or a vehicle alone. After treatment, small intestinal villus height (VH), crypt depth (CD), mucosal surface area (MSA), crypt proliferation index (CPI), apoptosis, and villus and crypt cell types were assessed. Antibiotic-treated CONV (Abx-CONV) mice had taller villi, deeper crypts, increased CPI, increased apoptosis, and greater MSA compared to vehicle-treated CONV mice. Minor differences were noted in enterocyte and enterochromaffin cell proportions between groups, but goblet and Paneth cell proportions were unchanged in Abx-CONV mice compared to vehicle-treated CONV mice (p>0.05). Antibiotics caused no significant changes in VH or MSA in GF mice when compared to vehicle-treated GF mice (p>0.05). Enteral administration of broad-spectrum antibiotics to mice with a conventional microbiome stimulates ordered small intestinal mucosal growth. Mucosal growth was not seen in germ-free mice treated with antibiotics, implying that intestinal mucosal growth is associated with change in the microbiome in this model.

Nursing Care of Low-Risk Newborns in Low Resource Setting: Nurses' Aides May Bridge the Gap at Community Hospitals

Objective: To study the role of a nurses' aide in the care for newborns weighing between 1500 and 2000 g at birth in a low resource setting.
 Study Design: Observational.
 Setting: The General hospital in 1994-95, in a public sector, located in a remote area in India
 Intervention: A female ward assistant with seven years of schooling trained, on-the-job, to keep babies warm, initiate maternal breastfeeding, and to detect rapid breathing. The nursing staff from the pediatric ward supervised her performance. A separate "warm room" appropriately heated for preterm and sick babies became a makeshift nursery. The nursing staff administered enteral feeding, oxygen, and antibiotics. Services of the resident doctors or general duty medical officers were not available.
 Results: The survival rate was nearly 100% for babies with birthweights between 1,500 and 2,000 g (none referred out).
 Conclusions: A nurses' aide may facilitate the delivery of special care for newborns where nursing personnel are grossly inadequate and saving babies weighing between 1,500 and 2,000 g may need minimal inputs. It may be worthwhile to target 1,500 and 2,000 g birthweight categories even when resources are meager.
 What is already known about this subject?
 
 Low resource settings face staff shortages, especially nursing staff.
 Health workers with midwifery skills can deliver nearly 90% of essential care services for maternal and neonatal health.
 A substantial proportion of neonatal deaths occur among moderately low birth weight babies.
 
 What does this study add?
 
 It is possible to train a semi-literate person to facilitate early breastfeeding and to keep a baby warm.
 A large proportion of deaths among babies with birthweight ranging from 1500 to 2000 g are preventable with meager resources.
 
 How might this impact on clinical practice or future developments?
 The facilities facing shortage of nursing staff in low resource settings, may employ nurses’ aide to deliver basic newborn care.

Современные подходы к профилактике некротизирующего энтероколита у недоношенных новорожденных

Necrotizing enterocolitis (NEC) is the most life-threatening disease of the gastrointestinal tract in newborns. Current strategies and methods of NEC prevention affect the pathogenetic mechanisms of the disease development. The promotion of breastfeeding and the use of early minimal enteral nutrition with native breast milk are the main links in prevention. Immunoglobulins, antiinflammatory cytokines, and other biologically active substances found in breast milk prevent the development of NEC. A change in diet and the use of donor milk lead to a decrease in the incidence of NEC. The use of antenatal steroids in women at risk of preterm birth, control of hypoxia and normalization of the respiratory parameters also reduce the risk of NEC development. For normal colonization of the intestine, the use of probiotics is recommended. The use of oral antibacterial drugs, which are recommended in some multicomponent methods of prevention, often leads to negative results. The use of oral antifungal drugs in modern neonatology is not excluded. The use of oral immunoglobulins is ineffective. Key words: necrotizing enterocolitis, breast milk, enteral antibiotics, oral antifungal drugs, probiotics

Hydrosurgical Debridement of Grade VI External Fixator Pin Site Infection

Background: Pin site infection is a common complication with external fixation, with a reported incidence of 26%–71% in the context of limb reconstruction. The Checketts and Otterburn (C&O) classification is frequently used, with minor infections (C&O I–III) treated with pin site care and enteral antibiotics. Major infections (C&O IV–VI) require removal of the infected pin or fine wire. Surgical debridement is indicated where the infection persists following pin removal (C&O grade VI). The Versajet hydrosurgery system (Smith & Nephew, Memphis, Tennessee) utilizes a saline jet to debride biological tissue. Methods: A retrospective review was conducted on all patients who underwent Versajet hydrosurgery debridement with C&O grade VI pin site infections between January 2011 and January 2021. Data regarding patient demographics, fixator type, indication for the initial surgery, and treatment outcome were recorded. Results: The cohort comprised seven males (87.5%) and one female (12.5%) with a mean age of 41.4 years ± 17.74 (range 16–61). Mean follow-up was 11.8 months ± 6.2 (range 7–25). The mean time in external fixator was 155 days ± 85.19 (range 83–354), and the mean time between fixator removal and Versajet debridement was 46 days ± 33.83 (range 3–116). No perioperative complications were experienced, and all patients (n = 8, 100%) were found to be infection-free at the last clinical review, with healed overlying soft tissue. Conclusion: The Versajet hydrosurgical debridement system is effective in managing C&O grade VI pin site infections. The method is reproducible and provides long-term clearance of infection, allowing subsequent soft tissue healing.

1126. Short-Course Therapy and Transition to Enteral Antibiotics for Uncomplicated Bacteremia Due to Enterobacterales Species

Abstract Background Gram-negative bacteremia historically has been treated with 10-14 days of parenteral antibiotics. However, data supporting this practice are lacking, and recent evidence shows equivalent outcomes for short-course (SC) therapy (7 days) and early (by day 5) conversion to highly bioavailable enteral (PO) antibiotics for Enterobacterales bacteremia. Methods Under a QI framework, we used PDSA cycles to reduce treatment duration and increase use of PO levofloxacin or trimethoprim-sulfamethoxazole for uncomplicated Enterobacterales bacteremia among Infectious Diseases (ID) clinicians at a children’s hospital in Boston, MA. We conducted an education session on evidence to support these practices for ID faculty and fellows in October 2020. In December 2020, we implemented standardized recommendations for a 7-day duration and early PO transition for eligible patients (≥ 3-months-old, ≤ 2 days monomicrobial bacteremia, with source control and return to baseline clinical status) that could be inserted automatically into electronic consult notes. In February 2021, we reinforced this practice to ID providers. We collected data before and after these interventions on ID recommendations and on patients’ actual antibiotic management. Results From 11/01/20 to 05/31/21, mean recommended treatment decreased from 10.6 to 9.5 days; however, mean duration received was similar (11.2 vs 11.7 days) (Figure 1). The percentage of patients for whom ID recommended PO conversion and in whom transition to PO agents by day 5 occurred increased from 27% to 37.5%. Figure 1. Change in average duration of antibiotics recommended and received, in days Conclusion Education and creation of automated standardized recommendations led to decreased recommended treatment durations and increased PO conversions for Enterobacterales bacteremia, but only modestly. This quality improvement initiative demonstrates the potential benefits of education and electronic documentation tools to facilitate evidence-based practice changes, but also highlights the difficulty in changing practice even amongst ID clinicians. Further PDSA cycles will be targeted at increasing more consistent awareness among a large ID division in addition to other stakeholders. Disclosures Gabriella S. Lamb, MD, MPH, Nothing to disclose

Effective Enteral Treatment of Antibiotic for Patient with Respiratory Failure and Septic Shock in the Intensive Care Unit

Background: Pneumonia is a lung infection involving pulmonary alveoli caused by microbes, including bacteria, viruses, and fungi. It is a major infection that causes hospitalization and death worldwide and exacts an enormous cost in economic and human terms. The study to assess clinical outcomes for a critically ill patient treated with an enteral antibiotic for bacterial pneumonia is still limited. Case: We reported a case of pneumonia from 68 years old patient that caused respiratory failure and septic shock in the intensive care unit treated by enteral antibiotic and had a good outcome. Conclusion: Pneumonia can cause respiratory failure and septic conditions. Optimum antibiotic management is one of the methods to solve this problem. The benefit of utilizing enteral antibiotics is substantial and probably appropriate in certain patients.

Impact of enteral prophylactic antibiotics on the trends of inflammatory markers following laparoscopic colorectal cancer surgery: A retrospective and prospective Cohort Study

BackgroundThe study aimed to assess the effect of oral prophylactic antibiotics (OAB) with mechanical bowel preparation (MBP) on the serial measurement of postoperative inflammatory markers and clinical outcomes of the patients undergoing laparoscopic colorectal cancer resection surgery. MethodsA retrospective and prospective data collection was carried out from January 2019 to March 2020 for the patients undergoing laparoscopic colorectal cancer resection. Daily measurements of inflammatory markers were obtained up to 7 days following surgery. The measurements of inflammatory markers were compared between patients who received a 1 week course of OAB along with MBP to those who only received MBP. ResultsThere were a total of 110 patients that were divided into 2 groups: patients who received OAB and MBP (n = 44, 40%) and those who had MBP only (n = 66, 60%). There was no significant difference between the patient characteristics and preoperative staging of the cancer between the 2 groups. The overall length of stay was significantly lower in the patients who received OAB (9.09 days [SD 7.94] vs. 6.63 days [SD 4.96], P 0.02). The patients with OAB and MAP had persistently and significantly low levels of white blood cell count, CRP, and neutrophil count throughout the postoperative period as compared to those who only had MBP. ConclusionThe study demonstrated reduction in serial measurement of inflammatory markers throughout postoperative stay for the patients receiving preoperative OAB. The use of OAB helps in physiological recovery of the patient by reducing the inflammatory process postoperatively.

Reducing PICC Placement in Pediatric Osteomyelitis: A Diamond in the Deimplementation Rough?

Reducing PICC Placement in Pediatric Osteomyelitis: A Diamond in the Deimplementation Rough?

Fecal microbiome alterations in pediatric patients with short bowel syndrome receiving a rotating cycle of gastrointestinal prophylactic antibiotics.

Pediatric patients with short bowel syndrome (SBS) are at risk of developing small intestinal bacterial overgrowth (SIBO). Prevention of SIBO using cyclic enteric antibiotics has been implemented to control the balance in microbial ecosystems, although its effectiveness has not been well studied. This study aimed to explore the change in the gut microbial composition in SBS patients during cyclic antibiotic phases and antibiotic-free period, and to compare the microbiota composition between healthy controls and SBS patients. SBS patients taking oral metronidazole alternating with trimethoprim-sulfamethoxazole (TMP-SMT) and antibiotic-free conditions as a '10-day cyclic protocol' were involved in fecal microbiome study using Illumina 16S sequencing. When healthy control possessed the majority of Bacteroidetes spp. (54%) and Firmicutes spp. (33%), the microbial composition in SBS patients especially Firmicutes spp. and Proteobacteria spp. was prominently changed in each phase of treatment. In antibiotic-free period, SBS patients displayed 49% Firmicutes and 36% Proteobacteria. However, higher Proteobacteria than Firmicutes were detected at the commencement of metronidazole (58% versus 33%). Similarly, 56% Proteobacteria and 27% Firmicutes were found during TMP-SMT. Escherichia coli increased prominently during the antibiotic periods. Prophylactic antibiotics change the gut microbiota composition in an unfavorable direction, especially when repeatedly used for a long period. This practice should be reconsidered. III.

Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice

Since alterations in the intestinal microbiota may induce systemic inflammation and polarization of macrophages to the M1 state, the microbiome role in atherosclerosis, an M1-driven disease, requires evaluation. We aimed to determine if antibiotic (Abx) induced alterations to the intestinal microbiota interferes with atherosclerotic plaque inflammation resolution after lipid-lowering in mice. Hyperlipidemic Apoe−/− mice were fed a western diet to develop aortic atherosclerosis with aortas then transplanted into normolipidemic wild-type (WT) mice to model clinically aggressive lipid management and promote atherosclerosis inflammation resolution. Gut microbial composition pre and post-transplant was altered via an enteral antibiotic or not. Post aortic transplant, after Abx treatment, while plaque size did not differ, compared to Apoe−/− mice, Abx– WT recipient mice had a 32% reduction in CD68-expressing cells (p = 0.02) vs. a non-significant 12% reduction in Abx+ WT mice. A trend toward an M1 plaque CD68-expresing cell phenotype was noted in Abx+ mice. By 16S rRNA sequence analysis, the Abx+ mice had reduced alpha diversity and increased Firmicutes/Bacteroidetes relative abundance ratio with a correlation between gut Firmicutes abundance and plaque CD68-expressing cell content (p < 0.05). These results indicate that in a murine atherosclerotic plaque inflammation resolution model, antibiotic-induced microbiome perturbation may blunt the effectiveness of lipid-lowering to reduce the content of plaque inflammatory CD68-expressing cells.

Opportunities for Stewardship in the Transition From Intravenous to Enteral Antibiotics in Hospitalized Pediatric Patients.

Pediatric patients hospitalized with bacterial infections often receive intravenous (IV) antibiotics. Early transition to enteral antibiotics can reduce hospital duration, cost, and complications. We aimed to identify opportunities to transition from IV to enteral antibiotics, describe variation of transition among hospitals, and evaluate feasibility of novel stewardship metrics. This multisite retrospective cohort study used the Pediatric Health Information System to identify pediatric patients hospitalized with pneumonia, neck infection, orbital infection, urinary tract infection (UTI), osteomyelitis, septic arthritis, or skin and soft tissue infection (SSTI) between 2017 and 2018. Opportunity days were defined as days on which patients received both IV antibiotics and enteral medications, suggesting enteral tolerance. Percent opportunity was defined as opportunity days divided by days on any antibiotics. Both outcomes excluded IV antibiotics that have no alternative oral formulation. We evaluated outcomes per infection and antibiotic and assessed across-hospital variation. We identified 88,522 aggregate opportunity days in 100,103 hospitalizations. On 57% of the antibiotic days, there was an opportunity to switch patients to enteral therapy, with greatest opportunity days in SSTI, neck infection, and pneumonia encounters, and with clindamycin, ceftriaxone, and ampicillin-sulbactam. Percent opportunity varied by infection (73% in septic arthritis to 40% in pneumonia). There was significant across-hospital variation in percent opportunity for all infections. This multicenter study demonstrated the potential opportunity to transition from IV to enteral therapy in over half of antibiotic days. Opportunity varied by infection, antibiotic, and hospital. Across-hospital variation demonstrated likely missed opportunities for earlier transition and the need to define optimal transition times. Stewardship efforts promoting earlier transition for highly bioavailable antibiotics could reduce healthcare utilization and promote high-value care. We identified feasible stewardship metrics.

Discharge Home After Transition to Oral Antibiotics: No Jeopardy.

Transitioning children from intravenous to enteral antibiotics is a daily occurrence for providers caring for children in hospitals. These children have clinically improved but require additional days of medication to complete an effective course of therapy. Some clinicians make the change to enteral antibiotics and discharge the child immediately, whereas others watch the child in the hospital setting on the enteral antibiotic therapy for a day or more. In their study, Stromberg et al1 suggest that prolonged observation is not the national norm, that the practice of observation after transitioning therapy has wide variability nationally, and that observation after transitioning therapy is likely unnecessary for children with skin and soft tissue infections (SSTIs). The authors’ findings beg the question: When do you deviate from the norm? The Infectious Diseases Society of America’s SSTI guidelines recommend cephalexin or clindamycin for cases of SSTI in which the child is stable and does not have bacteremia or intravascular infection; but vancomycin is listed as first-line therapy for complicated SSTIs.2 In the current study, the authors found that despite the fact that children in this cohort were considered to have “uncomplicated” SSTI, ∼20% of these children received vancomycin during their hospital stay before transitioning to oral therapy. Vancomycin use in SSTIs can add significant cost to a hospitalization,3 entails additional diagnostic testing for safety and therapeutic monitoring, and adds risk of nephrotoxicity4. This study builds on previous …

Establishment of a Controlled Human Infection Model with a Lyophilized Strain of Shigella sonnei 53G.

Controlled human infection models (CHIMs) are useful for vaccine development. To improve on existing models, we developed a CHIM using a lyophilized preparation of Shigella sonnei strain 53G produced using current good manufacturing practice (cGMP). Healthy adults were enrolled in an open-label dose-ranging study. Following administration of a dose of rehydrated S. sonnei strain 53G, subjects were monitored for development of disease. The first cohort received 500 CFU of 53G, and dosing of subsequent cohorts was based on results from the previous cohort. Subjects were administered ciprofloxacin on day 5 and discharged home on day 8. Subjects returned as outpatients for clinical checks and sample collection. Attack rates increased as the dose of S. sonnei was increased. Among those receiving the highest dose (1,760 CFU), 70% developed moderate to severe diarrhea, 50% had dysentery, and 40% had fever. Antilipopolysaccharide responses were observed across all cohorts. An S. sonnei CHIM using a lyophilized lot of strain 53G was established. A dose in the range of 1,500 to 2,000 CFU of 53G was selected as the dose for future challenge studies using this product. This model will enable direct comparison of study results between institutions and ensure better consistency over time in the challenge inoculum.IMPORTANCE Controlled human infection models (CHIMs) are invaluable tools utilized to understand the human response to infection, potentially leading to protective immune mechanisms and allowing efficacy testing of enteric countermeasures, including vaccines, antibiotics, and other products. The development of an improved Shigella CHIM for both Shigella sonnei and Shigella flexneri is consistent with international efforts, supported by international donors and the World Health Organization, focused on standardizing Shigella CHIMs and using them to accelerate Shigella vaccine development. The use of lyophilized Shigella challenge strains rather than plate-grown inoculum preparations is considered an important step forward in the standardization process. Furthermore, the results of studies such as this justify the development of lyophilized preparations for additional epidemiologically important S. flexneri serotypes, including S. flexneri 3a and S. flexneri 6.