Effect Of Antibiotic Use Research Articles

1773. Evaluation of Fluoroquinolone Prophylaxis in Preventing Bacterial Infection in Neutropenic Afebrile Patients Without Leukemias or HSCT: A Systematic Review

Abstract Background Per 2010 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer, routine use of fluoroquinolone (FQ) chemoprophylaxis in low-risk populations (defined as those with solid tumors or lymphoma undergoing chemotherapy) is not recommended to prevent febrile neutropenic episodes as it was not found to impact all-cause mortality. Since these guidelines were published, there have been additional randomized trials (RCTs) of FQ chemoprophylaxis in patients with cancer. Our objective was to assess the efficacy of FQ vs placebo in preventing probable or confirmed bacterial infection in patients with cancer who did not have leukemias or hematopoietic stem cell transplant (HSCT). Secondary outcomes of interest included febrile episodes, mortality, and adverse effects of antibiotic use. Methods Medline via PubMed, The Cochrane Central Register of Controlled Trials, and SCOPUS from inception through 2/17/2022 were searched. We included RCTs in English comparing FQ to placebo in preventing neutropenic fever and bacterial infections in patients with cancer who did not have leukemias or HSCT. Results We included 5 RCTs (N= 3158). The rates of probable or confirmed bacterial infection in patients with cancer revealed 541/1562 (34.6%) infections in the FQ group and 679/1560 (43.5%) in the placebo group (OR: 0.68, 95% CI:0.59,0.79, I2 = 57%, p=0.002). In evaluating development of febrile episodes, 300/1566 (19.2%) events were noted in the FQ group and 407/1555 (26.2%) in the placebo group (OR: 0.58, 95% CI:0.41,0.83, I2 = 0%, p< 0.001). Mortality events in the FQ group were 113/1597(7.1%) and 124/1508 (8.2%) in the placebo group (OR: 0.76, 95% CI:0.53,1.1, I2 = 7%, p=0.15). Adverse events associated with antibiotic use in the studies were more frequent in the FQ group. Figure 1Forest Plot of Mortality in included studiesFigure 2Results on Development of Fevers in included studies.Figure 3Forest plot of Probable or Proven Infection in included studies. Conclusion Although evidence does not show that FQ prophylaxis provides mortality benefit, it did show a decrease in development of bacterial infections and febrile episodes. This suggests that treatment may still provide clinical benefit to this population of patients, but must be weighed against risks and consequences of long-term antibiotic use, which were not reported by the included studies. Disclosures All Authors: No reported disclosures.

The Effect of Antibiotic Use in Surgery on the Incidence of Postsurgical Cataract Endophthalmitis

Endophthalmitis is a rare complication that can occur either endogenous or exogenous. Postsurgical endophthalmitis remains the primary exogenous etiology. Its complications remain formidable and involve the functional prognosis see anatomical eye. All interest of the question resides in preoperative prevention by incising on the measures of asepsis and antisepsis and per operatory by administering the antibiotic. Intracameral cefuroxime reduces the incidence of postoperative endophthalmitis of similar or slightly increased efficacy compared to the intravenous tract.

The time-varying association between previous antibiotic use and antibiotic resistance

ObjectivesThe objective of the study was to estimate how the time elapsed from previous antibiotic use is associated with antibiotic resistance. MethodsData comprised electronic medical records of all patients in an Israeli hospital who had a positive bacterial culture from 2016 to 2019. These included susceptibility testing results and clinical and demographic data. Mixed-effects time-varying logistic models were fitted to estimate the association between the time elapsed since the last use of aminoglycosides and gentamicin resistance (n = 13 095), cephalosporins and ceftazidime resistance (n = 13 051), and fluoroquinolones and ciprofloxacin resistance (n = 15 364) while adjusting for multiple covariates. ResultsFor all examined antibiotics, previous antibiotic use had a statistically significant association with resistance (p < 0.001). These associations exhibited a clear decreasing pattern over time, which we present as a flexible function of time. Nonetheless, previous antibiotic use remained a significant risk factor for resistance for at least 180 days when the adjusted ORs were 1.94 (95% CI, 1.40–2.69), 1.33 (95% CI, 1.10–1.61), and 2.25 (95% CI, 1.49–3.41) for gentamicin, ceftazidime, and ciprofloxacin, respectively. DiscussionThe association between prior antibiotic use and resistance decreases over time. Commonly used cut-offs for prior antibiotic use can either misclassify patients still at higher risk when too recent or provide a diluted estimate of the effects of antibiotic use on future resistance when too distant. Hence, prior antibiotic use should be considered a time-dependent risk factor for resistance in both epidemiological research and clinical practice.

Long-term use of broad-spectrum antibiotics affects Ly6Chi monocyte recruitment and IL-17A and IL-22 production through the gut microbiota in tumor-bearing mice treated with chemotherapy.

The protective effects of antibiotics against infection in cancer patients treated with chemotherapy remains unclear and related studies have been performed in healthy or pathogen-infected animal models. Here, we aimed to study the effects of antibiotic use on intestinal infection in tumor-bearing mice treated with chemotherapy and to determine the underlying mechanisms. Subcutaneous CT26 tumor-bearing mice were assigned to four groups: the control (Ctrl) group without any treatment, the antibiotic (ATB) group treated with a mixture of ampicillin, streptomycin, and colistin, the 5-fluorouracil (FU) group treated with four cycles of intraperitoneal injections of FU, and the ATB + FU group treated with the combination of ATB and FU. Gut microbial composition was determined and mesenteric lymph nodes (mLNs) were isolated for bacterial culturing. Intestinal permeability and integrity were assessed and the expression of cytokines was analyzed by quantitative PCR, ELISA, or flow cytometry (FCM). Monocytes in the colonic lamina propria (LP) were measured by FCM. Compared with the Ctrl and FU groups, the numbers of positive bacterial culturing results for mLNs were higher, and gut bacterial compositions were altered in the ATB and ATB + FU groups, with significantly decreased alpha diversity in the ATB + FU group. Intestinal integrity regarding the expression of tight junction proteins and intestinal permeability were not impaired significantly after treatments, but the colons were shorter in the ATB + FU group. The expression levels of intestinal IL-17A and IL-22, as well as the percentages of IL-17A+ cells in the colonic LP of the ATB + FU group, were lower than those in the FU group. The percentages of Ly6Chi monocytes in the colonic LP were lower, but those in the spleen were higher in the ATB + FU group than in the FU group. The mRNA levels of colonic CCL8 were reduced in the ATB + FU group. Antibiotic use is associated with an increased incidence of intestinal infections in tumor-bearing mice treated with chemotherapy, which might in turn be associated with a dysregulated gut microbiota that inhibits colonic monocyte recruitment and IL-17A and IL-22 production.

Implementation of antimicrobial stewardship programs

Background: The antimicrobial stewardship program (ASP) is a coordinated intervention designed to improve and measure the appropriate antibiotics use by selecting an optimal antibiotic drug regimen, including dosing, therapy duration, and administration route. The implementation of ASPs decreases the consumption, cost, and adverse effects of antibiotic use. Additionally, it improves the clinical outcomes, and decreases Clostridium difficile infection and antimicrobial resistance.Current Concepts: To overcome the antimicrobial resistance and implement ASPs worldwide, various efforts are underway, such as enacting ASP guidelines, developing core elements for ASP implementation, introducing ASPs to the healthcare accreditation system, and providing healthcare facilities with adequate incentives to implement ASPs. In Korea, ASP guidelines were published in September 2021, and core elements for ASP implementation are being developed at the time of writing. However, there is a shortage of personnel required for the ASP team, including healthcare workforce and infectious disease specialists for leading the team Moreover, financial support for ASP implementation in the National Health Insurance Service is not provided yet. The awareness of hospital leadership and clinicians prescribing antibiotics for ASP implementation is still low. The reimbursement system establishment and workforce for ASPs are prerequisite for the implementation of ASPs.Discussion and Conclusion: At the national level, it is necessary to provide financial support for ASPs in healthcare facilities, nurture the healthcare workforce in performing ASPs, and advocate ASP education and publicity.

The effect of antibiotic use on endodontic post-operative pain and flare-up rate: a systematic review with meta-analysis.

Aim Antibiotics are widely used to prevent flare-ups after endodontic treatment of non-vital teeth. This systematic review assessed the effect of antibiotic administration on post-endodontic treatment pain and flare-up rate.Methods Five major databases including Web of Science, Cochrane Library, PubMed, Scopus and Embase were searched to identify randomised clinical trials (RCTs) published until September 2020. Retrieved papers were critically appraised using the revised Cochrane risk of bias tool (RoB 2). To reduce the clinical heterogeneity, the included studies were divided into two groups: studies on symptomatic non-vital teeth and studies on asymptomatic non-vital teeth. The primary outcomes were 'post-operative pain' and 'flare-up rate'. The data of included studies were statistically combined through meta-analysis using random-effect model. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence.Results Six RCTs involving two RCTs (N = 61) on symptomatic teeth and four RCTs (N = 310) on asymptomatic teeth were included. In two RCTs on asymptomatic teeth, prophylactic antibiotic had been used, while in the remaining two RCTs, antibiotics had been administered after treatment. Quantitative synthesis of the RCTs showed that antibiotic administration following endodontic treatment of symptomatic non-vital teeth has no effect on pain severity at 24 hours following treatment (weighted mean difference [WMD] = -0.03; 95% confidence interval [CI]: -0.53 to 0.47), and the use of antibiotics before endodontic treatment of asymptomatic non-vital teeth has no effect on flare-up rate (relative risk [RR] = 0.58; 95% CI: 0.22-1.54). The GRADE approach revealed that the overall quality of evidence on the topic is low.Conclusions The antibiotic administration following endodontic treatment of symptomatic non-vital teeth has no effect on pain severity at 24 hours following treatment. Also, prophylactic antibiotics are ineffective in reducing the flare-up rate following treatment of asymptomatic non-vital teeth. However, to evaluate the effect of post-treatment antibiotics on flare-up rate in asymptomatic non-vital teeth, more high-quality RCTs are needed.

Oral colonization of Acinetobacter baumannii in intensive care units: Risk factors, incidence, molecular epidemiology, association with the occur of pneumonia and sepsis, and infection control measures.

Objective(s):Oral colonization of Acinetobacter baumannii can lead to infections such as pneumonia and sepsis. We aimed to evaluate oral colonization of hospitalized patients in ICUs and to examine risk factors for oral colonization, molecular epidemiology, and incidence of pneumonia and sepsis. Materials and Methods:The study began in February 2021. Oral cultures were taken. The microorganisms were identified by a Maldi-tof MS mass spectrometry device. Colistin resistance genes were investigated by polymerase chain reaction. Clonal relationships were determined by pulsed-field gel electrophoresis. Results: A. baumannii was found in 21 of 96 patients’ oral cultures. Pneumonia and sepsis due to A. baumannii were detected in 14 and 5 patients, respectively. The mean growth time of A. baumannii from oral cultures was 11.8 days, and the meantime for the occurrence of pneumonia after oral growth was 5.2 days. We determined a plasmid mediated mcr-2 colistin resistance gene in a colistin susceptible A. baumannii strain. It is the first report of the plasmid mediated mcr-2 colistin resistance gene in our country. In total, fourteen different A. baumannii genotypes were determined in PFGE. It was determined that the effects of antibiotic use, oral motor dysfunction, mechanical ventilation, intubation, orogastric tube use, and total parenteral nutrition intake on oral colonization were statistically significant.Conclusion:Oral colonization of A. baumannii is a significant concern in ICUs. We believe that it is important to take oral cultures and follow the risk factors and take infection control measures to prevent oral colonization of resistant isolates in ICUs.

Effects of Antibiotic Use on Saliva Antibody Content and Oral Microbiota in Sprague Dawley Rats.

Antibiotics are often used to treat systemic diseases not associated with the oral cavity. This application of antibiotics may affect the healthy oral microbiota community, as it destroys the balance between specific bacterial populations throughout the ecosystem and may lead to dysbacteriosis. We hypothesized that the effects on antibiotics on oral microbiota regulation and function would affect antibody content in saliva, depending on the antibiotic type. To address this, a total of 24 Sprague Dawley rats (divided into 4 cages, 6 per pen) were administered amoxicillin (AMX), spiramycin (SP), metronidazole (MTZ), or water (control) daily for 14 days (gavage). After treatment was completed, high-throughput sequencing of 16S rRNA genes was used to determine changes in the composition, metabolic function, and diversity of oral microbiota in the rats. Enzyme-linked immunosorbent assay was used to detect antibodies in saliva, including SIgA, IgG, and IgM. Results showed that AMX, MTZ, and SP significantly affected oral microbiota composition, diversity, and metabolic function in rats. AMX induced substantial changes in the rat salivary antibody concentrations. At the genus level, the relative abundance of Rothia and Haemophilus was higher in the AMX group than in the other groups. In conclusion, antibiotics-induced changes in oral microbiota populations may be associated with changes in salivary antibody concentrations. However, the specific interaction mechanisms remain unknown, and it is still unclear whether significant changes in the oral microbiota cause changes in salivary antibody concentrations or vice versa.

Short-term and long-term effects of antimicrobial use on antimicrobial resistance in broiler and turkey farms

ABSTRACT Antimicrobials have been widely used in poultry, promoting antimicrobial resistance (AMR) emergence and spread. Resistant bacteria selected by antimicrobial use (AMU) can contaminate the farm environment and transfer resistance genes to other bacteria, providing opportunities for persistence and (re-)colonization of subsequent flocks and potentially jeopardizing antimicrobial treatments. We investigated the effects of AMU on AMR in poultry in the long-term (due to historical AMU in the farm) and in the short-term (due to current AMU in a flock). Litter samples from 35 broiler and 35 turkey farms in North-East Italy were sampled longitudinally for AMR testing of E. coli indicator bacteria in 2019/2020. Differences in AMR as a function of historical AMU (Defined Daily Doses in 2016–2018), current AMU in the sampled flock, farm size and season were tested using Generalized Estimating Equation regression analysis. In both broilers and turkeys, the highest resistance levels were observed for sulfamethoxazole (>70%), followed by ampicillin (54–60%). Only a few positive associations between historical levels of penicillin use and the specific resistance levels to penicillin in broiler farms, and the overall historical AMU and resistance to trimethoprim in turkey flocks, were significant. Current AMU showed significant effects on resistance to sulfamethoxazole, trimethoprim, ciprofloxacin and tetracycline in turkey flocks. Significant effects of farm size on some AMR levels were also identified. We found a stronger association between current AMU and AMR compared to historical AMU and AMR. AMR persistence in the farm environment in the absence of direct AMU pressure needs to be further investigated. RESEARCH HIGHLIGHTS Sulfamethoxazole and ampicillin resistance are the highest in E. coli isolates of both broilers and turkeys. Short-term effects of antibiotic use on resistance are seen more often than long-term effects. Historical penicillin use is associated with penicillin resistance in broilers. There is an association between historical use and resistance to trimethoprim in turkeys.

Effects of Tylosin, a Direct-Fed Microbial and Feedlot Pen Environment on Phenotypic Resistance among Enterococci Isolated from Beef Cattle Feces.

In two sequential replicates (n = 90 and n = 96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, not fed) the macrolide tylosin. Diluted fecal samples were spiral-plated on plain and antibiotic-supplemented m-Enterococcus agar. In the first replicate, tylosin significantly (p < 0.05) increased the relative quantity of erythromycin-resistant enterococci. This effect was diminished in cattle fed the DFM in conjunction with tylosin, indicating a macrolide susceptible probiotic may help mitigate resistance. A similar observed effect was not statistically significant (p > 0.05) in the second replicate. Isolates were speciated and resistance phenotypes were obtained for E. faecium and E. hirae. Susceptible strains of bacteria fed as DFM may prove useful for mitigating the selective effects of antibiotic use; however, the longer-term sustainability of such an approach remains unclear.

The Effect of Antibiotic Use on Microorganism Distribution and Antibiotic Resistance in Hospital Infections in the Covid-19 Pandemic

The Effect of Antibiotic Use on Microorganism Distribution and Antibiotic Resistance in Hospital Infections in the Covid-19 Pandemic

Antibiotic Usage Reduced Overall Survival by over 70% in Non-small Cell Lung Cancer Patients on Anti-PD-1 Immunotherapy.

There is an increasing use of immunotherapy for non-small cell lung cancer (NSCLC) patients. The present study analysed the effect of antibiotic use on the outcome of NSCLC patients undergoing treatment with anti-programmed cell death-1 (anti-PD-1) immunotherapy. This was a retrospective study of 69 NSCLC patients. Eighteen out of 69 patients received antibiotics within 21 days before or within 21 days after start of anti-PD-1 therapy. Patients treated with anti-PD-1 antibodies receiving antibiotics had greatly decreased objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) compared to those who did not use antibiotics. Multivariate analysis showed that antibiotic treatment of patients on anti-PD-1 antibody therapy was an independent negative predictive factor of PFS; however, it was not a significant independent predictive factor of OS. Use of antibiotics within 21 days before and after anti-PD-1 treatment initiation in patients with NSCLC strongly reduced OS and PFS, suggesting the two treatments should not be combined.

Management of wound infection after appendectomy: are parenteral antibiotics useful?

This study investigated the use of antibiotics in the treatment of wound infections after appendectomy. The subjects were 72 patients with post-operative wound infections at a district general hospital in Jordan. All patients received daily antiseptic dressings with povidone-iodine 10% in alcohol. The patients were randomized in a single-blind trial to receive either no antibiotics or parenteral antibiotics metronidazole and cefoxitin. There was no significant effect of antibiotic use in patients with early inflamed or severely inflamed appendicitis. However, for patients with perforated appendicitis the mean length of hospital stay and the mean frequency of change of dressings were significantly reduced. We conclude that antibiotics do not offer any advantage in post-appendectomy wound infections except for cases of perforated appendix.

Antibiotics and fecundability among female pregnancy planners: a prospective cohort study.

To what extent is female preconception antibiotic use associated with fecundability? Preconception antibiotic use overall was not appreciably associated with fecundability. Antibiotics are commonly used by women and are generally thought to be safe for use during pregnancy. However, little is known about possible effects of antibiotic use on fecundability, the per-cycle probability of conception. Previous research on this question has been limited to occupational rather than therapeutic exposure. We analyzed data from an Internet-based preconception cohort study of 9524 female pregnancy planners aged 21-45 years residing in the USA and Canada who had been attempting to conceive for six or fewer cycles at study entry. Participants enrolled between June 2013 and September 2020 and completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. The questions pertaining to antibiotic type and indication were added to the PRESTO questionnaires in March 2016. We assessed antibiotic use in the previous 4 weeks at baseline and on each follow-up questionnaire. Participants provided the name of the specific antibiotic and the indication for use. Antibiotics were classified based on active ingredient (penicillins, macrolides, nitrofurantoin, nitroimidazole, cephalosporins, sulfonamides, quinolones, tetracyclines, lincosamides), and indications were classified by type of infection (respiratory, urinary tract, skin, vaginal, pelvic, and surgical). Participants reported pregnancy status on follow-up questionnaires. We used proportional probabilities regression to estimate fecundability ratios (FR), the per-cycle probability of conception comparing exposed with unexposed individuals, and 95% confidence intervals (CI), adjusting for sociodemographics, lifestyle factors, and reproductive history. Overall, women who used antibiotics in the past 4 weeks at baseline had similar fecundability to those who had not used antibiotics (FR: 0.98, 95% CI: 0.89-1.07). Sulfonamides and lincosamides were associated with slightly increased fecundability (FR: 1.39, 95% CI: 0.90-2.15, and FR: 1.58 95% CI: 0.96-2.60, respectively), while macrolides were associated with slightly reduced fecundability (FR: 0.70, 95% CI: 0.47-1.04). Analyses of the indication for antibiotic use suggest that there is likely some confounding by indication. Findings were imprecise for some antibiotic classes and indications for use owing to small numbers of antibiotic users in these categories. There are likely heterogeneous effects of different combinations of indications and treatments, which may be obscured in the overall null results, but cannot be further elucidated in this analysis. There is little evidence that use of most antibiotics is associated with reduced fecundability. Antibiotics and the infections they treat are likely associated with fecundability through differing mechanisms, resulting in their association with increased fecundability in some circumstances and decreased fecundability in others. This study was supported through funds provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (R01-HD086742, R21-HD072326). L.A.W. has received in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, Fertility Friend, and Kindara for primary data collection in PRESTO. The other authors have no conflicts of interest to disclose. N/A.

Coffee Consumption Modulates Amoxicillin-Induced Dysbiosis in the Murine Gut Microbiome.

The microbiome is essential for host health, and perturbations resulting from antibiotic use can lead to dysbiosis and disease. Diet can be a powerful modulator of microbiome composition and function, with the potential to mitigate the negative effects of antibiotic use. Thus, it is necessary to study the impacts of diet and drug interactions on the gut microbiome. Coffee is a commonly consumed beverage containing many compounds that have the potential to affect the microbiome, including caffeine, polyphenols, and fiber. We supplemented mice with caffeinated and decaffeinated coffee in conjunction with amoxicillin, and used 16S rRNA amplicon sequencing of fecal samples to investigate changes in diversity and composition of the murine fecal microbiome. We found that antibiotics, regardless of coffee supplementation, caused significant disruption to the murine fecal microbiome, enriching for Proteobacteria, Verrucomicrobia, and Bacteroidetes, but reducing Firmicutes. While we found that coffee alone did not have a significant impact on the composition of the fecal microbiome, coffee supplementation did significantly affect relative abundance metrics in mice treated with amoxicillin. After caffeinated coffee supplementation, mice treated with amoxicillin showed a smaller increase in Proteobacteria, specifically of the family Burkholderiaceae. Correspondingly we found that in vitro, Burkholderia cepacia was highly resistant to amoxicillin, and that it was inhibited by concentrations of caffeine and caffeinated coffee comparable to levels of caffeine in murine ceca. Overall, this work shows that coffee, and possibly the caffeine component, can impact both the microbiome and microbiome members during antibiotic exposure.

Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis.

This study evaluates the impact of the use of antibiotics on the effectiveness of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). A literature search was conducted in various electronic databases to identify studies, which evaluated the impact of antibiotic use on the survival of patients with advanced/metastatic NSCLC who have been treated with nivolumab. Six studies, comprising a total of 787 patients with 37.2% females and of age range 30–90 years, were included in the study. A lack of smoking history was reported in 14.4% of the patients. A meta-analysis was conducted in 678 and 713 patients for PFS and OS, respectively. The pooled HR was 1.95 (95% CI: 1.13–3.37, P = 0.016) for PFS and 2.70 (95% CI: 1.81–4.02, P < 0.001) for OS. Among patients exposed to antibiotics, the median PFS and OS were reduced by 1.6 months (95% CI: 1.5–1.7) and 8.8 months (95% CI: 8.5–9.1), respectively. Our study indicates that, among patients with advanced/metastatic NSCLC, the use of antibiotics with nivolumab led to a decrease in the median OS by more than 8 months. Studying the mechanism of the effect of antibiotics on the efficacy of nivolumab in patients with NSCLC should also be prioritized.

Efficacy of postoperative antibiotic use after tibial plateau leveling osteotomy in dogs: A systematic review.

A systematic review of published data to determine whether postoperative antibiotic use after tibial plateau leveling osteotomy (TPLO) decreases infection rates. Systematic review. A broad bibliographic search was performed in three online databases through March 2020 for publications on postoperative antibiotic use after TPLO in dogs. Search terms included dog, canine, TPLO, tibial plateau leveling osteotomy, infection, antibiotic, and antimicrobial. Articles that met inclusion criteria were evaluated for level of evidence (LoE) by a modified Oxford Level of Evidence (mOLE) and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) classification and evaluation. Thirteen studies met the inclusion criteria. Effect of antibiotic use was the primary question in four studies. Among those, 50% (2/4) were assigned a mOLE of 1b and a GRADE of moderate, while the other 50% (2/4) were assigned a mOLE of 4b or 4c with a GRADE of low. The two studies with the highest LoE did not provide evidence of the benefit of antibiotic usage. Results of only one study provided evidence to support the use of postoperative antibiotics. The remaining nine studies provided evaluation of antibiotic use secondarily and were all assigned a low LoE. Among these, 78% (7/9) provided evidence to support the use of postoperative antibiotics. We found little evidence to support the use of postoperative antibiotics to reduce the risk of surgical site infections in dogs after TPLO. The answer to this clinical question is complicated by the lack of prospective studies and inconsistent treatment protocols in the evaluated studies. The clinical impact of postoperative antibiotic administration on infection rates after TPLO is uncertain.

The effect of antibiotic use within 30 days of initiation of immune checkpoint inhibitor (ICI) efficacy in patients with metastatic urothelial carcinoma (mUC) in real-world setting.

417 Background: There is emerging evidence that patients (pts) treated with immune-checkpoint inhibitors (ICIs) may have a poorer response in the setting of antibiotic use (ABx), possibly due to negative impact on gut microbiota. Our group previously demonstrated that Abx use 60 days before or 60 days in mUC pts after initiation of ICI therapy did not have a significant impact on overall survival (OS) in real-world setting. We now studied the effect of Abx use within 30 days of initiation of ICI on OS in the same cohort of mUC patients. Methods: We performed a retrospective analysis of adult pts with mUC treated at the Cleveland Clinic between 2015 and 2020. Pts included in the study received at least 2 cycles of ICI therapy with either atezolizumab or pembrolizumab. Statistical analysis included study of OS in weeks using the Kaplan Meier method and rank log test, Fischer’s exact test, and Kruskal-Wallis test. Results: A total of 115 pts that received ICI therapy were included. 57 pts received atezolizumab and 58 pts received pembrolizumab. 38 pts (33%) received antibiotics and 77pts (67%) did not. The most commonly used Abx used were Cephalosporins (27%), Penicillins/Carbapenems (25%), Flouroquinolones (23%), and Bactrim (11%). 18 pts received Abx within 30 days before initiation of ICI, 13 pts received Abx within 30 days after initiation of ICI, and 7 pts received Abx before and after initiation of ICI. There was no statistical difference in OS in the group of pts that received Abx 30 days prior to initiation of ICI with median OS of 5.95 months (95% CI 3.22-13.67, p=0.0695) compared to 12.39 months (95% CI 10.09 – 18.6) in those who did not receive Abx. Similarly, there was no statistical difference in OS in the group of pts that received Abx 30 days after initiation of ICI with median OS of 5.09 months (95% CI 2.53-22.57, p=0.2339) compared to 12.02 months (95% CI 8.6`-17.02 Table). Conclusions: In our single institution study of mUC patients receiving ICI treatment, the use of Abx did not affect the OS. Although there was a trend for better OS seen in pts who did not receive Abx, it was not statistically significant (Table). Due to the limitations of a retrospective analysis and small sample size, further studies are warranted taking into account other factors that may affect gut microbiota in mUC pts. [Table: see text]

A One Health approach to assessing occupational exposure to antimicrobial resistance in Thailand: The FarmResist project.

This Southeast Asia-Europe research project will use a One Health approach to identify the major parameters responsible for the presence of animal-associated antimicrobial resistant bacteria in animal production facilities in Thailand and the risk of their transmission from animals to humans. We will focus on traditional, small, extensive pig and poultry farms where information on antibiotic use is scarce and animals live in close contact with humans. This cross-sectional study will be based on the epidemiological analysis of the antimicrobial resistance (AMR) present in fecal samples from animals and humans. Extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) and Enterobacteriaceae resistant to colistin will be actively searched in the feces of farm animals (pigs and poultry), small wild rodents and farmers. Phenotypic (selective plating) and genotypic (multilocus seuquence typing and sequencing) methods will be used for the detection of AMR, the identification of antibiotic resistance genes (ARGs) and the characterization of strains carrying resistance genes. Questionnaires will be administered to investigate the effects of antibiotic use, farm characteristics and biosecurity measures on the occurrence of AMR in animals. Subsequently, the fecal carriage of AMR and ARGs in farmers will be compared to a control population with no occupational contacts with animals, thus enabling an estimation of the risk of transmission of AMR/ARGs from animals to farmers.

Global personalization of antibiotic therapy in critically ill patients

ABSTRACT Introduction: Sepsis from bacterial infection remains a significant cause of morbidity and mortality. Antibiotic use continues to increase in the community and secondary care. This is driven by the potential benefits to the individual patient of a course of antibiotics. Far less attention is given to the potential adverse effects of antibiotic use in our view. These costs may be significant to both the individual and society. Areas covered: We review the evidence underpinning the costs and benefits of antibiotic use. We also discuss strategies to personalize medicine in this area that maximize the benefit to cost ratio for patients and society. Expert opinion: The body’s innate immune response to infection is similar to that of other inflammatory insults. Our view is as clinicians we need to differentiate these responses and hence require an accurate method to determine a diagnosis of a bacterial infection and monitor illness severity. Without this, clinicians will continue to prescribe significant volumes of unnecessary antibiotics in cases of non-bacterial inflammatory states.