Impact Of Antibiotic Exposure Research Articles

The impact of antibiotic exposure on antibiotic resistance gene dynamics in the gut microbiota of inflammatory bowel disease patients.

While antibiotics are commonly used to treat inflammatory bowel disease (IBD), their widespread application can disturb the gut microbiota and foster the emergence and spread of antibiotic resistance. However, the dynamic changes to the human gut microbiota and direction of resistance gene transmission under antibiotic effects have not been clearly elucidated. Based on the Human Microbiome Project, a total of 90 fecal samples were collected from 30 IBD patients before, during and after antibiotic treatment. Through the analysis workflow of metagenomics, we described the dynamic process of changes in bacterial communities and resistance genes pre-treatment, during and post-treatment. We explored potential consistent relationships between gut microbiota and resistance genes, and established gene transmission networks among species before and after antibiotic use. Exposure to antibiotics can induce alterations in the composition of the gut microbiota in IBD patients, particularly a reduction in probiotics, which gradually recovers to a new steady state after cessation of antibiotics. Network analyses revealed intra-phylum transfers of resistance genes, predominantly between taxonomically close organisms. Specific resistance genes showed increased prevalence and inter-species mobility after antibiotic cessation. This study demonstrates that antibiotics shape the gut resistome through selective enrichment and promotion of horizontal gene transfer. The findings provide insights into ecological processes governing resistance gene dynamics and dissemination upon antibiotic perturbation of the microbiota. Optimizing antibiotic usage may help limit unintended consequences like increased resistance in gut bacteria during IBD management.

Prolonged Antibiotic Exposure during Adolescence Dysregulates Liver Metabolism and Promotes Adiposity in Mice

Antibiotic administration during early life has been shown to have lasting effects on the gut microbiota, which have been linked to sustained alterations in liver metabolism and adiposity. Recent investigations have discerned that the gut microbiota continues to develop toward an adult-like profile during adolescence. However, the impact of antibiotic exposure during adolescence on metabolism and adiposity is unclear. Herein, a retrospective analysis of Medicaid claims data was performed, which indicated that tetracycline class antibiotics are commonly prescribed for the systemic treatment of adolescent acne. The purpose of this was to discern the impact of a prolonged tetracycline antibiotic exposure during adolescence on the gut microbiota, liver metabolism, and adiposity. Male C57BL/6T specific pathogen-free mice were administered a tetracycline antibiotic during the pubertal/postpubertal adolescent growth phase. Groups were euthanized at different time points to assess immediate and sustained antibiotic treatment effects. Antibiotic exposure during adolescence caused lasting genera-level shifts in the intestinal bacteriome and persistent dysregulation of metabolic pathways in the liver. Dysregulated hepatic metabolism was linked to sustained disruption of the intestinal farnesoid X receptor-fibroblast growth factor 15 axis, a gut-liver endocrine axis that supports metabolic homeostasis. Antibiotic exposure during adolescence increased subcutaneous, visceral, and marrow adiposity, which intriguingly manifested following antibiotic therapy. This preclinical work highlights that prolonged antibiotic courses for the clinical treatment of adolescent acne may have unintended deleterious effects on liver metabolism and adiposity.

Innate and Peripheral Immune Alterations after Traumatic Brain Injury Are Regulated in a Gut Microbiota-Dependent Manner in Mice.

Traumatic brain injury (TBI) patients are at high risk for disruption of the gut microbiome. Previously, we have demonstrated that broad-spectrum antibiotic exposure after TBI drastically alters the gut microbiota and modulates neuroinflammation, neurogenesis, and long-term fear memory. However, these data did not determine if the impact of antibiotic exposure on the brain's response to injury was mediated directly by antibiotics or indirectly via modulation of the gut microbiota. We designed two different approaches to address this knowledge gap. One was utilizing fecal microbiota transplantation (FMT) from control and antibiotic-treated mice (treated with vancomycin, neomycin, ampicillin, and metronidazole [VNAM]) into germ-free (GF) mice prior to injury, and the other was exposing specific pathogen-free (SPF) mice to a 2-week period of antibiotics prior to injury but discontinuing antibiotics 72 h prior to injury. GF mice receiving FMT from VNAM-treated mice (GF-VNAM) demonstrated reduced gut bacterial alpha diversity and richness compared with GF mice receiving control FMT. At 7 days post-injury, GF-VNAM had increased microglial activation, reduced infiltration of T cells, and decreased neurogenesis. Similarly, SPF mice exposed to antibiotics prior to but not after injury demonstrated similar alterations in neuroinflammation and neurogenesis compared with control mice. These data support our hypothesis implicating the gut microbiota as an important modulator of the neuroinflammatory process and neurogenesis after TBI and provide an exciting new approach for neuroprotective therapeutics for TBI.

Effect of Antibiotic Exposure on Staphylococcus epidermidis Responsible for Catheter-Related Bacteremia.

Coagulase-negative staphylococci (CoNS) and especially Staphylococcus epidermidis are responsible for health care infections, notably in the presence of foreign material (e.g., venous or central-line catheters). Catheter-related bacteremia (CRB) increases health care costs and mortality. The aim of our study was to evaluate the impact of 15 days of antibiotic exposure (ceftobiprole, daptomycin, linezolid and vancomycin) at sub-inhibitory concentration on the resistance, fitness and genome evolution of 36 clinical strains of S. epidermidis responsible for CRB. Resistance was evaluated by antibiogram, the ability to adapt metabolism by the Biofilm Ring test® and the in vivo nematode virulence model. The impact of antibiotic exposure was determined by whole-genome sequencing (WGS) and biofilm formation experiments. We observed that S. epidermidis strains presented a wide variety of virulence potential and biofilm formation. After antibiotic exposure, S. epidermidis strains adapted their fitness with an increase in biofilm formation. Antibiotic exposure also affected genes involved in resistance and was responsible for cross-resistance between vancomycin, daptomycin and ceftobiprole. Our data confirmed that antibiotic exposure modified bacterial pathogenicity and the emergence of resistant bacteria.

The Association of Antibiotic (ATB) exposure prior to immune checkpoint inhibitor (ICI) treatment on early emergency room and hospitalization utilization: A population-based study.

304 Background: ICIs are becoming a common therapeutic option for many solid tumors. Prior studies have shown that ATB exposure can negatively impact ICI outcomes through gut microbiome changes leading to poorer overall survival; however, less is known about the potential impact of ATB exposure on toxicities from ICI. We undertook a population-based retrospective cohort study in patients receiving ICIs to evaluate the impact of ATB exposure on early acute care use, defined as emergency department visit or hospitalization, within 30 days of initiation of ICI therapy. Methods: Administrative data was utilized to identify a cohort of cancer patients > 65 years of age receiving ICIs from June 2012 to October 2018 in Ontario, Canada. We linked databases deterministically to obtain socio-demographic and clinical co-variates, ATB prescription claims and acute care utilization. Patients were censored if they died within 30 days of initiating ICI therapy. The impact of ATB exposure within 60 days prior to starting ICI on early acute care use was evaluated using multi-variable logistic regression models, adjusted for age, gender, rurality, recent hospitalization within 60 days prior to starting ICI and comorbidity score. Results: Among 2737 patients (median age 73 years), 43% received Nivolumab, 41% Pembrolizumab and 13% Ipilimumab, most commonly for lung cancer (53%) or melanoma (34%). Of these patients, 19% had ATB within 60 days prior to ICI with a median ATB treatment duration of 9 days (SD = 13). 647 (25%) patients had an acute care episode within 30 days of starting ICIs; 182 (7%) patients passed away within 30 days without acute care use and were censored from further analyses. Any ATB exposure within 60 days prior to ICI was associated with greater likelihood of acute care use (aOR = 1.34 95% CI [1.07-1.67] p = 0.01). A dose effect was seen based on weeks of ATB exposure within 60 days prior to ICI (aOR = 1.12 per week [1.04-1.21] p = 0.004) and early acute care use. ATB class analysis identified that exposure to penicillins (aOR = 1.54 [1.11-2.15] p = 0.01) and fluoroquinolones (aOR = 1.55 [1.11-2.17] p = 0.01) within 60 days of starting ICIs were associated with a greater likelihood of acute care use, while there was no significant association between cephalosporin exposure and early acute care use (p > 0.05). Conclusions: Exposure to ATBs, specifically fluoroquinolones and penicillins, prior to ICI therapy is associated with greater likelihood of hospitalization or emergency room visits within 30 days after initiation of ICIs, even after adjustment for relevant co-variates including age, comorbidity score and recent hospitalization prior to ICI initiation. Further studies are required to better understand the mechanisms of recent ATB exposure on early acute care use among patients receiving ICIs.

Abstract D057: Impact of antibiotic exposure on the overall survival in patients receiving immune checkpoint inhibitors: Does race matter?

Abstract Background: Immune checkpoint inhibitors (ICIs) are commonly used in the treatment of multiple types of cancer. Several small studies have identified an association between antibiotic exposure and ICI failure. Furthermore, ICI failure has also been associated with decreased tumor mutation burden (TMB), with racial disparities being noted. However, to date there are no studies that have investigated the relationship of potential racial disparities and antibiotic exposure on clinical outcomes in patients receiving ICI therapy. The purpose of our systematic review and meta-analysis is to determine the impact of antibiotic (ATB) exposure on overall survival in patients receiving ICI therapy. An additional goal is to determine if racial disparities are present. Methods: We conducted a systematic review and meta-analysis utilizing PRISMA guidance of all randomized controlled trials, or observational studies that evaluated the impact of antibiotic exposure on ICI efficacy. We excluded studies that did not report overall survival. The primary outcome of this study is overall survival (OS) among ICI patients with antibiotic exposure, compared to patients who received ICI therapy alone. Secondary outcomes include response rate (RR), and progression-free survival (PFS). An a priori subgroup analysis for the primary outcome will be conducted based on race, cancer type, and specific ICI utilized. Results: A total of twelve studies (n=1,868 patients) were included in the final analysis. Among all patients, the most common reasons for ICI use were NSCLC (n=1,180), melanoma (n=316) and RCC (n=238). Among all patients, the most commonly used ICI was anti PD-1/PD-L1 (n=708), nivolumab (n=440) and pembrolizumab (n=63). Of the total patients analyzed, 446 patients (23.9%) received ATB within 6 months surrounding ICI therapy, and 1,422 patients (76.1%) did not receive any ATB surrounding ICI therapy. No studies reported ethnicity in their published results. Patients treated with ATB had lower overall survival compared to those without antibiotic exposure (ATB- 7.5 months; No ATB- 18.9 months). RR (ATB- 14.7%; No ATB 50.9%) and PFS (ATB- 2.4 months; No ATB- 5.1 months) were also shorter. Conclusions: ATB use was associated with less overall survival compared to non-ATB use in patients receiving ICI therapy. Our findings suggest that measures to promote reduced ATB use in patients receiving ICI therapy may help to improve clinical outcomes. No studies in the final analysis reported race and ethnicity. While it is hypothesized that race and ethnicity may play a role in ICI response, further research to evaluate the role of race and ethnicity is needed, which may help clinicians to better identify patients most likely to benefit from ICI therapy. Citation Format: Armani B Hayes, John Allen. Impact of antibiotic exposure on the overall survival in patients receiving immune checkpoint inhibitors: Does race matter? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D057.

Impact of antibiotic exposure on the efficacy of immune checkpoint blockade in MSI-H metastatic CRC.

161 Background: Immunotherapy has improved outcomes for many patients (pts) with advanced cancers found to be microsatellite instability high (MSI-H). However, not all MSI-H pts exhibit the same efficacy from immunotherapy. Previous studies have suggested that concomitant antibiotic use while receiving immunotherapy may result in poorer outcomes. We aimed to evaluate what factors impacted immune checkpoint blockade (ICB) response in pts with MSI-H metastatic colorectal cancer (mCRC) treated at a large academic referral center. Methods: We completed a single-site, retrospective review of 45 pts with MSI-H mCRC that received ICB. Data was collected including patient demographics, tumor and mutational data, ICB agent, length of treatment, and antibiotic use. Both single and multi-course antibiotic use was included from 2 weeks prior until 6 weeks following ICB treatment. Fisher’s exact test was used to evaluate the association of response and covariables. Log rank test was used to compare progression free survival (PFS) between subgroups. Results: A majority of pts were male (n = 25, 56%) and Caucasian (n = 30, 66%) with right sided tumors (n = 26, 62%). Combination Nivolumab and Ipilimumab was used in 7 (16%) with single agent Nivolumab in 10 (22%) and single agent pembrolizumab in 28 (62%). Of the pts in this cohort, 28 (62%) received antibiotics with 11 (39%) receiving a single round of antibiotics and 17 (61%) receiving multiple courses. Those that did not receive antibiotics had a greater response (partial or complete) at first scan while on ICB therapy (75% vs 32%, p = 0.01). No significant difference was noted between class of antibiotic, age, sex, or tumor sidedness. The median 12 month PFS (12-PFS) was also higher in the group that did not require antibiotics but was not statistically significant (82% vs 72%, p = 0.298). Conclusions: This study shows that MSI-H mCRC pts that received antibiotics while on ICB had impaired response rate and a trend towards lower PFS. This suggests alteration of the gut microbiome may impact ICB response warranting a larger, prospective study.

The Impact of Peri-Transplant Antibiotic Exposure on Outcomes in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Background Survival after allogeneic hematopoietic stem cell transplantation (ASCT) has significantly improved with early recognition of sepsis and prompt empiric antibiotic (AB) therapy during periods of neutropenia. However, empiric AB treatment and prophylaxis practices have increased the duration of AB exposure in ASCT patients. Recent studies in adult ASCT patients have shown that perturbations in intestinal microbiome diversity are associated with the development of acute graft vs. host disease (aGVHD). Furthermore, even brief exposure to broad-spectrum ABs in the early phase of transplant is an independent risk factor for 5-year transplant-related mortality (TRM) in adults. However, the impact of AB exposure in the pediatric ASCT population is not understood. Objective To describe the association between AB exposure during the peri-transplant period (day-28 through day+28) and the development of aGVHD and/or TRM within the first year in children undergoing ASCT. Methods This is a retrospective cohort study of children who underwent ASCT at Boston Children's Hospital between 1/1/2012 and 12/31/2016 (n=296). We collected demographics, comorbidities, transplant information, infections, ABs, and clinical outcome data. The primary exposure is overall AB exposure from day -28 through day +28 measured as cumulative days of therapy (DOT) where each individual AB received within a 24-hour window counts as one DOT. This was further divided into cumulative AB exposure within 2-week periods during this time frame. The primary outcome is the development of aGVHD and/or TRM within the first year post-transplant. Results Of the 296 patients included in the analysis, 20.9% developed aGVHD and 9.46% developed TRM at one year post-transplant (overall mortality = 21.6%). The median cumulative AB DOT during the period from day -28 to day +28 of transplant was 63.3 days [IQR 45.5-85.5]. The top five ABs received, in decreasing order of frequency, were: trimethorprim/sulfamethoxazole, piperacillin/tazobactam, ciprofloxacin, meropenem, and gentamicin. In a multivariate model, patients who received > 60 DOT of ABs during the 57 days peri-transplant had higher odds of aGVHD and/or TRM (OR = 2.20, 95% CI: 1.21 to 4.02; P = 0.01). Exposure to more than 14 DOT of any AB in the first 2-weeks post-ASCT (day 0 to day +14) had significant risk of aGVHD and/or TRM in the first year compared to other 2-weeks periods in the 57-days peri-transplant (OR = 2.28, 95% CI: 1.03 to 5.02; P= 0.042). Conclusion Our preliminary analysis indicates that high AB exposure during the peri-transplant period in children may be associated with higher risk of development of aGVHD and/or TRM in the first year post-transplant. This study prompts future investigation of the mechanistic relationship between the gut microbiome and pediatric ASCT outcomes and underscores the importance of antimicrobial stewardship in this population.

The impact of antibiotic exposure in water and zebrafish gut microbiomes: A 16S rRNA gene-based metagenomic analysis

In order to supply human demand for food, the aquaculture industry has been growing fast in the last years, being fish usually cultivated in overcrowded conditions. Hence, to prevent the rapidly disease spreading, antibiotics may be applied to both sick and healthy animals. Due to its broad spectrum, oxytetracycline (OTC) is one of the most used antibiotics in food-production. Yet, although useful to prevent infections, antibiotics may reshape aquatic animals' microbiome, disturbing hosts’ welfare. However, the impact of this exposure to the organism microbiome and its surrounding environment is poorly understood. Then, the objective of this study was to analyze in detail the long-term effect of OTC in both zebrafish gut and water microbiomes. Zebrafish adults were exposed, via water, for two months to three concentrations of OTC (0, 10 and 10000 μg/L). Total DNA was extracted from gut and water samples and the V3–V4 region of the bacterial 16 S rRNA gene was sequenced using Illumina technology. Results of alpha and beta-diversity analyses revealed that long-term exposure to OTC impacted both zebrafish gut and water microbiomes. In water samples, effects were observed even at the lowest (10 μg/L) OTC concentration tested resulting in an increase in Deltaproteobacteria, namely the Myxococcales and Bdellovibrionales orders. On the other hand, effects on zebrafish gut were only observed at the highest concentration with the selection of Alphaproteobacteria and Actinobacteria classes. Although these classes are common in fish gut, the increase of Actinobacteria may represent a health problem since some genera like Gordonia are linked to some human infection disease. Nevertheless, in both gut and water, it was observed a decrease in Gamaproteobacteria, probably due to OTC mode of action. In silico functional metagenomic analysis revealed that OTC exposure selected general detoxification mechanisms. In addition, the abundance of functional genes involved in Quorum Sensing (QS) increased under OTC exposure suggesting that QS may help bacteria to survive OTC stress. Thus, future studies should consider post-exposure scenarios for a deeper analysis of the water and zebrafish gut resistome, since bacteria may react differently after exposure ceased.

Dissemination of multiple carbapenem resistance genes in an in vitro gut model simulating the human colon.

Carbapenemase-producing Enterobacteriaceae (CPE) pose a major global health risk. Mobile genetic elements account for much of the increasing CPE burden. To investigate CPE colonization and the impact of antibiotic exposure on subsequent resistance gene dissemination within the gut microbiota using a model to simulate the human colon. Gut models seeded with CPE-negative human faeces [screened with BioMérieux chromID® CARBA-SMART (Carba-Smart), Cepheid Xpert® Carba-R assay (XCR)] were inoculated with distinct carbapenemase-producing Klebsiella pneumoniae strains (KPC, NDM) and challenged with imipenem or piperacillin/tazobactam then meropenem. Resistant populations were enumerated daily on selective agars (Carba-Smart); CPE genes were confirmed by PCR (XCR, Check-Direct CPE Screen for BD MAX™). CPE gene dissemination was tracked using PacBio long-read sequencing. CPE populations increased during inoculation, plateauing at ∼105 log10 cfu/mL in both models and persisting throughout the experiments (>65 days), with no evidence of CPE 'washout'. After antibiotic administration, there was evidence of interspecies plasmid transfer of blaKPC-2 (111742 bp IncFII/IncR plasmid, 99% identity to pKpQIL-D2) and blaNDM-1 (∼170 kb IncFIB/IncFII plasmid), and CPE populations rose from <0.01% to >45% of the total lactose-fermenting populations in the KPC model. Isolation of a blaNDM-1K. pneumoniae with one chromosomal single-nucleotide variant compared with the inoculated strain indicated clonal expansion within the model. Antibiotic administration exposed a previously undetected K. pneumoniae encoding blaOXA-232 (KPC model). CPE exposure can lead to colonization, clonal expansion and resistance gene transfer within intact human colonic microbiota. Furthermore, under antibiotic selective pressure, new resistant populations emerge, emphasizing the need to control exposure to antimicrobials.

The Impact of Antibiotic Exposure during Prenatal and Infant Period on Childhood Overweight and Obesity: A Meta-Analysis of Population-Based Cohort Studies

Background/Aim: Studies have reported inconsistent results concerning the association of antibiotic exposure during prenatal and infant period with childhood overweight/obesity. We performed a meta-analysis to examine whether antibiotics exposure in early life increases the risk of childhood overweight/obesity. Methods: PubMed, Embase, Medline and Web of Science were searched using different combinations of two groups of keywords: ‘antibiotic(s)’ and ‘overweight/obesity/weight gain/adipogenesis/adiposity/body mass’. Cohort studies that reported the association of antibiotics use during prenatal or infant period (0-2 years) with childhood (3–12 years) overweight/obesity were eligible. Where possible, adjusted risk estimates were pooled using a random effects model; otherwise unadjusted estimates were pooled. Statistical heterogeneity was assessed with I2 statistics; the values of 25%, 50% and 75% were considered to indicate low, medium and high heterogeneity, respectively. We conducted a subgroup analysis to identify the sources of heterogeneity according to the gender of children. Results: In total, eight cohort studies were identified and sex-specific risk estimates were included in the meta-analysis. The overall pooled odds ratio (OR) of childhood overweight/obesity for pregnant women and infant exposed to antibiotics compared with those who are not exposed to antibiotics was 1.19 (95%confidence interval (CI) 1.08, 1.31; I2=85%); In subgroup analysis, the overall pooled OR was 1.52 for boys (1.20, 1.93; I2=22%) and 1.15 for girls (0.90, 1.46; I2=0%). The ORs for childhood overweight and obesity tended to be lower for females compared with males. Conclusions: Our results indicated that antibiotic exposure during prenatal and infant period was moderately associated with childhood overweight and obesity. Gender difference could be explained by the generally lower risk of overweight in girls. Further research might be needed to better understand the mechanism of gender difference on the antibiotics–overweight/obesity relationship. This finding has public health implications, given the antibiotic abuse in many countries.

Antibiotic Use Does Not Appear to Influence Response to Nivolumab.

Microbiota is known to influence response to anticancer immunotherapy. We examined whether antibiotic usage could impact nivolumab efficacy in patients treated for non-small-cell lung cancer (NSCLC). Seventy-four patients with NSCLC were included in this retrospective study. They received nivolumab between 2015 and 2016 (3 mg/kg i.v. q2w). The association between RECIST response and antibiotic usage was determined using Chi-square and Cox proportional hazard model. A total of 17, 21 and 36 patients experienced response, stable disease and progression disease under nivolumab. Only 15 (20.3%) patients were exposed to antibiotic medication in the 3 months before the first nivolumab injection or during treatment. We found a similar response rate for the two populations, without impact of antibiotic exposure (Chi-square test p=0.75). Moreover, we observed no impact of antibiotic medication on progression-free survival under nivolumab (log-rank test, p=0.72). Microbiota modification induced by antibiotics does not appear to affect the efficacy of nivolumab in patients with NSCLC.

The Impact of Antibiotic Exposure and Concentration on Resistance in Bacteria

How many generations are needed for bacteria to gain antibiotic resistance and to what extent does antibiotic concentration make a difference? To address these questions, pure Escherichia coli was cultured on nutrient agar in the presence of low, medium, and high concentrations of amoxicillin. Surviving bacteria were repeatedly cultured for four consecutive generations, and the sensitivity of bacteria was measured within each generation. We measured antibiotic sensitivity by evaluating the diameter of the inhibition zone around antibiotic-saturated discs of all three amoxicillin concentrations. Although exposing bacteria to extremely heavy antibiotic concentrations resulted in greater inhibition zones around antibiotic-saturated discs, there were no major differences in sensitivity relative to the much lower concentrations studied. We also found that bacteria gained significant resistance upon first exposure to the antibiotic. In fact, the reduction in average inhibition zones was much greater in early generations than in late generations. We conclude that E. coli can gain major resistance upon surviving early exposure to amoxicillin, which suggests that antibiotic courses of medication should be prescribed to completely clear the body of bacterial infection upon first antibiotic exposure.

Impact of antibiotic exposure on the risk of colorectal cancer.

Gut microbiota has been postulated to serve as a significant promoter of CRC formation, and colonic dysbiosis was previously reported in CRC tissue. Our aim was to evaluate the association between the type and cumulative duration of antibiotic exposure and CRC risk. We conducted a nested case-control study using a large population-based database from the UK. Cases were defined as those with any medical code of CRC. Subjects with known familial CRC syndromes or IBD were excluded from the study. For every case, four eligible controls matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy before index date. Adjusted ORs and 95%CIs were estimated using conditional logistic regression analysis. A total of 20,990 cases and 82,054 controls were identified. The adjusted OR for CRC among subjects first exposed to penicillins >10 years prior to index date was 1.11 (95%CI 1.02-1.20). The risk increased significantly with the number of penicillin exposures up to 1.20 (95%CI 1.11-1.31) for >10 courses. The risk also increased with the average number of penicillin treatments per-year (exposure intensity) with an OR of 1.04 (95%CI 1.01-1.08) per one additional treatment per year. Exposure to anti-viral or anti-fungal therapy was not associated with CRC risk. Past exposure to multiple courses of penicillins is related to a modest elevation in CRC risk.

Impact of antibiotic exposure on occurrence of nosocomial carbapenem-resistant Acinetobacter baumannii infection: a case control study.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is one of the most important healthcare associated diseases worldwide. Although antibiotic use is recognized as a risk factor for CRAB infection, the impact of antibiotic class and length of use on CRAB infection is still unclear. A case-control study was conducted in adult intensive care units and general wards of Songklanagarind Hospital, a tertiary-care hospital in southern Thailand, to investigate the effect of different antibiotic exposure and the duration of use on the risk of developing CRAB infection. Cases were defined as patients with carbapenem-susceptible A. baumannii (CSAB) or CRAB infection. Controls were randomly selected from patients and matched 1:1 with cases using ward and date of admission. Multinomial logistic regression was used to compute relative risk ratios (RRR) and 95% confidence intervals (CI) for CRAB infection. Of 197 cases with A. baumannii infection, there were 139 with CRAB infection and 58 with CSAB infection. Compared to the control group, use of fluoroquinolones, broad-spectrum cephalosporins and carbapenems for more than three days increased the risk of CRAB infection with RRR (95% CI) of 81.2 (38.1-862.7), 31.3 (9.9-98.7) and 112.1 (7.1-1770.6), respectively. The RRR (95% CI) for one to three day treatment of fluoroquinolones, broad-spectrum cephalosporins and carbapenems were 5.4 (0.8-38.7), 6.2 (0.1-353.2) and 63.3 (15.6-256.9), respectively. Long-term use of certain antibiotics and even short term use of carbapenems increased the risk of CRAB infection. In this setting, use of these antibiotics, especially carbapenems, should be limited to reduce CRAB infection.

Impact of antibiotic exposure on the risk of colorectal cancer.

1599 Background: Previous reports revealed colonic dysbiosis in tumor tissue from cases with colorectal cancer (CRC) showing lower levels of microbial diversity and an enrichment of certain bacteri...

Impact de l'exposition des populations sur le risque de résistance bactérienne

Exposure of populations to antibiotics is a condition for the emergence and the diffusion of bacteria resistant to antibiotics. Analysis of epidemiological causality between antibiotic exposure and expansion of antibiotic resistance in human pathogens requires the study of the basis for the emergence and the subsequent epidemic spread of the strains. Emergence of antibiotic resistance under the selective pressure of antibiotics is unavoidable. However, the rapidity of the emergence depends on several parameters including the biochemical mechanism and the genetic support of the resistance and on the couple bacteria/antibiotic considered. Several of these parameters may be studied and measured in vitro. In vivo, relationship between antibiotic exposure and risk for infection or colonisation by pneumococci resistant to beta-lactams or macrolides and methicillin-resistant staphylococci are among the best studied models. In particular for pneumococci, quantitative relationship between antibiotic consumption and resistance, including geographical correlations have been shown but do not allow to establish any causality relationship. Overall, there is no doubt on the question of the impact of antibiotic exposure and the risk of antibiotic resistance. However, the quantification of the risks remains to be accurately studied.