Estimating the cost of antibiotic use on future collateral resistance: a retrospective comparison of cefuroxime versus cefazolin and amoxicillin/clavulanate

Background: Quantitative estimates of collateral resistance induced by antibiotic use are scarce. This study compared the effects of treatment with amoxicillin/clavulanate or cefazolin, compared to cefuroxime, on future resistance to ceftazidime among hospitalized patients. Methods: A retrospective analysis of patients with positive bacterial cultures hospitalized in an Israeli hospital during 2016-2019 was conducted. Patients were restricted to those treated with either amoxicillin/clavulanate, cefazolin, or cefuroxime and re-hospitalized with a positive bacterial culture during the following year. A 1:1 matching was performed for each patient in the amoxicillin/clavulanate and cefazolin groups, to a single patient from the cefuroxime group, yielding 185:185 and 298:298 matched patients. Logistic regression and g-formula (standardization) were used to estimate the odds ratio (OR), risk difference (RD), and number needed to harm (NNH). Results: Cefuroxime induced significantly higher resistance to ceftazidime than amoxicillin/clavulanate or cefazolin: the marginal OR was 1.76) 95%CI 1.16-2.83) compared to amoxicillin/clavulanate, and 1.98 (95%CI 1.41- 2.8) compared to cefazolin; The RD was 0.118 (95%CI 0.031-0.215) compared to amoxicillin/clavulanate, and 0.131 (95%CI 0.058-0.197) compared to cefazolin. We also estimated the NNH: replacing amoxicillin/clavulanate or cefazolin with cefuroxime would yield ceftazidime-resistance in one more patient for every 8.5 (95% CI 4.66-32.14) or 7.6 (95% CI 5.1-17.3) patients re-hospitalized in the following year. Conclusions: Our results indicate that treatment with amoxicillin/clavulanate or cefazolin is preferable to cefuroxime, in terms of future collateral resistance. The results presented here are a first step towards quantitative estimations of the ecological damage caused by different antibiotics.

Post-Ureteroscopy Infections Are Linked to Pre-Operative Stent Dwell Time over Two Months: Outcomes of Three European Endourology Centres

Background: The aim of this study is to investigate outcomes of pre-operative stent dwell time on infectious complications following ureteroscopy and stone treatment to identify a time cut-off. Material and Methods: Three tertiary referral centres in Europe retrospectively collected outcomes of ureteroscopy and laser fragmentation (URSL) for all patients with pre-operative indwelling ureteric stents over a period of up to 5 years. Data was collected on patient details, stone demographics, stent dwell time, complications and stone free rate (SFR). Matching for age, sex, operative time, stone size and post-operative stent insertion. To examine for a threshold effect, monthly cut-offs were used to compare post-ureteroscopic febrile UTIs. Binomial logistic regression was used (SPSS v.24) with a significance level set at 0.0036. The risk ratio (RR) with a 95% confidence interval (CI) and the number needed to harm (NNH) are reported. Results: There were 467 patients with a pre-operative stent for analysis. These patients (n = 315) were matched to non-stented controls after excluding 152 patients to achieve adequate matching. There was a significant difference in rates of post-ureteroscopic febrile UTI between stented vs non-stented patients (RR = 2.67, 95% CI: 1.10–6.48, p = 0.03). On adjustment, a dwell time of more than two months was associated with an increased risk of post-ureteroscopic febrile UTI (RR = 3.94, 95% CI: 1.30–12.01, p = 0.02), this increased risk rose with longer dwell time. At stent time longer than four months was associated with a significantly increased risk of post-ureteroscopic febrile UTI (5% vs. 15%, RR = 3.09, 95% CI: 1.56–6.10, p = 0.001), with the number needed to harm at 10. Conclusions: Overall infectious complication rates from URSL are low. The risk of post-operative UTI after four months of dwell time is nearly tripled compared to less than four months.

Applicability of the Chronic Liver Failure-Consortium score in patients with cirrhosis and bacterial infections: a single-clinic experience

Background. The frequency and characteristics of acute-on-chronic liver failure (ACLF) are reported in numerous articles from different countries. The aim of the study was to assess the cirrhosis decompensation in patients with bacterial infections based on the Chronic Liver Failure-Consortium (CLIF-C) score in one of the city clinics in Belarus. Materials and methods. The patients underwent laboratory and instrumental studies during the hospitalization. The assessment of the syndrome of acute-on-chronic liver failure was performed using the CLIF-C score. Bacterial infections were diagnosed on the basis of standard criteria. Results. The study included 151 cirrhotic patients, 87 males and 64 females. Median age was 55 years (Q1 = 43; Q3 = 61). Cirrhosis was predominantly due to alcohol addiction — 83 patients (55 %). ACLF was diagnosed in 44 of 151 patients with cirrhosis (29.1 %; 95% confidence interval (CI) 22.0–37.1). Bacterial infections were detected in 67 people (44.4 %; 95% CI 36.3–52.7). Most often patients had liver failure that was detected by an increase in serum bilirubin level. Among individuals with upper gastrointestinal bleedings, number needed to harm for developing ACLF was 3.3 (95% CI 2.2–4.4). The risk of developing ACLF grade 2 and 3 in cirrhotic patients with infections was 8.2, with 95% CI 1.0–69.6 (number needed to harm was 12.9; 95% CI 10.7–15.0). Bacterial infections increase the risk of acute decompensation in patients with cirrhosis (odds ratio = 2.0, p = 0.048). Conclusions. The CLIF-C score is quite applicable in our cohort of patients with cirrhosis.

Cardiovascular risks associated with use of non-steroidal anti-inflammatory drugs in patients with non-obstructive coronary artery disease

Aim To examine whether non-aspirin non-steroidal anti-inflammatory drugs (NSAID) use is associated with increased cardiovascular risks in patients with non-obstructive coronary artery disease (CAD). Methods and results Using Danish medical registries, we conducted a population-based cohort study in Western Denmark during 2008–2017. We identified all patients undergoing first-time coronary computed tomography angiography (CCTA) due to suspected CAD (n = 35,399), with results showing no (n = 28,581) or non-obstructive CAD (n = 6,818). Multivariate Cox regression was used to compute hazard ratios of major adverse cardiac events (MACE) including incident myocardial infarction, coronary intervention, or death. The rate of MACE increased by 33% for any NSAID use compared with non-use (hazard ratio 1.33, 95% confidence interval (CI) 1.06 to 1.68) in patients with no CAD and by 48% (1.48, 95% CI 1.06 to 2.07) in patients with non-obstructive CAD. Rate difference of MACE, per 100 person-years, was 0.38 (95% CI 0.08 to 0.67) in patients with no CAD (number needed to harm 267) and 1.08 (95% CI 0.06 to 2.11) in patients with non-obstructive CAD (number needed to harm 92). Current use of older COX-2 inhibitors was associated with the highest hazard ratio in patients with non-obstructive CAD, both when ascertained as pre-CCTA use (2.9-fold increase) and from time-varying use (1.8-fold increase). Conclusion NSAID use in patients with CCTA-confirmed no and non-obstructive CAD was associated with an increased cardiovascular risk compared with non-use. The absolute risk differences and numbers needed to harm were considered clinically relevant, particularly in patients with non-obstructive CAD.

Excess Mortality in Aspirin and Dipyrone (Metamizole) Co‐Medicated in Patients With Cardiovascular Disease: A Nationwide Study

Background Pain is a major issue in our aging society. Dipyrone (metamizole) is one of the most frequently used analgesics. Additionally, it has been shown to impair pharmacodynamic response to aspirin as measured by platelet function tests. However, it is not known how this laboratory effect translates to clinical outcome. Methods and Results We conducted a nationwide analysis of a health insurance database in Germany comprising 9.2 million patients. All patients with a cardiovascular event in 2014 and subsequent secondary prevention with aspirin were followed up for 36 months. Inverse probability of treatment weighting analysis was conducted to investigate the rate of mortality, myocardial infarction, and stroke/transient ischemic attack between patients on aspirin‐dipyrone co‐medication compared with aspirin‐alone medication. Permanent aspirin‐alone medication was given to 26,200 patients, and 5946 patients received aspirin–dipyrone co‐medication. In the inverse probability of treatment weighted sample, excess mortality in aspirin–dipyrone co‐medicated patients was observed (15.6% in aspirin‐only group versus 24.4% in the co‐medicated group, hazard ratio [HR], 1.66 [95% CI, 1.56–1.76], P <0.0001). Myocardial infarction and stroke/transient ischemic attack were increased as well (myocardial infarction: 1370 [5.2%] versus 355 [5.9%] in aspirin‐only and co‐medicated groups, respectively; HR, 1.18 [95% CI, 1.05–1.32]; P =0.0066, relative risk [RR], 1.14; number needed to harm, 140. Stroke/transient ischemic attack, 1901 [7.3%] versus 506 [8.5%] in aspirin‐only and co‐medicated groups, respectively; HR, 1.22 [95% CI, 1.11–1.35]; P <0.0001, RR, 1.17, number needed to harm, 82). Conclusions In this observational, nationwide analysis, aspirin and dipyrone co‐medication was associated with excess mortality. This was in part driven by ischemic events (myocardial infarction and stroke), which occurred more frequently in co‐medicated patients as well. Hence, dipyrone should be used with caution in aspirin‐treated patients for secondary prevention.

SP10.1.9 Delay to Elective Colorectal Cancer Surgery and its Potential Implications: A Systematic Review and Meta-analysis

Aim The ongoing Covid-19 pandemic has interrupted surgical treatment of colorectal cancer (CRC). This systematic review will assess literature concerning the risk of delay of elective surgery for CRC patients, focusing on overall survival (OS) and disease-free survival (DFS). Methods A systematic review was performed as per PRISMA guidelines (PROSPERO ID: CRD42020189158). Medline, EMBASE and Scopus were searched. Patients over 18 with a diagnosis of colon or rectal cancer who received elective surgery as primary treatment were included. Delay was defined as the period between CRC diagnosis and day of surgery. Metanalyses of the outcomes OS and DFS were conducted. Forest plots, funnel plots, tests of heterogeneity, and estimated Number Needed to Harm (NNHs) were produced. Results Of 3753 articles identified, seven met the inclusion criteria. Encompassing 314560 patients, three of the seven studies showed a delay to elective resection was associated with poorer OS or DFS. OS was assessed at a one-month delay, the HR for six datasets was 1.13 (95%CI 1.02-1.26, p = 0.020) and at three months the HR for three datasets was 1.57 (95%CI 1.16-2.12, p = 0.004). Estimated NNHs for a delay at one month and three months were 35 and 10 respectively. Delay was non-significantly negatively associated with DFS on metanalysis. Conclusions This review recommends elective surgery for CRC patients is not postponed longer than four weeks, as evidence suggests extended delays from diagnosis are associated with poorer outcomes. Focused research is essential so patient groups can be prioritized based on risk-factors for future pandemics.

732 Delay to Elective Colorectal Cancer Surgery and its Potential Implications During the Covid-19 Pandemic: A Systematic Review and Metanalysis

Aim The ongoing Covid-19 pandemic has interrupted the surgical treatment of colorectal cancer (CRC). This systematic review will assess literature concerning the risk of delay of elective surgery for CRC patients, focusing on overall survival (OS) and disease-free survival (DFS). Method A systematic review was performed as per PRISMA guidelines (PROSPERO ID: CRD42020189158). Medline, EMBASE and Scopus were searched. Delay to elective surgery was defined as the period between CRC diagnosis and the day of surgery. Metanalyses of the outcome’s OS and DFS were conducted. Forest plots, funnel plots, and tests of heterogeneity were produced. An estimated Number Needed to Harm (NNH) was calculated for statistically significant pooled Hazard Ratios (HRs). Results Of 3753 articles identified, seven met the inclusion criteria. Encompassing 314560 patients, three of the seven studies showed that a delay to elective resection is associated with poorer OS or DFS. OS was assessed at a one-month delay, the HR for six datasets was 1.13 (95%CI 1.02-1.26, p = 0.020) and at three months the pooled HR for three datasets was 1.57 (95%CI 1.16-2.12, p = 0.004). Estimated NNHs for a delay at one month and three months were 35 and 10 respectively. Delay was non-significantly negatively associated with DFS on meta-analysis. Conclusions This review recommends that elective surgery for CRC patients is not postponed, as evidence suggests delays from diagnosis are associated with poorer outcomes. Focused research is essential so that patient groups can be prioritized based on risk factors for future pandemics.

Indirect Meta-Analysis of Brexpiprazole Versus Aripiprazole in the Acute Treatment of Schizophrenia

Background: Brexpiprazole and aripiprazole are atypical antipsychotics that act as partial agonists at the dopamine D2 receptor. No head-to-head trial comparing brexpiprazole and aripiprazole in the treatment of schizophrenia is available. Here, we carry out a systematic review and comparison of the efficacy and safety of brexpiprazole and aripiprazole in schizophrenia treatment.Methods: We employed an indirect meta-analysis to determine effect sizes from randomised placebo-controlled trials with brexpiprazole and aripiprazole in the acute treatment of schizophrenia. We compared responder rates, incidences of adverse events and serious adverse events, the number needed to treat (NNT) for response, number needed to harm (NNH) for adverse events or treatment discontinuation, and likelihood to be helped or harmed (LHH) as efficacy and safety indices of the two drugs. Results: Five studies for each drug were included in the analysis. Similar risk differences vs. placebo were observed for responder rates under brexpiprazole (10.2%, p = 0.0015) and aripiprazole (10.3%, p = 0.0003). Higher incidences of adverse events and serious adverse events were seen under aripiprazole compared with brexpiprazole, however, the risk differences were not statistically significant. The NNT for response was 11 for both substances. For brexpiprazole compared with placebo, we did not find an increase of adverse events (NNH = 27, not significant), however, we found an increased number of adverse events for aripiprazole versus placebo (NNH = 17, p < 0.05). For both drugs, benefits were encountered more often than harms, with an LHH for any adverse event of 2.41 for brexpiprazole and 1.56 for aripiprazole, respectively. Conclusions: The likelihood to be helped rather than harmed was greater with brexpiprazole compared to aripiprazole for the total rate of adverse events (ratio of brexpiprazole LHH/aripiprazole LHH = 1.54).

Proton pump inhibitors and risk of gastric cancer: population-based cohort study

ObjectiveTo determine whether new users of proton pump inhibitors (PPIs) are at an increased risk of gastric cancer compared with new users of histamine-2 receptor antagonists (H2RAs).DesignUsing the UK Clinical Practice Research Datalink, we conducted a population-based cohort study using a new-user active comparator design. From 1 January 1990 to 30 April 2018, we identified 973 281 new users of PPIs and 193 306 new users of H2RAs. Cox proportional hazards models were fit to estimate HRs and 95% CIs of gastric cancer, and the number needed to harm was estimated using the Kaplan-Meier method. The models were weighted using standardised mortality ratio weights using calendar time-specific propensity scores. Secondary analyses assessed duration and dose–response associations.ResultsAfter a median follow-up of 5.0 years, the use of PPIs was associated with a 45% increased risk of gastric cancer compared with the use of H2RAs (HR 1.45, 95% CI 1.06 to 1.98). The number needed to harm was 2121 and 1191 for five and 10 years after treatment initiation, respectively. The HRs increased with cumulative duration, cumulative omeprazole equivalents and time since treatment initiation. The results were consistent across several sensitivity analyses.ConclusionThe findings of this large population-based cohort study indicate that the use of PPIs is associated with an increased risk of gastric cancer compared with the use of H2RAs, although the absolute risk remains low.