Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial.

Importance: The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear. Objective: To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone. Design, Setting, and Participants: Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019. Intervention: Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147). Main Outcome and Measures: The primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days. Results: Among 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, -4.7% [95% CI, -14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, -11.8% [95% CI, -23.0% to -0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group). Conclusion and Relevance: In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis. Trial Registration: ClinicalTrials.gov Identifier: NCT02281929.

Effect of Intraoperative Single-Shot Application of Vancomycin in Liver Transplant Recipients on Postoperative Infections With Enterococcus faecium and Enterococcus faecalis.

OBJECTIVES: Infections are major causes of morbidity and mortality in the early postoperative period after liver transplant. We observed a high rate of enterococcal infections at our center. Therefore, we added an intraoperative single shot of vancomycin to the standard regimen of meropenem given over 5 days. The aim of this study was to determine the prevalence of both Enterococcus faecium and Enterococcus faecalis infections during the first 28 days after surgery depending on the type of antibiotic prophylaxis and their implications on mortality and morbidity. MATERIALS AND METHODS: Our retrospective cohort analysis included 179 patients: 93 patients received meropenem only and 86 patients were treated with meropenem plus vancomycin. RESULTS: During the first 28 days after transplant, microbiological tests showed that 51 patients (28.5%) were positive for Enterococcus faecium and 25 patients (14.0%) were positive for Enterococcus faecalis. Enterococcus faecium infections appeared significantly more often in patients without vancomycin (P = .013). In the second week after transplant, there was a significant reduction in Enterococcus faecium infections in the meropenem plus vancomycin group (P = .015). Enterococcus faecalis infections occurred more often in the patients receiving meropenem alone, but results were not statistically significant (P = .194). There was a trend toward more frequent renal replacement therapy in the meropenem plus vancomycin group. We found no differences between the groups regarding survival after 1 and 2 years, length of hospital stay, or duration in the intensive care unit. Overall 1-year survival was 78.8% (141/179 patients). CONCLUSIONS: Although postoperative Enterococcus species infections can be reduced after liver transplant by adding vancomycin to the intraoperative antibiotic regimen, it does not improve the long-term outcomes.

Prevention of severe infectious complications after colorectal surgery using preoperative orally administered antibiotic prophylaxis (PreCaution): study protocol for a randomized controlled trial.

BACKGROUND: Colorectal surgery is frequently complicated by surgical site infections (SSIs). The most important consequences of SSIs are prolonged hospitalization, an increased risk of surgical reintervention and an increase in mortality. Perioperative intravenously administered antibiotic prophylaxis is the standard of care to reduce the risk of SSIs. In the last few decades, preoperative orally administered antibiotics have been suggested as additional prophylaxis to further reduce the risk of infection, but are currently not part of routine practice in most hospitals. The objective of this study is to evaluate the efficacy of a preoperative orally administered antibiotic prophylaxis (Pre-OP) in addition to intravenously administered perioperative antibiotic prophylaxis to reduce the incidence of deep SSIs and/or mortality after elective colorectal surgery. METHODS/DESIGN: The PreCaution trial is designed as a multicenter, double-blind, randomized, placebo-controlled clinical trial that will be carried out in The Netherlands. Adult patients who are scheduled for elective colorectal surgery are eligible to participate. In total, 966 patients will be randomized to receive the study medication. This will either be Pre-OP, a solution that consists of tobramycin and colistin sulphate, or a placebo solution. The study medication will be administered four times daily during the 3 days prior to surgery. Perioperative intravenously administered antibiotic prophylaxis will be administered to all patients in accordance with national infection control guidelines. The primary endpoint of the study is the cumulative incidence of deep SSIs and/or mortality within 30 days after surgery. Secondary endpoints include both infectious and non-infectious complications of colorectal surgery, and will be evaluated 30 days and/or 6 months after surgery. DISCUSSION: To date, conclusive evidence on the added value of preoperative orally administered antibiotic prophylaxis in colorectal surgery is lacking. The PreCaution trial should determine the effects of orally administered antibiotics in preventing infectious complications in elective colorectal surgery. TRIAL REGISTRATION: Netherlands Trial Register, ID: NTR6113 . Registered on 11 October 2016; EudraCT 2015-005736-17.

Preoperative surveillance rectal swab is associated with an increased risk of infectious complications in pancreaticoduodenectomy and directs antimicrobial prophylaxis: an antibiotic stewardship strategy?

BACKGROUND: Despite improvements in the perioperative care, the morbidity rate after pancreaticoduodenectomy (PD) is still higher than 50%. The aim of this study was twofold: first, to assess the correlation between preoperative rectal swab (RS) and intraoperative bile cultures; to examine the impact of RS isolates on postoperative course after PD. METHODS: An observational study was conducted analyzing all consecutive PD performed from January 2015 to July 2016. Based on the positivity/negativity of preoperative RS for multi-drug resistant bacteria, two groups of patients were identified (RS+ vs. RS-) and then compared. RESULTS: Three hundred thirty-eight patients were considered for the analysis. RS culture showed a perfect correlation (species and phenotypic antibiotic susceptibility pattern) with bile culture in 157 patients (86.7%). Fifty patients (14.8%) had a RS+. Preoperative biliary drain (PBD) was the single independent preoperative risk factor associated to RS+ (p = 0.021, OR = 2.6, 95% CI = 1.5-11.7). Infective complications (IC) and mortality were independently correlated to RS+ (p = 0.013, OR = 2.9, 95% CI = 1.3-6.7; p = 0.009 OR = 3.4, 95% CI = 1.8-14.9, respectively). CONCLUSIONS: Preoperative surveillance RS-culture's positivity correlates to biliary colonization that occurs after PBD. IC and mortality after PD are associated with RS+. Preoperative RS can direct antibiotic prophylaxis to reduce morbidity and mortality after PD.

Temporary Intra-Operative Portocaval Shunts, Post-Operative Infections, and Mid-Term Survival after Cava-Sparing Liver Transplantation.

BACKGROUND: Temporary intra-operative portocaval shunts (TPCS) are believed to improve outcomes after cava-sparing liver transplantation. We hypothesize that decompression of the portal venous system via a TPCS reduces gut congestion, thereby decreasing bacterial translocation. Thus, we sought to clarify whether transplantation with a TPCS alters rates of post-operative infections and survival. PATIENTS AND METHODS: Patients undergoing liver transplantation (n = 189) were stratified by usage of a TPCS and the type of intra-operative antibiotic prophylaxis. Rates of post-operative infections were analyzed using the χ2 test. The log-rank test was used to compare 120-d survival. RESULTS: The analysis of patients transplanted with a TPCS and meropenem revealed increased infection rates with gut-specific pathogens (Escherichia coli, Escherichia faecalis, Escherichia faecium; p = 0.04) and equal 120-d survival in comparison with patients transplanted without a TPCS. When vancomycin was added to meropenem infection rates did not differ and patients transplanted with a TPCS had better survival in comparison with patients transplanted without a TPCS (p = 0.02). Within the TPCS group, the administration of meropenem and vancomycin was associated with improved survival in comparison with meropenem only (p = 0.03). CONCLUSION: Survival of patients may be improved by usage of a TPCS when gut-specific pathogens are covered by intra-operative antibiotic prophylaxis.

Bloodstream infections caused by Klebsiella pneumoniae in onco-hematological patients: clinical impact of carbapenem resistance in a multicentre prospective survey.

The aim of this study was to identify risk factors for mortality in patients suffering from hematological malignancies (HMs) with bloodstream infections (BSIs) caused by Klebsiella pneumoniae (KP). We conducted a prospective cohort study on KP BSI in 13 Italian hematological units participating in the HEMABIS registry-SEIFEM group. The outcome measured was death within 21 days of BSI onset. Survivor and non-survivor subgroups were compared and Cox regression analysis was conducted to identify independent predictors of mortality. A total of 278 episodes of KP BSI were included in the study between January 2010 and June 2014. We found that 161 (57.9%) KP isolates were carbapenem resistant (CRKP). The overall 21-day mortality rate was 36.3%. It was significantly higher for patients with CRKP BSI (84/161, 52.2%) than for those with BSI caused by carbapenem susceptible KP (CSKP) (17/117, 14.5%; P < 0.001). Septic shock (HR 3.86), acute respiratory failure (HR 2.32), inadequate initial antimicrobial therapy (HR 1.87) and carbapenem resistance by KP isolates (HR 1.85) were independently associated with mortality. A subanalysis was conducted in only 149 patients with CRKP BSI who had received ≥48 hr of adequate antibiotic therapy, and combination therapy was independently associated with survival (HR 0.32). Our study shows that in recent years carbapenem resistance has dramatically increased in HM patients with KP BSI in Italy and is associated with a worse outcome. The optimal management of such infections and the definition of new empirical/targeted antimicrobial strategies in HM patients can still be considered unmet clinical needs. Am. J. Hematol. 91:1076-1081, 2016. © 2016 Wiley Periodicals, Inc.

Preventive Ceftriaxone in Patients with Stroke Treated with Intravenous Thrombolysis: Post Hoc Analysis of the Preventive Antibiotics in Stroke Study.

BACKGROUND: The Preventive Antibiotics in Stroke Study (PASS), a randomized open-label masked endpoint trial, showed that preventive ceftriaxone did not improve functional outcome at 3 months in patients with acute stroke (adjusted common OR 0.95; 95% CI 0.82-1.09). Post-hoc analyses showed that among patients who received intravenous thrombolysis (IVT), patients who received ceftriaxone had a significantly better outcome as compared with the control group. This study aimed to gain more insight into the characteristics of these patients. METHODS: In PASS, 2,550 patients were randomly assigned to preventive antibiotic treatment with ceftriaxone or standard care. In current post-hoc analysis, 836 patients who received IVT were included. Primary outcome included functional status on the modified Rankin Scale, analyzed with adjusted ordinal regression. Secondary outcomes included infection rate and symptomatic intracerebral hemorrhage (sICH) rate. RESULTS: For all patients in PASS, the p value for the interaction between IVT and preventive ceftriaxone regarding functional outcome was 0.03. Of the 836 IVT-treated patients, 437 were administered ceftriaxone and 399 were allocated to the control group. Baseline characteristics were similar. In the IVT subgroup, preventive ceftriaxone was associated with a significant reduction in unfavorable outcome (adjusted common OR 0.77; 95% CI 0.61-0.99; p = 0.04). Mortality at 3 months was similar (OR 0.75; 95% CI 0.48-1.18). Preventive ceftriaxone was associated with a reduction in infections (OR 0.43; 95% CI 0.28-0.66), and a trend towards an increased risk for sICH (OR 3.09; 95% CI 0.85-11.31). Timing of ceftriaxone administration did not influence the outcome (aOR 1.00; 95% CI 0.98-1.03; p = 0.85). CONCLUSIONS: According to the post-hoc analysis of PASS, preventive ceftriaxone may improve the functional outcome in IVT-treated patients with acute stroke, despite a trend towards an increased rate of post-IVT-sICH.

How Best to Manage the Spinal Epidural Abscess? A Current Systematic Review.

BACKGROUND: A spinal epidural abscess is a medical emergency. Despite urgent surgical intervention and adjuvant antibiotic therapy, neurologic prognosis remains variable and guarded. The optimal approach to managing this condition is debated with substantial variability in clinical practice, dependent on patient demographic and pretreatment neurologic status as well as radiologic appearance. METHODS: A systematic search in MEDLINE and similar databases was conducted for literature published from 1990 to 2015 using the search term "spinal epidural abscess", limiting the search results to human studies published in the English language. Case series that consisted of fewer than 10 patients were excluded. The evidence strength was graded according to the Grades of Recommendation Assessment, Development, and Evaluation criteria. RESULTS: The search yielded 1843 patients from 34 retrospective case series. Ten studies compared surgical and medical management, with no significant difference in patients with good outcome (odds ratio, 0.65; P = 0.11) or neurologic improvement (odds ratio, 1.11; P = 0.69). However, failure rates after initial medical management requiring surgical intervention ranged from 10% to 50%. Three of 4 studies evaluating timing of surgery reported large effect sizes for neurologic outcome if early surgery was performed (P < 0.01). Other prognostic factors from a neurologic perspective included admission neurologic status, patient age, and diabetes mellitus. CONCLUSIONS: Surgery with adjuvant antibiotics remains the optimal treatment for the neurologically symptomatic patient with spinal epidural abscess. If antibiotic therapy alone is considered for the neurologically intact patient, we recommend interdisciplinary medical and surgical consultations with an in-depth dialogue on the potential for failure in isolated medical management and the recommendation for close neurologic monitoring.

Splenectomy results from an 18-year single centre experience.

INTRODUCTION: Splenectomy is performed both as an emergency procedure following trauma and electively when indicated for haematological disease. Postsplenectomy patients receive immunotherapy vaccines and continuous antibiotic prophylaxis. Despite well documented concerns regarding complications and overwhelming postsplenectomy infection (OPSI) risk, there appears to be only a small amount of consistent data on long-term outcomes. The authors therefore present their postsplenectomy patient outcomes over an 18-year follow-up period. METHODS: One hundred and five postsplenectomy patients operated on between 1991 and 2011 were identified from pathology codes and their case notes were reviewed. Eighty-eight patients (83.8%) were followed up for at least five years or until death. RESULTS: Of the 105 splenectomy patients (58 were male), the median age was 54 years (range: 10-87 years) and the median survival was 80 months. Operative morbidity and mortality rates were 21.0% (n=22) and 8.6% (n=9) respectively. Thirty-seven patients (27 males) underwent an emergency splenectomy with a median age, operative morbidity and operative mortality of 51 years, 13.5% and 21.6% (n=8) respectively. This compares with 68 patients (35 males) undergoing an elective splenectomy with the same parameters respectively of 55 years, 25.0% and 1.5% (n=1). Excluding operative deaths, multivariate analysis revealed age (p=0.002) as the only significant and independent prognostic indicator. Immunotherapy and antibiotic prophylaxis rates for the emergency cohort were 92.6% and 88.9% respectively, compared with 90.2% and 93.4% for the elective cohort. At follow-up, no patients were readmitted with OPSI. CONCLUSIONS: Over an 18-year period and a diverse indication for splenectomy, we have identified no evidence of OPSI. However, a significant operative mortality was associated with traumatic splenic rupture.

Estudo descritivo sobre a antibioticoprofilaxia na rupturaprematura pré-termo de membranas / Perinatal results of antibioticprophyxalis with erythromycin in preterm premature rupture of the membranes

Objetivo: avaliar os resultados perinatais do uso profilático de estearato de eritromicina nas pacientesinternadas na unidade de gestação alto risco da Maternidade Carmela Dutra (MCD), Florianópolis–SC, com diagnóstico de ruptura prematura pré-termo de membranas (RPM). Métodos: estudo descritivo com análise de todas as pacientes internadas com o diagnóstico de RPM e com idade gestacional entre 20 semanas e 33 semanas e cinco dias. Foram excluídas da pesquisa gestantes com históriade hipersensibilidade à eritromicina, com sinais clínicos e/ou laboratoriais de corioamnionite, que estavam emtrabalho de parto ou que faziam uso de antibióticos no momento da internação. A amostra obtida entre 1º de abril de 2007 e 15 de maio de 2008 foi de 22 pacientes. Resultados e conclusões: o tempo médio de latência foi de 12 dias. Não houve casos confirmados decorioamnionite. Uma (4,54%) gestante desenvolveu quadro de endometrite puerperal. Não houve óbitos maternos. Dois (9,09%) recém-nascidos desenvolveram sepse. A taxa de óbito neonatal foi de 13,63%. Apesarda nossa pequena casuística, o uso de eritromicina nas pacientes com RPM parece estar associado a umadiminuição na taxa de corioamnionite.

Objective: The purposes of this study were to evaluate perinatal results of the prophylactic use of erythromycin to patients admitted in the high-riskgestation unit at Carmela Dutra Maternity Hospital, Florianópolis – SC with preterm premature rupture ofmembranes (PROM). Methods: We performed a descriptive analysis ofall patients with PROM and gestational age between 20 weeks and 33 weeks plus 5 days. Patients with erythromycin allergy, with chorioamnionitis signs orwomen who already being prescribed antibiotics were excluded from this study. Enrolment was from April 1,2007, until May 15, 2008. Twenty-two women had been followed up in this study. Results and Conclusions: The medium latency period was 12 days. There was not confirmed chorioamnionitis case. The occurrence of endometritis was 4,54%. There was not maternal death. The occurrence of neonatal sepsis was 9,09% and theoccurrence of neonatal deaths was 13,63%. Despite our small casuistry, the prophylactic use of erythromycinseems to reduce the chorioamnionitis rate.

Prophylactic antibiotics to reduce morbidity and mortality in neonates with umbilical artery catheters.

BACKGROUND: Umbilical artery catheters are often used in unwell neonates. Infection related to the use of these catheters may cause significant morbidity and mortality. The use of prophylactic antibiotics has been advocated for all newborns with umbilical artery catheters in order to reduce the risk of colonisation and acquired infection. Countering this is the possibility that harm, such as the emergence of antibiotic resistant organisms, may outweigh benefit. OBJECTIVES: The primary objective was to assess whether prophylactic antibiotics reduce mortality and morbidity in neonates with umbilical artery catheters. Two different policies regarding the prophylactic use of antibiotics in neonates with umbilical artery catheters were reviewed: 1) a policy of prophylactic antibiotics for the duration of catheterisation (or other fixed duration of antibiotic treatment) versus placebo or no treatment among neonates with umbilical artery catheters; 2) a policy of continuing versus discontinuing prophylactic antibiotics among neonates with umbilical artery catheters who had been started on antibiotics at the time of catheterisation but whose initial cultures to rule out sepsis are negative. SEARCH STRATEGY: MEDLINE (January 1950 to May 2007), CINAHL (1982 to May 2007), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), the Cochrane Neonatal Group Specialised Register and reference lists of articles were searched. SELECTION CRITERIA: Randomised and some non-randomised (i.e., quasi-randomised trials) controlled trials of adequate quality in which newborn infants with umbilical artery catheters are randomised to receive prophylactic antibiotics versus placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewer authors independently assessed trial quality. MAIN RESULTS: Two quasi-randomised trials have been included. However, given their poor quality, we have not pooled the results. There were no statistically significant differences in important outcomes in either study. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised trials to support or refute the use of prophylactic antibiotics when umbilical artery catheters are inserted in newborn infants, and no evidence to support or refute continuing antibiotics once initial cultures rule out infection in newborn infants with umbilical artery catheters.

Clarithromycin in coronary heart disease: excess mortality in the long term.

(1) Based on an attractive hypothesis implicating inflammation caused by Chlamydia pneumoniae in cardiovascular disease, several clinical trials have tested whether antibiotic therapy has a long-term preventive effect. (2) One trial showed an increase in mortality 3 years after a 2-week course of clarithromycin in patients with coronary heart disease (9.8% versus 7.8% in the placebo group). This difference resulted mainly from higher cardiovascular mortality (5.1% versus 3.5%). (3) A meta-analysis of all trials of antichlamydial antibiotics (mainly macrolides) in the prevention of cardiac events showed no difference between the groups in terms of cardiac morbidity or mortality. However, trials with more than 2 years of follow-up suggest that antimicrobial chemotherapy is associated with a statistically significant increase in mortality. (4) In practice, pending further information on the long-term effects of antimicrobial chemotherapy in coronary heart disease patients, these disturbing results suggest that the drugs are best avoided--especially macrolides--except in situations where their use is clearly warranted.

Hepatitis B en situaciones especiales / Hepatitis B in special situations

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Prophylactic antibiotics to reduce morbidity and mortality in neonates with umbilical artery catheters.

BACKGROUND: Umbilical artery catheters are often used in unwell neonates. Infection related to the use of these catheters may cause significant morbidity and mortality. The use of prophylactic antibiotics has been advocated for all newborns with umbilical artery catheters in order to reduce the risk of colonisation and acquired infection. Countering this is the possibility that harm may outweigh benefit. OBJECTIVES: The primary objective was to assess whether prophylactic antibiotics, in neonates with umbilical artery catheters, reduce mortality and morbidity. In separate comparisons, we planned to review two different policies regarding the prophylactic use of antibiotics in neonates with umbilical artery catheters: 1) among neonates with umbilical artery catheters, a policy of prophylactic antibiotics for the duration of catheterisation (or other fixed duration of antibiotic treatment) versus placebo or no treatment; 2) among neonates with umbilical artery catheters who had been started on antibiotics at the time of catheterisation but whose initial cultures to rule out sepsis are negative, a policy of continuing versus discontinuing prophylactic antibiotics. SEARCH STRATEGY: We searched MEDLINE (January 1966 to February 2004), CINAHL (1982 to February 2004), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004), the Cochrane Neonatal Group Specialised Register and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials of adequate quality in which newborn infants with umbilical artery catheters are randomised to receive prophylactic antibiotics versus placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality. MAIN RESULTS: No study met the criteria for inclusion in this review. REVIEWERS' CONCLUSIONS: There is no evidence from randomised trials to support or refute the use of prophylactic antibiotics when umbilical artery catheters are inserted in newborn infants, or to support or refute continuing antibiotics once initial cultures rule out infection in newborn infants with umbilical artery catheters.