Rational empiric antibiotic therapy in clinical practice and policy making: uncertainties, probabilities, and ethics

A significant proportion of the in-hospital antimicrobial consumption is used in the empiric setting, making empiric therapy an important target of stewardship interventions.Empiric antimicrobial therapy is the antimicrobial regimen that is started when the definite clinical diagnosis, causative agent and/or resistance pattern are yet unknown. Empiric therapy is accompanied by a varying level of uncertainty. In daily clinical practice, this uncertainty about the source, pathogen and susceptibility pattern are often managed by prescribing relatively broad-spectrum antimicrobial therapy. This has potential negative effects, such as toxicity and selective pressure resulting in antimicrobial resistance. Balancing the potential benefits and drawbacks of more broad-spectrum therapy is a substantial challenge, in particular when the level of uncertainty is high.This thesis aims to address the uncertainties most relevant in daily clinical practice in empiric antimicrobial therapy, to determine how they affect daily decision making, and to explore how this can be translated in antimicrobial policy making and antimicrobial stewardship.LUMC / Geneeskund

Faecal microbiota replacement to eradicate antimicrobial resistant bacteria in the intestinal tract - a systematic review

Purpose of review Antimicrobial resistance is a rising threat to global health and is associated with increased mortality. Intestinal colonisation with multidrug-resistant organisms (MDRO) can precede invasive infection and facilitates spread within communities and hospitals. Novel decolonisation strategies, such as faecal microbiota transplantation (FMT), are being explored. The purpose of this review is to provide an update on how the field of FMT for MDRO decolonisation has developed during the past year and to assess the efficacy of FMT for intestinal MDRO decolonisation. Recent findings Since 2020, seven highly heterogenous, small, nonrandomised cohort studies and five case reports have been published. In line with previous literature, decolonisation rates ranged from 20 to 90% between studies and were slightly higher for carbapenem-resistant Enterobacteriaceae than vancomycin-resistant Enterococcus. Despite moderate decolonisation rates in two studies, a reduction in MDRO bloodstream and urinary tract infections was observed. Summary and implications Although a number of smaller cohort studies show some effect of FMT for MDRO decolonisation, questions remain regarding the true efficacy of FMT (taking spontaneous decolonisation into account), the optimal route of administration, the role of antibiotics pre and post-FMT and the efficacy in different patient populations. The observed decrease in MDRO infections post-FMT warrants further research.Immunogenetics and cellular immunology of bacterial infectious disease

Complicated carriage with methicillin-resistant Staphylococcus aureus: evaluation of the effectiveness of decolonization regimens advised in the Dutch national guideline

Methicillin-resistant Staphylococcus aureus (MRSA) colonization leads to increased infection rates and mortality. Decolonization treatment has been proven to prevent infection and reduce transmission. As the optimal antimicrobial strategy is yet to be established, different regimens are currently prescribed to patients. This study aimed to evaluate the efficacy of the decolonization treatments recommended by the Dutch guideline. A retrospective multicenter cohort study was conducted in five Dutch hospitals. All patients who visited the outpatient clinic because of complicated MRSA carriage between 2014 and 2018 were included. We obtained data on patient characteristics, clinical and microbiological variables relevant for MRSA decolonization, environmental factors, decolonization regimen, and treatment outcome. The primary outcome was defined as three negative MRSA cultures after treatment completion. Outcomes were stratified for the first-line treatment strategies. A total of 131/224 patients were treated with systemic antibiotic agents. Treatment was successful in 111/131 (85%) patients. The success rate was highest in patients treated with doxycycline-rifampin (32/37; 86%), but the difference from any of the other regimens did not reach statistical significance. There was no difference in the success rate of a 7-day treatment compared to that with 10 to 14 days of treatment (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.39 to 253; P= 1.00). Side effects were reported in 27/131 (21%) patients and consisted mainly of mild gastrointestinal complaints. In a multivariable analysis, an immunocompromised status was an independent risk factor for failure at the first treatment attempt (OR, 4.65; 95% CI, 125 to 17.25; P =0.02). The antimicrobial combinations recommended to treat complicated MRSA carriage yielded high success rates. Prolonged treatment did not affect treatment outcome. A randomized trial is needed to resolve whether the most successful regimen in this study (doxycycline plus rifampin) is superior to other combinations.Immunogenetics and cellular immunology of bacterial infectious disease

The association of female sex with management and mortality in patients with Staphylococcus aureus bacteraemia

Objectives: The association of biological female sex with outcome in patients with Staphylococcus aureus bacteraemia remains unresolved. The aim of this study was to determine the independent association of female sex with management and mortality in patients with S. aureus bacteraemia.Methods: This is a post hoc analysis of prospectively collected data from the S. aureus Bacteraemia Group Prospective Cohort Study. Adult patients with monomicrobial S. aureus bacteraemia at Duke University Medical Center were enrolled from 1994 to 2020. Univariable and multivariable Cox regression analyses were performed to assess differences in management and mortality between females and males.Results: Among 3384 patients with S. aureus bacteraemia, 1431 (42%) were women. Women were, as compared with men, more often Black (581/1431 [41%] vs. 620/1953 [32%], p < 0.001), haemodialysis dependent (309/1424 [22%] vs. 334/1940 [17%], p 0.001) and more likely to be infected with methicillinresistant S. aureus (MRSA) (697/1410 [49%] MRSA in women vs. 840/1925 [44%] MRSA in men, p 0.001). Women received shorter durations of antimicrobial treatment (median 24 [interquartile range 14-42] vs. 28 [interquartile range 14-45] days, p 0.005), and were less likely to undergo transesophageal echocardiography as compared with men (495/1430 [35%] vs. 802/1952 [41%], p < 0.001). Despite these differences, female sex was not associated with 90-day mortality in either univariable (388/1431 [27%] in women vs. 491/1953 [25%] in men, p 0.204) or multivariable analysis (adjusted hazard ratio for women 0.98 [95% CI, 0.85-1.13]).Discussion: Despite significant differences in patient characteristics, disease characteristics, and management, women and men with S. aureus bacteraemia have a similar mortality risk. Annette C. Westgeest, Clin Microbiol Infect 2023;29:1182Immunogenetics and cellular immunology of bacterial infectious disease

Global differences in the management of Staphylococcus aureus bacteremia: no international standard of care

BackgroundDespite being the leading cause of mortality from bloodstream infections worldwide, little is known about regional variation in treatment practices for Staphylococcus aureus bacteremia (SAB). The aim of this study was to identify global variation in management, diagnostics, and definitions of SAB.MethodsDuring a 20-day period in 2022, physicians throughout the world were surveyed on SAB treatment practices. The survey was distributed through listservs, e-mails, and social media.ResultsIn total, 2031 physicians from 71 different countries on 6 continents (North America [701, 35%], Europe [573, 28%], Asia [409, 20%], Oceania [182, 9%], South America [124, 6%], and Africa [42, 2%]) completed the survey. Management-based responses differed significantly by continent for preferred treatment of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacteremia, use of adjunctive rifampin for prosthetic material infection, and use of oral antibiotics (P P –4 days of positive blood cultures, responses ranged from 2 days in 31% of European respondents to 7 days in 38% of Asian respondents (P ConclusionsLarge practice variations for SAB exist throughout the world, reflecting the paucity of high-quality data and the absence of an international standard of care for the management of SAB.Immunogenetics and cellular immunology of bacterial infectious disease

Diagnostic accuracy of urine biomarkers for urinary tract infection in older women: a case-control study

ObjectivesUrinary tract infection (UTI) is common among older women. However, diagnosis is challenging because of frequent chronic lower urinary tract symptoms, cognitive impairment, and a high prevalence of asymptomatic bacteriuria (ASB). Current urine diagnostics lack specificity, leading to unnecessary treatment and antimicrobial resistance. This study aimed to evaluate the diagnostic accuracy of 12 urine biomarkers for diagnosing UTI in older women.MethodsIn this case-control study, cases were women ≥65 years with ≥2 new-onset lower urinary tract symptoms, pyuria, and one uropathogen ≥104 CFU/mL. Controls were asymptomatic and classified as ASB (one uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Urine biomarker concentrations were measured through liquid chromatography-mass spectrometry and ELISA. Diagnostic accuracy parameters of individual biomarkers and a biomarker model were derived from receiver operating characteristic curves.ResultsWe included 162 community-dwelling and institutionalized older women. Five urine inflammatory biomarkers demonstrated high discriminative ability (area under the curve ≥0.80): interleukin 6, azurocidin, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinases 2, and C-X-C motif chemokine 9. Azurocidin exhibited the highest diagnostic accuracy (sensitivity 86% [95% CI 75%–93%] and specificity 89% [95% CI 82%–94%] at 16.7 ng/mmol creatinine). A combined biomarker and pyuria model showed improved diagnostic accuracy in patients with UTI and ASB, compared with pyuria alone.DiscussionWe identified several urine biomarkers that accurately differentiated older women with UTI from asymptomatic women, including ASB. These findings represent a potential advancement towards improved diagnostics for UTI in older women and warrant validation in a diverse population.Immunogenetics and cellular immunology of bacterial infectious disease

Preoperative oral antibiotics in colon surgery

Immunogenetics and cellular immunology of bacterial infectious disease

Taking a Rational Approach to a Reported Antibiotic Allergy

Up to 10% of hospitalized patients have an antibiotic allergy label in their medical file, most frequently concerning penicillins. However, the vast majority of reported allergies to antibiotics does not represent a "true" allergy but are due to drug intolerance, idiosyncratic reactions or symptoms of the concurrent infectious disease. Since antibiotic allergy labels result in deviation from first-choice antimicrobial therapy, tackling the issue of incorrect antibiotic allergy labelling, already at young age, is a core element of antibiotic stewardship. In this article, we describe the structured approach to the patient with a presumed antibiotic allergy with emphasis on key elements of allergy-specific history taking and the limited risk of cross-allergic reactions between beta-lactam subclasses.Immunogenetics and cellular immunology of bacterial infectious disease

Re: 'Development of diagnostic prediction tools for bacteraemia caused by 3rd generation cephalosporin-resistant Enterobacteriaceae in suspected bacterial infections' by Rottier, et al

Medical Microbiolog

Time to positivity of blood cultures supports early re-evaluation of empiric broad-spectrum antimicrobial therapy

Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc