Ignorance of pre-ED healthcare setting is a factor leading to inappropriate initial antibiotic treatment of sepsis in ED and poor outcomes in ICU

ObjectivesAppropriate initial antibiotic therapy is critical for successfully treating sepsis. In the emergency department (ED), clinicians often rely on septic symptoms to guide empirical therapy. The aim of this study was to investigate whether history of contacting pre-ED healthcare setting is easy to be neglected and whether the patients received more inappropriate initial antibiotic therapy and developed poorer outcomes.MethodsSeptic patients (n = 453) admitted from ED to the intensive care unit (ICU) between 2014 and 2017 were retrospectively selected. Appropriate antibiotic treatment or not was determined by checking whether the selected antibiotics can effectively eradicate the bacteria identified. Various indexes were compared between patients with appropriate and inappropriate initial antibiotic treatments, including septic symptoms (qSOFA scores) in ED, septic-severity change in ICU (SOFA-score ratios), and septic outcomes (APACHE II scores, stay length, 30-day survival probability). These indexes were also compared between pre-ED healthcare and pre-ED community patients.ResultsIn comparison with pre-ED community patients, pre-ED healthcare patients received more inappropriate initial antibiotic treatment in ED, showing poorer outcomes in ICU, including septic severity, stay-lengths in ICU and 30-day survival probabilities. Pre-ED settings is more significant than qSOFA scores to predict the inappropriate initial antibiotic treatment.ConclusionsPre-ED healthcare settings, which are indexes for infection with antibiotic resistant pathogens, are easy to be neglected in the first hour in ED. We suggested that standard operating procedure for getting enough information of pre-ED settings should be incorporated to the 1 h bundle of sepsis guideline.     

Shorter antibiotic courses in the immunocompromised: the impossible dream?

BackgroundA growing number of studies have demonstrated similar outcomes with shorter courses of antibiotics for bacterial infections. Immunocompromised patients are frequently excluded from these studies despite anticipated benefits associated with shortening antibiotic courses (including lower risks of antibiotic toxicity, Clostridioides difficile infection, drug-resistant pathogens, and microbiome alterations).ObjectivesTo critically review the literature that assesses shorter antibiotic courses in immunocompromised patients, specifically among solid organ transplant recipients and neutropenic fever (NF) syndromes among patients on antineoplastic chemotherapy and undergoing haematopoietic cell transplant.SourcesReferences were identified through searches of PubMed, Embase, MEDLINE, and clinical guidelines documents.ContentAmong organ transplant recipients, the majority of studies assessing outcomes associated with shorter antibiotic courses have been retrospective but have demonstrated similar rates of clinically relevant endpoints. Patients with high- and low-risk NF have been well-studied, including enrolment in randomized studies, albeit with heterogeneous patient populations and outcomes assessed. Clinical improvement-guided adoption of shorter courses has been associated with fewer antibiotic days and similar rates of fever recurrence and mortality.ImplicationsSimilar to studies demonstrating efficacy in immunocompetent patients, shorter antibiotic courses should be considered for immunocompromised hosts with presumed bacterial infections. Organ recipients and patients with NF syndromes should be prioritized for study in randomized controlled clinical trials assessing shorter course therapy.     

Failure of antibiotic therapy in Staphylococcus epidermidis infection of implantable venous access devices in patients with AIDS,as documented by molecular typing

ObjectiveTo study the efficacy and safety of high-concentration antibiotic locks in association with systemic antibiotherapy in Staphylococcus epidermidis infections of totally implantable venous access devices (TIVADs) in patients with AIDS.MethodsThirty-one episodes of S. epidermidis TIVAD infection were observed in nine patients. Locks consisted of high concentrations of aminoglycosides or vancomycin according to antibiogram results (susceptibility results obtained with the disk diffusion technique). Genotyping of bacterial strains was performed by pulsed-field gel electrophoresis (PFGE) in 26 of the 31 infectious episodes.ResultsThe infections occurred within a median period of 62 catheter-days. The median duration of systemic antibiotic therapy was 17.5 days in association with a median of three antibiotic locks. Failure as defined by the occurrence of a novel episode within 2 months was observed in 17 of the 31 infections (58%). According to the PFGE results, relapse with the same strain of S. epidermidis or reinfection with a different strain of S. epidermidis could be assigned to 10 episodes which failed to respond to therapy. Relapse was observed in six of 10 episodes. Four episodes were followed by the occurrence of a novel infection with a different S. epidermidis strain. In one patient, a relapse occurred despite TIVAD removal.Conclusion: Our observations further document the poor efficacy of associating antibiotic locks with systemic antibiotic therapy for the treatment of TIVAD infections in patients with AIDS.     

Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection,a cohort study

ObjectiveShort-course aminoglycosides as adjunctive empirical therapy to β-lactams in patients with a clinical suspicion of sepsis are used to broaden antibiotic susceptibility coverage and to enhance bacterial killing. We quantified the impact of this approach on 30-day mortality in a subset of sepsis patients with a Gram-negative bloodstream infection.MethodsFrom a prospective cohort study conducted in seven hospitals in the Netherlands between June 2013 and November 2015, we selected all patients with Gram-negative bloodstream infection (GN-BSI). Short-course aminoglycoside therapy was defined as tobramycin, gentamicin or amikacin initiated within a 48-hour time window around blood-culture obtainment, and prescribed for a maximum of 2 days. The outcome of interest was 30-day all-cause mortality. Confounders were selected a priori for adjustment using a propensity score analysis with inverse probability weighting.ResultsA total of 626 individuals with GN-BSI who received β-lactams were included; 156 (24.9%) also received aminoglycosides for a median of 1 day. Patients receiving aminoglycosides more often had septic shock (31/156, 19.9% versus 34/470, 7.2%) and had an eight-fold lower risk of inappropriate treatment (3/156, 1.9% versus 69/470, 14.7%). Thirty-day mortality was 17.3% (27/156) and 13.6% (64/470) for patients receiving and not receiving aminoglycosides, respectively; yielding crude and adjusted odds ratios for 30-day mortality for patients treated with aminoglycosides of 1.33 (95% CI 0.80–2.15) and 1.57 (0.84–2.93), respectively.ConclusionsShort-course adjunctive aminoglycoside treatment as part of empirical therapy with β-lactam antibiotics in patients with GN-BSI did not result in improved outcomes, despite better antibiotic coverage of pathogens.     

Recommendations for antibacterial therapy in adults with COVID-19 – an evidence based guideline

ScopeThe Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19).MethodsWe performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology.Questions addressed by the guideline and RecommendationsWe assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.     

The infectious complications of atopic dermatitis

ObjectiveAtopic dermatitis (AD) is a chronic inflammatory skin disease that is complicated by an increased risk for skin and systemic infections. Preventive therapy for AD is based on skin barrier improvement and anti-inflammatory treatments, whereas overt skin and systemic infections require antibiotics or antiviral treatments. This review updates the pathophysiology, diagnosis, management, controversy of antibiotic use, and potential treatments of infectious complications of AD.Data SourcesPublished literature obtained through PubMed database searches and clinical pictures.Study SelectionsStudies relevant to the mechanisms, diagnosis, management, and potential therapy of infectious complications of AD.ResultsSkin barrier defects, type 2 inflammation, Staphylococcus aureus colonization, and cutaneous dysbiosis are the major predisposing factors for the increased infections in AD. Although overt infections require antibiotics, the use of antibiotics in AD exacerbation remains controversial.ConclusionInfectious complications are a comorbidity of AD. Although not common, systemic bacterial infections and eczema herpeticum can be life-threatening. Preventive therapy of infections in AD emphasizes skin barrier improvement and anti-inflammatory therapy. The use of antibiotics in AD exacerbation requires further studies.     

How to: implement procalcitonin testing in my practice

BackgroundAdding procalcitonin (PCT) to antibiotic stewardship algorithms may improve antibiotic use. However, PCT protocols need to be adapted to clinical settings and patient populations.ObjectivesTo review PCT use in different medical settings and patient populations.SourcesMost recent trials and meta-analyses investigating PCT for antibiotic stewardship were reviewed.ContentSeveral trials found PCT-guided antibiotic stewardship to reduce antibiotic exposure and associated side-effects among patients with respiratory infection and sepsis. Decisions regarding antibiotic use in an individual patient are complex and should be based on the pre-test probability for bacterial infection, the severity of presentation and the results of PCT. In the context of a low pre-test probability for bacterial infections and a low-risk patient, a low PCT level helps to rule out bacterial infection and empiric antibiotic therapy can be avoided. In the context of a high pre-test probability for bacterial infections and/or a high-risk patient with sepsis, monitoring of PCT over time helps to track the resolution of infection and decisions regarding early stop of antibiotic treatment. Although these concepts have been successful in several respiratory infection and sepsis trials, some studies failed to show an added benefit of PCT due to factors such as low protocol adherence and relying on single rather than repeat PCT measurements.ImplicationAs an adjunct to other clinical and laboratory parameters, PCT provides information about risk for bacterial infection and resolution of infection, and improves antibiotic stewardship decisions, thereby offering more individualized treatment courses with overall reduced antibiotic exposure.     

Timing of antibiotics in septic patients: a prospective cohort study

ObjectivesTo evaluate the effect of timing and appropriateness of antibiotics administration on mortality in patients diagnosed with sepsis according to the Sepsis-3 definition.MethodsThis prospective cohort study was conducted in patients diagnosed with sepsis according to the Sepsis-3 definition at the emergency department of Korea University Ansan Hospital from January 2016 to January 2019. The time to antibiotics was defined as the time in hours from emergency department arrival to the first antibiotic administration. Cox proportional hazards regression analysis was used to estimate the association between time to antibiotics and 7-, 14- and 28-day mortality.ResultsOf 482 patients enrolled onto this study, 203 (42.1%) of 482 and 312 (64.7%) of 482 were diagnosed with septic shock and high-grade infection respectively. The median time to receipt of antibiotic therapy was 115 minutes. Antibiotics were administered within 3 and 6 hours in 340 (70.4%) of 482 and 450 (93.2%) of 482 patients respectively. Initial appropriate empirical antibiotics were administered in 375 (77.8%) of 482 patients. The time to and appropriateness of the initial antibiotics were not associated with 7-, 14- and 28-day mortality in multivariate analysis. The Sequential Organ Failure Assessment (SOFA) score (adjusted hazard ratio (aHR) 1.229, 95% confidence interval (CI) 1.093–1.381, p 0.001) and initial lactate levels (aHR 1.128, 95% CI 1.034–1.230, p 0.007), Charlson comorbidity index (aHR 1.115, 95% CI 1.027–1.210, p 0.014), 2-hour lactate level (aHR 1.115, 95% CI 1.027–1.210, p 0.009) and SOFA score (aHR 1.077, 95% CI 1.013–1.144, p 0.018) affected 7-, 14- and 28-day mortality respectively. Subgroup analysis with septic shock, bacteraemia and high-grade infection did not affect mortality rates.ConclusionsTime to receipt of antibiotics may not affect the prognosis of patients with sepsis if a rapid and well-trained resuscitation is combined with appropriate antibiotic administration within a reasonable time.     

Procalcitonin: “To Follow or Not to Follow” That's the Question

How to cite this article: Todi SK. Procalcitonin: “To Follow or Not to Follow” That''s the Question. Indian J Crit Care Med 2021;25(5):484–485.

Sepsis has been recognized as an important cause of mortality globally, more so in resource-limited regions.¹ It accounts for 19.7% of all global deaths. Timely antibiotic therapy in patients with septic shock is associated with a significant decrease in mortality in observational studies.² Though this has not been uniformly noted in patients with sepsis without shock. Moreover, empirical use of appropriate antibiotic therapy has also been associated with a significant decrease in infection-related and all-cause mortality in critically ill patients.³ This has led to a widespread use of early broad-spectrum antibiotics in patients with septic shock. Unfortunately, despite the lack of robust evidence, similar practice is usually followed in patients with infection without organ dysfunction or shock. This has resulted in the emergence of multidrug-resistant (MDR) bacterial infections not only in hospitals but also in the community, which leads to a vicious cycle of prescribing further empirical broad-spectrum antibiotics for a new infection especially hospital-acquired. In the absence of a reliable method to “rule in” or “rule out” infection, it will be difficult to curb the upfront use of antibiotics. Decreasing antibiotic burden in the intensive care unit (ICU) and in the individual patient will be possible by sending appropriate microbiological cultures and deescalating antibiotics wherever possible and to decrease the duration of antibiotic therapy. As cultures are often negative and may only yield colonizing organisms, the scope of de-escalation may be limited especially in settings with MDR infection with limited options for de-escalation. Shortening the duration of antibiotics without compromising the efficacy may be the only way to achieve the goal of decreasing antibiotic exposure. Assessment of clinical improvement is the current prevalent practice of deciding on the duration of antibiotic therapy. This practice is based predominantly on a subjective assessment, which has led to a widely variable practice of antibiotic duration, which on an average is longer than what is probably desirable. Utilizing biomarkers like Procalcitonin has been recommended for decreasing the duration of antibiotic therapy.⁴To discuss the impact of a biomarker on the duration of antibiotic therapy, one needs to ascertain what should be an “ideal” duration of therapy. This will depend on multiple factors, with some situations requiring “prolonged” therapy like immunosuppressed state, the severity of infection (debatable), sites of infection like endocarditis, and microbiological factors like staphylococcal bacteremia and MDR gram-negative infection. Even in these situations exact duration of therapy is arbitrary and is dependent on the clinical response of the patient. On the other hand, in most other situations duration of antibiotic therapy may be “shorter”. The current practice of prescribing antibiotics for a certain minimum number of days, usually seven days is not based on sound evidence. There is a growing literature of evidence that the duration of antibiotic therapy can be shortened even further in most infections including severe infection. Recent trials in intra-abdominal infections requiring surgery have compared four days of antibiotics with seven days and have found equivalent results.⁵ The generalizability of these results is not possible in many situations and also clinical trials on the duration of antibiotic therapy are not available for many infections encountered in clinical practice in ICU. It is evident that the duration of antibiotic therapy requires individualization and is a field where personalized medicine can be readily practiced. Procalcitonin is the biomarker most commonly studied in this regard. Earlier studies on procalcitonin use in various infectious diseases had shown a decrease in duration of antibiotic therapy without any harmful effect with the use of this biomarker. This was achieved by serially measuring procalcitonin values and stopping the antibiotic when the level came below a certain percentage of baseline (usually 80%) or below a certain cutoff value usually less than 0.5 µg/mL. Relapse of infection was not noticed in these trials, with some trials even showing a decrease in mortality.⁶ Thus, the use of procalcitonin was recommended in sepsis guidelines to decrease the duration of antibiotic therapy.In a study published this issue, the author randomized 90 patients (45 in each arm) admitted with sepsis/septic shock to a procalcitonin-guided duration of antibiotic therapy or institutional protocol-based therapy. Procalcitonin value of <0.1 µg/mL was taken as the cut-off for stopping antibiotic therapy. Clinical response was also considered in both arms while considering the duration of antibiotic therapy. Patients requiring a short course of therapy like elective surgery or prolonged course of therapy like endocarditis, immunocompromised patients were excluded from the study. Duration of antibiotic therapy was significantly shorter in the procalcitonin group of 5 days vs 8 days in the control group. ICU length of stay, duration of mechanical ventilation, and duration of inotrope requirement were also significantly higher in the control group. Secondary infection defined as the occurrence of a new infection at another site was significantly higher in the control group, probably due to longer ICU stay and longer duration of mechanical ventilation. Reinfection rate which was defined as recurrence of infection at the same site was similar in both the group and also there were no significant differences in mortality between the groups. There were baseline differences in the groups, with septic shock patients being significantly higher in the control group, though the severity of score markers like SOFA and APACHE II and lactate levels were surprisingly similar between the two groups and bacteremia was more common in the procalcitonin group, which could be due to less robust randomization due to small sample size. Historically, clinicians are reluctant to shorten the duration of therapy in patients with sepsis and septic shock, which leads to prolonged antibiotic therapy and the authors should be commended to undertake this study in the septic shock population. Despite limitations, this study emphasizes the scope of safely decreasing the duration of antibiotic therapy in these groups of patients.Similar to the present study most of the studies on duration of antibiotic therapy have used clinical response along with procalcitonin levels to adjudicate duration of antibiotic justifying shortening the duration only in patients with positive clinical response. In practice, “positive clinical response” is an not all-or-none phenomenon with various parameters like fever, leukocytosis showing favorable or unfavorable trends that might be concordant or discordant and the composite response assessment remains a subjective impression. Moreover, the duration of antibiotic therapy in the control arm in many studies on procalcitonin has been of more than seven days duration which is contrary to the present evidence of shorter duration even in a sicker group of patients. Studies comparing the use of procalcitonin where the control arm had a shorter duration of antibiotic have not yielded significant results. The use of the procalcitonin strategy in infections with MDR organisms or immunosuppressed patients has also not been well studied as these were excluded from many procalcitonin studies. Despite these limitations, the current trend of prescribing a longer duration of antibiotics can only be curbed by judicious use of biomarkers like procalcitonin along with antibiotic stewardship practices. In the absence of a willingness to shorten the duration of antibiotics based on the procalcitonin result, the utility of this biomarker will not be realized. Moreover, the need for serial measurement of this expensive test also adds to the cost of care in ICU. Future research agenda on the utility of procalcitonin would be to compare this molecule with a relatively inexpensive biomarker like C-reactive protein on decreasing duration of therapy and total antibiotic burden in a critically ill patient with sepsis and septic shock and its effect on other important clinical and economic parameters like resource utilization, secondary bacterial and fungal infection, incidence of MDR bacterial infection and Clostridium difficle infection. This should be achieved without increasing the incidence of relapse or reinfection. The utility of the use of this biomarker in patients infected with MDR infection or immunosuppressed patients also needs to be studied. It might even be prudent to study the negative impact of the use of this molecule which may lead to unnecessary prolongation of antibiotic duration in patients who have clinically responded but not yet reached the procalcitonin cutoff. The control arm duration of antibiotic therapy in procalcitonin should be shorter in accordance with the recent guidelines. Approach to the duration of antibiotic therapy in patients with initial norma procalcitonin values and what should be the ideal frequency of repeating this marker need also be studied. Last but not the least, compliance with antibiotic stewardship practices of deescalating or stopping antibiotic based on a protocolized algorithm of procalcitonin value need to be studied in critically ill patient population.⁷     

Development of a time-to-positivity assay as a tool in the antibiotic management of septic patients

Optimal use of antibiotics is a key component of the management of sepsis. The purpose of this study was to develop a modification of the time-to-positivity (T(pos)) assay for use in the acute management of septic patients. Initial laboratory experiments, followed by ex-vivo validation and pilot studies, were performed with a small number of healthy human volunteers and 46 septic patients on a general intensive care unit, chosen on the basis of their antibiotic regimen. The study demonstrated that the T(pos) assay could be used as a surrogate for antimicrobial activity, and provided preliminary data to demonstrate how this approach might be used to monitor the efficacy of antibiotic therapy in septic patients. The T(pos) assay might offer a quick and convenient way to improve the efficacy of antibiotic therapy in septic patients, and further prospective large-scale studies are now warranted.     

Rates,predictors and mortality of community-onset bloodstream infections due to Pseudomonas aeruginosa: systematic review and meta-analysis

BackgroundPseudomonas aeruginosa is mostly a nosocomial pathogen affecting predisposed patients. However, community-onset bloodstream infections (CO-BSI) caused by this organism are not exceptional.ObjectivesTo assess the predisposing factors for CO-BSI due to P. aeruginosa (CO-BSI-PA) and the impact in mortality of inappropriate empirical antimicrobial therapy.Data sourceA systematic literature search was performed in the Medline, Embase, Cochrane Library, Scopus and Web of Science databases.Study eligibility criteria and participants: Articles published between 1 January 2002 and 31 January 2018 reporting at least of 20 adult patients with CO-BSI due to P. aeruginosa were considered.InterventionEmpiric antimicrobial therapy for CO-BSI-PA.MethodsA systematic review and a meta-analysis were conducted for risk factors and to evaluate if inappropriate empiric antimicrobial therapy increased mortality in CO-BSI-PA using a Mantel-Haenszel effects model.ResultsTwelve studies assessing data of 1120 patients were included in the systematic review. Solid tumour (33.1%), haematologic malignancy (26.4%), neutropenia (31.7%) and previous antibiotic use (44.8%) were the most prevalent predisposing factors. Septic shock was present in 42.3% of cases, and 30-day crude mortality was 33.8%. Mortality in meta-analysis (four studies) was associated with septic shock at presentation (odds ratio, 22.31; 95% confidence interval, 3.52–141.35; p 0.001) and with inappropriate empiric antibiotic therapy (odds ratio, 1.83; 95% confidence interval, 1.12–2.98l p 0.02).ConclusionsCO-BSI-PA mostly occurred in patients with predisposing factors and had a 30-day mortality comparable to hospital-acquired cases. Inappropriate empirical antibiotic therapy was associated with increased mortality. Appropriate identification of patients at risk for CO-BSI-PA is needed for empirical treatment decisions.     

Diagnostic and prognostic role of procalcitonin (PCT) and MR‐pro‐Adrenomedullin (MR‐proADM) in bacterial infections

Rapid diagnosis of bacterial infections is crucial for adequate antibiotic treatment. Serum molecules such as Procalcitonin (PCT) have been used as biomarkers of infection. Recently, the mid‐regional pro‐Adrenomedullin (MR‐proADM) has been evaluated in combination with PCT for sepsis diagnosis. The diagnostic role of PCT and MR‐proADM both in sepsis and in localized infections together with their contribution to effective antibiotic therapy has been evaluated. One hundred and eighty‐two patients with bacterial infection has been enrolled: PCT and MR‐proADM were measured at admission (T = 0), at 12–24 h (T = 1) and in the third or fifth day of antibiotic therapy (T = 3–5). ROC curve (receiver operating characteristic) and post‐test probability were calculated. MR‐proADM increased with the severity of the infection. PCT resulted significantly higher in sepsis than localized infection. After antibiotic therapy, PCT significantly decreased in localized respiratory infections and in sepsis, while MR‐proADM decreased significantly after antibiotic therapy only in patients with severe sepsis/septic shock. The threshold values of PCT and MR‐proADM were >0.1 ng/mL and >0.8 nmol/L, respectively. The combined use of PCT and MR‐proADM increased the post‐test probability of the diagnosis of bacterial infections compared to PCT alone. In conclusion, PCT and MR‐proADM combination improves the diagnosis of bacterial infection and contribute to prognosis and antibiotic therapy effectiveness.     

Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study

Objectives

Sepsis guidelines recommend obtaining blood cultures before starting anti-infective therapy in patients with sepsis. However, little is known of how antibiotic treatment before sampling affects bacterial growth. The aim of this study was to compare the results of blood cultures drawn before and during antibiotic therapy.

Molecular diagnosis of polymicrobial brain abscesses with 16S-rDNA-based next-generation sequencing

ObjectivesBrain abscesses lead to high mortality despite antibiotic and surgical treatment. Identification of causative bacteria is important to guide antibiotic therapy, but culture-based methods and molecular diagnostics by Sanger sequencing of 16S PCR products are hampered by antibiotic treatment and the often polymicrobial nature of brain abscesses. We have applied 16S-rRNA-based next-generation sequencing (NGS) for metagenomic analysis of intracranial abscess (brain and epidural) and meningitis samples.MethodsSeventy-nine samples from 54 patients with intracranial abscesses or meningitis were included. DNA was subjected to 16S PCR. Amplicons were analysed with the Illumina MiSeq system, sequence reads were blasted versus the NCBI 16S bacterial database and analysed using MEGAN software. Results were compared to those of gram-staining, culture and Sanger sequencing.ResultsThe NGS workflow was successful for 51 intracranial abscesses (46 brain and five epidural) and nine meningitis samples. Inclusion of (mono)bacterial meningitis samples allowed us to establish a cut-off criterion for the exclusion of contaminating sequences. In total 86 bacterial taxa were identified in brain abscesses by NGS, with Streptococcus intermedius and Fusobacterium nucleatum as most prevalent species; Propionibacterium and Staphylococcus spp. were associated with epidural abscesses. NGS identified two or more bacterial taxa in 31/51 intracranial abscesses, revealing the polymicrobial nature of these infections and allowing the discrimination of up to 16 bacterial taxa per sample.ConclusionThese results extend earlier studies showing that NGS methods expand the spectrum of bacteria detected in brain abscesses and demonstrate that the MiSeq platform is suitable for metagenomic diagnostics of this severe infection.     

What is the evidence base of used aggregated antibiotic resistance percentages to change empirical antibiotic treatment? A scoping review

ObjectivesAntibiotic resistance requires continuous monitoring by experts to decide whether empirical antibiotic therapies (EATs) should be replaced by alternative antibiotics. The exact moment and criteria for this change are unclear and generally based on consensus between experts. This scoping review aims to identify from the literature the resistance thresholds used for a change in EAT and the criteria on which they are based.MethodsScoping review for which a comprehensive structured literature search was conducted. Rayyan, software for systematic reviews, was used for the screening of abstracts and titles. Data sources were Pubmed and a hand-search of reference lists and grey literature. Papers were eligible if they concerned any type of bacterial infectious disease and mentioned or defined antibiotic resistance thresholds for decision-making purposes for EAT. The inclusion and analysis of articles was done by two researchers; any conflicts were resolved through discussion or by consulting a third reviewer.ResultsWe identified 3146 unique papers. Following title/abstract screening, 125 papers were comprehensively read, and 16 papers were included. The included papers gave thresholds for urinary tract infections, respiratory tract infections, meningitis, skin and soft tissue infections, gonorrhoea, and bone and joint infections. Six criteria were found that were commonly used to base the thresholds on. These were: disease severity, efficacy of treatment, adverse drug events, risk of Clostridioides difficile infection, costs, and increased resistance. The number of criteria used to define each threshold varied from one to six between papers.ConclusionsThe thresholds used for EATs are few, commonly based on expert opinion estimates, and can therefore have broad ranges. Used criteria underlying reported thresholds are heterogenous and require standardization. Considering the rising trend in resistance, there is a clear need for rigid tools to determine thresholds in order to support guideline development with the best and timely evidence.     

The impact of selenium administration on severe sepsis or septic shock: a meta-analysis of randomized controlled trials

IntroductionThe efficacy of selenium administration to treat severe sepsis or septic shock remains controversial. We conduct a systematic review and meta-analysis to explore the impact of selenium administration on severe sepsis or septic shock.MethodsWe search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2020 for randomized controlled trials (RCTs) assessing the effect of selenium administration on severe sepsis or septic shock. Meta-analysis is performed using the random-effect model.ResultsFive RCTs involving 1482 patients are included in the meta-analysis. Overall, compared with control group in septic patients, selenium administration is not associated with reduced 28-day mortality (RR=0.93; 95% CI=0.73 to 1.19; P=0.58), but results in substantially decreased all-cause mortality (RR=0.78; 95% CI=0.63 to 0.98; P=0.03) and length of hospital stay (MD=-3.09; 95% CI=-5.68 to -0.50; P=0.02).ConclusionSelenium administration results in notable decrease in all-cause mortality and length of hospital stay, but shows no substantial influence on the 28-day mortality, length of ICU stay, duration of vasopressor therapy, the incidence of acute renal failure, adverse events, and serious adverse events for septic patients.     

A systematic review and meta-analysis on the antibiotic resistance of Neisseria meningitidis in the last 20 years in the world

BackgroundNeisseria meningitidis is one of the most important causes of meningitis and pathogens-associated deaths in developing and developed countries. Effective anti-microbial agents are pivotal to treat and control N. meningitidis infections. The aim of the present study was to systematically review published studies on the antibiotic resistance of N. meningitidis in the last 20 years (2000–2020) in the world.MethodsPublished researches were identified through a literature search using reputable databases including PubMed, Scopus, and Web of Science. Finally, 24 studies were included for a random-effects model meta-analysis.ResultsThe overall resistance to most commonly used antibiotics such as ceftriaxone, cefotaxime, ciprofloxacin and rifampin was low, ranging from 1 to 3.4%. However, non-sensitivity to penicillin, as the first-line antibiotic against N. meningitidis, was higher (27.2%). Altogether, the resistance to the first-line antibiotics (except penicillin) is still low indicating these drugs are effective against meningococcal meningitis. We also found a significant gap between MIC and disk diffusion for evaluating resistance to antibiotics in which disk diffusion overestimate the resistance rate.ConclusionsTo properly management and prevent the spread of N. miningitidis isolates resistant antibiotics, it is necessary to monitor the pattern of antibiotic susceptibility regionally and globally using the MIC methods.     

Risk factors of multidrug-resistant bacteria in community-acquired urinary tract infections

BackgroundUrinary tract infections (UTIs) are one of the most seen infection among community.ObjectivesIn this cross-sectional study we aimed to investigate the risk factors of multidrug-resistant (MDR) bacteria that caused community-acquired UTI (CA-UTI).MethodsConsecutive patients admitted to the Urology and Infectious Diseases policlinics with the diagnosis of CA-UTI were included in the study. A standard form including possible predisposing factors for MDR bacteria was applied.ResultsIn total, 240 patients (51.3% females) were enrolled in the study. The mean age of participants were 59.8 ± 18.3 years old. Escherichia coli (n =166; 69.2%)was the most frequently isolated bacteria and its incidence was higher in females than in males (p=0.01). In total, 129 (53.8%) of the identified pathogens were MDR bacteria. According to multivariate analysis, the use of antibiotics three or more times increased the risk of infection with MDR bacteria by 4.6 times, the history of urinary tract infection in the last 6 months by 2 times, being male and over 65 years old by 3 times.ConclusionDoctors should consider prescribing broad-spectrum antibiotics in patients with severe UTIs with a history of UTI, advanced age, male gender, and multiple antibiotic usage, even if they have a CA-UTI.