Antibiotic resistance among major pathogens compared to hospital treatment guidelines and antibiotic use in Nordic hospitals 2010-2018

Background The Nordic countries have comparable nationwide antibiotic resistance surveillance systems and individual antibiotic stewardship programmes. The aim of this study was to assess antibiotic resistance among major pathogens in relation to practice guidelines for hospital antibiotic treatment and antibiotic use in Nordic countries 2010-2018. Methods Antibiotic resistance among invasive isolates from 2010-2018 and aggregated antibiotic use were obtained from the European Centre for Disease Prevention and Control. Hospital practice guidelines were obtained from national or regional guidelines. Results Antibiotic resistance levels among Escherichia coli and Klebsiella pneumoniae were similar in all Nordic countries in 2018 and low compared to the European mean. Guidelines for acute pyelonephritis varied; 2nd generation cephalosporin (Finland), 3rd generation cephalosporins (Sweden, Norway), ampicillin with an aminoglycoside or aminoglycoside monotherapy (Denmark, Iceland and Norway). Corresponding guidelines for sepsis of unknown origin were 2nd (Finland) or 3rd (Sweden, Norway, Iceland) generation cephalosporins, carbapenems, (Sweden) combinations of penicillin with an aminoglycoside (Norway, Denmark), or piperacillin-tazobactam (all Nordic countries). Methicillin-resistant Staphylococcus aureus rates were 0-2% and empirical treatment with anti-MRSA antibiotics was not recommended in any country. Rates of penicillin non-susceptibility among Streptococcus pneumoniae were low (Peer reviewe

Hospital adoption of antimicrobial stewardship programmes in Gulf Cooperation Council countries: A review of existing evidence

© 2018 International Society for Chemotherapy of Infection and Cancer Antimicrobial resistance is increasing at an alarming rate in the Gulf Cooperation Council (GCC) owing to the overuse and misuse of antimicrobials. Novel and rare multidrug-resistant strains can spread globally since the region is host to the largest expatriate population in the world as well as a pilgrimage destination for more than 4 million people annually. Adoption of antimicrobial stewardship programmes (ASPs) could improve the use of antimicrobials and reduce antimicrobial resistance in the region. However, despite the established benefits of these interventions, little is known about the level of their adoption in the region and the impact of these programmes on antimicrobial use and resistance. This study aimed to review existing evidence on the level of adoption of ASPs, the facilitators and barriers to their adoption, and outcomes of their adoption in GCC hospitals

Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae : Antibiotic consumption, Detection and Resistance Epidemiology

ESBL-producing Enterobacteriaceae are emerging worldwide and they are frequently multi-drug resistant, thus limiting treatment options for infections caused by these pathogens. The overall aim of the thesis was to investigate ESBL-producing Enterobacteriaceae in a Swedish county. First, we developed a molecular method, a multiplex PCR assay for identification of SHV, TEM and CTX-M genes in clinical isolates of Enterobacteriaceae with an ESBL phenotype. From 2002 until the end of 2007 all isolates of ESBL-producing Enterobacteriaceae in Östergötland, Sweden were further investigated. The prevalence of ESBL-producing Enterobacteriaceae was low, <1%, but increasing,while the antibiotic consumption remained unchanged. CTX-M enzymes, particularly CTX-M group 1, dominate in our region as well as in the rest of Europe. Furthermore, we have investigated antimicrobial susceptibility by performing MIC-testing in a large, well-characterized population of CTX-M-producing E. coli. Only three oral antimicrobial agents (fosfomycin, nitrofurantoin and mecillinam) demonstrated susceptibility above 90%. High susceptibility, >90%, was also demonstrated for carbapenems, colistin, tigecycline and amikacin. Sixty-eight per cent of ESBL-producing E. coli was multi-resistant, and the most common multi-resistance pattern was the ESBL phenotype with decreased susceptibility to trimethoprim, trimethoprim-sulfamethoxazole, ciprofloxacin, gentamicin and tobramycin. Isolates belonging to CTX-M group 9 are generally more susceptible to antibiotics than the CTX-M group 1-producing E. coli. Finally, a prospective multicentre case-control study examined the prevalence of ESBL-producing Enterobacteriaceae in faecal samples before and after travel abroad and the risk factors of acquisition. Sixty-eight of 226 travellers (30%) had ESBL-producing Enterobacteriaceae in the faecal flora. The geographical area visited had the highest impact on acquisition, with highest the risk for travellers visiting the Indian subcontinent, followed by Asia and Africa north of the equator. Also, acquisition of ESBL-producing Enterobacteriaceae during travel is associated with abdominal symptoms such as diarrhoea. Age also seemed to affect the risk of acquiring ESBL-producing Enterobacteriaceae, the highest risks were found among travellers ≥ 65 years. This thesis has contributed to increased understanding of the epidemiology of ESBL-producing Enterobacteriaceae and their susceptibility to both beta-lactam and non-beta-lactam agents

Cryopreservation of autologous bone flaps following decompressive craniectomy : A new method reduced positive cultures without increase in post-cranioplasty infection rate.

INTRODUCTION: Cranioplasty (CP) after decompressive craniectomy (DC) is a common neurosurgical procedure. Implementation of European Union (EU) directives recommending bacterial cultures before cryopreservation, lead to increased number of autologous bone flaps being discarded due to positive cultures. A new method for handling bone flaps prior to cryopreservation, including the use of pulsed lavage, was developed. RESEARCH QUESTION: The aim was to evaluate the effect of a new method on proportion of positive bacterial cultures and surgical site infection (SSI) following CP surgery. MATERIAL AND METHODS: Sixty-one bone flaps from 53 consecutive DC surgery patients were retrospectively included and the study period was divided into before and after method implementation. Patient demographics, laboratory and culture results, type of CP and occurrence of SSI were analyzed. RESULTS: Twenty-six and 18 bone flaps were available for analysis during the first and second period, respectively. The proportion of positive bacterial cultures was higher in the first period compared to the second (n ​= ​9(35%) vs 0(0%); p ​= ​0.001), and thus the use of custom made implants was considerably higher in the first study period (p ​= ​0.001). There was no difference in the frequency of post-cranioplasty SSI between the first and second study period (n ​= ​3 (11.5%) vs 1 (4.8%), p ​= ​0.408). DISCUSSION AND CONCLUSION: The new method for handling bone flaps resulted in a lower frequency of positive bacterial cultures, without increased frequency of post-cranioplasty SSI, thus demonstrating it is safe to use, allows compliance with the EU-directives, and may reduce unnecessary discarding of bone flaps

Delay of appropriate antibiotic treatment is associated with high mortality in patients with community-onset sepsis in a Swedish setting

Early appropriate antimicrobial therapy is crucial in patients with sepsis and septic shock. Studies often focus on time to first dose of appropriate antibiotics, but subsequent dosing is equally important. Our aim was to investigate the impact of fulfillment of early treatment, with focus on appropriate administration of first and second doses of antibiotics, on 28-day mortality in patients with community-onset severe sepsis and septic shock. A retrospective study on adult patients admitted to the emergency department with community-onset sepsis and septic shock was conducted 2012-2013. The criterion early appropriate antibiotic treatment was defined as administration of the first dose of adequate antibiotics within 1h, and the second dose given with less than 25% delay after the recommended dose interval. A high-risk patient was defined as a septic patient with either shock within 24h after arrival or red triage level on admittance according to the Medical Emergency Triage and Treatment System Adult. Primary endpoint was 28-day mortality. Of 90 patients, less than one in four (20/87) received early appropriate antibiotic treatment, and only one in three (15/44) of the high-risk patients. The univariate analysis showed a more than threefold higher mortality among high-risk patients not receiving early appropriate antibiotic treatment. Multivariable analysis identified early non-appropriate antibiotic treatment as an independent predictor of mortality with an odds ratio for mortality of 10.4. Despite that the importance of early antibiotic treatment has been established for decades, adherence to this principle was very poor.Funding Agencies|County of Ostergotland [2013/466-31]</p

Two-year follow-up of patients with post-COVID-19 condition in Sweden: a prospective cohort study

Background Few studies have reported the long-term health effects of COVID-19. The regional population-based Linkoping COVID-19 study (LinCoS) included all patients hospitalised due to COVID-19 during the first pandemic wave. Four months post-discharge, over 40% (185/433) experienced persisting symptoms and activity/ participation limitations, indicating post-COVID-19 condition (PCC). The present follow-up study aimed to determine the long-term recovery among these patients 24 months post-admission.Methods This prospective cohort study included all patients from LinCoS with PCC at four months post-discharge. We repeated the same structured interview at a 24-month follow-up to identify persisting symptoms and their impact on daily life. Intercurrent health issues were identified by reviewing medical records.Findings Of 185 patients with PCC at 4 months post-discharge, 181 were alive at the 24-month assessment and 165 agreed to participate. Of those, 21% (35/165) had been readmitted to hospital for various causes in the interim period. The majority of patients (139/165, 84%) reported persisting problems affecting everyday life at 24 months. Significant improvements were seen in the prevalence and magnitude of some symptoms/limitations compared with four months post-discharge. Cognitive, sensorimotor, and fatigue symptoms were the most common persisting symptoms at 24 months. No clear difference was evident between individuals treated in the intensive care unit (ICU) and non-ICU-treated individuals. Approximately half of those who were on sick leave related to PCC at four months after infection were on sick leave at 24 months.Interpretation This is one of the first studies to report 2-year outcomes in patients with PCC following COVID-19 hospitalisation. Despite some improvements over time, we found a high prevalence of persisting symptoms and a need for long-term follow-up and rehabilitation post COVID-19 infection

Case Report : Subtherapeutic Vancomycin and Meropenem Concentrations due to Augmented Renal Clearance in a Patient With Intracranial Infection Caused by Streptococcus intermedius

Streptococcus intermedius occasionally causes brain abscesses that can be life-threatening, requiring prompt antibiotic and neurosurgical treatment. The source is often dental, and it may spread to the eye or the brain parenchyma. We report the case of a 34-year-old man with signs of apical periodontitis, endophthalmitis, and multiple brain abscesses caused by Streptococcus intermedius. Initial treatment with meropenem and vancomycin was unsuccessful due to subtherapeutic concentrations, despite recommended dosages. Adequate concentrations could be reached only after increasing the dose of meropenem to 16 g/day and vancomycin to 1.5 g x 4. The patient exhibited high creatinine clearance consistent with augmented renal clearance, although iohexol and cystatin C clearances were normal. Plasma free vancomycin clearance followed that of creatinine. A one-day dose of trimethoprim-sulfamethoxazole led to an increase in serum creatinine and a decrease in both creatinine and urea clearances. These results indicate that increased tubular secretion of the drugs was the cause of suboptimal antibiotic treatment. The patient eventually recovered, but his left eye needed enucleation. Our case illustrates that augmented renal clearance can jeopardize the treatment of serious bacterial infections and that high doses of antibiotics are needed to achieve therapeutic concentrations in such cases. The mechanisms for regulation of kidney tubular transporters of creatinine, urea, vancomycin, and meropenem in critically ill patients are discussed.Funding Agencies|Swedish government [LIO-887221]; VINNOVA, collaboration platform for innovation of existing antibiotics (PLATINEA) [2018-03340]</p

Risk factors and outcome due to extended-spectrum beta-lactamase-producing uropathogenic Escherichia coli in community-onset bloodstream infections: A ten-year cohort study in Sweden

Objective To study clinical outcome and risk factors associated with extended-spectrum beta-lactamase (ESBL)-producing uropathogenic Escherichia coli (UPEC) in community-onset bloodstream infections (CO-BSI). Methods This was a population-based cohort study including patients with pheno- and genotype-matched ESBL-producing E. coli and non-ESBL- E. coli in urine and blood samples collected in 2009-2018 in southeast Sweden. Seventy-seven episodes of ESBL-UPEC satisfying the inclusion criteria were matched 1:1 with 77 non-ESBL-UPEC for age, gender, and year of culture. Results The most common ST-type and ESBL gene was ST131 (55%), and bla(CTX-M-15) (47%), respectively. Risk factors for ESBL-UPEC were: previous genitourinary invasive procedure (RR 4.66; p = 0.005) or history of ESBL-producing E. coli (RR 12.14; p = 0.024). There was significant difference between ESBL-UPEC and non-ESBL-UPEC regarding time to microbiologically appropriate antibiotic therapy (27:15 h vs. 02:14 h; p = &amp;lt;0.001) and hospital days (9 vs. 5; p = &amp;lt;0.001), but no difference in 30-day mortality (3% vs. 3%; p = &amp;gt;0.999) or sepsis within 36 hours (51% vs. 62%; p = 0.623) was observed. Conclusion The predominant risk factors for ESBL-UPEC were history of ESBL-Ec infection and history of genitourinary invasive procedure. The overall mortality was low and the delay in appropriate antibiotic therapy did not increase the risk for 30-day mortality or risk for sepsis within 36 hours among patients infected with ESBL UPEC. However, these results must be regarded with some degree of caution due to the small sample size.Funding Agencies|Alf Grants, Region Ostergotland [LIO-793191, LIO-899871]</p

Travel-associated faecal colonization with ESBL-producing Enterobacteriaceae : incidence and risk factors

Objectives To study the acquisition of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) among the faecal flora during travel, with a focus on risk factors, antibiotic susceptibility and ESBL-encoding genes. Methods An observational prospective multicentre cohort study of individuals attending vaccination clinics in south-east Sweden was performed, in which the submission of faecal samples and questionnaires before and after travelling outside Scandinavia was requested. Faecal samples were screened for ESBL-PE by culturing on ChromID ESBL and an in-house method. ESBL-PE was confirmed by phenotypic and genotypic methods. Susceptibility testing was performed with the Etest. Individuals who acquired ESBL-PE during travel (travel-associated carriers) were compared with non-carriers regarding risk factors, and unadjusted and adjusted ORs after manual stepwise elimination were calculated using logistic regression. Results Of 262 enrolled individuals, 2.4% were colonized before travel. Among 226 evaluable participants, ESBL-PE was detected in the post-travel samples from 68 (30%) travellers. The most important risk factor in the final model was the geographic area visited: Indian subcontinent (OR 24.8, P &lt; 0.001), Asia (OR 8.63, P &lt; 0.001) and Africa north of the equator (OR 4.94, P  = 0.002). Age and gastrointestinal symptoms also affected the risk significantly. Multiresistance was seen in 77 (66%) of the ESBL-PE isolates, predominantly a combination of reduced susceptibility to third-generation cephalosporins, trimethoprim/sulfamethoxazole and aminoglycosides. The most common species and ESBL-encoding gene were Escherichia coli (90%) and CTX-M (73%), respectively. Conclusion Acquisition of multiresistant ESBL-PE among the faecal flora during international travel is common. The geographical area visited has the highest impact on ESBL-PE acquisition.Funding Agencies|Medical Research Council of Southeast Sweden|FORSS-12368FORSS-36511FORSS-87551|ALF grants, Ostergotland County Council|LIO-10885LIO-16741LIO-61341LIO-127281|</p