Enterococcal Infections the First Year after Liver Transplantation-A Prospective Cohort Study.

This study aimed to investigate the incidence of enterococcal infections and determine risk factors associated with enterococcal bloodstream infection (BSI) within the first year post-liver transplantation (LTx). We included 321 adult liver transplant recipients transplanted from 2011 to 2019 in a prospective cohort study. Cumulative incidence of enterococcal infections and risk factors associated with BSI were investigated in a competing risk model and time-updated Cox models, respectively. A total of 223 enterococcal infections were identified in 89 recipients. The cumulative incidences of first enterococcal infection and first enterococcal BSI were 28% (95% CI (23-33)) and 11% (CI (7-14)), respectively. Risk factors associated with enterococcal BSI were previous infections in the biliary tract (HR, 33; CI (15-74); p < 0.001), peritoneum (HR, 8.1; CI (3-23); p < 0.001) or surgical site (HR, 5.5; CI (1.4-22); p = 0.02), recipient age (HR per 10 years increase, 1.2; CI (1.03-1.6); p = 0.03), and cold ischemia time (HR per one hour increase, 1.2; CI (1.1-1.3); p < 0.01). Enterococcal infections are highly prevalent the first year post-LTx, and recipients with enterococcal infections in the biliary tract, peritoneum, or surgical site are at increased risk of BSI. These findings may have implications for the choice of empiric antibiotics early post-LTx.

Relapse of Neonatal Escherichia coli Meningitis: Did We Miss Something at First?

Relapse of neonatal meningitis is most commonly caused by Escherichia coli. Management to prevent relapse varies and evidence is limited. We present four cases of relapsing neonatal E. coli meningitis in Denmark in 2016-2017 and review the current literature on this subject. During the primary episodes, our patients received cephalosporin for 3 weeks and gentamicin for the first 3 days. The only identified risk factor was delayed CSF sterilization in three of four cases and no repeated lumbar puncture. Relapse occurred after 2-28 days; one case with ventriculitis and one with empyema. Relapses were treated for 6-14 weeks with monotherapy. No children had an underlying disease predisposing to E. coli meningitis. There is generally a trend towards reducing invasive procedures, e.g., lumbar puncture and the length of intravenous antibiotics in pediatric infectious diseases, but our cases highlight a condition where the opposite might be needed.

ESBL-production in Escherichia coli and Klebsiella pneumoniae isolates from Nigeria.

The worldwide increase in infections caused by extended-spectrum beta-lactamase- (ESBL) and AmpC-producing Enterobacteriaceae (ESBL-E) is a concern. Surveillance is extensive in Europe, North America, and Asia. Yet, there is no summarizing surveillance in Africa. This study aimed to perform a preliminary investigation on the prevalence of ESBL-E in the northeastern part of Nigeria. However, of the 60 samples collected, we were able to culture 15 Escherichia coli and 7 Klebsiella spp. only. In the collection of clinical hospital samples, we found eight of 15 E. coli isolates to be ESBL (53%) and two out of seven Klebsiella spp. to be ESBL/AmpC (29%). Due to the limitations of this study, our findings cannot take a broad view on the prevalence of ESBL-E, in Nigeria and other parts of Africa. Yet, to know which genes encode ESBL in Nigeria, and to know exact prevalence of every ESBL gene would be of importance.

Does macrolide use confer risk of out-of-hospital cardiac arrest compared with penicillin V? A Danish national case-crossover and case-time-control study.

INTRODUCTION AND OBJECTIVES: Macrolides have been associated with proarrhythmic properties, but the evidence is conflicting. We evaluated the risk of out-of-hospital cardiac arrest (OHCA) associated with specific macrolides in a retrospective study. Associations between specific macrolides and OHCA were examined by conditional logistic regression analyses in case-crossover and case-time-control models, using penicillin-V treatment as the comparative reference. From nationwide registries, we identified all OHCAs in Denmark from 2001 to 2010 and use of antibiotics. ETHICS: The present study was approved by the Danish Data Protection Agency (Danish Data Protection Agency (ref.no. 2007-58-0015, local ref.no. GEH-2014-017, (I-Suite.nr. 02 735)). PARTICIPANTS: We identified 29 111 patients with an OHCA. Of these, 514 were in macrolide treatment ≤7 days before OHCA and 1237 in penicillin-V treatment. RESULTS: In the case-crossover analyses, overall macrolide use was not associated with OHCA with penicillin V as negative comparative reference (OR=0.90; 95% CI 0.73 to 1.10). Compared with penicillin-V treatment, specific macrolides were not associated with increased risk of OHCA: roxithromycin (OR=0.97; 95% CI 0.74 to 1.26), erythromycin (OR=0.68; 95% CI 0.44 to 1.06), clarithromycin (OR=0.95; 95% CI 0.61 to 1.48) and azithromycin (OR=0.85; 95% CI 0.57 to 1.27).Similar results were obtained using case-time-control models: overall macrolide use (OR=0.81; 95% CI 0.62 to 1.06) and specific macrolides (roxithromycin (OR=0.70; 95% CI 0.49 to 1.00), erythromycin (OR=0.67; 95% CI 0.38 to 1.18), clarithromycin (OR=0.75; 95% CI 0.41 to 1.39) or azithromycin (OR=1.17; 95% CI 0.70 to 1.95)). CONCLUSION: The risk of OHCA during treatment with macrolides was similar to that of penicillin V, suggesting no additional risk of OHCA associated with macrolides.

Incidence of HACEK bacteraemia in Denmark: A 6-year population-based study.

OBJECTIVES: Bacteria with common microbiological and clinical characteristics are often recognized as a particular group. The acronym HACEK stands for five fastidious genera associated with infective endocarditis (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella). Data on the epidemiology of HACEK are sparse. This article reports a 6-year nationwide study of HACEK bacteraemia in Denmark. METHODS: Cases of HACEK bacteraemia occurring during the years 2010-2015 were retrieved from the national Danish microbiology database, covering an average surveillance population of 5.6 million per year. RESULTS: A total of 147 cases of HACEK bacteraemia were identified, corresponding to an annual incidence of 0.44 per 100000 population. The annual incidence for males was 0.56 per 100000 and for females was 0.31 per 100000. The median age was 56 years (range 0-97 years), with variation among the genera. One hundred and forty-three isolates were identified to the species level and six to the genus level: Haemophilus spp, n=55; Aggregatibacter spp, n=37; Cardiobacterium spp, n=9; Eikenella corrodens n=21; and Kingella spp, n=27. CONCLUSIONS: This is the first study on the incidence of HACEK bacteraemia in a large surveillance population and may inspire further studies on the HACEK group. Haemophilus spp other than Haemophilus influenzae accounted for most cases of HACEK bacteraemia in Denmark, with Aggregatibacter spp in second place.

Impact of appropriate empirical antibiotic treatment on recurrence and mortality in patients with bacteraemia: a population-based cohort study.

BACKGROUND: Data on the impact of empirical antibiotic treatment (EAT) on patient outcome in a population-based setting are sparse. We assessed the association between EAT and the risk of recurrence within one year, short-term- (2-30 days) and long-term (31-365 days) mortality in a Danish cohort of bacteraemia patients. METHODS: A cohort study including all patients hospitalized with incident bacteraemia during 2007-2008 in the Copenhagen City and County areas and the North Denmark Region. EAT was defined as the antibiotic treatment given at the 1st notification of a positive blood culture. The definition of recurrence took account of pathogen species, site of infection, and time frame and was not restricted to homologous pathogens. The vital status was determined through the civil registration system. Association estimates between EAT and the outcomes were estimated by Cox and logistic regression models. RESULTS: In 6483 eligible patients, 712 (11%) had a recurrent episode. A total of 3778 (58%) patients received appropriate EAT, 1290 (20%) received inappropriate EAT, while EAT status was unrecorded for 1415 (22%) patients. The 2-30 day mortality was 15.1%, 17.4% and 19.2% in patients receiving appropriate EAT, inappropriate EAT, and unknown EAT, respectively. Among patients alive on day 30, the 31-365 day mortality was 22.3% in patients given appropriate EAT compared to 30.7% in those given inappropriate EAT. Inappropriate EAT was independently associated with recurrence (HR 1.25; 95% CI = 1.03-1.52) and long-term mortality (OR 1.35; 95% CI = 1.10-1.60), but not with short-term mortality (OR 0.85; 95% CI = 0.70-1.02) after bacteraemia. CONCLUSIONS: Our data indicate that appropriate EAT is associated with reduced incidence of recurrence and lower long-term mortality following bacteraemia.

Fecal carriage of extended-spectrum and AmpC ß-lactamase-producing Enterobacteriaceae in surgical patients before and after antibiotic prophylaxis.

The impact of antibiotic prophylaxis on fecal carriage of ESBL-/AmpC-/carbapenemase-producing Enterobacteriaceae (CPE) was investigated. Patients admitted for elective surgery or diagnostic procedure in a Department of Surgical Gastroenterology (SG) (n= 450) and Orthopedic Surgery (OS) (n= 300) provided a fecal swab at admission and responded to a questionnaire on possible exposures. SG patients received gentamicin/penicillin G (±metronidazole); OS patients received cefuroxime. Two days after surgery a second swab was taken. From SG patients, 6% of first swabs and 9% of second swabs were positive for ESBL-/AmpC-producers. A similar carriage rate was observed in OS patients (6% and 8%, respectively). No CPE were detected. Escherichia coli was the predominant species and blaCTX-M-15 (29% and 22%) and blaCTX-M-14 (11% and 17%) were the most prevalent ESBL genotypes among SG and OS patients. Two different prophylactic antibiotic regimens had no impact on carriage rates. Previous hospitalization and antimicrobial treatment were associated with carriage for SG patients.

Spectrum of microorganisms in infected walled-off pancreatic necrosis - impact on organ failure and mortality.

OBJECTIVE: Data on the microbial spectrum in infected pancreatic necrosis are scarce. Only few studies have addressed this issue in a larger, consecutive group of patients treated by a standardized algorithm. Since 2005 endoscopic, transmural drainage and necrosectomy (ETDN) has been the treatment of choice for walled-off necrosis in our centre. The present study evaluated the microbial spectrum of infected pancreatic necrosis and the possible relationship between infected necrosis, organ failure, and mortality. Furthermore, we investigated whether the aetiology of pancreatitis, use of external drainage, and antibiotic treatment influenced the microbial findings. METHODS: Retrospective review of medical charts on 78 patients who underwent ETDN in our tertiary referral centre between November 2005 and November 2011. RESULTS: Twenty-four patients (31%) developed one or more organ failures, 23 (29%) needed treatment in the intensive care unit (ICU), and 9 (11%) died during hospital admission. The prevailing microbial findings at the index endoscopy were enterococci (45%), enterobacteriaceae (42%), and fungi (22%). There was a significant association between the development of organ failure (p < 0.001), need of treatment in ICU (p < 0.002), in-hospital mortality (p = 0.039) and infected necrosis at the time of index endoscopy. Enterococci (p < 0.0001) and fungi (p = 0.01) were found more frequently in patients who died during admission as compared to survivors. CONCLUSION: Different microbes in pancreatic necrosis may influence the prognosis. We believe that a detailed knowledge on the microbial spectrum in necrotizing pancreatitis may be utilized in the treatment to improve the outcome.

Characterization of third-generation cephalosporin-resistant Escherichia coli from bloodstream infections in Denmark.

The aim of the study was to investigate the molecular epidemiology of 87 third-generation cephalosporin-resistant Escherichia coli (3GC-R Ec) from bloodstream infections in Denmark from 2009. Sixty-eight of the 87 isolates were extended-spectrum beta-lactamase (ESBL) producers, whereas 17 isolates featured AmpC mutations only (without a coexpressed ESBL enzyme) and 2 isolates were producing CMY-22. The majority (82%) of the ESBL-producing isolates in our study were CTX-M-15 producers and primarily belonged to phylogroup B2 (54.4%) or D (23.5%). Further, one of the two CMY-22-producing isolates belonged to B2, whereas only few of the other AmpCs isolates belonged to B2 and D. Pulsed-field gel electrophoresis revealed that both clonal and nonclonal spread of 3GC-R Ec occurred. ST131 was detected in 50% of ESBL-producing isolates. The remaining ESBL-producing isolates belonged to 17 other sequence types (STs), including several other internationally spreading STs (e.g., ST10, ST69, and ST405). The majority (93%) of the ESBL-producing isolates and one of the CMY-22-producing isolates were multiresistant. In conclusion, 3GC-R in bacteriaemic E. coli in Denmark was mostly due to ESBL production, overexpression of AmpC, and to a lesser extent to plasmid-mediated AmpC. The worldwide disseminated CTX-M-15-ST131 was strongly represented in this collection of Danish, bacteriaemic E. coli isolates.

Impact of positive chest X-ray findings and blood cultures on adverse outcomes following hospitalized pneumococcal lower respiratory tract infection: a population-based cohort study.

BACKGROUND: Little is known about the clinical presentation and outcome of pneumococcal lower respiratory tract infection (LRTI) without positive chest X-ray findings and blood cultures. We investigated the prognostic impact of a pulmonary infiltrate and bacteraemia on the clinical course of hospitalized patients with confirmed pneumococcal LRTI. METHODS: We studied a population-based multi-centre cohort of 705 adults hospitalized with LRTI and Streptococcus pneumoniae in LRT specimens or blood: 193 without pulmonary infiltrate or bacteraemia, 250 with X-ray confirmed pneumonia, and 262 with bacteraemia. We compared adverse outcomes in the three groups and used multiple regression analyses to adjust for differences in age, sex, comorbidity, and lifestyle factors. RESULTS: Patients with no infiltrate and no bacteraemia were of similar age but had more comorbidity than the other groups (Charlson index score ≥1: no infiltrate and no bacteraemia 81% vs. infiltrate without bacteraemia 72% vs. bacteraemia 61%), smoked more tobacco, and had more respiratory symptoms. In contrast, patients with a pulmonary infiltrate or bacteraemia had more inflammation (median C-reactive protein: no infiltrate and no bacteraemia 82 mg/L vs. infiltrate without bacteraemia 163 mg/L vs. bacteraemia 316 mg/L) and higher acute disease severity scores. All adverse outcomes increased from patients with no infiltrate and no bacteraemia to those with an infiltrate and to those with bacteraemia: Length of hospital stay (5 vs. 6 vs. 8 days); intensive care admission (7% vs. 20% vs. 23%); pulmonary complications (1% vs. 5% vs. 14%); and 30-day mortality (5% vs. 11% vs. 21%). Compared with patients with no infiltrate and no bacteraemia, the adjusted 30-day mortality rate ratio was 1.9 (95% confidence interval (CI) 0.9-4.1) in patients with an infiltrate without bacteraemia and 4.1 (95% CI 2.0-8.5) in bacteraemia patients. Adjustment for acute disease severity and inflammatory markers weakened these associations. CONCLUSIONS: Hospitalization with confirmed pneumococcal LRTI is associated with substantial morbidity and mortality even without positive chest X-ray findings and blood cultures. Still, there is a clinically important outcome gradient from LRTI patients with pneumococcal isolation only to those with detected pulmonary infiltrate or bacteraemia which is partly mediated by higher acute disease severity and inflammation.

Characterization and transfer studies of macrolide resistance genes in Streptococcus pneumoniae from Denmark.

Over the last decade, erythromycin resistance has been increasing in frequency in Streptococcus pneumoniae in Denmark. In the present study, 49 non-related erythromycin-resistant S. pneumoniae isolates from invasive sites and 20 isolates from non-invasive sites were collected; antimicrobial susceptibility was tested, and they were genotyped and serotyped. Gene transfer was studied for selected isolates. The frequency of erm(B) was significantly higher in non-invasive isolates compared to invasive isolates (p = 0.001). For the first time, mef(I) was detected in 1 isolate in Denmark. All tested mef(E) isolates had an identical mef(E) sequence, apart from 1 gene with a point mutation, and mef(E) was correlated to 7 different sero-types. The tested erm(B) sequences were 99.3% similar with 5 point mutations at different positions distributed among different serotypes, which did not cause a detectable influence on the protein. Transformation was detectable in 5 out of 13 isolates and transfer of erm(B), mef(I) and mef(E) was detected. To our knowledge, this is the first time mef(I) has been proved transformable. Gene transfer by conjugation was not detectable. Erythromycin resistance in pneumococcal isolates is likely to be caused primarily by horizontal spread of mef(E) and erm(B), as well as clonal spread of a serotype 14 strain carrying mef(A) primarily detected in invasive isolates.

Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine.

AIM: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children <16 years with quality surveillance data, just prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine immunization programme October 2007. METHODS: Clinical and microbiological records on cases of IPD in children <16 years admitted to Hvidovre Hospital, Denmark 1996-2007, were retrospectively reviewed. RESULTS: We identified 106 cases of IPD. The annual incidence of IPD was 11 per 100 000 in children <16 years, but considerably higher, 62 per 100 000, in children <2 years. Additionally, of the children with pneumococcal meningitis 86% were <2 years. We observed no fatalities. A total of 10% developed sequelae, but of the patients with pneumococcal meningitis 27% developed sequelae. Nine patients had known risk factors. The Streptococcus pneumoniae serotype was available for 81 cases. Seventy-five percent of the IPD cases in children aged <2 years were caused by one of the serotypes contained within PCV7, compared to only 24% in children >/=2 years. CONCLUSION: Our data indicate that an estimated 75% of all IPD cases among children <2 years are caused by PCV7 serotypes and might therefore be prevented by PCV7 vaccination.