Intravenous mecillinam compared with other ß-lactams as targeted treatment for Escherichia coli or Klebsiella spp. bacteraemia with urinary tract focus.

BACKGROUND: Mecillinam (amdinocillin) is active against Gram-negative bacteria. Clinical data on the efficacy of IV mecillinam for severe urinary tract infections is sparse. OBJECTIVES: To assess the effectiveness of targeted IV mecillinam compared with other ß-lactams for bacteraemia with Escherichia coli and Klebsiella spp. and a urinary tract focus. PATIENTS AND METHODS: We performed a retrospective cohort study at five university hospitals in the Capital Region of Denmark from 1 January 2012 to 31 December 2017. We used Cox proportional hazard regression to compare the primary composite endpoint (all-cause mortality or bacteraemia recurrence within 30 days) between patients treated with mecillinam versus ampicillin, cefuroxime, piperacillin/tazobactam and meropenem. RESULTS: We included 1129 patients in the primary analysis, of which 146 were given IV mecillinam as targeted treatment. We found no significant difference in the primary endpoint between patients treated with mecillinam versus ampicillin and cefuroxime, but found a higher risk for the primary endpoint in the piperacillin/tazobactam and meropenem groups, with adjusted HRs of 2.22 (95% CI 1.24-3.97, P < 0.01) and 2.48 (95% CI 1.04-5.93, P = 0.04), respectively, compared with mecillinam. CONCLUSIONS: The results of this study suggest that IV mecillinam may be a suitable targeted treatment for bacteraemia with a urinary tract focus. However, these results need confirmation by randomized controlled studies.

Antibiotic prophylaxis for transrectal prostate biopsy-a new strategy.

BACKGROUND: Fluoroquinolones are extensively used as prophylaxis for transrectal ultrasound-guided biopsy of the prostate (TRUBP). Emerging fluoroquinolone resistance and selection of multiresistant organisms warrant new prophylactic strategies. Pivmecillinam and amoxicillin/clavulanic acid have mutual synergistic activity and the combination of these agents has a broad coverage of the majority of microorganisms causing infectious complications after TRUBP and may be a valuable future prophylactic regimen. PATIENTS AND METHODS: This was a retrospective cohort study of 2624 men that underwent TRUBP at a Danish university hospital. The patients were divided into three groups. Group 1 (n = 1220) received ciprofloxacin before TRUBP, Group 2 (n = 240) received a combination of pivmecillinam and amoxicillin/clavulanic acid before TRUBP and Group 3 (n = 1161) received an extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid before and for 2 days after TRUBP. RESULTS: One hundred and ten out of 148 (74.3%) post-TRUBP infections were caused by Escherichia coli, Klebsiella pneumoniae or Enterococcus faecalis. Group 3 with the extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid had a significantly lower rate of bacteraemia (0.9%) as compared with Group 1 (1.8%) and Group 2 (3.7%). A significant fall in the proportion of ESBL-producing Enterobacteriaceae was observed from the period when ciprofloxacin was used as prophylaxis (8.1%) compared with the subsequent period when pivmecillinam and amoxicillin/clavulanic acid was used (5.9%). CONCLUSIONS: The combination of pivmecillinam and amoxicillin/clavulanic acid is an attractive prophylaxis for TRUBP from a clinical, bacteriological and ecological point of view as compared with ciprofloxacin.

A Dedicated Mycosis Flask Increases the Likelihood of Identifying Candidemia Sepsis.

INTRODUCTION: Candidemia is a severe condition associated with high mortality, and fungi are often not covered by empiric antimicrobial regimes for sepsis. Therefore, the shortest possible time to detection of yeast in the blood is of the essence. MATERIALS AND METHODS: We performed a cohort study of blood culture flasks drawn from patients aged 18 or older in the capital region of Denmark. In 2018 a blood cultures set consisted of two aerobic and two anaerobic flasks. This was changed in 2020 to two aerobic, one anaerobic, and one mycosis flask. We used time-to-event statistics to model time to positivity and compared 2018 with 2020; further, we stratified analyses on the blood culture system used (BacTAlert™ vs. BACTEC™) and high-risk vs. low-risk departments. RESULTS: We included 175,416 blood culture sets and 107,077 unique patients. We found an absolute difference in the likelihood of identifying fungi in a blood culture set of 1.2 (95% CI: 0.72; 1.6) pr. 1.000 blood culture sets corresponding to the number needed to treat 853 (617; 1382). In high-risk departments, the absolute difference was profound, whereas it was negligible and statistically non-significant in low-risk departments 5.2 (95% CI: 3.4; 7.1) vs. 0.16 (-0.17; 0.48) pr. 1.000 blood culture sets. CONCLUSIONS: We found that including a mycosis flask in a blood culture set increases the likelihood of identifying candidemia. The effect was mainly seen in high-risk departments.

Haemophilus influenzae septicaemia and urinary tract infection associated with nefrocalcinosis: case report.

Haemophilus influenzae is an uncommon uropathogen with fastidious growth requirements, which must be taken into consideration in the diagnostic process. We present a rare case of urosepsis with H. influenzae in a young patient with nefrocalcinosis.

[The first two cases of Candida auris in Denmark].

This is a case report of the first two cases of Candida auris in Denmark. Patient 1 was known to be colonized with C. auris when transferred from a foreign hospital to a Danish hospital. The patient was isolated during the entire hospitalization and the room was thoroughly cleaned after discharge. Patient 2 who had no travel history spent five hours in the room of Patient 1 after disinfection. One month later, C. auris was found in the blood of Patient 2. Transmission from Patient 1 to Patient 2 must be suspected.

Neurological Complications in COVID-19 Patients: Can Analysis of Specific Antibodies and Viral RNA in Paired Cerebrospinal Fluid and Serum be Used for Accurate Diagnosis of SARS-CoV-2 Neuroinflammatory Disease? A Case Series.

Background: Neurological complications during and after SARS-CoV-2 infection have been frequently described. The detection of either SARS-CoV-2 RNA or specific antibodies against SARS-CoV-2 in cerebrospinal fluid in the context of concomitant neurological manifestations indicates neuroinfection. Methods and Results: This is a retrospective descriptive analysis of cerebrospinal fluids and serum samples from 2 hospitalized patients and autopsy findings from 2 patients who died at home. Samples were analysed by 3 independent enzyme-linked immunosorbent assays. Specific antibodies against SARS-CoV-2 were detected in cerebrospinal fluids and paired serum in all 4 cases. Levels of antibodies in cerebrospinal fluids were highest in samples from a deceased man with critical progression of COVID-19 and detectable SARS-CoV-2 viral RNA in cerebrospinal fluid, serum, 4 brain biopsies and 15 additional tissue samples, though immunohistochemical staining for SARS-CoV-2 in brain tissue did not detect the virus. Conclusion: Detection of SARS-CoV-2 antibodies in paired serum and cerebrospinal fluid may support the presence of SARS-CoV-2 neuroinflammatory disease in patients with COVID-19 and neurological manifestations.

Update 2016-2018 of the Nationwide Danish Fungaemia Surveillance Study: Epidemiologic Changes in a 15-Year Perspective.

As part of a national surveillance programme initiated in 2004, fungal blood isolates from 2016-2018 underwent species identification and EUCAST susceptibility testing. The epidemiology was described and compared to data from previous years. In 2016-2018, 1454 unique isolates were included. The fungaemia rate was 8.13/100,000 inhabitants compared to 8.64, 9.03, and 8.38 in 2004-2007, 2008-2011, and 2012-2015, respectively. Half of the cases (52.8%) involved patients 60-79 years old and the incidence was highest in males ≥70 years old. Candida albicans accounted for 42.1% of all isolates and Candida glabrata for 32.1%. C. albicans was more frequent in males (p = 0.03) and C. glabrata in females (p = 0.03). During the four periods, the proportion of C. albicans decreased (p < 0.001), and C. glabrata increased (p < 0.001). Consequently, fluconazole susceptibility gradually decreased from 68.5% to 59.0% (p < 0.001). Acquired fluconazole resistance was found in 4.6% Candida isolates in 2016-2018. Acquired echinocandin resistance increased during the four periods 0.0%, 0.6%, 1.7% to 1.5% (p < 0.0001). Sixteen echinocandin-resistant isolates from 2016-2018 harboured well-known FKS resistance-mutations and one echinocandin-resistant C. albicans had an FKS mutation outside the hotspot (P1354P/S) of unknown importance. In C. glabrata specifically, echinocandin resistance was detected in 12/460 (2.6%) in 2016-2018 whereas multidrug-class resistance was rare (1/460 isolates (0.2%)). Since the increase in incidence during 2004-2011, the incidence has stabilised. In contrast, the species distribution has changed gradually over the 15 years, with increased C. glabrata at the expense of C. albicans. The consequent decreased fluconazole susceptibility and the emergence of acquired echinocandin resistance complicates the management of fungaemia and calls for antifungal drug development.