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Purpose There is variability in the pharmacokinetics (PK) of antibiotics (AB) in critically ill patients. Therapeutic drug monitoring (TDM) could overcome this variability and increase PK target attainment. The objective of this study was to analyse the effect of a dose-adaption strategy based on daily TDM on target attainment. Methods This was a prospective, partially blinded, and randomised controlled trial in patients with normal kidney function treated with meropenem (MEM) or piperacillin/tazobactam (PTZ). The intervention group underwent daily TDM, with dose adjustment when necessary. The predefined PK/pharmacodynamic (PK/PD) target was 100 % fT.sub.>4MIC [percentage of time during a dosing interval that the free (f) drug concentration exceeded 4 times the MIC]. The control group received conventional treatment. The primary endpoint was the proportion of patients that reached 100 % fT.sub.>4MIC and 100 % fT.sub.>MIC at 72 h. Results Forty-one patients (median age 56 years) were included in the study. Pneumonia was the primary infectious diagnosis. At baseline, 100 % fT.sub.>4MIC was achieved in 21 % of the PTZ patients and in none of the MEM patients; 100 % fT.sub.>MIC was achieved in 71 % of the PTZ patients and 46 % of the MEM patients. Of the patients in the intervention group, 76 % needed dose adaptation, and five required an additional increase. At 72 h, target attainment rates for 100 % fT.sub.>4MIC and 100 % fT.sub.>MIC were higher in the intervention group: 58 vs. 16 %, p = 0.007 and 95 vs. 68 %, p = 0.045, respectively. Conclusions Among critically ill patients with normal kidney function, a strategy of dose adaptation based on daily TDM led to an increase in PK/PD target attainment compared to conventional dosing., Author(s): Jan J. De Waele [sup.1], S. Carrette [sup.1], M. Carlier [sup.2], V. Stove [sup.2], J. Boelens [sup.2], G. Claeys [sup.2], I. Leroux-Roels [sup.2], E. Hoste [sup.1], P. Depuydt [sup.1], [...]

The aim of this study was to assess the reliability of rapid antigen detection tests (RADT) for Streptococcus pyogenes (GAS) and Streptococcus pneumoniae on pleural fluid samples for diagnosis of parapneumonic effusion/empyema (PPE) and their potential for improving pathogen identification rates. Sixty-three pleural samples were included from 54 patients on which GAS and S. pneumoniae RADT (BinaxNOW), culture, 16S rRNA PCR, and S. pneumoniae-specific PCR were performed. GAS RADT showed a sensitivity of 95.2% and a specificity of 100%. Pneumococcal RADT showed a sensitivity of 100% and specificity of 88.6%. Both RADT increased the pathogen identification rate in PPE compared to culture., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Accurate susceptibility result of temocillin (TMO) is important for treating infections caused by multidrug-resistant Enterobacterales. This multicenter study aimed to investigate the performance of routine temocillin testing assays against Enterobacterales challenging strains. Forty-seven selected clinical isolates were blindly analyzed by 12 Belgian laboratories using VITEK® 2 (n = 5) and BD Phoenix™ (n = 3) automated systems, ETEST® gradient strip (n = 3), and disk (3 brands) diffusion method (DD; n = 6) for temocillin susceptibility using standardized methodology. Results were interpreted using EUCAST 2023 criteria and compared to the broth microdilution (BMD; Sensititre™ panel) method used as gold standard. Methods' reproducibility was assessed by testing 3 reference strains in triplicate. A total of 702 organism-drug results were obtained against 33 TMO-susceptible and 14 TMO-resistant isolates. Excluding Proteae species (P. mirabilis and M. morganii), the essential agreement rates were excellent (91.5-100%) for all MIC-based methods. The highest category agreement was achieved by ETEST® (97.5%) followed by VITEK® 2 (93.2%), disk diffusion (91.6%), and BD Phoenix™ (88.5%). BD Phoenix™ and paper disk diffusion overcalled resistance (11.5% and 6.8% of major discrepancies, respectively), while ROSCO tablets diffusion and VITEK® 2 generated higher very major discrepancies (7.1% and 4.2% respectively). Inter-assay reproducibility was unsatisfactory using recommended E. coli ATCC 25922 strain but was excellent with E. coli ATCC 35218 and K. pneumoniae ATCC 700603 strains. This interlaboratory study suggests that routine testing methods provide accurate and reproducible TMO categorization results except for Proteae species., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hypervirulent Klebsiella pneumoniae (hvKp) raised concern worldwide. We studied 22 hvKp clinical invasive isolates referred to the Belgian national reference laboratory between 2014 and 2020. Sixty-four percent of the isolates expressed K2 capsular serotype and belonged to 7 different MLST lineages, while 32% expressed K1 (all belonging to ST23) and were associated with liver abscesses. Primary extra-hepatic infections were reported in 36% and sepsis for 95% of the patients with 30% of deaths. Improved clinical and microbiological diagnostics are required as hvKp may represent an underestimated cause of community-acquired invasive infections in Belgium., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

On the first of January 2019, the European Committee on Antimicrobial Susceptibility Testing, EUCAST, introduced the concept of "area of technical uncertainty" (ATU). The aim was to report on the incidence of ATU test results in a selection of common bacterial species and the subsequent impact on antimicrobial resistance categorization and workload. A retrospective analysis of clinical samples collected from February 2019 until November 2019 was performed. Susceptibility to amoxicillin-clavulanic acid and piperacillin-tazobactam in Enterobacterales (Escherichia spp., Klebsiella spp., Proteus spp.), piperacillin-tazobactam in Pseudomonas aeruginosa, and amoxicillin-clavulanic acid and cefuroxime in Haemophilus influenzae was studied. Disk diffusion antibiotic susceptibility testing was read and interpreted by ADAGIO 93400 automated system (Bio-Rad, France). In case of an inhibition zone in the ATU, strains were retested using gradient minimal inhibitory concentration method (Etest, BioMérieux, France). Overall, 14,164 isolate-antibiotic combinations were tested in 7922 isolates, resulting in 1204 (8.5%) disk zone diameters in the ATU region. Retesting of ATUs with Etest resulted in a category change from S to R for amoxicillin-clavulanic acid in 63/498 (12.7%) of Escherichia spp., 2/58 (3.4%) of Klebsiella spp., 2/37 (5.4%) of Proteus spp., and 6/125 (4.8%) of Haemophilus influenzae. For piperacillin-tazobactam, a category change from S to R was found in 33/92 (35.9%) of Pseudomonas aeruginosa. We conclude that ATU testing has a substantial impact on the correct interpretation of antimicrobial resistance, at the expense of turn-around time and with the cost of additional workload., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

For patients with bloodstream infections, rapid initiation of the appropriate antimicrobial therapy is essential in reducing mortality and morbidity. New developments and automation in clinical microbiology labs speed up the identification and susceptibility results but are expensive. To gain insight in the added value of the new workflows, we simulated the possible impact of rapid identification and susceptibility tests on a real-life cohort of 158 positive blood culture episodes. Our routine workflow was theoretically challenged against two new workflows, one based on rapid identification with MALDI-TOF MS and one based on molecular testing. First, we observed an important role of the rapid communication of the gram stain results, as about one third of patients needed an adaptation of the antimicrobial therapy based on these results. Antibiotic adaptation based on the microorganism identification was necessary in 10% and in another 25% of cases after the availability of the susceptibility results. The added value of the newer workflow methods lies mainly in the field of the rapid identification and was rather limited in our cohort. In conclusion, for optimizing the blood culture workflow, each microbiology lab should critically scan its own workflow and know its own blood culture epidemiology, before investing in expensive or time-consuming processes.

The workup and interpretation of urine cultures is not always clear-cut, especially for midstream samples contaminated with commensals. Standard urine culture (SUC) protocols are designed in favor of growth of uropathogens at the expense of commensals. In selected clinical situations, however, it is essential to trace fastidious or new uropathogens by expanding the urine culture conditions (EUC). The aim of our study was to map the microflora in midstream urine specimens from healthy controls by means of EUC, in view of the interpretation of bacterial culture results in symptomatic patients. Midstream urine specimens from 101 healthy controls (86 females and 15 males) were examined using both SUC and EUC. Whilst 73 % of samples examined by SUC showed no growth at 10 3  colony-forming units (CFU)/mL, 91 % of samples examined by EUC grew bacterial species in large numbers (≥10 4  CFU/mL). Asymptomatic bacteriuria, as defined by the European guidelines for urinalysis, was detected in six samples with both protocols. EUC revealed 98 different species, mostly Lactobacillus, Staphylococcus, Streptococcus, and Corynebacterium. None of the samples grew Staphylococcus saprophyticus, Corynebacterium urealyticum, or Aerococcus urinae. Samples from females contained higher bacterial loads and showed higher bacterial diversity compared to males. Midstream urine of healthy controls contains large communities of living bacteria that comprise a resident microflora, only revealed by EUC. Hence, the use of EUC instead of SUC in a routine setting would result in more sensitive but less specific results, requiring critical interpretation. In our view, EUC should be reserved for limited indications.

Treatment of cystitis in primary care is usually empirical, guided by the prior probability of causal pathogens and their susceptibility. To re-evaluate empirical treatment guidelines, the actual distribution and susceptibility of uropathogens was examined and compared with two previous surveys in Belgium over the past 20 years. Because of the alarming increase in carriage of extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Escherichia coli, this specific resistance was explored. From May 2014 to December 2015, 120 general practitioners collected midstream urine specimens from adult pre- and postmenopausal female patients with suspected cystitis. A dipslide was inoculated and sent for microbiological analysis. Anal swabs were collected for ESBL and carbapenemase detection. Of 265 enrolled patients, 203 (79.3 %) had a positive culture. Escherichia coli (81.6 %) was the most frequently isolated uropathogen, followed by Staphylococcus saprophyticus (8 %), confirming the results of the 1995 and 2005 surveys. The susceptibility of E. coli remained nearly 100 % for nitrofurantoin and fosfomycin, decreased from nearly 100 % in 1995 to 94.2 % for quinolones, from 73.2 to 55.5 % for ampicillin, and from 83.3 to 76.3 % for trimethoprim-sulfamethoxazole (TMP-SMX). In E. coli present in positive urine cultures, ESBLs were found in 2.5 % and carbapenemases were absent. In fecal specimens, ESBL-producing E. coli were found in 7.9 % and carbapenemases were not detected. Over a 20-year period, the distribution of uropathogens in women with cystitis remained unchanged. Susceptibility remained excellent for nitrofurantoin and fosfomycin. For TMP-SMX, ampicillin, and quinolones, there was a decrease.

We compared the accuracy of direct susceptibility testing (DST) with conventional antimicrobial susceptibility testing (AST), both using disk diffusion, on clinical samples. A total of 123 clinical samples (respiratory tract samples, urine, vaginal and abdominal abscess discharges, bile fluid and a haematoma punctate) were selected on various indications; direct inoculation on Mueller-Hinton agar and antibiotic paper disks were applied. In parallel, standard culture, identification and AST on the colonies grown overnight was executed. Both AST and DST were interpreted after identification of the isolates. The results from both AST and DST for 11 antibiotics tested on 97 samples with Gram-negative rods showed 93.4 % total agreement, 1.6 % minor discordances, 4.6 % major discordances and 0.4 % very major discordances. Analysing the discordant results, DST predominantly resulted in more resistant isolates than AST. This was mostly due to the presence of resistant mutants or an additional isolate. The remaining discordances were seen for isolates with inhibition zones close to the clinical breakpoint. For the 26 samples yielding staphylococci, a total agreement of 100 % was observed for the nine antibiotics tested. Overall, the highest percentage of discordant results occurred for the β-lactam antibiotics amoxicillin-clavulanate (13.4 %) and cefuroxime (12.4 %). When used selectively and interpreted carefully, DST on clinical samples is potentially very useful in the management of critically ill patients, as the time to results is shortened by approximately 24 h. However, we recommend to communicate results with reservations and confirm by conventional AST.

Biowaste or the organic fraction of domestic waste, for instance kitchen, fruit and garden waste, is collected selectively in several European communities. The complementary fraction is called the dry or non recyclable fraction. A Dutch study reported that 92% of the participants that have a weekly collection service of both fractions (biowaste and non recyclable fraction) and 80% of the participants in the alternating collection program (one week biowaste and the next week non recyclable fraction) are pleased with separate collection of biowaste. Dominating problems that arise in case of alternating collection are a repulsive odor and an infestation with flies and maggots. By expanding the definition of biowaste to include non recyclable or soiled paper like dirty newspapers, table napkins and paper handkerchiefs, most of these problems can be overcome without changing the way compostable waste is collected and processed. The expanded definition of biowaste was used in this paper. Over a 12 month period a quality survey of the collected biowaste was conducted by the composting facility Intercompost, Hoeselt, Belgium. A special aspect was the fact that in one participating community baby diapers were included in the soiled paper fraction; this is called "biowaste+". The biowaste+ had a 10% non recyclable paper fraction opposed to only 1-2% of non recyclable paper present in the conventional biowaste. Baby diapers were a rather notable part (more than 80%) of this non recyclable paper fraction of biowaste+ and as a consequence might contribute to a large extent to improve the collection and treatment of biowaste. It was demonstrated that rural districts yielded about 35% more biowaste than more urban districts; resp. +/- 122 kg biowaste/capita. year versus +/- 90 kg biowaste/capita. year. In Hoeselt the biowaste+ yield was about 130 kg/capita.year. Biowaste+ is also separately collected in another Belgium community, namely Brecht. The purity level of the biowaste+ and the amount of non recyclable paper (including diapers) were comparable with the results of Hoeselt. In Hoeselt the biowaste+ fraction is composted aerobically. In Brecht on the other hand, the biowaste+ is processed using the Dry Anaerobic Composting process (DRANCO). The latter process is discussed in more detail. The biological start-up of the dry anaerobic composting installation at Brecht, Belgium, is reported. The reactor has a total volume of 808 m3 and a design capacity of 730 m3. After 2 months of start up, the fermentor was at full loading rate, i.e. 8 kg bVS/m3 reactor.day and the installation was working at full capacity, i.e. 40 ton/day.(ABSTRACT TRUNCATED AT 400 WORDS)