Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose.
Background/Objectives: Non-fermenting Gram-negative bacilli (NFGNB) represent a significant clinical challenge due to their intrinsic and acquired resistance, particularly in immunocompromised patients. Infections cause by NFGNB are associated with high morbidity and mortality, especially among patients with cystic fibrosis and hematologic malignancies. This study aimed to assess the in vitro susceptibility of clinically relevant NFGNB isolates to two newer antibiotics, cefiderocol and aztreonam/avibactam, and an established antibiotic, trimethoprim/sulfamethoxazole. Methods: This retrospective, monocentric study analysed 94 NFGNB isolates (30 Pseudomonas aeruginosa, 30 Acinetobacter sp., 24 Stenotrophomonas maltophilia, and 10 Burkholderia cepacia complex). Susceptibility testing for cefiderocol, aztreonam/avibactam, and trimethoprim/sulfamethoxazole was conducted using gradient strip method. MIC values were interpreted using EUCAST breakpoints, ECOFFs, or alternative criteria when necessary. Results: All S. maltophilia isolates were susceptible to cefiderocol (FCR) and aztreonam/avibactam (A/A) based on ECOFFs, with one strain resistant to trimethoprim–sulfamethoxazole (COT). Burkholderia cepacia complex strains also showed high susceptibility to FCR, with only one isolate exceeding the ECOFF for A/A, and 20% resistant to COT. All Acinetobacter sp. isolates were susceptible to FCR; however, most MIC values clustered at or just below the ECOFF value. In P. aeruginosa, one isolate was resistant to FCR, and three isolates (10%) were resistant to A/A. Interestingly, confirmed carbapenemase producers remained susceptible to both FCR and A/A. Most A/A MIC values for P. aeruginosa were just below the ECOFF. Conclusions: Cefiderocol and aztreonam/avibactam demonstrated promising in vitro activity against clinically relevant NFGNB, including carbapenem-resistant strains. These findings support their potential role as therapeutic options for difficult-to-treat infections, particularly in immunocompromised patients.
Background: Sepsis remains a leading cause of morbidity and mortality, particularly when caused by multidrug-resistant organisms (MDROs). Early identification of colonising or infecting pathogens may inform initial antimicrobial selection. Surveillance cultures, providing microbiological data prior to infection onset, could guide timely and targeted therapy. This retrospective study analysed routine surveillance culture results from patients with bloodstream infection (BSI) episodes, assessing pathogen prevalence, resistance phenotypes, and concordance with specimen type in haemato-oncology (HO) and acute care (AC) settings. Methods: Data were retrieved from the institutional Laboratory Information System of the Department of Clinical Microbiology and ATB Centre, General University Hospital in Prague, covering 1 January to 31 December 2024. All positive blood cultures containing ESCAPE pathogens (excluding Clostridioides difficile) were reviewed. Corresponding surveillance culture records were analysed to evaluate concordance with subsequent BSI episodes. Results: In 2024, 6046 AC and 7267 HO surveillance cultures were performed; MDRO prevalence was 5% and 6.56%, respectively. ESBL-producing Enterobacterales predominated (AC 86.9%, HO 81.6%). In HO, BSI-causing Gram-negative and Gram-positive pathogens were frequently detected in rectal swabs, whereas in AC, concordance was higher with upper and lower respiratory tract samples. Rectal screening detected 100% of E. coli and K. pneumoniae BSI episodes in HO. Other specimen types showed limited concordance. Conclusions: Surveillance culture utility varies by specimen type and clinical setting. In both HO and AC units, these cultures provided valuable insights into colonisation and resistance patterns, supporting early risk stratification and guiding initial therapy in high-risk patients.
Background: Fosfomycin (FOS) is an older antimicrobial agent newly rediscovered as a possible treatment for infections with limited therapeutic options (e.g., Gram-negative bacteria with difficult-to-treat resistance, DTR), especially in intravenous form. However, for correct usage of FOS, it is necessary to have a reliable susceptibility testing method suitable for routine practice and robust interpretation criteria. Results: The results were interpreted according to 2023 interpretation criteria provided by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). DTR Gram-negatives were more likely to be resistant to FOS (45% in Enterobacterales and 20% in P. aeruginosa) than non-DTR (10% and 6.7%, resp.). All isolates of S. aureus were susceptible to FOS. In Gram-negatives, all agreement values were unacceptable. Etest® performed better in the DTR cohort (categorical agreement, CA, 80%) than in the non-DTR cohort (CA 45.7%). There were no very major errors (VREs) observed in P. aeruginosa. S. aureus had surprisingly low essential agreement (EA) rates (53% for MRSA and 47% for MSSA) for Etest®, but categorical agreement was 100%. Methods: A total of 130 bacterial isolates were tested and compared using the disc diffusion method (DD) and gradient strip method (Etest®) with the reference method (agar dilution, AD). The spectrum of isolates tested was as follows: 40 Enterobacterales (20 DTR vs. 20 non-DTR), 30 Pseudomonas aeruginosa (15 DTR vs. 15 non-DTR), and 60 Staphylococcus aureus (30 methicillin-susceptible, MSSA, vs. 30 methicillin-resistant, MRSA). Conclusions: Neither one of the tested methods was identified as a suitable alternative to AD. It would be beneficial to define more interpretation criteria, at least in some instances.
Streptococcus pyogenes, group A streptococci (GAS) bacteriaemia, is a life-threatening infection with high mortality, requiring fast diagnosis together with the use of appropriate antibiotic therapy as soon as possible. Our study analysed data from 93 patients with GAS bacteraemia at the General University Hospital in Prague between January 2006 and March 2024. In the years 2016–2019 there was an increase in GAS bacteraemia. Mortality in the period 2006–2019 was 21.9%; in the period 2020–2024, the mortality increased to 41.4%, p = 0.08. At the same time, in the post-2020 period, the time from hospital admission to death was reduced from 9.5 days to 3 days. A significant predictor of worse outcome in this period was high levels of procalcitonin, >35.1 µg/L (100% sensitivity and 82.35% specificity), and lactate, >5 mmol/L (90.91% sensitivity and 91.67% specificity). Myoglobin was a significant predictor in both compared periods, the AUC was 0.771, p = 0.044, and the AUC was an even 0.889, p ≤ 0.001, respectively. All isolates of S. pyogenes were susceptible to penicillin, and resistance to clindamycin was 20.3% from 2006–2019 and 10.3% in 2020–2024. Appropriate therapy was initiated in 89.1%. and 96.6%, respectively. We hypothesise that the increase in mortality after 2020 might be due to a decrease in the immune status of the population.
Bacterial resistance surveillance is one of the main outputs of microbiological laboratories and its results are important part of antimicrobial stewardship (AMS). In this study, the susceptibility of specific bacteria to selected antimicrobial agents was tested. The susceptibility of 90 unique isolates of pathogens of critical priority obtained from clinically valid samples of ICU patients in 2017–2021 was tested. 50% of these fulfilled difficult-to-treat resistance (DTR) criteria and 50% were susceptible to all antibiotics included in the definition. 10 Enterobacterales strains met DTR criteria, and 2 (20%) were resistant to colistin (COL), 2 (20%) to cefiderocol (FCR), 7 (70%) to imipenem/cilastatin/relebactam (I/R), 3 (30%) to ceftazidime/avibactam (CAT) and 5 (50%) to fosfomycin (FOS). For Enterobacterales we also tested aztreonam/avibactam (AZA) for which there are no breakpoints yet. The highest MIC of AZA observed was 1 mg/l, MIC range in the susceptible cohort was 0.032–0.064 mg/l and in the DTR cohort (incl. class B beta-lactamase producers) it was 0.064–1 mg/l. Two (13.3%) isolates of Pseudomonas aeruginosa (15 DTR strains) were resistant to COL, 1 (6.7%) to FCR, 13 (86.7%) to I/R, 5 (33.3%) to CAT, and 5 (33.3%) to ceftolozane/tazobactam. All isolates of Acinetobacter baumannii with DTR were susceptible to COL and FCR, and at the same time resistant to I/R and ampicillin/sulbactam. New antimicrobial agents are not 100% effective against DTR. Therefore, it is necessary to perform susceptibility testing of these antibiotics, use the data for surveillance (including local surveillance) and conform to AMS standards.