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.
- Klíčová slova
- antimicrobial resistance, aztreonam/avibactam, cefiderocol, immunocompromised patients, non-fermenting gram-negative bacilli, susceptibility,
- Publikační typ
- časopisecké články MeSH
The impact of remdesivir on renal and liver functions remains a matter of concern in advanced COVID-19 patients with high illness severity and presence of viral load. The laboratory results of the 114 patients (males 55.8%, age 71 (59; 77) years) with a detectable viral load treated with remdesivir were compared with the controls. Baseline plasmatic creatinine (PCr) < 150 µmol/l in patients on remdesivir decreased equally to controls (- 6 (- 20; 9) vs. - 8 (- 24; 2) µmol/l, n = 170, p = 0.11). The similar trends were found for baseline PCr ≥ 150 µmol/l (- 57 (- 129; - 15) µmol/l for remdesivir group vs. - 65 (- 111; - 7) µmol/l, p > 0.9). Changes of PCr were independent of the remdesivir therapy, the statistically significant confounders were baseline PCr levels (p < 0.001), hospital length-of-stay (p < 0.001), leukocyte-to-lymphocyte ratio (p = 0.025). The plasmatic urea (PU) mildly increased in the remdesivir group (1 (- 2; 5) mmol/l vs. 0 (- 3; 2) mmol/l in the controls, p = 0.009), its levels were related to remdesivir (p = 0.026), age (p = 0.002), PCr (p < 0.001), hospital length-of-stay (p < 0.001), IPPV (p = 0.035). Regarding the liver function tests the significant relationships to remdesivir therapy were found only for GGT (p = 0.007) and ALT (p = 0.044). The levels of PCr were decreasing over the hospitalisation period including patients with mild-to-moderate renal insufficiency. The multivariate regression analysis excluded an impact of remdesivir on the PCr changes yet admitted an impact on the levels of urea, GGT and ALT.
- Klíčová slova
- Intensive care, Liver function tests, Remdesivir, Renal function, SARS-CoV-2, Viral load,
- MeSH
- adenosinmonofosfát * analogy a deriváty terapeutické užití škodlivé účinky MeSH
- alanin * analogy a deriváty terapeutické užití škodlivé účinky MeSH
- antivirové látky * terapeutické užití škodlivé účinky MeSH
- COVID-19 * virologie patofyziologie MeSH
- farmakoterapie COVID-19 * MeSH
- jaterní testy MeSH
- játra * účinky léků patofyziologie MeSH
- kreatinin krev MeSH
- ledviny * účinky léků patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- močovina krev MeSH
- SARS-CoV-2 izolace a purifikace MeSH
- senioři MeSH
- virová nálož * účinky léků MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adenosinmonofosfát * MeSH
- alanin * MeSH
- antivirové látky * MeSH
- kreatinin MeSH
- močovina MeSH
- remdesivir MeSH Prohlížeč
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.
- Klíčová slova
- Etest, agar dilution, difficult-to-treat, disc diffusion, fosfomycin, susceptibility,
- Publikační typ
- časopisecké články MeSH
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.
- Klíčová slova
- GAS bacteriaemia, Streptococcus pyogenes, appropriate therapy, lactate, myoglobin, procalcitonin,
- Publikační typ
- časopisecké články MeSH
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.
- Klíčová slova
- Antimicrobial stewardship, Aztreonam/avibactam, Cefiderocol, Ceftazidime/avibactam, Ceftolozane/tazobactam, Colistin, Difficult-to-treat resistance, Fosfomycin, Imipenem/cilastatin/relebactam,
- MeSH
- antibakteriální látky * farmakologie terapeutické užití MeSH
- azabicyklické sloučeniny * MeSH
- aztreonam MeSH
- cefalosporiny * MeSH
- cefiderokol MeSH
- gramnegativní bakterie MeSH
- kolistin farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Pseudomonas aeruginosa MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky * MeSH
- avibactam MeSH Prohlížeč
- azabicyklické sloučeniny * MeSH
- aztreonam MeSH
- cefalosporiny * MeSH
- cefiderokol MeSH
- kolistin MeSH
BACKGROUND: Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). METHODS: A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65-79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. RESULTS: Patients with estimated GFR (eGFR) <30 mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30 mL/min (89.75 vs 186.0 mg/L, P < .0001; 200.5 vs 830.0 mg/L, P < .0001; and 126.0 vs 408.0 mg/L, P < .0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10-13 h after dose administration was dependent on eGFR (r2 = 0.6144, P < .0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100 mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. CONCLUSION: Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity.
- Klíčová slova
- UTI, aminoglycosides, dialysis, kidney impairment, pharmacokinetics,
- Publikační typ
- časopisecké články MeSH
Trace elements and vitamins, collectively known as micronutrients, are essential for basic metabolic reactions in the human body. Their deficiency or, on the contrary, an increased amount can lead to serious disorders. Research in recent years has shown that long-term abnormal levels of micronutrients may be involved in the etiopathogenesis of some neurological diseases. Acute and chronic alterations in micronutrient levels may cause other serious complications in neurological diseases. Our aim was to summarize the knowledge about micronutrients in relation to selected neurological diseases and comment on their importance and the possibilities of therapeutic intervention in clinical practice.
- Klíčová slova
- Huntington’s disease, Parkinson’s disease, autoimmune disorders, epilepsy, micronutrients, multiple sclerosis, neurodegenerative disorders, neuropathy, stroke,
- MeSH
- lidé MeSH
- mikroživiny MeSH
- nemoci nervového systému * MeSH
- stopové prvky * MeSH
- vitamin A MeSH
- vitaminy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mikroživiny MeSH
- stopové prvky * MeSH
- vitamin A MeSH
- vitaminy MeSH
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: We introduce a relatively new difficult-to-treat resistance (DTR) category to specialists. It significantly influences the predictability of morbidity and mortality in patients with invasive infections caused by DTR strains. Therefore, surveillance of DTR is an important tool of antimicrobial stewardship (AMS) and widely contributes to cooperation between microbiologists and clinicians. We also report the prevalence of strains meeting the criteria for the category in a teaching hospital. METHODS: This retrospective cohort single center study included invasive isolates of gram-negative rods from patients hospitalized in the General University Hospital in Prague in 2009-2013 and in 2017-2021. RESULTS: From a total of 1 732 (920 and 812, respectively) unique strains of gram-negative rods isolated from blood cultures in both periods, 6.6 % were carbapenem-resistant in 2009-2013 and 6.0 % in 2017-2021; 3.7 % were identified as DTR in both periods. Most of the DTR strains were A. baumannii (23.1 % and 45.0 %, respectively) and P. aeruginosa (22.2 % and 15.3 %, respectively). We identified no carbapenem-resistant E. coli and therefore no DTR E. coli. CONCLUSION: Infections caused by bacterial strains with a DTR phenotype are grave complications and are tricky to manage. The prevalence of severe infections caused by these strains was relatively low in the studied facility. Antibiotics with anti-DTR effects should be considered the last resort, so it is very important to comply with AMS rules and examine the susceptibility of these agents.
- MeSH
- antibakteriální látky * farmakologie terapeutické užití MeSH
- Escherichia coli * MeSH
- gramnegativní bakterie MeSH
- karbapenemy MeSH
- mikrobiální testy citlivosti MeSH
- retrospektivní studie MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky * MeSH
- karbapenemy MeSH
The study presents a novel vancomycin-releasing collagen wound dressing derived from Cyprinus carpio collagen type I cross-linked with carbodiimide which retarded the degradation rate and increased the stability of the sponge. Following lyophilization, the dressings were subjected to gamma sterilization. The structure was evaluated via scanning electron microscopy images, micro-computed tomography, and infrared spectrometry. The structural stability and vancomycin release properties were evaluated in phosphate buffered saline. Microbiological testing and a rat model of a wound infected with methicillin-resistant Staphylococcus aureus (MRSA) were then employed to test the efficacy of the treatment of the infected wound. Following an initial mass loss due to the release of vancomycin, the sponges remained stable. After 7 days of exposure in phosphate buffered saline (37°C), 60% of the material remained with a preserved collagen secondary structure together with a high degree of open porosity (over 80%). The analysis of the release of vancomycin revealed homogeneous distribution of the antibiotic both across and between the sponges. The release of vancomycin was retarded as proved by in vitro testing and further confirmed by the animal model from which measurable concentrations were observed in blood samples 24 hours after the subcutaneous implantation of the sponge, which was more than observed following intraperitoneal administration. The sponge was also highly effective in terms of reducing the number of colony-forming units in biopsies extracted from the infected wounds 4 days following the inoculation of the wounds with the MRSA solution. The presented sponges have ideal properties to serve as wound dressing for prevention of surgical site infection or treatment of already infected wounds.
- MeSH
- antibakteriální látky farmakokinetika MeSH
- hojení ran účinky léků MeSH
- kapři MeSH
- karbodiimidy farmakokinetika MeSH
- kolagen farmakokinetika MeSH
- krysa rodu Rattus MeSH
- methicilin rezistentní Staphylococcus aureus účinky léků MeSH
- obvazy MeSH
- vankomycin farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- karbodiimidy MeSH
- kolagen MeSH
- vankomycin MeSH
