Antibiotics

Porcine respiratory disease complex (PRDC) has been a major animal health, welfare, and economic problem in Hungary; therefore, great emphasis should be put on both the prevention and control of this complex disease. As antibacterial agents are effective tools for control, antibiotic susceptibility testing is indispensable for the proper implementation of antibacterial therapy and to prevent the spread of resistance. The best method for this is to determine the minimum inhibitory concentration (MIC) by the broth microdilution method. In our study, we measured the MIC values of 164 Actinobacillus pleuropneumoniae, 65 Pasteurella multocida, and 118 Streptococcus suis isolates isolated from clinical cases against the following antibacterial agents: amoxicillin, ceftiofur, cefquinome, oxytetracycline, doxycycline, tylosin, tilmicosin, tylvalosin, tulathromycin, lincomycin, tiamulin, florfenicol, colistin, enrofloxacin, and sulfamethoxazole-trimethoprim. Outstanding efficacy against A. pleuropneumoniae isolates was observed with ceftiofur (100%) and tulathromycin (100%), while high levels of resistance were observed against cefquinome (92.7%) and sulfamethoxazole-trimethoprim (90.8%). Ceftiofur (98.4%), enrofloxacin (100%), florfenicol (100%), and tulathromycin (100%) were found to be highly effective against P. multocida isolates, while 100% resistance was detected against the sulfamethoxazole-trimethoprim combination. For the S. suis isolates, only ceftiofur (100%) was not found to be resistant, while the highest rate of resistance was observed against the sulfamethoxazole-trimethoprim combination (94.3%). An increasing number of studies report multi-resistant strains of all three pathogens, making their monitoring a high priority for animal and public health. Full article

This cross-sectional study investigated the microbial landscape and antibiotic-resistance patterns in patients with bacterial pneumonia, with a focus on the impact of COVID-19. Sputum samples from individuals with bacterial pneumonia, including coronavirus disease 2019-positive polymerase chain reaction (COVID-19-PCR+), COVID-19-PCR− and non-COVID-19 patients, were analyzed. Surprisingly, the classic etiological factor of bacterial pneumonia, Streptococcus pneumoniae, was rarely isolated from the sputum samples. Furthermore, the frequency of multidrug-resistant pathogens was found to be higher in non-COVID-19 patients, highlighting the potential impact of the pandemic on antimicrobial resistance. Strains obtained from COVID-19-PCR+ patients exhibited significant resistance to commonly used antibiotics, including fluoroquinolones and cephalosporins. Notably, the ESKAPE pathogens, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, and Enterobacter aerogenes, were identified among the isolated microorganisms. Our findings underscore the urgent need for infection control measures and responsible antibiotic use in healthcare settings, as well as the importance of enhancing pneumonia diagnostics and implementing standardized laboratory protocols. Full article

Metallodrugs have a potent application in various medical fields. In the current study, we used a novel Palladium(II) thiazolinyl picolinamide complex that was directly fabricated over the titanium implant to examine its potency in inhibiting dual-species biofilms and exopolysaccharides. Additionally, inhibition of mono- and dual-species biofilms by coated titanium plates in an in vitro joint microcosm was performed. The study was carried out for 7 days by cultivating mono- and dual-species biofilms on titanium plates placed in both growth media and artificial synovial fluid (ASF). By qPCR analysis, the interaction of co-cultured biofilms in ASF and the alteration in gene expression of co-cultured biofilms were studied. Remarkable alleviation of biofilm accumulation and EPS secretion was observed on the coated titanium plates. The effective impairment of biofilms and EPS matrix of biofilms on Pd(II)-E-coated titanium plates were visualized by Scanning Electron Microscopy. Moreover, coated titanium plates improved the adhesion of osteoblast cells, which is crucial for a bone biomaterial. The potential bioactivity of coated plates was also confirmed at the molecular level using qPCR analysis. The stability of coated plates in ASF for 7 days was examined with FESEM-EDAX analysis. Collectively, the present study provided an excellent anti-infective effect on Pd(II)-E-coated titanium plates without affecting their biocompatibility with bone cells. Full article

Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a major public health concern. We aimed to evaluate the prevalence of CR-GNB and the frequency of carbapenemase-encoding genes in a tertiary referral center from El Bajio, Mexico. A cross-sectional study was conducted between January and October 2022; Gram-negative bacilli (GNB) were screened for in vitro resistance to at least one carbapenem. CR-GNB were further analyzed for carbapenemase-production through phenotypical methods and by real-time PCR for the following genes: bla_KPC, bla_GES, bla_NDM, bla_VIM, bla_IMP, and bla_OXA-48. In total, 37 out of 508 GNB were carbapenem-resistant (7.3%, 95% CI 5.2–9.9). Non-fermenters had higher rates of carbapenem resistance than Enterobacterales (32.5% vs. 2.6%; OR 18.3, 95% CI 8.5–39, p < 0.0001), and Enterobacter cloacae showed higher carbapenem resistance than other Enterobacterales (27% vs. 1.4%; OR 25.9, 95% CI 6.9–95, p < 0.0001). Only 15 (40.5%) CR-GNB had a carbapenemase-encoding gene; Enterobacterales were more likely to have a carbapenemase-encoding gene than non-fermenters (63.6% vs. 30.8%, p = 0.08); bla_NDM-1 and bla_NDM-5 were the main genes found in Enterobacterales; and bla_IMP-75 was the most common for Pseudomonas aeruginosa. The mcr-2 gene was harbored in one polymyxin-resistant E. cloacae. In our setting, NDM was the most common carbapenemase; however, less than half of the CR-GNB showed a carbapenemase-encoding gene. Full article

Fever of unknown origin (FUO) is a medical term describing fever that lasts for at least three weeks without a diagnosis being reached after extensive diagnostic evaluation. Therefore, this study aimed to identify the common pathogens causing FUO in patients admitted to Abbasia Fever Hospital in Egypt from January 2020 to December 2022, their antimicrobial susceptibility profiles, and associated resistance genes. The study also aimed to investigate the burden of multidrug-resistant (MDR) pathogens and the priority pathogens nominated by the World Health Organization (WHO) for posing the greatest threat to human health due to antibiotic resistance. During the study period, about 726 patients were diagnosed with FUO. After extensive investigations, the cause of the FUO was found to be infectious diseases in 479/726 patients (66.0%). Of them, 257 patients had positive bacterial cultures, including 202 Gram-negative isolates that comprised Klebsiella pneumoniae (85/202; 42.1%), Escherichia coli (71/202; 35.1%), Acinetobacter baumannii (26/202; 12.9%), and Pseudomonas aeruginosa (14/202; 6.9%) and 55 Gram-positive isolates, including Staphylococcus aureus (23/55; 41.8%), Streptococcus pneumoniae (7/55; 12.7%), and Enterococcus spp. (25/55; 45.5%). The MDR phenotype was shown by 68.3% and 65.5% of the Gram-negative and Gram-positive isolates, respectively. Carbapenem resistance (CR) was shown by 43.1% of the Gram-negative isolates. Of the 23 S. aureus isolates obtained from research participants, 15 (65.2%) were methicillin-resistant S. aureus (MRSA). A high-level aminoglycoside resistance (HLAR) phenotype was found in 52.0% of the Enterococcus sp. isolates. The PCR screening of resistance genes in the MDR isolates showed that bla_OXA−48 was the most prevalent (84%) among the carbapenemase-coding genes, followed by bla_VIM (9%) and then bla_IMP (12%). The ESBL-coding genes bla_TEM, bla_CTX-M,aac(6′)-Ib, and bla_SHV, were prevalent in 100%, 93.2%, 85,% and 53.4% of the MDR isolates, respectively. This study updates the range of bacteria that cause FUO and emphasizes the burden of multidrug resistance and priority infections in the region. The obtained data is of relevant medical importance for the implementation of evidence-based antimicrobial stewardship programs and tailoring existing empirical treatment guidelines. Full article

Introduction: The use of antibiotics leads to antibiotic resistance (ABR). Different methods have been used to predict and control ABR. In recent years, artificial intelligence (AI) has been explored to improve antibiotic (AB) prescribing, and thereby control and reduce ABR. This review explores whether the use of AI can improve antibiotic prescribing for human patients. Methods: Observational studies that use AI to improve antibiotic prescribing were retrieved for this review. There were no restrictions on the time, setting or language. References of the included studies were checked for additional eligible studies. Two independent authors screened the studies for inclusion and assessed the risk of bias of the included studies using the National Institute of Health (NIH) Quality Assessment Tool for observational cohort studies. Results: Out of 3692 records, fifteen studies were eligible for full-text screening. Five studies were included in this review, and a narrative synthesis was carried out to assess their findings. All of the studies used supervised machine learning (ML) models as a subfield of AI, such as logistic regression, random forest, gradient boosting decision trees, support vector machines and K-nearest neighbours. Each study showed a positive contribution of ML in improving antibiotic prescribing, either by reducing antibiotic prescriptions or predicting inappropriate prescriptions. However, none of the studies reported the engagement of AB prescribers in developing their ML models, nor their feedback on the user-friendliness and reliability of the models in different healthcare settings. Conclusion: The use of ML methods may improve antibiotic prescribing in both primary and secondary settings. None of the studies evaluated the implementation process of their models in clinical practices. Prospero Registration: (CRD42022329049). Full article

The Arcobacter genus comprises a group of bacteria widely distributed in different habitats that can be spread throughout the food chain. Fluoroquinolones and aminoglycosides represent the most common antimicrobial agents used for the treatment of Arcobacter infections. However, the increasing trend of the antimicrobial resistance of this pathogen leads to treatment failures. Moreover, the test implementation and interpretation are hindered by the lack of reference protocols and standard interpretive criteria. The purpose of our study was to assess the antibiotic resistance pattern of 17 A. butzleri strains isolated in Central Italy from fresh vegetables, sushi, chicken breast, and clinical human samples to provide new and updated information about the antimicrobial resistance epidemiology of this species. Antimicrobial susceptibility testing was carried out by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)’s disc diffusion method. All the strains were multidrug resistant, with 100% resistance to tetracyclines and cefotaxime (third generation cephalosporins). Some differences were noticed among the strains, according to the isolation source (clinical isolates, food of animal origin, or fresh vegetables), with a higher sensitivity to streptomycin detected only in the strains isolated from fresh vegetables. Our data, together with other epidemiological information at the national or European Union (EU) level, may contribute to developing homogeneous breakpoints. However, the high prevalence of resistance to a wide range of antimicrobial classes makes this microorganism a threat to human health and suggests that its monitoring should be considered by authorities designated for food safety. Full article

Drain-associated intracerebral infections are life-threatening emergencies. Their treatment is challenging due to the limited penetration of antibiotics to the site of infection, resulting in potentially inadequate exposure. The emergence of multidrug-resistant pathogens might force the use of off-label intrathecal (IT) doses of antibiotics. We reviewed the literature on general aspects determining intrathecal dosing regimen, using pharmacometric knowledge. We summarised clinical experience with IT doses of antibiotics that are usually not used intrathecally, as well as the outcome of the cases and concentrations reached in the cerebrospinal fluid (CSF). Factors determining the IT regimen are the size of the ventricle system and the CSF drainage volume. With regard to pharmacometrics, pharmacokinetic/pharmacodynamic indices are likely similar to those in non-cerebral infections. The following number (N) of cases were described: benzylpenicillin (>50), ampicillin (1), ceftazidime (2), cephaloridine (56), ceftriaxone (1), cefotiam (1), meropenem (57), linezolid (1), tigecycline (15), rifampicin (3), levofloxacin (2), chloramphenicol (3) and daptomycin (8). Many side effects were reported for benzylpenicillin in the 1940–50s, but for the other antibiotics, when administered correctly, all side effects were minor and reversible. These data might help when choosing an IT dosing regimen in case there is no alternative option due to antimicrobial resistance. Full article

Background: Although ceftazidime/avibactam (CAZ/AVI) has become an important option for treating adults and children, no data or recommendations exist for neonates. We report a neonatal sepsis case due to CAZ/AVI-resistant bla_KPC-2-harboring Klebsiella pneumoniae carrying bla_VEB-25 and the use of a customized active surveillance program in conjunction with enhanced infection control measures. Methods: The index case was an extremely premature neonate hospitalized for 110 days that had been previously treated with multiple antibiotics. Customized molecular surveillance was implemented at hospital level and enhanced infection control measures were taken for early recognition and prevention of outbreak. Detection and identification of bla_VEB-25 was performed using next-generation sequencing. Results: This was the first case of a bloodstream infection caused by KPC-producing K. pneumoniae that was resistant to CAZ/AVI without the presence of a metalo-β-lactamase in the multiplex PCR platform in a neonate. All 36 additional patients tested (12 in the same NICU and 24 from other hospital departments) carried wild-type bla_VEB-1 but they did not harbor bla_VEB-25. Conclusion: The emergence of bla_VEB-25 is signal for the horizontal transfer of plasmids at hospital facilities and it is of greatest concern for maintaining a sharp vigilance for the surveillance of novel resistance mechanisms. Molecular diagnostics can guide appropriate antimicrobial therapy and the early implementation of infection control measures against antimicrobial resistance. Full article

Background: The aims of this study were to describe pharmacokinetic/pharmacodynamic target attainment in intensive care unit (ICU) patients treated with continuously infused ß-lactam antibiotics, their associated covariates, and the impact of dosage adjustment. Methods: This prospective, observational, cohort study was performed in three ICUs. Four ß-lactams were continuously infused, and therapeutic drug monitoring (TDM) was performed at days 1, 4, and 7. The primary pharmacokinetic/pharmacodynamic target was an unbound ß-lactam plasma concentration four times above the bacteria’s minimal inhibitory concentration during the whole dosing interval. The demographic and clinical covariates associated with target attainment were evaluated. Results: A total of 170 patients were included (426 blood samples). The percentages of empirical ß-lactam underdosing at D1 were 66% for cefepime, 43% for cefotaxime, 47% for ceftazidime, and 14% for meropenem. Indexed creatinine clearance was independently associated with treatment underdose if increased (adjusted odds ratio per unit, 1.01; 95% CI, 1.00 to 1.01; p = 0.014) or overdose if decreased (adjusted odds ratio per unit, 0.95; 95% CI, 0.94 to 0.97; p < 0.001). Pharmacokinetic/pharmacodynamic target attainment was significantly increased after ß-lactam dosage adjustment between day 1 and day 4 vs. no adjustment (53.1% vs. 26.2%; p = 0.018). Conclusions: This study increases our knowledge on the optimization of ß-lactam therapy in ICU patients. A large inter- and intra-patient variability in plasmatic concentrations was observed, leading to inadequate exposure. A combined indexed creatinine clearance and TDM approach enables adequate dosing for better pharmacokinetic/pharmacodynamic target attainment. Full article

The important periodontal disease pathogen Porphyromonas gingivalis produces thick biofilms that increase its pathogenicity. Finding natural antimicrobial agents is crucial because of the rise in antibiotic resistance. The purpose of this study was to determine if plant extracts such as Symphytum officinale (S) and Panax Ginseng (G) were effective against P. gingivalis separately and in combination with a common antibiotic, metronidazole (F). Six different dilutions were produced using the plant extracts in different concentrations and antibiotics separately and in combination with F, G, and S using the two-fold serial dilution technique. To evaluate the effects of these substances, biofilm inhibition experiments were conducted. Plaque samples were collected from periodontitis patients to isolate P. gingivalis, and a standard strain of P. gingivalis (ATCC 33277) was purchased. Additionally, Acylated Homoserine Lactones (AHLs) detection was carried out to look for any activity that would interfere with quorum sensing. GraphPad Prism was used for statistical analysis with a p-value < 0.05. The combinations of Symphytum officinale and metronidazole (S+F) showed the maximum effectiveness in biofilm inhibition (98.7%), which was slightly better than G+F (98.2%), with substantial variations in biofilm inhibition levels in different treatment regimes. Notably, the patient isolate was more active than the standard strain. Additionally, the plant extracts and their combinations at particular dilutions had notable inhibitory effects on the generation of AHL (p < 0.05). The study highlights the possibility of Symphytum officinale and Panax Ginseng as effective treatments for P. gingivalis biofilm and AHLs, both on their own and in combination with metronidazole. These organic substances may open the door to cutting-edge methods of treating periodontal disorders. Full article

Antimicrobial resistance (AMR) has emerged as an urgent global public health issue that requires immediate attention. Methicillin-resistant staphylococci (MRS) is a major problem, as it may cause serious human and animal infections, eventually resulting in death. This study determined the proportional distribution, genetic characteristics, and antimicrobial susceptibility of mecA- or mecC-carrying staphylococci isolated from food chain products. A total of 230 samples were taken from meat, food, fermented food, and food containers. Overall, 13.9% (32/230) of the samples were identified to have Staphylococcus aureus isolates; of those, 3.9% (9/230) were MRS, with eight mecA-positive and one mecC-positive samples, and 1.3% (3/230) methicillin-resistant Staphylococcus aureus (MRSA). MRSA strains belonging to three sequence types (ST9, ST22, and a newly identified ST), three different spa types (T005, t526, and a newly identified type), and three different SCCmec types (IV, V, and an unidentified SCCmec) were detected. Additionally, eight mecA-positive staphylococcal isolates were identified as S. haemolyticus, S. sciuri, S. simulans, and S. warneri, while the mecC-harboring isolate was S. xylosus. The enterotoxin gene, SEm, was detected at 1.56% in S. aureus, whereas SEq was detected at 0.31%, and SEi was also found in MRSA. Our study emphasizes the importance of enhanced hygiene standards in reducing the risk of occupational and foodborne MRSA infections associated with the handling or consumption of meat, food, and preserved food products. Full article

The incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing since 2008, with Gyeonggi Province in South Korea being particularly vulnerable due to its large number of healthcare facilities. This study examines the trends of CRE occurrence in Gyeonggi Province over the past four years and the epidemiological characteristics of the infected patients. Patients with positive CRE blood cultures admitted to healthcare facilities in Gyeonggi Province from January 2018 to December 2021 were evaluated in this study. Risk factors for CRE-related death were analyzed using data from patients who died within 30 days of the last blood sampling. Older adults aged 70 years and above constituted the majority of patients with CRE bacteremia. Antibiotic use did not significantly affect mortality risk. Non-survivors were more common in tertiary hospitals and intensive care units and included patients with hypertension, malignant tumors, and multiple underlying diseases. Klebsiella pneumoniae was the most common CRE strain, with Klebsiella pneumoniae carbapenemase being the predominant carbapenemase. Our study suggests the endemicity of CRE in Gyeonggi Province and highlights the increasing isolation of CRE strains in South Korean long-term care hospitals within the province. Further, infection control measures and government support specific to each healthcare facility type are crucial. Full article

The COVID-19 era brought about new medical challenges, which, together with nosocomial bacterial infections, resulted in an enormous burden for the healthcare system. One of the most alarming nosocomial threats was carbapenem-resistant Klebsiella pneumoniae (CRKP). Monitoring CRKP incidence and antimicrobial resistance globally and locally is vitally important. In a retrospective study, the incidence of CRKP in the pre-COVID-19 period (2017–2019) and the COVID-19 pandemic (2020–2022) was investigated in the Central Military Hospital in Ružomberok, Slovak Republic. The relative incidence of CRKP significantly increased during the COVID-19 period—by 4.8 times, from 0.18 to 0.76%. At the same time, 47% of CRKP-positive patients also had COVID-19. Twenty-six KPC and sixty-nine NDM-producing isolates were identified. CRKPs isolated in the year 2022 were submitted to whole genome sequencing, and their susceptibility was tested to cefiderocol, ceftazidime–avibactam, imipenem–relebactam and meropenem–vaborbactam, with excellent results. KPC-producing isolates were also highly susceptible to colistin (92%). The NDM isolates revealed lower susceptibility rates, including only 57% colistin susceptibility. ST-307 prevailed in KPC and ST-11 in NDM isolates. Despite the excellent activity of new antimicrobials, rational antibiotic policy must be thoroughly followed, supported by complementary treatments and strict anti-epidemic precautions. Full article

Bacterial contamination of semen has become an important contributor to the reduced shelf life of insemination doses in the poultry industry, which is why antibiotics (ATBs) are an important component of semen extenders. Due to a global rise in antimicrobial resistance, the aim of this study was to assess the efficiency of selected commercially available semen extenders to prevent possible bacterial contamination of rooster ejaculates. Two selected extenders free from or containing 31.2 µg/mL kanamycin (KAN) were used to process semen samples from 63 healthy Lohmann Brown roosters. Phosphate-buffered saline without ATBs was used as a control. The extended samples were stored at 4 °C for 24 h. Sperm motility, viability, mitochondrial activity, DNA integrity and the oxidative profile of each extended sample were assessed following 2 h and 24 h of storage. Furthermore, selective media were used to quantify the bacterial load and specific bacterial species were identified with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The results indicate that semen extenders enriched with KAN ensured a significantly higher preservation of sperm quality in comparison to their KAN-free counterparts. Bacterial load was significantly decreased in diluents supplemented with ATBs (p ≤ 0.001); however, KAN alone was not effective enough to eradicate all bacteria since several Escherichia coli, Enterococcus faecalis, Enterococcus faecium and Micrococcus luteus were retrieved from samples extended in KAN-supplemented commercial extenders. As such, we may suggest that more focus should be devoted to the selection of an optimal combination and dose of antibiotics for poultry extenders, which should be accompanied by a more frequent bacteriological screening of native as well as extended poultry semen. Full article

Although antimicrobial peptides (AMPs) have highly desirable intrinsic characteristics in their commercial product development as new antimicrobials, the limitations of AMPs from experimental to scale development include the low oral bioavailability, and high production costs due to inadequate in vitro/in vivo gene expression- and low scale. Plectasin has good bactericidal activity against Staphylococcus and Streptococcus, and the selective bactericidal activity greatly reduces the damage to the micro-ecosystem when applied in vivo. However, its expression level was relatively low (748.63 mg/L). In view of these situations, this study will optimize and modify the structure of Plectasin, hoping to obtain candidates with high expression, no/low toxicity, and maintain desirable antibacterial activity. Through sequence alignment, Plectasin was used as a template to introduce the degenerate bases, and the screening library was constructed. After three different levels of screening, the candidate sequence PN7 was obtained, and its total protein yield in the supernatant was 5.53 g/L, with the highest value so far for the variants or constructs from the same ancestor source. PN7 had strong activity against several species of Gram-positive bacteria (MIC value range 1~16 μg/mL). It was relatively stable in various conditions in vitro; in addition, the peptide showed no toxicity to mice for 1 week after intraperitoneal injection. Meanwhile, PN7 kills Staphylococcus aureus ATCC 43300 with a mode of a quicker (>99% S. aureus was killed within 2 h, whereas vancomycin at 2× MIC was 8 h.) and longer PAE period. The findings indicate that PN7 may be a novel promising antimicrobial agent, and this study also provides a model or an example for the design, modification, or reconstruction of novel AMPs and their derivatives. Full article

Ceftazidime–avibactam (CAZ-AVI) is an active antibiotic combination of a β-lactam–β-lactamase inhibitor against carbapenemase-producing Enterobacterales. Reports of resistance to CAZ-AVI other than metallo-β-lactamases have increased in recent years. The aim of this study was to analyze KPC-Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI from the intestinal carriage of hospitalized elderly patients in Italy, in February 2018–January 2020. Characterization of CAZ-AVI-resistant KP isolates, including MLST, resistome, virulome and plasmid content, was performed by WGS analysis. Out of six CAZ-AVI-resistant KP isolates, three belonged to ST101 and three to ST512; two isolates produced KPC-3 (both ST512), four had mutated KPC-3 (KPC-31, in ST101 and ST512, and KPC-46, both ST101). All CAZ-AVI-resistant KP isolates were multidrug-resistant and carried several resistance genes. The yersiniabactin ybt9 gene cluster was present in all ST101 isolates, while, in ST512 isolates, no virulence genes were detected. Several plasmids were detected: IncF was present in all isolates, as well as IncR and Col440 in ST101 and IncX3 in ST512 isolates. In conclusion, it is important to monitor the circulation of K. pneumoniae resistant to CAZ-AVI to prevent the spread of clones causing difficult-to-treat infections. The presence of mutated KPC-3 in high-risk K. pneumoniae clones resistant to CAZ-AVI in hospitalized patients deserves attention. Full article

Probiotics are among those products, the use of which is increasing, and they are available primarily as food/dietary supplements, as well as in the form of medicines. This study aims to assess the attitudes and practices of health professionals and students of health sciences, give a short overview of the probiotics currently on the market, and conduct a screening of five food supplements and one drug with respect to antibiotic resistance. Nearly half of the respondents in our survey state that probiotics have no side effects, while only 6.3% believe that the use of probiotics can lead to antibiotic resistance. In addition, more than 40% of the participants throw unused probiotics into municipal waste. The market analysis results indicate that probiotic products on the Serbian market have highly variable CFU counts, while the declared health claims cover numerous beneficial health effects, and they are sometimes even registered as medicines. Lactobacilli are frequently present in probiotic supplements, and are sold in pharmacies and online. The experimental results showed that antibiotic resistance is present in different types of lactobacilli in probiotic products. The risk of using probiotics, regardless of their beneficial health effects, should be taken into account in the future. An update to the regulations governing probiotics, including a stipulation for antimicrobial resistance (AMR) testing, should be established, and guidelines for their proper use and disposal put into place. Full article

Among the pathogenic free-living amoebae (FLA), Naegleria fowleri is the etiological agent of a fatal disease known as primary amoebic meningoencephalitis (PAM). Once infection begins, the lesions generated in the central nervous system (CNS) result in the onset of symptoms leading to death in a short period of time. Currently, there is no standardized treatment against the infection, which, due to the high virulence of the parasite, results in a high case fatality rate (>97%). Therefore, it is essential to search for new therapeutic sources that can generate a rapid elimination of the parasite. In recent years, there have already been several successful examples of drug repurposing, such as Nitroxoline, for which, in addition to its known bioactive properties, anti-Balamuthia activity has recently been described. Following this approach, the anti-Naegleria activity of Nitroxoline was tested. Nitroxoline displayed low micromolar activity against two different strains of N. fowleri trophozoites (IC₅₀ values of 1.63 ± 0.37 µM and 1.17 ± 0.21 µM) and against cyst stages (IC₅₀ of 1.26 ± 0.42 μM). The potent anti-parasitic activity compared to the toxicity produced (selectivity index of 3.78 and 5.25, respectively) in murine macrophages and human cell lines (reported in previous studies), together with the induction of programmed cell death (PCD)-related events in N. fowleri make Nitroxoline a great candidate for an alternative PAM treatment. Full article