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003) emerged as an independent predictor of mortality; non-survival patients most frequently had pneumonia (

= 0.009) or mechanical ventilation (

= 0.049).

Ceftazidime-avibactam showed high efficacy in infections caused by MDR Gram-negative pathogens with limited therapeutic options.

Ceftazidime-avibactam showed high efficacy in infections caused by MDR Gram-negative pathogens with limited therapeutic options.Finding a suitable alternative to the small pool of existing antifungal agents is a vital task in contemporary agriculture. Therefore, intensive research has been conducted globally to uncover environmentally friendly and efficient agents that can suppress pathogens resistant to the currently used antimycotics. Here, we tested the activity of boric acid (BA) and its derivative phenylboronic acid (PBA) in controlling the early blight symptoms in tomato plants infected with pathogenic fungus Alternaria alternata. By following the appearance and intensity of the lesions on leaves of the tested plants, as well as by measuring four selected physiological factors that reflect plant health, we have shown that both BA and PBA act prophylactically on fungal infection. They did it by reducing the amount and severity of early blight symptoms, as well as by preventing deterioration of the physiological traits, occurring upon fungal inoculation. Phenylboronic acid was more efficient in suppressing the impact of A. alternata infection. Therefore, we conclude that BA, and even more so PBA, may be used as agents for controlling early blight on tomato plants, as they are both quite effective and environmentally friendly.As bioactive small proteins with antimicrobial and immunomodulatory activities that are naturally produced by all living organisms, antimicrobial peptides (AMPs) have a marked potential as next-generation antibiotics. However, their development as antibacterial agents is limited by low stability and cytotoxicity. D-BMAP18, a membrane-permeabilizing antimicrobial peptide composed of D-amino acids, has shown good antibacterial and anti-inflammatory activities but also a non-negligible cytotoxicity against eukaryotic cell lines. In this study, a prodrug has been developed that extends the peptide with a negatively charged, inactivating sequence containing the cleavage site for neutrophil elastase (NE). The ultimate goal was to allow the activation of D-BMAP18 by endogenous elastase only at the site of infection/inflammation, enabling a slow and targeted release of the pharmacologically active peptide. In vitro activation of Pro-D-BMAP18 was confirmed using purified NE. Its antimicrobial and cytotoxic activities were tested in the presence and absence of elastase and compared to those of the parental form. The prodrug had minimal activity in the absence of elastase, while its proteolysis product retained an appreciable antimicrobial activity but lower cytotoxicity. Moreover, Pro-D-BMAP18 was found to be correctly converted to D-BMAP18 in the presence of CF sputum as a model of the lung environment and showed good antimicrobial activity under these conditions.New approaches to deal with the growing concern associated with antibiotic-resistant bacteria are in high demand [...].The Aggregatibacter actinomycetemcomitans JP2 genotype is associated with high leukotoxin production and severe (aggressive) periodontitis. The aim of this study was to compare the antimicrobial susceptibility of JP2 and non-JP2 genotype strains. Minimal inhibitory concentrations (MICs) of 11 antimicrobials were determined for 160 A. actinomycetemcomitans of serotype a, b, or c, mostly isolated in Sweden or Ghana. MIC distributions for benzylpenicillin and fusidic acid revealed a more susceptible subpopulation for 38 serotype b strains, including the 32 of the JP2 genotype, with a benzylpenicillin MIC range of 0.125-0.5 mg/L. In contrast, benzylpenicillin MIC ≤ 16 mg/L was the estimated 99.5% epidemiological cutoff (ECOFF) of all strains. Beta-lactamase production was not detected. The fusidic acid MIC distribution of 11 strains of Aggregatibacter aphrophilus agreed with that found in non-JP2 strains. Cefotaxime, meropenem, levofloxacin, and trimethoprim-sulfamethoxazole MICs were all ≤0.25 mg/L, while MIC90 values for amoxicillin, azithromycin and tetracycline were 1 mg/L. Metronidazole MICs varied between 0.5 and >256 mg/L. The discrepant findings indicate that A. actinomycetemcomitans may be divided into two separate wild types, with a suggested intrinsic reduced susceptibility for benzylpenicillin in the majority of non-JP2 genotype strains. Possible implications for the treatment of A. actinomycetemcomitans infections are discussed.Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of life-threatening endovascular infections. Endothelial cell (EC) damage is a key factor in the pathogenesis of these syndromes. However, genetic factors related to the EC damage have not been well studied. This study aims to identify genetic determinants that impact human EC damage by screening the genome-wide Nebraska Transposon Mutant Library (NTML). A well-established MTT assay was used to test the in vitro damage of human EC cell line (HMEC-1) caused by each mutant strain in the NTML. We first confirmed some global regulators and genes positively impact the EC damage, which is consistent with published results. These data support the utility of the high-throughput approach. Importantly, we demonstrated 317 mutants significantly decreased the EC damage, while only 6 mutants enhanced the EC damage vs. parental JE2 strain. The majority of these genes have not been previously defined to affect human EC damage. Interestingly, many of these newly identified genes are involved in metabolism, genetic and environmental information processing, and cellular processes. These results advance our knowledge of staphylococcal genetic factors related to human EC damage which may provide novel targets for the development of effective agents against MRSA endovascular infection.The outbreak of COVID-19 has significantly changed the epidemiology of respiratory tract infection in several ways. The implementation of non-pharmaceutical interventions (NPIs) including universal masking, hand hygiene, and social distancing not only resulted in a decline in reported SARS-CoV-2 cases but also contributed to the decline in the non-COVID-19 respiratory tract infection-related hospital utilization. Moreover, it also led to the decreased incidence of previous commonly encountered respiratory pathogens, such as influenza and Streptococcus pneumoniae. Although antimicrobial agents are essential for treating patients with COVID-19 co-infection, the prescribing of antibiotics was significantly higher than the estimated prevalence of bacterial co-infection, which indicated the overuse of antibiotics or unnecessary antibiotic use during the COVID-19 pandemic. Furthermore, inappropriate antimicrobial exposure may drive the selection of drug-resistant microorganisms, and the disruption of infection control in COVID-19 setting measures may result in the spread of multidrug-resistant organisms (MDROs). In conclusion, NPIs could be effective in preventing respiratory tract infection and changing the microbiologic distribution of respiratory pathogens; however, we should continue with epidemiological surveillance to establish updated information, antimicrobial stewardship programs for appropriate use of antibiotic, and infection control prevention interventions to prevent the spread of MDROs during the COVID-19 pandemic.Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. LDC195943 mouse d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTIs; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here, we present data from a post hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.The increasing number of nosocomial pathogens with resistances towards last resort antibiotics, like linezolid for gram positive bacteria, leads to a pressing need for screening and, consequently, suitable screening media. Some national guidelines on infection prevention (e.g., in Germany) have already recommended screening for linezolid-resistant bacteria, despite an accurate screening medium that was not available yet. In this study, we analyzed the performance and reliability of the first commercial chromogenic medium, CHOMagar™ LIN-R, for screening of linezolid-resistant gram-positive isolates. Thirty-four pure bacterial cultures, 18 positive blood cultures, and 358 nasal swab screening samples were tested. This medium efficiently detected linezolid-resistant S. epidermidis isolates from pure bacterial cultures and from positive blood cultures with a high sensitivity (100%) and specificity (100%). Among the 358 nasal swab screening samples prospectively tested, 10.9% were cultured with linezolid-resistant isolates (mostly S. epidermidis). Of note, slight growth was observed for 7.5% samples with linezolid-susceptible isolates of S. epidermidis (n = 1), S. aureus (n = 1), Enterococcus faecalis (n = 4), Lactobacillus spp. (n = 3), gram negatives (n = 18). Moreover, few Candida spp. also cultured on this medium (1.4%).An increase in the rate of complications after prostate biopsy (PB) due to increased antibiotic-resistant bacteria is a global issue. We report the safety of aztreonam as a prophylactic antibiotic in patients undergoing PB. We investigated the complication rates according to several antibiotic regimens, including aztreonam. We hypothesized that PB complications increased following a rise in antibiotic-resistant bacteria. We examined the annual rates of complications among patients in our hospital (clinical cohort) and the Korea Health Insurance Review and Assessment Service (HIRA) cohort. Data regarding complications, hospitalization, emergency room (ER) visits, and febrile urinary tract infections occurring within 2 weeks after PB were recorded. The rate of complications was significantly lower in patients who received oral quinolone and intravenous aztreonam than in those who received oral quinolone. The complication rates did not increase throughout the study period. Additionally, 1754 patients from the HIRA cohort were included. The rates of complications, hospitalizations, and ER visits did not increase among these patients. Oral quinolone combined with intravenous aztreonam reduced the rate of febrile complications compared to quinolone alone and was safe to use after PB. Therefore, we recommend intravenous aztreonam with oral quinolone as a prophylactic antibiotic regimen before PB.

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