Fever is associated with earlier antibiotic onset and reduced mortality in patients with sepsis admitted to the ICU

To evaluate the association of body temperature with mortality in septic patients admitted to the ICU from the ward. In addition, we intend to investigate whether the timing of antibiotic administration was different between febrile and afebrile patients and whether this difference contributed to mortality. This is a retrospective cohort study that included sepsis patients admitted to the ICU from the ward between July 2017 and July 2019. Antibiotic administration was defined as the initiation of antimicrobial treatment or the expansion of the antimicrobial spectrum within 48 h prior to admission to the ICU. Regarding vital signs, the most altered vital sign in the 48 h prior to admission to the ICU was considered. Two hundred and eight patients were included in the final analysis. Antibiotic administration occurred earlier in patients with fever than in patients without fever. Antibiotic administration occurred before admission to the ICU in 27 (90.0%) patients with fever and in 101 (64.7%) patients without fever (p = 0.006). The mortality rate in the ICU was 88 in 176 (50.0%; 95% CI 42.5–57.5%) patients without fever and 7 in 32 (21.9%; 95% CI 6.7–37.0%) patients with fever (p = 0.004). In the multivariate analysis, absence of fever significantly increased the risk of ICU mortality (OR 3.462; 95% CI 1.293–9.272). We found an inverse association between body temperature and mortality in patients with sepsis admitted to the ICU from the ward. Although antibiotic administration was earlier in patients with fever and precocity was associated with reduced mortality, the time of antibiotic administration did not fully explain the lower mortality in these patients.

Biological Effects of Quinolones: A Family of Broad-Spectrum Antimicrobial Agents

Broad antibacterial spectrum, high oral bioavailability and excellent tissue penetration combined with safety and few, yet rare, unwanted effects, have made the quinolones class of antimicrobials one of the most used in inpatients and outpatients. Initially discovered during the search for improved chloroquine-derivative molecules with increased anti-malarial activity, today the quinolones, intended as antimicrobials, comprehend four generations that progressively have been extending antimicrobial spectrum and clinical use. The quinolone class of antimicrobials exerts its antimicrobial actions through inhibiting DNA gyrase and Topoisomerase IV that in turn inhibits synthesis of DNA and RNA. Good distribution through different tissues and organs to treat Gram-positive and Gram-negative bacteria have made quinolones a good choice to treat disease in both humans and animals. The extensive use of quinolones, in both human health and in the veterinary field, has induced a rise of resistance and menace with leaving the quinolones family ineffective to treat infections. This review revises the evolution of quinolones structures, biological activity, and the clinical importance of this evolving family. Next, updated information regarding the mechanism of antimicrobial activity is revised. The veterinary use of quinolones in animal productions is also considered for its environmental role in spreading resistance. Finally, considerations for the use of quinolones in human and veterinary medicine are discussed.

Approach to Searching for the Producers of Antibiotics That Overcome Drug Resistance of Microorganisms

Currently, the problem of antibiotic resistance of opportunistic and pathogenic microorganisms is extremely urgent. In order to find new effective natural antibiotics, it is necessary to intensify the search process. In the gradual selection of the most promising producers, we introduced the stage of determining the antibiotic activity of the culture fluid of the studied natural strains against the clinical isolates of hospital microorganisms with multiple resistance to medical antibiotics. Determining the species affiliation of potential producers allows to select those producers of a particular species that differ in the antimicrobial spectrum of activity from those described in the literature. Four strains of actinomycetes that showed activity against resistant clinical isolates of yeast Candida albicans, C.famata, C.parapsilosis and Cryptococcus neoformans were selected, namely: Nocardia soli INA 01217, Streptomyces bottropensis INA 01214, S.chromofuscus INA 01211 and S.netropsis INA 01190. The N.soli INA 01217 strain also shows antibiotic activity against the Gram-negative bacterium Escherichia coli ATCC 25922. These strains of actinobacterial producers were selected for subsequent chemical studies of the antimicrobial compounds formed by them.

Molecular Identification and Characterization of Probiotic Bacillus Species with the Ability to Control Vibrio spp. in Wild Fish Intestines and Sponges from the Vietnam Sea

Vibriosis in farmed animals is a serious threat to aquaculture worldwide. Using probiotics and anti-Vibrio antimicrobial substances in aquaculture systems can be a means of preventing Vibrio infections. Therefore, we aimed to characterize and compare 16 potential anti-Vibrio probiotics (Vi+) isolated from marine sponges and fish intestines collected from the Vietnam Sea, as well as an anti-Vibrio bacteriocin to fully explore their application potentials. 16S rRNA sequencing confirmed all Vi+ to be Bacillus species with different strain variants across two sample types. An obvious antimicrobial spectrum toward Gram-negative bacteria was observed from intestinal Vi+ compared to sponge-associated Vi+. The reason was the higher gene frequency of two antimicrobial compounds, non-ribosomal peptides (NRPS) and polyketide type-I (PKS-I) from intestinal Vi+ (66.7%) than sponge-associated Vi+ (14.3% and 0%, respectively). Additionally, a three-step procedure was performed to purify an anti-Vibrio bacteriocin produced by B. methylotrophicus NTBD1, including (i) solvent extraction of bacteriocin from cells, (ii) hydrophobic interaction chromatography, and (iii) reverse-phase HPLC. The bacteriocin had a molecular weight of ~2–5 kDa, was sensitive to proteolysis and thermally stable, and showed a broad antimicrobial spectrum, all of which are essential properties for promising feed additives. This study provides necessary information of the potential of probiotic Bacillus species with anti-Vibrio antimicrobial properties to study their further use in sustainable aquaculture.

Sitafloxacin Inhibits TNFα Release from Monocytic THP-1 Cells Stimulated by LPS

Sepsis is a systemic reaction to infection and excessive production of inflammatory cytokines and chemokines. It sometimes results in septic shock. The present study was designated to find out which quinolone antibiotic reduces TNFα production the most and to elucidate its mechanisms. We examined which quinolone antibiotic reduced TNFα production from THP-1 cells stimulated by lipopolysaccharide (LPS). Then, we examined the mechanism of inhibition of TNFα production by the antibiotic. STFX most effectively reduced TNFα concentrations within LPS-stimulated THP-1 cells supernatant. STFX suppressed TNFα production in a dose-dependent manner. We found that STFX did not inhibit the NF-kB, ERK, or p38 pathways, nor did it inhibit the production of TNFα mRNA. The percentage of intracellular TNFα was increased in cells stimulated by LPS and with STFX compared to that of cells stimulated by LPS alone. In conclusion, one of the mechanisms reducing TNFα production from LPS-stimulated THP-1 cells treated with STFX involves inhibition of TNFα release from these cells. STFX has a broad antimicrobial spectrum for gram-positive, gram-negative, and anaerobic bacteria, and may be effective for treating sepsis by both killing bacteria and suppressing inflammation.

In Vitro Probitotic Evaluation of Saccharomyces boulardii with Antimicrobial Spectrum in a Caenorhabditis elegans Model

In the present study, we screened for potential probiotic yeast that could survive under extreme frozen conditions. The antimicrobial and heat-stable properties of the isolated yeast strains Saccharomyces boulardii (S. boulardii) (KT000032, KT000033, KT000034, KT000035, KT000036, and KT000037) was analyzed and compared with commercial probiotic strains. The results revealed that the tested S. boulardii KT000032 strain showed higher resistance to gastric enzymes (bile salts, pepsin, and pancreatic enzyme) at low pH, with broad antibiotic resistance. In addition, the strain also showed efficient auto-aggregation and co-aggregation abilities and efficient hydrophobicity in the in-vitro and in-vivo C. elegens gut model. Further, the KT000032 strain showed higher antimicrobial efficiency against 13 different enteropathogens and exhibited commensal relationships with five commercial probiotic strains. Besides, the bioactive compounds produced in the cell-free supernatant of probiotic yeast showed thermo-tolerance (95 °C for two hours). Furthermore, the thermo-stable property of the strains will facilitate their incorporation into ready-to-eat food products under extreme food processing conditions.

The Use of Catalytic Amounts of Selected Cationic Surfactants in the Design of New Synergistic Preservative Solutions

Preservation using combinations of antibacterial molecules has several advantages, such as reducing the level of usage and broadening their antimicrobial spectrum. More specifically, the use of quaternary ammonium surfactants (QAS)—which are profusely used in hair care products and some are known as efficient antimicrobial agents—is limited due to some potential cytotoxicity concerns. This study shows that the concentration of some widely used cosmetic preservatives can be decreased when combined with very small quantities of QAS, i.e., Polyquaternium-80 (P-80) and/or Didecyldimethylammonium chloride (DDAC). The antimicrobial activity of their mixtures was first evaluated by determining the minimum inhibitory concentration (MIC) before and after the addition of QAS. Following up on this finding and targeting an ultimate consumer friendly antimicrobial blend, yet with optimal safety, we chose to utilize the food-grade preservative Maltol as the main natural origin antimicrobial agent mixed with minimum concentrations of QAS to improve its moderate antimicrobial properties. The preservatives were tested for MIC values, challenge tests and synergy using the fractional inhibitory concentration index (FICI). The antimicrobial efficacy of Maltol was found to be synergistically improved by introducing catalytic amounts of P-80 and/or DDAC.

Varied-shaped gold nanoparticles with nanogram killing efficiency as potential antimicrobial surface coatings for the medical devices

Medical device-associated infections are a serious medical threat, particularly for patients with impaired mobility and/or advanced age. Despite a variety of antimicrobial coatings for medical devices being explored to date, only a limited number have been introduced for clinical use. Research into new bactericidal agents with the ability to eradicate pathogens, limit biofilm formation, and exhibit satisfactory biocompatibility, is therefore necessary and urgent. In this study, a series of varied-morphology gold nanoparticles in shapes of rods, peanuts, stars and spherical-like, porous ones with potent antibacterial activity were synthesized and thoroughly tested against spectrum of Candida albicans, Pseudomonas aeruginosa, Staphylococcus aureus clinical strains, as well as spectrum of uropathogenic Escherichia coli isolates. The optimization of gold nanoparticles synthesis allowed to develop nanomaterials, which are proved to be significantly more potent against tested microbes compared with the gold nanoformulations reported to date. Notably, their antimicrobial spectrum includes strains with different drug resistance mechanisms. Facile and cost-efficient synthesis of gold nanoparticles, remarkable bactericidal efficiency at nanogram doses, and low toxicity, underline their potential for development as a new coatings, as indicated by the example of urological catheters. The presented research fills a gap in microbial studies of non-spherical gold nanoparticles for the development of antimicrobial coatings targeting multidrug-resistant pathogens responsible for device-associated nosocomial infections.