ascorbic-acid and Gram-Negative-Bacterial-Infections

Nephrotoxicity is a dose-limiting factor of colistin, a last-line therapy for multidrug-resistant Gram-negative bacterial infections. An earlier animal study revealed a protective effect of ascorbic acid against colistin-induced nephrotoxicity. The present randomized controlled study was conducted in 28 patients and aimed to investigate the potential nephroprotective effect of intravenous ascorbic acid (2 g every 12 h) against colistin-associated nephrotoxicity in patients requiring intravenous colistin. Thirteen patients received colistin plus ascorbic acid, whereas 15 received colistin alone. Nephrotoxicity was defined by the RIFLE classification system. Additionally, urinary neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-beta-d-glucosaminidase (NAG) were measured as markers of renal damage, and plasma colistin concentrations were quantified. The baseline characteristics, clinical features, and concomitant treatments of the patients in the two groups were comparable. The incidences of nephrotoxicity were 53.8% (7/13) and 60.0% (9/15) in the colistin-ascorbic acid group and the colistin group, respectively (P = 0.956; relative risk [RR], 0.9; 95% confidence interval, 0.47 to 1.72). In both groups, the urinary excretion rates of NGAL and NAG on day 3 or 5 of colistin treatment and at the end of colistin treatment were significantly higher than those at the respective baselines (P < 0.05). However, the urinary excretion rates of these biomarkers at the various times during colistin treatment did not differ significantly between the groups (P > 0.05). The plasma colistin concentrations in the two groups were not significantly different (P > 0.28). The clinical and microbiological outcomes and mortality of the patients in the two groups were not significantly different. This preliminary study suggests that ascorbic acid does not offer a nephroprotective effect for patients receiving intravenous colistin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01501968.).

Topics: Acetylglucosaminidase; Acute-Phase Proteins; Adult; Aged; Animals; Anti-Bacterial Agents; Ascorbic Acid; Colistin; Female; Gram-Negative Bacterial Infections; Humans; Kidney; Lipocalin-2; Lipocalins; Male; Middle Aged; Proto-Oncogene Proteins

Stenotrophomonas maltophilia is an environmental bacterium that has gained a lot of attention, as a nosocomial pathogen associated with significant mortality rates. Biofilm formation is considered the corner stone for establishing infections in many bacteria including S. maltophilia. The aim of this study was the genotypic characterization of the different virulence-associated genes and the investigation of the effect of ascorbic acid on S. maltophilia biofilm formation. A total of 20 S. maltophilia isolates from different sources were included in this study. Genes encoding different virulence factors were investigated genotypically. These included stmPr1, stmPr2, smlt3773 locus, smf-1, rpfF, rmlA and spgM. Biofilm formation was investigated phenotypically. The effect of ascorbic acid on biofilm formation was investigated using MIC as well as sub-inhibitory concentrations. Many of the isolates harbored both serine proteases genes stmPr-1 and stmPr-2. Fourteen (70%) of the 20 isolates carried stmPr-1 and 15 (75%) had stmPr-2. Most of the isolates (95%) possessed smlt-3773 locus. Genes linked to biofilm formation such as smf-1, rpfF, rmlA and spgM, were found in (90%), (45%), (85%) and (30%) of the isolates, respectively. Phenotypically, all S. maltophilia isolates (100%) were biofilm producers. Fifteen (75%) were strong biofilm producers and 5 (25%) were moderate biofilm producers. In attempts to seek a non-chemotherapeutic alternative that can hinder biofilm formation without provoking antimicrobial resistance, the results, herein, showed that ascorbic acid inhibits biofilm formation in a dose-dependent manner.

Topics: Ascorbic Acid; Biofilms; Gram-Negative Bacterial Infections; Humans; Stenotrophomonas maltophilia; Virulence

This study investigated the effects of dietary vitamin C on the growth, and head kidney, spleen and skin immunity, structural integrity and related signaling molecules mRNA expression levels of young grass carp (Ctenopharyngodon idella). A total of 540 grass carp (264.37 ± 0.66 g) were fed six diets with graded levels of vitamin C (2.9, 44.2, 89.1, 133.8, 179.4 and 224.5 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila and the survival rate recorded for 14 days. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) decreased lysozyme (LA) and acid phosphatase (ACP) activities, and complement 3 and complement 4 (C4) contents (P < 0.05), down-regulated the mRNA levels of antimicrobial peptides [liver expressed antimicrobial peptide (LEAP) 2A, LEAP-2B, hepcidin, β-defensin] and anti-inflammatory cytokines-related factors, interleukin (IL) 4/13A, IL-4/13B (only in head kidney), IL-10, IL-11, transforming growth factor (TGF) β1, TGF-β2, inhibitor of κBα and eIF4E-binding protein 1 (P < 0.05), and up-regulated pro-inflammatory cytokines-related factors, tumor necrosis factor α, interferon γ2, IL-1β, IL-6, IL-8, IL-12 P35 (only in spleen), IL-12 P40, IL-15, IL-17D, nuclear factor κB p65, IκB kinases (IKKα, IKKβ, IKKγ), target of rapamycin and ribosomal protein S6 kinase 1 mRNA levels (P < 0.05) in the head kidney and spleen under injection fish of A. hydrophila, suggesting that vitamin C deficiency could decrease fish head kidney and spleen immunity and cause inflammation. Meanwhile, compared with optimal vitamin C supplementation, vitamin C deficiency decreased the activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase, glutathione S-transferases and glutathione reductase (P < 0.05), and down-regulated zonula occludens (ZO) 1, ZO-2, Claudin-b, -c, -3c, -7a, -7b, B-cell lymphoma-2, inhibitor of apoptosis protein, NF-E2-related factor 2 mRNA levels (P < 0.05), increased reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl contents (P < 0.05), and up-regulated Claudin-12, 15a, -15b, Fas ligand, mitogen-activated protein kinase kinase 6, p38 mitogen-activated protein kinase, B-cell lymphoma protein 2 associated X protein, apoptotic protease activating factor-1, caspase-3, -7, -8, -9, Kelch-like ECH-associating protein (Keap) 1a and Keap 1b mRNA le

Topics: Aeromonas hydrophila; Animal Feed; Animals; Apoptosis; Ascorbic Acid; Ascorbic Acid Deficiency; Carps; Diet; Dietary Supplements; Dose-Response Relationship, Drug; Fish Diseases; Fish Proteins; Gram-Negative Bacterial Infections; Head Kidney; Immunity, Innate; Random Allocation; Signal Transduction; Spleen

Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy.. A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD)-based dosing approach.. Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87-11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9-9.2; P < .001) and age (1.03; 1.0-1.05; P = .028), whereas a strong independent renal-protective role emerged for ascorbic acid (0.27; .12-.57; P < .001).. In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antidotes; Ascorbic Acid; Blighia; Colistin; Critical Illness; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Sepsis; Young Adult

This study attempts to describe the effects of different administration periods of dietary β-glucan and Vit C on the non-specific immune response, physiological parameters and disease resistance of Nile tilapia against Aeromonas hydrophila infection. Therefore, a feeding trial (288 fish) was conducted to determine the best administration period (7, 15, 30 and 45 days) for a Nile tilapia diet supplemented with 0.1% β-glucan and 600 mg Vit C/kg diet. After the administration period, three different groups of 96 fish were exposed to one of the following three stresses: cold-induced stress, transport-induced stress, and A. hydrophila challenge. Hematological, biochemical and immunological responses were analyzed before and/or after stress. Cold-induced stress increased cortisol levels and reduced the leukocyte count in fish fed the test diet for seven days compared with the other periods. After transport-induced stress, fish fed the test diet for seven days required more hours to return to the baseline levels of cortisol and neutrophils. Moreover, independently of the administration period, fish needed 24 h for leukocyte and glucose levels to return to the initial values. The lowest survival after bacterial infection was observed in fish test diet for seven days. Based on fish hematological and biochemical responses, diet supplemented with 0.1% of β-glucan and 600 mg of Vit C/kg fed for at least 15 days is recommended for Nile tilapia especially when fish are likely to encounter transport-induced stress, and this stress was more severe than cold-induced stress or bacterial challenge.

Topics: Aeromonas hydrophila; Analysis of Variance; Animal Husbandry; Animals; Aquaculture; Ascorbic Acid; beta-Glucans; Brazil; Cichlids; Cold Temperature; Dietary Supplements; Disease Resistance; Fish Diseases; Gram-Negative Bacterial Infections; Stress, Physiological

The in vivo activities of inulin and ascorbic acid were evaluated experimentally via using 450 Nile tilapia (Oreochromis niloticus) that were distributed into 3 equal groups (each of three replicates). Fish of the first group served as a control and received a balanced diet free from inulin and vitamin C. The second fed on balanced diet supplemented with inulin (5 g kg(-1)), whereas, the third one received a balanced diet supplemented with vitamin C (500 mg kg(-1)). The survival and growth performances were evaluated. Blood samples were collected from the experimented tilapia, one and two months from the onset of the experiment to measure the hematocrit (HCT) values, nitroblue tetrazolium (NBT), and lysozyme activity. The protective effect of the two compounds was evaluated via challenge infection using pathogenic Aeromonas hydrophila. The body weight gain (g); specific growth rate (%), and survival (%) were significantly increased (p < 0.05) in group supplemented with inulin and vitamin C after one and two months of exposures vs. the control. The HCT values showed non-significant changes in both supplemented groups after one and two months. The NBT was significantly increased (p < 0.05) in the 3rd and 2nd group after one and two months, respectively. On the other hand, a significant increase (p < 0.05) in the lysozyme activity has been observed in the 3rd group and in both supplemented groups at 1 and 2 months; respectively. The challenge infection showed an improved relative level of protection (RLP) in the 2 supplemented groups vs. the control. These results suggest that vitamin C at dose rate of 500 mg for one month could be a potential, less expensive, and promising dietary supplementation than inulin that would positively affect growth, hematology, innate immunity, and resistance of Nile tilapia (O. niloticus) in aquaculture.

Topics: Adjuvants, Immunologic; Aeromonas hydrophila; Animals; Ascorbic Acid; Body Constitution; Body Weight; Cichlids; Diet; Dietary Supplements; Female; Fish Diseases; Gram-Negative Bacterial Infections; Inulin; Male; Survival Analysis

Teleost fish lack the enzyme for endogenous synthesis of ascorbic acid (AA), an essential micronutrient for fish. The aim of this study was to examine the effect of higher levels of dietary vitamin C on growth, nutritional quality, and immunomodulation in the Indian major carp, rohu (Labeo rohita). Four groups of L. rohita were fed experimental diets containing either no vitamin C (control) or supplemented with vitamin C at 500 mg kg(-1) (Exp-1), 1000 mg kg(-1) (Exp-2), or 1500 mg kg(-1) (Exp-3) for 60 days. Growth parameters (NWG, ADG, and SGR), serological parameters (TSP, TSA, TSG, and A:G), haematological parameters (TLC, TEC, Hct, MCV, and MCH), and different non-specific immunological parameters (PR, PI, respiratory burst activity, and bactericidal activity) were evaluated during the experimental trial. Fish fed a vitamin C-supplemented diet showed higher specific growth rate (SGR) up to 1000 mg kg(-1) compared with control fish. Different haematological and serological parameters along with non-specific immune parameters were influenced by vitamin C supplementation. Among the non-specific immune parameters phagocytic activity (PR and PI) and respiratory burst activity (NBT cells) were significantly (P < or = 0.05) enhanced by increasing doses of vitamin C supplementation. Higher levels of dietary vitamin C significantly (P < or = 0.05) enhanced protection against Aeromonas hydrophila (AH1) infection compared with controls. Results from this study help to establish the beneficial effect of vitamin C on growth and immunmodulation in rohu (L. rohita).

Topics: Adjuvants, Immunologic; Aeromonas hydrophila; Alanine Transaminase; Animal Feed; Animals; Ascorbic Acid; Aspartate Aminotransferases; Cyprinidae; Diet; Dietary Supplements; DNA; Fish Diseases; Gram-Negative Bacterial Infections; Liver; Muscles; Phagocytosis; RNA; Survival Analysis

In order to determine the efficacy and immunoreversal effect of the 4 dietary immunomodulators, viz. lactoferrin, beta-1,3 glucan, levamisole and vitamin C, on disease resistance of a commercially important catfish, Clarias batrachus, fish were fed diets supplemented with various levels of these substances in 2 subgroups, healthy and immunocompromised, during a 30 d trial. An artificial immunosuppressive state was induced by giving 3 intraperitoneal (i.p.) injections of cyclophosphamide (CYP) at a dose level of 200 mg kg(-1) body weight at 1 wk intervals in the immunocompromised vaccinated subgroup and 3 consecutive injections 3 d before challenge in the immunocompromised non-vaccinated subgroup. On the first day of the experiment, the fish were vaccinated against a formalin-killed Aeromonas hydrophila bacterin. After 30 d, antibody titre (as measured through bacterial agglutination titre) and disease resistance against A. hydrophila were determined. The results demonstrate that all 4 immunomodulators were capable of significantly (p < 0.05) enhancing the specific immune response; this was evident through raised antibody titre and protection against A. hydrophila in both healthy and immunocompromised vaccinated subgroups compared to their respective controls. Similarly, all 4 substances significantly raised the survival rates in immunocompromised and healthy non-vaccinated fish. Thus, these substances were capable of reducing the immunosuppression induced by CYP injections in both vaccinated and non-vaccinated fish compared to their respective controls. Among the 4 substances studied, beta-1,3 glucan was found to be the most effective immunomodulator, followed by levamisole, lactoferrin and vitamin C in Asian catfish. Therefore, the results support the introduction of these substances into the diet of fish grown in farms under immunosuppressive/stressful conditions in order to enhance protection against infection and offer economic benefits.

Topics: Adjuvants, Immunologic; Aeromonas hydrophila; Animals; Antibodies; Ascorbic Acid; Bacterial Vaccines; beta-Glucans; Catfishes; Cyclophosphamide; Dietary Supplements; Fish Diseases; Gram-Negative Bacterial Infections; Immunity, Innate; Immunocompromised Host; Lactoferrin; Levamisole; Survival Analysis; Time Factors

The aim of this study was to examine the immunomodulatory effect of high levels of dietary vitamin C in healthy and immunocompromised rohu (Labeo rohita) treated with aflatoxin B1 (AFB1). Four groups of rohu were fed experimental diets containing either no vitamin C or supplemented with vitamin C at 500 ppm for 60 days. On the first day of feeding, one group fed the high vitamin C diet and one fed the vitamin C deficient diet, were injected intraperitoneally with a single doses of AFB1 at 1.25 mg kg(-1) body weight. The effect of AFB1 and high dietary vitamin C on specific and non-specific immunity, and disease resistance against Aeromonas hydrophila were examined in the rohu. The ability of vitamin C to counteract immunosuppression induced by AFB1 was also examined. Specific immunity indicated by haemagglutination and haemolysin titres against sheep red blood cells (SRBC), and bacterial agglutination appeared to be unaffected by either the AFB1 treatment or the vitamin C enriched diet. A significant reduction was observed in the non-specific immunity of AFB1-treated fish, however, indicated by lowered bactericidal and lysozyme activities. High dietary vitamin C, on the other hand, enhanced the non-specific immunity of fish, including an enhanced phagocytic ratio and increased serum lysozyme activity. Feeding a high level of dietary vitamin C to AFB1-treated fish increased these parameters to levels similar to those found in control fish. High dietary vitamin C significantly (p < 0.05) enhanced protection against Aeromonas hydrophila infection in both healthy and immunocompromised fish. Results from this study help to establish the beneficial effect of dietary vitamin C on AFB1-induced immunosuppression, as well as confirming the immunostimulatory effect of vitamin C in rohu.

Topics: Aeromonas hydrophila; Aflatoxin B1; Agglutination Tests; Animal Feed; Animals; Antioxidants; Ascorbic Acid; Cyprinidae; Fish Diseases; Fisheries; Gram-Negative Bacterial Infections; Immunity, Innate; Immunization; Immunocompromised Host; Injections, Intraperitoneal; Random Allocation

Topics: Aeromonas; Animals; Antibodies; Ascorbic Acid; Aspartate Aminotransferases; Blood Proteins; Diet; Disease Susceptibility; Furunculosis; Gram-Negative Bacterial Infections; Hematocrit; Hemoglobins; Pyridoxine; Salmon