Dataset Information

Pentoxifylline Alone or in Combination with Gentamicin or Vancomycin Inhibits Live Microbe-Induced Proinflammatory Cytokine Production in Human Cord Blood and Cord Blood Monocytes In Vitro.

ABSTRACT: Neonatal sepsis and its accompanying inflammatory response contribute to substantial morbidity and mortality. Pentoxifylline (PTX), a phosphodiesterase inhibitor which suppresses transcription and production of proinflammatory cytokines, is a candidate adjunctive therapy for newborn sepsis. We hypothesized that PTX decreases live microbe-induced inflammatory cytokine production in newborn blood. Cord blood was stimulated with live microorganisms commonly encountered in newborn sepsis (Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, or Candida albicans) and simultaneously treated with antimicrobial agents (gentamicin, vancomycin, or amphotericin B) and/or clinically relevant concentrations of PTX. Microbial colony counts were enumerated by plating, supernatant cytokines were measured by multiplex assay, intracellular cytokines and signaling molecules were measured by flow cytometry, and mRNA levels were measured by quantitative reverse transcription-PCR. PTX inhibited concentration-dependent E. coli-, S. aureus-, S. epidermidis-, and C. albicans-induced tumor necrosis factor (TNF) and E. coli-induced interleukin-1? (IL-1?) production in whole blood, with greater suppression of proinflammatory cytokines in combination with antimicrobial agents. Likewise, PTX suppressed E. coli-induced monocytic TNF and IL-1?, whereby combined PTX and gentamicin led to significantly greater reduction of TNF and IL-1?. The anti-inflammatory effect of PTX on microbe-induced proinflammatory cytokine production was accompanied by inhibition of TNF mRNA expression and was achieved without suppressing the production of the anti-inflammatory IL-10. Of note, microbial colony counts in newborn blood were not increased by PTX. Our findings demonstrated that PTX inhibited microbe-induced proinflammatory cytokine production, especially when combined with antimicrobial agents, without enhancing microbial proliferation in human cord blood in vitro, thus supporting its utility as candidate adjunctive agent for newborn sepsis.

SUBMITTER: Speer EM

PROVIDER: S-EPMC6256750 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pentoxifylline Alone or in Combination with Gentamicin or Vancomycin Inhibits Live Microbe-Induced Proinflammatory Cytokine Production in Human Cord Blood and Cord Blood Monocytes <i>In Vitro</i>.

Speer Esther M EM Diago-Navarro Elizabeth E Ozog Lukasz S LS Dowling David J DJ Hou Wei W Raheel Mahnoor M Fries Bettina C BC Levy Ofer O

Antimicrobial agents and chemotherapy 20181126 12

Neonatal sepsis and its accompanying inflammatory response contribute to substantial morbidity and mortality. Pentoxifylline (PTX), a phosphodiesterase inhibitor which suppresses transcription and production of proinflammatory cytokines, is a candidate adjunctive therapy for newborn sepsis. We hypothesized that PTX decreases live microbe-induced inflammatory cytokine production in newborn blood. Cord blood was stimulated with live microorganisms commonly encountered in newborn sepsis (<i>Escheri ...[more]

PMID: 30275087

Similar Datasets

Project description:BackgroundThe treatment of grafts with vancomycin for ligament reconstruction in knee surgery is the current standard. However, high antibiotic concentrations have chondrotoxic effects.PurposeTo test the chondrotoxicity of clindamycin, gentamicin and vancomycin in comparable concentrations. In vitro and in vivo effective concentrations hugely vary from drug to drug. To allow for comparisons between these three commonly used antibiotics, the concentration ranges frequently used in orthopedic surgical settings were tested.Study designControlled laboratory study.MethodsHuman cartilage from 10 specimens was used to isolate chondrocytes. The chondrocytes were treated with clindamycin (1 mg/mL and 0.5 mg/mL), gentamicin (10 mg/mL and 5 mg/mL) or vancomycin (10 mg/mL and 5 mg/mL), at concentrations used for preoperative infection prophylaxis in ligament surgery. Observations were taken over a period of 7 days. A control of untreated chondrocytes was included. To test the chondrotoxicity, a lactate dehydrogenase (LDH) test and a water-soluble tetrazolium salt (WST-1) assay were performed on days 1, 3 and 7. In addition, microscopic examinations were performed after fluorescence staining of the cells at the same time intervals.ResultsAll samples showed a reasonable vitality of the cartilage cells after 72 h. However, clindamycin and gentamicin both showed higher chondrotoxicity in all investigations compared to vancomycin. After a period of 7 days, only chondrocytes treated with vancomycin showed reasonable vitality.ConclusionsThe preoperative treatment of ligament grafts with vancomycin is the most reasonable method for infection prophylaxis, in accordance with the current study results regarding chondrotoxicity; however, clindamycin and gentamicin cover a wider anti-bacterial spectrum.Clinical relevanceThe prophylactic antibiotic treatment of ligament grafts at concentrations of 5 mg/mL or 10 mg/mL vancomycin is justifiable and reasonable. In specific cases, even the use of gentamicin and clindamycin is appropriate.

Project description:The findings of clinical and in vitro research support the theory that infective endocarditis (IE)-causing bacteria form biofilms and that biofilms negatively affect treatment outcomes. The purpose of the present study was to quantify the biofilm formation of methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates obtained from patients with IE and to evaluate the in vitro activities of daptomycin and vancomycin alone and in combination with rifampin (rifampicin) or gentamicin while monitoring the isolates for the development of resistance. A high-inoculum, stationary-phase infection model of IE was used to simulate the pharmacokinetics in humans of daptomycin at 6 mg/kg of body weight/day, vancomycin at 1.25 g every 12 h (q12h) alone and in combination with rifampin at 300 mg every 8 h, and gentamicin at 1.3 mg/kg q12h. Two randomly selected clinical MRSA isolates were obtained from patients with IE; both MRSA isolates quantitatively produced biofilms. The time to bactericidal activity in the presence of daptomycin was isolate dependent but was achieved by 24 h for both MRSA isolates. Vancomycin did not achieve bactericidal activity throughout the experiment. At 24, 48, and 72 h, daptomycin-containing regimens had significantly more activity (greater declines in the mean number of CFU/g) than any of the vancomycin-containing regimens (P = 0.03). Rifampin and gentamicin antagonized or delayed the bactericidal activity of daptomycin (against MRSA B346846 for rifampin and against both isolates for gentamicin) in the first 24 h. Increases in the daptomycin and vancomycin MICs were not observed. We conclude that in an IE model of biofilm-forming MRSA, daptomycin monotherapy has better in vitro activity than daptomycin in combination with rifampin or gentamicin or any vancomycin-containing regimen studied within the first 24 h. Further investigations are needed to understand the initial delay in bactericidal activity observed when gentamicin or rifampin is combined with daptomycin.

Dataset Information

Pentoxifylline Alone or in Combination with Gentamicin or Vancomycin Inhibits Live Microbe-Induced Proinflammatory Cytokine Production in Human Cord Blood and Cord Blood Monocytes In Vitro.

Publications

Pentoxifylline Alone or in Combination with Gentamicin or Vancomycin Inhibits Live Microbe-Induced Proinflammatory Cytokine Production in Human Cord Blood and Cord Blood Monocytes <i>In Vitro</i>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets