scholarly journals Human recombinant lactoferrin acts synergistically with antimicrobials commonly used in neonatal practice against coagulase-negative staphylococci and Candida albicans causing neonatal sepsis

2008 ◽  
Vol 57 (9) ◽  
pp. 1113-1121 ◽  
Author(s):  
Mohan Pammi Venkatesh ◽  
Liang Rong

Neonatal sepsis causes significant mortality and morbidity. Coagulase-negative staphylococci (CoNS) and Candida frequently cause neonatal sepsis at >72 h of age. Lactoferrin, which is present in human milk, is a component of innate immunity and has broad-spectrum antimicrobial activity. The synergistic effects of lactoferrin with antibiotics against neonatal isolates have not been systematically evaluated. Here, eight clinical strains (seven neonatal) of CoNS and three strains (two neonatal) of Candida albicans were studied. MIC50 and MIC90 values of human recombinant lactoferrin (talactoferrin; TLF), vancomycin (VAN) and nafcillin (NAF) against CoNS, and of TLF, amphotericin B (AMB) and fluconazole (FLC) against C. albicans, were evaluated according to established guidelines. Antimicrobial combinations of TLF with NAF or VAN against CoNS, and TLF with AMB or FLC against C. albicans, were evaluated by a chequerboard method with serial twofold dilutions. Synergy was evaluated by the median effects principle, and combination indices and dose reduction indices were reported at 50, 75 and 90 % inhibitory effect at several drug-dose ratios. It was found that TLF acted synergistically with NAF and VAN against CoNS, and with AMB and FLC against C. albicans, at multiple dose effects and drug-dose ratios with few exceptions. In synergistic combinations, drug reduction indices indicated a significant reduction in doses of antibiotics, which may be clinically relevant. Thus TLF acts synergistically with anti-staphylococcal and anti-Candida agents commonly used in neonatal practice and is a promising agent that needs to be evaluated in clinical studies.

2019 ◽  
Vol 7 (1) ◽  
pp. 46
Author(s):  
Soja Vijayan ◽  
Gopalan A. Velayudhan Nair ◽  
Dhanya Narayanan

Background: Sepsis remains a leading cause of mortality and morbidity, especially during the first five days of life and in low and middle-income countries. The purpose of this study was to note the clinical features and analyze the relationship between the septic screen and blood culture positive sepsis in the neonatal unit.Methods: A one-year descriptive cross-sectional study was carried out at the NICU of a teaching hospital in India.Results: The incidence of clinically suspected septicemia was 19.3 per 1000 live births and the incidence of blood culture positive septicemia was 2.9 per 1000 live births among the inborn of the hospital. The most common clinical features were poor suck and lethargy in culture positive sepsis. The most common organisms causing sepsis were Coagulase negative staphylococci and Klebsiella. In the septic screen CRP was found to have a statistically significant association with blood culture positive sepsis. CRP also had the highest sensitivity and negative predictive value among the studied parameters.Conclusions: Incidence of blood culture positive sepsis was 2.9 per 1000 live births among the inborn of the hospital. The most common clinical features were poor suck and lethargy in culture positive sepsis. The most common organism isolated in neonatal sepsis in the NICU was Coagulase negative staphylococcus. In resource poor settings, CRP continues to be an important tool in diagnosis and treatment of neonatal sepsis.


2019 ◽  
Vol 6 (2) ◽  
pp. 650
Author(s):  
Asifa Nazir

Background: Neonatal sepsis is a leading cause of neonatal mortality and morbidity. Early diagnosis and treatment with appropriate antibiotics are important to improve the prognosis of neonatal sepsis. Coagulase-negative Staphylococci (CoNS) have emerged as prominent pathogens in the neonatal intensive care unit. These infections are rarely fatal, but they cause significant morbidity, especially among very low birth weight infants. This study was done to know the prevalence of Coagulase-negative Staphylococci in neonatal sepsis and to determine their antibiotic susceptibility pattern.Methods: A prospective study was conducted on blood samples of suspected neonatal septicaemia between August 2017 and May 2018 received at Department of Microbiology, Government Medical College, Srinagar. Blood culture was done by automated blood culture system, (BacT/Alert) and identification and antibiotic susceptibility was done by VITEK2 method.Results: Out of 356 neonates screened, there were 185 (53.4%) positive blood cultures. Among the culture positive cases, 107 (57.83%) were male and 78 (42.16%) were female. Early Onset Septicaemia cases (130 [70.27%]) were found to be three times higher than late onset Septicaemia (55 [29.72%]). Coagulase-negative Staphylococci (CoNs) (30.27%) were the most common organisms isolated followed by Acinetobacter sp (15.1%), Klebsiella sp (5.4%) S. aureus (4.8%) and E. coli (4.8%). All the isolates of CoNS were sensitive to linezolid and vancomycin and tigecycline. Methicillin resistance was seen in 84% isolates.Conclusions: Present study highlights the emergence of Coagulase-negative Staphylococci (CoNS) as predominant cause of neonatal septicaemia. Most of the isolates were resistant to methicillin which is alarming and a cause for concern.


2005 ◽  
Vol 68 (3) ◽  
pp. 602-606 ◽  
Author(s):  
KARLA RIVERA-CARRILES ◽  
ALVARO ARGAIZ ◽  
ENRIQUE PALOU ◽  
AURELIO LÓPEZ-MALO

Antifungal susceptibilities of Zygosaccharomyces bailii to individual and binary mixtures of citral with selected phenolics were evaluated to identify synergistic combinations. Individual effects of citral, vanillin, thymol, carvacrol, and eugenol concentrations and combined effects of citral with the other phenolic compounds on the growth of Z. bailii were evaluated in potato dextrose agar, adjusted with sucrose to a water activity of 0.99 or 0.95, and hydrochloric acid to pH 4.5 or 3.5. MICs for individual and binary antimicrobial mixtures were identified and then transformed to fractional inhibitory concentrations. Inhibitory concentrations of citral and vanillin were higher than 650 ppm, whereas for thymol, eugenol, and carvacrol, concentrations were lower than 250 ppm for several of the studied water activity–pH conditions. Combining citral with the other phenolic compounds, fractional inhibitory concentration (FIC) and FICIndex varied from 0.216 to 0.582. FICIndex demonstrated synergistic effects on Z. bailii inhibition when citral was used in combination with vanillin, thymol, carvacrol, or eugenol. Therefore, the relative amount of antimicrobials could be greatly reduced.


2009 ◽  
Vol 58 (7) ◽  
pp. 936-944 ◽  
Author(s):  
Mohan Venkatesh ◽  
Liang Rong ◽  
Issam Raad ◽  
James Versalovic

Biofilms on catheters are responsible for catheter-related bloodstream infections (CRBSIs), which cause significant mortality and morbidity. Antimicrobial catheter-lock solutions may salvage precious catheters by eradicating biofilms. Staphylococcus epidermidis and Candida albicans are frequently isolated organisms in CRBSIs. We evaluated N-acetylcysteine (NAC), EDTA, ethanol and talactoferrin (TLF) individually and in combination with antibiotics against biofilms of S. epidermidis and C. albicans to identify effective catheter-lock solutions. Minimum biofilm-eradication concentrations causing 50 % inhibition (MBEC50) for EDTA, NAC, ethanol and TLF were determined against biofilms of S. epidermidis and C. albicans formed on 96-well microtitre plates. Biomass, mean thickness and viability of S. epidermidis and C. albicans biofilms were evaluated after exposure to MBEC50 concentrations of EDTA, NAC, ethanol and TLF. Antimicrobial combinations of EDTA, NAC, ethanol and TLF with nafcillin, vancomycin, fluconazole and amphotericin B were evaluated systematically for synergy using combination indices (CIs). EDTA, NAC, ethanol and TLF significantly reduced biofilm biomass and mean thickness (P<0.05, one-way ANOVA) of monomicrobial and polymicrobial biofilms as evaluated by confocal microscopy. CIs evaluated at equipotency ratios, and 50, 75 and 90 % effects, showed that EDTA, NAC, ethanol and TLF were synergistic (CI <1) with antibiotics (with few exceptions) against biofilms of S. epidermidis and C. albicans. EDTA, NAC, ethanol and TLF inhibit monomicrobial and polymicrobial biofilms of neonatal strains of S. epidermidis and C. albicans, and are synergistic with antibiotics. Catheter-lock solutions of EDTA, NAC and ethanol alone or in combination with antibiotics may be used to salvage infected catheters, which will directly impact on patient morbidity and health-care costs.


Author(s):  
Xiao-Feng Zhu ◽  
Xiao-Jin Li ◽  
Zhong-Lian Cao ◽  
Xiu-Jie Liu ◽  
Ping Yang ◽  
...  

Background: A Chinese folk medicine plant Pleurospermum lindleyanum possesses pharmacological activities of heat-clearing, detoxifying and preventing from hepatopathy, coronary heart disease, hypertension, and high altitude sickness. We isolated and characterized its constituents to investigate its synergistic effects against human hepatoma SMMC-7721 cells. Objective: The aim of this study was to explore the synergistic anti-cancer activities of isolates from P. lindleyanum with 5-FU on hepatoma SMMC-7721 cells in vitro and their primary mechanisms. Methods: Sequential chromatographic techniques were conducted for the isolation studies. The isolates structures were established by spectroscopic analysis as well as X-ray crystallographic diffraction. Growth inhibition was detected by MTT assay. The isobologram method was used to assess the effect of drug combinations. Flow cytometry and western blot were used to examine apoptosis and protein expression. Results: A new coumarin (16), along with sixteen known compounds, were isolated from the whole plant of P. lindleyanum and their structures were elucidated by spectroscopic methods. Four coumarins (2, 3, 5, and 16), two flavonoids (8 and 9) and three phytosterols and triterpenes (12-14) were found to synergistically enhance the inhibitory effect of 5-FU against SMMC-7721 cells. Among them, compounds 3 and 16 exhibited the best synergistic effects with IC50 of 5-FU reduced by 16-fold and 22-fold possessing the minimum Combination Index (CI) 0.34 and 0.27. The mechanism of action of combinations might be through synergistic arresting for the cell cycle at G1 phases and the induction of apoptosis. Moreover, western blotting and molecular docking revealed that compounds 3 or 5 might promote 5-FU-induced apoptosis by regulating the expression of Caspase 9 and PARP. Conclusion: Constituents from P. lindleyanum may improve the treatment effectiveness of 5-FU against hepatocellular carcinoma cells.


2021 ◽  
pp. e001681
Author(s):  
Oliver O'Sullivan ◽  
R Barker-Davies ◽  
R Chamley ◽  
E Sellon ◽  
D Jenkins ◽  
...  

Coronavirus disease 2019 (COVID-19) causes significant mortality and morbidity, with an unknown impact in the medium to long term. Evidence from previous coronavirus epidemics indicates that there is likely to be a substantial burden of disease, potentially even in those with a mild acute illness. The clinical and occupational effects of COVID-19 are likely to impact on the operational effectiveness of the Armed Forces. Collaboration between Defence Primary Healthcare, Defence Secondary Healthcare, Defence Rehabilitation and Defence Occupational Medicine resulted in the Defence Medical Rehabilitation Centre COVID-19 Recovery Service (DCRS). This integrated clinical and occupational pathway uses cardiopulmonary assessment as a cornerstone to identify, diagnose and manage post-COVID-19 pathology.


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 678
Author(s):  
Abdallah S. Abdelsattar ◽  
Rana Nofal ◽  
Salsabil Makky ◽  
Anan Safwat ◽  
Amera Taha ◽  
...  

The emergence and evolution of antibiotic-resistant bacteria is considered a public health concern. Salmonella is one of the most common pathogens that cause high mortality and morbidity rates in humans, animals, and poultry annually. In this work, we developed a combination of silver nanoparticles (AgNPs) with bacteriophage (phage) as an antimicrobial agent to control microbial growth. The synthesized AgNPs with propolis were characterized by testing their color change from transparent to deep brown by transmission electron microscopy (TEM) and Fourier-Transform Infrared Spectroscopy (FTIR). The phage ZCSE2 was found to be stable when combined with AgNPs. Both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated for AgNPs, phage, and their combination. The results indicated that MIC and MBC values were equal to 23 µg/mL against Salmonella bacteria at a concentration of 107 CFU/mL. The combination of 0.4× MIC from AgNPs and phage with Multiplicity of Infection (MOI) 0.1 showed an inhibitory effect. This combination of AgNPs and phage offers a prospect of nanoparticles with significantly enhanced antibacterial properties and therapeutic performance.


PEDIATRICS ◽  
1978 ◽  
Vol 62 (2) ◽  
pp. 202-204
Author(s):  
John T. McCarthy ◽  
Jules Amer

Although the complications and sequelae of varicella are rare, they can cause significant mortality and morbidity in both the normal and compromised patient. Eight cases of "pure" acute transverse myelitis (ATM) following varicella have previously been reported in the literature. We report the ninth case of postvaricella ATM in a 9-year-old girl. Her course was characterized by paraplegia, sensory Loss, hvperesthesia, and incontinence of urine and feces. All patients, except ours, recovered fully from ATM.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Yue Chen ◽  
Shuo Zhen ◽  
Laureano Asico ◽  
Pedro Jose ◽  
Chunyu Zeng

Oral NaCl produces stronger natriuresis and diuresis as compared with venous infusion of same amount of NaCl, indicating the existence of renal-gastric axis. Although numerous hormones are secreted in gastrointestinal tract, gastrin is evident one due to its natriuretic effects and taken-up by the renal proximal tubule (RPT) cells. We hypothesize that there is an interaction between gastrin and dopamine receptor in kidney, which synergistically increases sodium excretion, the impaired interaction would be involved in the pathogenesis of hypertension. In WKY rats, infusion of gastrin, via renal artery, induced natriuresis and diuresis, which was blocked in the presence of CI988, a gastrin receptor blocker. Similarly, the natriuretic and diuretic effect of fenoldopam, a D1-like receptor agonist, was blocked by the D1-like receptor antagonist, SCH23390 , indicating that gastrin and fenoldopam, via individual receptor, play natriuretic and diuretic effects. Our further study found that lower dosages of gastrin or fenoldopam could not induce natriuresis and diuresis alone, while putting together induced natriuretic and diuretic effects. The above-mentioned effects were lost in SHRs. We also found, in the presence of SCH23390 , gastrin-mediated natriuresis and diuresis was partially blocked. Similarly, in the presence of CI988, the natriuretic and diuretic effects of fenoldopam were partially blocked, indicating the interaction between gastrin and D1-like receptor. The gastrin/D1-like receptor interaction was also confirmed in the RPT cells. Stimulation of one receptor increased the expression of the other. Stimulation of either D1-like receptor or gastrin receptor inhibited the Na + -K + -ATPase activity in RPT cells, while in the presence of SCH23390 , the inhibitory effect of gastrin on Na + -K + -ATPase activity was partially blocked. In the presence of CI988, D1-like receptor-mediated inhibitory effect of Na + -K + -ATPase activity in RPT cells was partially inhibited. It indicated the synergistic effect between gastrin and D1-like receptor would increase the sodium excretion in WKY rats; the impaired interaction might be involved in the pathogenesis of hypertension.


Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2908 ◽  
Author(s):  
Guixing Ren ◽  
Zhenxing Shi ◽  
Cong Teng ◽  
Yang Yao

Breast cancer is the most frequently diagnosed cancer in women worldwide. The antiproliferative activities of biochanin A (BA) and ginsenoside Rh2 were determined by evaluating their inhibitory effect on MDA-MB-231 human breast cancer cell proliferation. The combination of BA with Rh2 was also assessed. In MDA cells, combination treatment led to a decrease in the EC50 values of BA and Rh2 to 25.20 μM and 22.75 μM, respectively. In MCF-7 cells, the EC50 values of combined BA and Rh2 decreased to 27.68 μM and 25.41 μM, respectively. BA combined with Rh2 also improved the inhibition of MDA-MB-231 and MCF-7 cell migration and invasion compared to the individual compounds. Western blot analysis demonstrated upregulation in p-p53, p-p38, and p-ASK1 proteins while levels of TRAF2 were downregulated. These results suggest that BA combined with Rh2 exhibits synergistic effects against MDA-MB-231 and MCF-7 cell proliferation.


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