Practical Measures to Control Device-Related Bacterial Infections

1993 ◽  
Vol 16 (11) ◽  
pp. 765-770 ◽  
Author(s):  
J.W. Costerton ◽  
A.E. Khoury ◽  
K.H. Ward ◽  
H. Anwar
Keyword(s):  
Bacterial Infections ◽  
Therapeutic Strategy ◽  
Inhibitory Concentration ◽  
Control Device ◽  
Causative Organism ◽  
Stage Of Development ◽  
Planktonic Bacteria ◽  
And Control

Direct examination of medical devices that have been foci of chronic device-related bacterial infections has shown that the causative organisms grow predominantly in slime-enclosed biofilms. These adherent biofilms are inherently resistant to host defences (antibodies, phagocytes) and to conventional antibiotic therapy. Device-related infections can be prevented by careful cleaning and sterilization of the device, and by the avoidance of any manipulations that would allow the formation of even the most rudimentary biofilm prior to implantation. Once a device-related infection has become established, both the Minimum Inhibitory Concentration (MIC) and the Biofilm Eliminating Concentration (BEC) of the causative organism must be determined and therapeutic strategy must aim at the use of the MIC to control the acute phase caused by planktonic bacteria and of the BEC to eliminate the biofilm nidus of infection. The removal of the colonized device should be considered early in the course of treatment if the BEC cannot be delivered to the colonized device. We describe a new bioelectric technology presently in the in vitro stage of development which, if it can be reproduced in vivo, will be very effective in the prevention and control of device-related bacterial infections.

scholarly journals Antimicrobial and Antihypercholesterolemic Activities of Pulicaria gnaphalodes

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090485 ◽  
Author(s):  
Syed Ali Raza Naqvi ◽  
Syed Muhammad Ali Shah ◽  
Laiba Kanwal ◽  
Muhammad Saeed ◽  
Atta-ul-Haq ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Methanol Extract ◽  
Ethanol Extract ◽  
Alternative Therapies ◽  
Zone Of Inhibition

Multidrug resistance has increased globally in the communities. Bacterial infections associated with health care have weakened the existing antimicrobial therapy and demand the search for alternative therapies. In the present investigation, the medicinal plant Pulicaria gnaphalodes from Quetta, Pakistan, has been screened for antimicrobial potential. In vitro antimicrobial efficacy of P gnaphalodes extracts (methanol and ethanol) was quantitatively evaluated on the basis of zone of inhibition against different bacteria and minimum inhibitory concentration (MIC). In vivo, antihypercholesterolemic activity is determined in different rat groups. The results of the study indicated that the ethanol extract of P gnaphalodes showed maximum zone of inhibition for Bacillus subtilis of 12.1 ± 1.1 mm from all others. The methanol extract showed maximum zone of inhibition for Staphylococcus aureus of 11.9 ± 1.0 mm and rifampicin showed maximum zone of inhibition of 23.1 ± 0.9 mm. The results of ethanol and methanol extract of P gnaphalodes against different bacteria revealed that this plant has greater antimicrobial activity. However, the plant extract shows nonsignificant antihypercholesterolemic activity. The extract of this plant can be utilized as medicine to inhibit several infections caused by some bacterial pathogens found in human body.

scholarly journals Antifungal Activity of Gentamicin B1 against Systemic Plant Mycoses

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2401
Author(s):  
Gaspar Banfalvi
Keyword(s):  
Antifungal Activity ◽  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Aminoglycoside Antibiotic ◽  
Pathogenic Fungi ◽  
Microsporum Gypseum ◽  
Antifungal Effect ◽  
Related Compounds

Background: Gentamicin is a broad-spectrum aminoglycoside antibiotic produced by Micromonospora purpurea bacteria, effective against Gram-negative bacterial infections. Major fractions of the gentamicin complex (C1, C1a, C2, C2a) possess weak antifungal activity and one of the minor components (A, A1–A4, B, B1, X), gentamicin B1 was found to be a strong antifungal agent. Methods: This work uses in vitro and in vivo dilution methods to compare the antifusarial, antiaspergillic and anticryptococcal effects of gentamicin derivatives and structurally-related congeners. Results: The in vitro antifusarial activity of gentamicin B1 (minimum inhibitory concentration (MIC) 0.4 μg/mL) and structurally-related compounds (MIC 0.8–12.5 μg/mL) suggests that the purpuroseamine ring substituents are responsible for the specific antimycotic effect. The functional groups of the garoseamine and 2-deoxystreptamine rings of gentamicin derivatives are identical in gentamicin compounds and are unlikely to exert a significant antifungal effect. Among soil dermatophytes, Microsporum gypseum was more susceptible to gentamicin B1 (MIC 3.1 µg/mL) than Trichophyton gypseum (MIC 25 µg/mL). The in vitro antifungal effect of gentamicin B1 against plant pathogenic fungi was comparable to primary antifungal agents. Conclusion: Gentamicin is already in medical use. In vitro and preclinical in vivo synergisms of gentamicin B1 with amphotericin B suggest immediate clinical trials starting with subtoxic doses.

scholarly journals FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 397 ◽  
Author(s):  
Meysam Sarshar ◽  
Payam Behzadi ◽  
Cecilia Ambrosi ◽  
Carlo Zagaglia ◽  
Anna Teresa Palamara ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Therapeutic Strategy ◽  
Uropathogenic Escherichia Coli ◽  
Design And Synthesis ◽  
High Affinity ◽  
Fimbrial Adhesins ◽  
Adhesive Molecules ◽  
Tract Infections

Chaperone-usher fimbrial adhesins are powerful weapons against the uropathogens that allow the establishment of urinary tract infections (UTIs). As the antibiotic therapeutic strategy has become less effective in the treatment of uropathogen-related UTIs, the anti-adhesive molecules active against fimbrial adhesins, key determinants of urovirulence, are attractive alternatives. The best-characterized bacterial adhesin is FimH, produced by uropathogenic Escherichia coli (UPEC). Hence, a number of high-affinity mono- and polyvalent mannose-based FimH antagonists, characterized by different bioavailabilities, have been reported. Given that antagonist affinities are firmly associated with the functional heterogeneities of different FimH variants, several FimH inhibitors have been developed using ligand-drug discovery strategies to generate high-affinity molecules for successful anti-adhesion therapy. As clinical trials have shown d-mannose’s efficacy in UTIs prevention, it is supposed that mannosides could be a first-in-class strategy not only for UTIs, but also to combat other Gram-negative bacterial infections. Therefore, the current review discusses valuable and effective FimH anti-adhesive molecules active against UTIs, from design and synthesis to in vitro and in vivo evaluations.

scholarly journals The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 165
Author(s):  
Beata Kowalska-Krochmal ◽  
Ruth Dudek-Wicher
Keyword(s):  
Monte Carlo ◽  
Bacterial Infections ◽  
Statistical Estimation ◽  
Therapeutic Strategy ◽  
Inhibitory Concentration ◽  
Therapeutic Strategies ◽  
Bacterial Strains ◽  
Method Choice ◽  
Reliable Assessment

Inefficiency of medical therapies used in order to cure patients with bacterial infections requires not only to actively look for new therapeutic strategies but also to carefully select antibiotics based on variety of parameters, including microbiological. Minimal inhibitory concentration (MIC) defines in vitro levels of susceptibility or resistance of specific bacterial strains to applied antibiotic. Reliable assessment of MIC has a significant impact on the choice of a therapeutic strategy, which affects efficiency of an infection therapy. In order to obtain credible MIC, many elements must be considered, such as proper method choice, adherence to labeling rules, and competent interpretation of the results. In this paper, two methods have been discussed: dilution and gradient used for MIC estimation. Factors which affect MIC results along with the interpretation guidelines have been described. Furthermore, opportunities to utilize MIC in clinical practice, with pharmacokinetic /pharmacodynamic parameters taken into consideration, have been investigated. Due to problems related to PK determination in individual patients, statistical estimation of the possibility of achievement of the PK/PD index, based on the Monte Carlo, was discussed. In order to provide comprehensive insights, the possible limitations of MIC, which scientists are aware of, have been outlined.

scholarly journals Activation of the Cholinergic Anti-Inflammatory Pathway as a Novel Therapeutic Strategy for COVID-19

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhen Qin ◽  
Kefa Xiang ◽  
Ding-Feng Su ◽  
Yang Sun ◽  
Xia Liu
Keyword(s):  
Vagus Nerve ◽  
Therapeutic Strategy ◽  
Inflammatory Pathway ◽  
Non Invasive ◽  
Anti Inflammatory ◽  
Approved Drugs ◽  
And Control ◽  
Anti Inflammation

The outbreak of coronavirus disease 2019 (COVID-19) underlined the urgent need for alleviating cytokine storm. We propose here that activating the cholinergic anti-inflammatory pathway (CAP) is a potential therapeutic strategy. However, there is currently no approved drugs targeting the regulatory pathway. It is evident that nicotine, anisodamine and some herb medicine, activate the CAP and exert anti-inflammation action in vitro and in vivo. As the vagus nerve affects both inflammation and specific immune response, we propose that vagus nerve stimulation by invasive or non-invasive devices and acupuncture at ST36, PC6, or GV20, are also feasible approaches to activate the CAP and control COVID-19. It is worth to investigate the efficacy and safety of the strategy in patients with COVID-19.

scholarly journals 1368. Assessment of the In Vivo Efficacy of Human-Simulated Epithelial Lining Fluid (ELF) Exposure of Meropenem/Nacubactam (MEM/NAC) Combination Against β-Lactamase-Producing Enterobacteriaceae in Neutropenic Lung Infection Model

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S419-S419 ◽  
Author(s):  
Tomefa E Asempa ◽  
Ana Motos ◽  
Kamilia Abdelraouf ◽  
Caterina Bissantz ◽  
Claudia Zampaloni ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Lung Infection ◽  
Infection Model ◽  
Bacterial Reduction ◽  
Treatment Groups ◽  
Class D ◽  
Dual Action ◽  
And Control

Abstract Background NAC is a novel dual action β-lactamase inhibitor with in vitro activity against class A, class C, and some class D β-lactamases and antibacterial activity against Enterobactaeriaceae. NAC is being developed as a combination therapy with MEM for the treatment of serious Gram-negative bacterial infections. This study evaluated the efficacy of the human-simulated ELF exposure of MEM/NAC, compared with those of MEM or NAC alone against β-lactamase-producing Enterobacteriaceae isolates in the neutropenic murine lung infection model. Methods Eight clinical MEM-resistant Enterobacteriaceae isolates harboring various β-lactamases (IMI, KPC, OXA, TEM, SHV, and AmpC) were utilized in the study. MEM and MEM:NAC (1:1) combination MICs were determined in triplicate via broth microdilution. ICR mice were rendered transiently neutropenic, and lungs were inoculated with 50 µL bacterial suspensions of 107 CFU/mL. Regimens in mice that simulated the human ELF exposures following doses of MEM 2g q8h and NAC 2g q8h (1.5 hours infusions) as monotherapies and in combination were established. Treatment mice received MEM human-simulated regimen (HSR), NAC HSR, or MEM/NAC HSR and control mice were vehicle-dosed. Treatment was started 2 hours after inoculation and continued for 24 hours. Efficacy was assessed as the change in log10CFU/lung at 24 hours compared with 0 hours controls. Results MEM and MEM/NAC MICs were 8–512 and 0.5–8 mg/L, respectively. The average log10CFU/lung at 0 hours across all isolates was 6.26 ± 0.26. Relative to 0 hours control, the mean bacterial growth at 24 hours in the untreated control mice, MEM HSR, and NAC HSR treatment groups were 2.93 ± 0.29, 2.72 ± 0.42, and 1.75 ± 0.80 log10CFU/lung, respectively. MEM/NAC HSR resulted in up to 2-log bacterial reduction in isolates with MEM/NAC MIC ≤4 mg/L. Conclusion MEM/NAC human-simulated ELF exposure produced enhanced efficacy against MEM-resistant β-lactamase-producing Enterobacteriaceae isolates with MEM/NAC MIC ≤4 mg/L. These data support a potential role for MEM/NAC for treatment of lung infections due to β-lactamase-producing Enterobacteriaceae and warrant further studies. This project has been funded in part under HHS BARDA Contract HHSO100201600038C. Disclosures C. Bissantz, F Hoffmann La Roche Ltd.: Employee, Salary. C. Zampaloni, F. Hoffmann-La Roche Ltd.: Employee, Salary. D. P. Nicolau, Hoffmann-La Roche Ltd.: Grant Investigator, Grant recipient.

scholarly journals Phage Therapy: a Step Forward in the Treatment of Pseudomonas aeruginosa Infections

2015 ◽  
Vol 89 (15) ◽  
pp. 7449-7456 ◽  
Author(s):  
Diana P. Pires ◽  
Diana Vilas Boas ◽  
Sanna Sillankorva ◽  
Joana Azeredo
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Therapeutic Strategy ◽  
Phage Therapy ◽  
Content Type ◽  
Common Causes ◽  
Health Care Associated Infections ◽  
Common Infection

Antimicrobial resistance constitutes one of the major worldwide public health concerns. Bacteria are becoming resistant to the vast majority of antibiotics, and nowadays, a common infection can be fatal. To address this situation, the use of phages for the treatment of bacterial infections has been extensively studied as an alternative therapeutic strategy. SincePseudomonas aeruginosais one of the most common causes of health care-associated infections, many studies have reported thein vitroandin vivoantibacterial efficacy of phage therapy against this bacterium. This review collects data of all theP. aeruginosaphages sequenced to date, providing a better understanding about their biodiversity. This review further addresses thein vitroandin vivoresults obtained by using phages to treat or preventP. aeruginosainfections as well as the major hurdles associated with this therapy.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

scholarly journals Role of interleukins in the pathogenesis of pulmonary fibrosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Xin She ◽  
Qing Yang Yu ◽  
Xiao Xiao Tang
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Strategy ◽  
Future Directions ◽  
Regulation Mechanisms ◽  
Underlying Mechanisms ◽  
Multiple Cells ◽  
The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

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