scholarly journals Application of Bacteriophages for Mycobacterial Infections, from Diagnosis to Treatment

2021 ◽  
Vol 9 (11) ◽  
pp. 2366
Author(s):  
Christopher G. Shield ◽  
Benjamin M. C. Swift ◽  
Timothy D. McHugh ◽  
Rebekah M. Dedrick ◽  
Graham F. Hatfull ◽  
...  

Mycobacterium tuberculosis and other non-tuberculous mycobacteria are responsible for a variety of different infections affecting millions of patients worldwide. Their diagnosis is often problematic and delayed until late in the course of disease, requiring a high index of suspicion and the combined efforts of clinical and laboratory colleagues. Molecular methods, such as PCR platforms, are available, but expensive, and with limited sensitivity in the case of paucibacillary disease. Treatment of mycobacterial infections is also challenging, typically requiring months of multiple and combined antibiotics, with associated side effects and toxicities. The presence of innate and acquired drug resistance further complicates the picture, with dramatic cases without effective treatment options. Bacteriophages (viruses that infect bacteria) have been used for decades in Eastern Europe for the treatment of common bacterial infections, but there is limited clinical experience of their use in mycobacterial infections. More recently, bacteriophages’ clinical utility has been re-visited and their use has been successfully demonstrated both as diagnostic and treatment options. This review will focus specifically on how mycobacteriophages have been used recently in the diagnosis and treatment of different mycobacterial infections, as potential emerging technologies, and as an alternative treatment option.

2020 ◽  
Vol 16 (2) ◽  
pp. 115-134
Author(s):  
Kaviarasan Lakshmanan ◽  
Gowramma Byran ◽  
Manal Mohammed

Background: Cancer is a disease characterized by the uncontrolled growth and spread of abnormal cells. Around the world, over 10 million cancer cases occur annually. Half of all men and one-third of all women will develop some form of cancer during their lifetime. It is one of the most feared diseases, primarily because half of those diagnosed with cancer die from it. There are several treatments available for cancer. Almost all traditional cytotoxic agents suffer from severe toxicities and other undesirable side effects. Objective: In recent years, the development of targeted medicines has made significant achievements. Unfortunately, though these agents can block key regulators of signaling pathways in cancer, multiple compensatory pathways always attenuate pharmacological effect of single-target drugs. In addition, poor response rates and acquired drug resistance also represent a significant barrier to widespread use of targeted medicines. More recently, a number of combinatorial therapies have expanded treatment options, which can directly block several key signaling pathways and create a synergistic effect. Conclusion: Therefore, in order to overcome these barriers, the present investigation aims to develop a new strategy for designing a single molecule with inhibition of two receptors (PARP1 and STAT3) simultaneously and producing enhanced anti-cancer activity with less and/or null toxicity.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Charity Wiafe Akenten ◽  
Kennedy Gyau Boahen ◽  
Kwadwo Sarfo Marfo ◽  
Nimako Sarpong ◽  
Denise Dekker ◽  
...  

Abstract Background The increasing incidence of multi-antibiotic-resistant bacterial infections, coupled with the risk of co-infections in malaria-endemic regions, complicates accurate diagnosis and prolongs hospitalization, thereby increasing the total cost of illness. Further, there are challenges in making the correct choice of antibiotic treatment and duration, precipitated by a lack of access to microbial culture facilities in many hospitals in Ghana. The aim of this case report is to highlight the need for blood cultures or alternative rapid tests to be performed routinely in malaria patients, to diagnose co-infections with bacteria, especially when symptoms persist after antimalarial treatment. Case presentation A 6-month old black female child presented to the Agogo Presbyterian Hospital with fever, diarrhea, and a 3-day history of cough. A rapid diagnostic test for malaria and Malaria microscopy was positive for P. falciparum with a parasitemia of 224 parasites/μl. The patient was treated with Intravenous Artesunate, parental antibiotics (cefuroxime and gentamicin) and oral dispersible zinc tablets in addition to intravenous fluids. Blood culture yielded Acinetobacter baumanii, which was resistant to all of the third-generation antibiotics included in the susceptibility test conducted, but sensitive to ciprofloxacin and gentamicin. After augmenting treatment with intravenous ciprofloxacin, all symptoms resolved. Conclusion Even though this study cannot confirm whether the bacterial infection was nosocomial or otherwise, the case highlights the necessity to test malaria patients for possible co-infections, especially when fever persists after parasites have been cleared from the bloodstream. Bacterial blood cultures and antimicrobial susceptibility testing should be routinely performed to guide treatment options for febril illnesses in Ghana in order to reduce inappropriate use of broad-spectrum antibiotics and limit the development of antimicrobial resistance.


1985 ◽  
Vol 5 (6) ◽  
pp. 470-475 ◽  
Author(s):  
Cindy Dunham ◽  
William D. Mattern ◽  
William C. McGaghie

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Fan Zhang ◽  
Olivia Ledue ◽  
Maria Jun ◽  
Cibelly Goulart ◽  
Richard Malley ◽  
...  

ABSTRACTStaphylococcus aureusis a major cause of morbidity and mortality worldwide.S. aureuscolonizes 20 to 80% of humans at any one time and causes a variety of illnesses. Strains that are resistant to common antibiotics further complicate management.S. aureusvaccine development has been unsuccessful so far, largely due to the incomplete understanding of the mechanisms of protection against this pathogen. Here, we studied the role of different aspects of adaptive immunity induced by anS. aureusvaccine in protection againstS. aureusbacteremia, dermonecrosis, skin abscess, and gastrointestinal (GI) colonization. We show that, depending on the challenge model, the contributions of vaccine-inducedS. aureus-specific antibody and Th1 and Th17 responses to protection are different: antibodies play a major role in reducing mortality duringS. aureusbacteremia, whereas Th1 or Th17 responses are essential for prevention ofS. aureusskin abscesses and the clearance of bacteria from the GI tract. Both antibody- and T-cell-mediated mechanisms contribute to prevention ofS. aureusdermonecrosis. Engagement of all three immune pathways results in the most robust protection under each pathological condition. Therefore, our results suggest that eliciting multipronged humoral and cellular responses toS. aureusantigens may be critical to achieve effective and comprehensive immune defense against this pathogen.IMPORTANCES. aureusis a leading cause of healthcare- and community-associated bacterial infections.S. aureuscauses various illnesses, including bacteremia, meningitis, endocarditis, pneumonia, osteomyelitis, sepsis, and skin and soft tissue infections.S. aureuscolonizes between 20 and 80% of humans; carriers are at increased risk for infection and transmission to others. The spread of multidrug-resistant strains limits antibiotic treatment options. Vaccine development againstS. aureushas been unsuccessful to date, likely due to an inadequate understanding about the mechanisms of immune defense against this pathogen. The significance of our work is in illustrating the necessity of generating multipronged B-cell, Th1-, and Th17-mediated responses toS. aureusantigens in conferring enhanced and broad protection againstS. aureusinvasive infection, skin and soft tissue infection, and mucosal colonization. Our work thus, provides important insights for future vaccine development against this pathogen.


Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 104
Author(s):  
James V. Rogers ◽  
Veronica L. Hall ◽  
Charles C. McOsker

Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship.


2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Faith Ukachukwu ◽  
Lori Snyder ◽  
Raid Alany

Pseudomonas aeruginosa and Staphylococcus aureus are bacteria pathogens that cause a myriad of infections affecting various sites in the body including the eyes, ears, lungs, skin, heart, bones, and blood amongst others. These bacteria can be disseminated via the blood to other parts of the body away from the primary site of infection and consequences vary from mild to severe with death occurring in certain instances. Both bacterial infections can occur individually, as well as in co-infection resulting in even worse outcomes. P. aeruginosa and S. aureus exhibit multidrug resistance against current antibiotic treatment regimens, which accentuates the challenge in managing the infections caused by these bacteria. To prevent the looming era of untreatable bacterial infections, alternative treatment regimens that are cost effective and accessible are needed. To explore novel treatment options, twenty-five organic compounds comprising fatty acids and their derivatives were screened for antibacterial activity in broth microdilution assay to determine the minimum inhibitory concentration and minimum bactericidal concentration against both P. aeruginosa and S. aureus. Five candidates (N–nonanoic acid, butyric acid, heptanoic acid, palmitoleic acid, and isopropyl myristate) were effective against P. aeruginosa. Seven candidates (N–nonanoic acid, palmitoleic acid, tridecanoic acid, sebaic acid, undecanoic acid, monolaurin, and monocaprin) were effective against S. aureus. Candidates such as N–nonanoic acid and palmitoleic acid were effective against both P. aeruginosa and S. aureus, demonstrating that the same fatty acids show potential to be used against both Gram negative and Gram positive bacterial infections.


2018 ◽  
Author(s):  
Jan V. Hirschmann

The skin can become infected by viruses, fungi, and bacteria, including some that ordinarily are harmless colonizing organisms. The most common fungal infections are caused by dermatophytes, which can involve the hair, nails, and skin. Potassium hydroxide (KOH) preparations of specimens from affected areas typically demonstrate hyphae, and either topical or systemic antifungal therapy usually cures or controls the process. The most common bacterial pathogens are Staphylococcus aureus and group A streptococci, which, alone or together, can cause a wide variety of disorders, including impetigo, ecthyma, and cellulitis. Topical antibiotics may suffice for impetigo, but ecthyma and cellulitis require systemic treatment. S. aureus, including methicillin-resistant strains, can also cause furuncles, carbuncles, and cutaneous abscesses. For these infections, incision and drainage without antibiotics are usually curative. Warts are the most common cutaneous viral infection, and eradication can be difficult, especially where the skin is thick, such as the palms and soles, or the patient is immunocompromised. Most therapies consist of trying to destroy the viruses by mechanical, chemical, or immune mechanisms. This review covers dermatophyte infections, yeast infections, bacterial infections, and viral infections of the skin. Figures show the classic annular lesion of tinea corporis, a typical kerion presenting as a zoophilic Microsporum canis infection of the scalp (tinea capitis), tinea corporis, tinea barbae, tinea pedis between and under the toes and on the plantar surface, inflammatory tinea pedis, tinea unguium, tinea manuum, angular cheilitis, prominent satellite lesions of discrete vesicles associated with candidiasis, facial candidiasis, Candida paronychia, tinea versicolor, nonbullous impetigo, bullous impetigo, ecthyma, leg cellulitis, erythema and edema on the cheeks, eyelids, and nose, furuncle, carbuncle, nasal folliculitis, pitted keratolysis, trichomycosis axillaris, necrotizing fasciitis, Fournier gangrene, folliculitis, plantar wart, condyloma acuminatum, and benign lesions of bowenoid papulosis. Tables list dermatophyte species, terminology of dermatophyte infections, topical agents for dermatophyte infections, treatment options for impetigo (adult doses), and treatment options for erythrasma.   This review contains 28 highly rendered figures, 5 tables, and 33 references


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