scholarly journals Clinical Indications and Compassionate Use of Phage Therapy: Personal Experience and Literature Review with a Focus on Osteoarticular Infections

Viruses ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 18 ◽  
Author(s):  
Olivier Patey ◽  
Shawna McCallin ◽  
Hubert Mazure ◽  
Max Liddle ◽  
Anthony Smithyman ◽  
...  
Keyword(s):  
Phage Therapy ◽  
Case Reports ◽  
Individual Case ◽  
Clinical Applications ◽  
Experimental Therapy ◽  
Compassionate Use ◽  
Osteoarticular Infections ◽  
Antibiotic Failure ◽  
Historical Accounts ◽  
Number Of Treatment

The history of phage therapy started with its first clinical application in 1919 and continues its development to this day. Phages continue to lack any market approval in Western medicine as a recognized drug, but are increasingly used as an experimental therapy for the compassionate treatment of patients experiencing antibiotic failure. The few formal experimental phage clinical trials that have been completed to date have produced inconclusive results on the efficacy of phage therapy, which contradicts the many successful treatment outcomes observed in historical accounts and recent individual case reports. It would therefore be wise to identify why such a discordance exists between trials and compassionate use in order to better develop future phage treatment and clinical applications. The multitude of observations reported over the years in the literature constitutes an invaluable experience, and we add to this by presenting a number of cases of patients treated compassionately with phages throughout the past decade with a focus on osteoarticular infections. Additionally, an abundance of scientific literature into phage-related areas is transforming our knowledge base, creating a greater understanding that should be applied for future clinical applications. Due to the increasing number of treatment failures anticipatedfrom the perspective of a possible post-antibiotic era, we believe that the introduction of bacteriophages into the therapeutic arsenal seems a scientifically sound and eminently practicable consideration today as a substitute or adjuvant to antibiotic therapy.

scholarly journals Phage Therapy: Towards a Successful Clinical Trial

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 827
Author(s):  
Andrzej Górski ◽  
Jan Borysowski ◽  
Ryszard Międzybrodzki
Keyword(s):  
Phage Therapy ◽  
Current Issue ◽  
Case Reports ◽  
Modern Medicine ◽  
Experimental Therapy ◽  
Compassionate Use ◽  
Regulatory Requirements ◽  
Therapy Quality ◽  
Positive Results

While phage therapy carried out as compassionate use (experimental therapy) has recently flourished, providing numerous case reports of supposedly healed patients, clinical trials aiming to formally prove their value in accord with current regulatory requirements have failed. In light of the current issue of increasing antibiotic resistance, the need for a final say regarding the place of phage therapy in modern medicine is evident. We analyze the possible factors that may favor success or lead to the failure of phage therapy: quality of phage preparations, their titer and dosage, as well as external factors that could also contribute to the outcome of phage therapy. Hopefully, better control of these factors may eventually bring about long-awaited positive results.

scholarly journals Sourcing phages for compassionate use

2019 ◽  
Vol 40 (1) ◽  
pp. 24 ◽  
Author(s):  
Jessica C Sacher ◽  
Jan Zheng ◽  
Shawna McCallin
Keyword(s):  
Antibiotic Resistance ◽  
Soviet Union ◽  
Phage Therapy ◽  
Clinical Medicine ◽  
Compassionate Use ◽  
Therapeutic Benefits ◽  
The Soviet Union ◽  
International Report ◽  
Antibiotic Failure ◽  
Resistance Rates

Antibiotic resistance is a phenomenon that knows no geographical borders, so addressing this crisis is a worldwide public health priority. While total global resistance rates are difficult to estimate and vary between countries, an international report asserts that the development of new antibacterials is essential to ensuring the future ability to treat bacterial infections1. Bacteriophage (phage) therapy is a likely contributor to resolving potentially devastating effects of antibiotic resistance, yet no phage product currently holds a marketing authorisation that would permit their free use in clinical medicine outside of former countries of the Soviet Union, where phage therapy is a long-standing practice2,3. In the interim, the compassionate use of phage therapy (cPT) remains a possible treatment avenue for cases of antibiotic failure, and several competency centres, physicians, and researchers have achieved therapeutic benefits with this option. As antibiotic resistance continues to rise, there is much to be done in order to streamline cPT efforts, particularly in terms of phage sourcing, in order to reach more patients in an efficient, effective, and safe manner. This article highlights how cPT can be coordinated, and describes the experience of cPT in Australia.

Herpetic Whitlow of the Hand in Infants

2020 ◽  
Author(s):  
Mohammad M. Al-Qattan ◽  
Nada G. AlQadri ◽  
Ghada AlHayaza
Keyword(s):  
Bacterial Infection ◽  
Case Reports ◽  
Case Series ◽  
Individual Case ◽  
Senior Author ◽  
Secondary Bacterial Infection ◽  
Clinical Appearance ◽  
History Of ◽  
Mode Of Transmission ◽  
Time Of Presentation

Abstract Introduction Herpetic whitlows in infants are rare. Previous authors only reported individual case reports. We present a case series of six infants. Materials and Methods This is a retrospective study of six cases of herpetic whitlows in infants seen by the senior author (MMA) over the past 23 years (1995–2017 inclusive). The following data were collected: age, sex, digit involved in the hand, mode of transmission, time of presentation to the author, clinical appearance, presence of secondary bacterial infection, presence of other lesions outside the hand, method of diagnosis, treatment, and outcome. Results All six infants initially presented with classic multiple vesicles of the digital pulp. In all cases, there was a history of active herpes labialis in the mother. Incision and drainage or deroofing of the vesicles (for diagnostic purposes) resulted in secondary bacterial infection. Conclusion The current report is the first series in the literature on herpetic whitlows in infants. We stress on the mode of transmission (from the mother) and establishing the diagnosis clinically. In these cases, no need for obtaining viral cultures or polymerase chain reaction; and no medications are required. Once the vesicles are disrupted, secondary bacterial infection is frequent and a combination of oral acyclovir and intravenous antibiotics will be required.

scholarly journals Leptomeningeal Carcinomatosis: A Clinical Dilemma in Neuroendocrine Neoplasms

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 277
Author(s):  
Leonidas Apostolidis ◽  
Jörg Schrader ◽  
Henning Jann ◽  
Anja Rinke ◽  
Sebastian Krug
Keyword(s):  
Brain Metastases ◽  
Median Overall Survival ◽  
Case Reports ◽  
Individual Case ◽  
Leptomeningeal Carcinomatosis ◽  
Neuroendocrine Neoplasms ◽  
Cns Involvement ◽  
Ki 67 ◽  
Sensory Deficits ◽  
Clinical Dilemma

Central nervous system (CNS) involvement by paraneoplastic syndromes, brain metastases, or leptomeningeal carcinomatosis (LC) in patients with neuroendocrine neoplasms (NEN) has only been described in individual case reports. We evaluated patients with LC in four neuroendocrine tumor (NET) centers (Halle/Saale, Hamburg, Heidelberg, and Marburg) and characterized them clinically. In the study, 17 patients with a LC were defined with respect to diagnosis, clinic, and therapy. The prognosis of a LC is very poor, with 10 months in median overall survival (mOS). This is reflected by an even worse course in neuroendocrine carcinoma (NEC) G3 Ki-67 >55%, with a mOS of 2 months. Motor and sensory deficits together with vigilance abnormalities were common symptoms. In most cases, targeted radiation or temozolomide therapy was used against the LC. LC appears to be similarly devastating to brain metastases in NEN patients. Therefore, the indication for CNS imaging should be discussed in certain cases.

scholarly journals Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

2017 ◽  
Vol 63 (11) ◽  
pp. 865-879 ◽  
Author(s):  
Ayman El-Shibiny ◽  
Salma El-Sahhar
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Clinical Applications ◽  
Western World ◽  
Resistant Bacteria ◽  
Vaccine Production ◽  
Bacterial Populations ◽  
Antibiotic Resistant

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.

scholarly journals New Case Reports with Phage Therapy-What is Needed for More?

2019 ◽  
pp. 35-37
Author(s):  
Karin Moelling
Keyword(s):  
Recent Article ◽  
Phage Therapy ◽  
Case Reports ◽  
Hospital Sewage

A recent article had the provocative title: A wake-up call: we need phage therapy now [1]. Indeed, there are very few sources for phages available if someone needs them urgently. Thus phages are needed and should be produced, characterized and banked and provided upon need, possibly on a European basis. It is not so difficult to collect phages: wherever there are bacteria, there are also their phages. Thus hospital sewage or general sewage is rich sources, and then they require purification, characterization, typing of their hosts, banking and catalogues.

scholarly journals A comparative analysis of the outcome of malaria case surveillance strategies in Sri Lanka in the prevention of re-establishment phase

2021 ◽  
Author(s):  
W. M. Kumudunayana T. de A. W Gunasekera ◽  
Risintha Premaratne ◽  
Deepika Fernando ◽  
Muzrif Munaz ◽  
M. G. Y. Piyasena ◽  
...  
Keyword(s):  
Sri Lanka ◽  
Case Reports ◽  
Individual Case ◽  
Case Detection ◽  
Malaria Surveillance ◽  
Blood Smears ◽  
Passive Case Detection ◽  
Routine Basis ◽  
Detection Strategies ◽  
Very High

Abstract Background Sri Lanka sustained its malaria-free status by implementing, among other interventions, three core case detection strategies namely Passive Case Detection (PCD), Reactive Case Detection (RACD) and Proactive Case Detection (PACD). The outcomes of these strategies were analysed in terms of their effectiveness in detecting malaria infections for the period from 2017-2019. Methods Comparisons were made between the surveillance methods and between years, based on data obtained from the national malaria database and individual case reports of malaria patients. The number of blood smears examined microscopically was used as the measure of the volume of tests conducted. The yield from each case detection method was calculated as the proportion of blood smears which were positive for malaria. Within RACD and PACD, the yield of sub categories of travel cohorts and spatial cohorts was ascertained for 2019. Results A total of 158 malaria cases were reported in 2017-2019. During this period between 666,325-725,149 blood smears were examined annually. PCD detected 95.6%, with a yield of 16.1 cases per 100,000 blood smears examined. RACD and PACD produced a yield of 11.2 and 0.3, respectively. The yield of screening the sub category of travel cohorts was very high for RACD and PACD being 806.5 and 44.9 malaria cases per 100,000 smears, respectively. Despite over half of the blood smears examined being obtained by screening spatial cohorts within RACD and PACD, the yield of both was zero over all three years. Conclusions The PCD arm of case surveillance is the most effective and, therefore, has to continue and be further strengthened as the mainstay of malaria surveillance. Focus on travel cohorts within RACD and PACD should be even greater. Screening of spatial cohorts, on a routine basis and solely because people are resident in previously malarious areas, may be wasteful, except in situations where the risk of local transmission is very high, or is imminent. These findings may apply more broadly to most countries in the post-elimination phase.

Abstract P101: Mechanical Thrombectomy in COVID-19 Positive Patients With Large Vessel Occlusion: Pooled Review of Individual Case Series

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Muhammad Z Memon ◽  
Taha Nisar ◽  
Amit Singla ◽  
Anil Nanda ◽  
Gaurav Gupta ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Mechanical Thrombectomy ◽  
Case Reports ◽  
Case Series ◽  
Individual Case ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Historic Data ◽  
Meta Analyses

Background: COVID-19 has been shown to induce a hypercoagulable state thereby increasing the risk of arterial thrombosis resulting in Large Vessel Occlusion Stroke (LVOs) Objective: We performed a systematic review of published reports to study the clinical characteristics, and outcomes of COVID-19 acute ischemic stroke (AIS) patients with LVO treated with mechanical thrombectomy (MT) and compared them with historical controls. Methods: We conducted a systematic literature search from December 2019 to July 2020 using multiple combinations of keywords from PubMed and Ovid databases according to the PRISMA meta-analyses and systemic reviews guidelines and then pooled data from individual case series. We included studies where COVID -19 associated LVO cases were treated with MT and their clinical outcomes were reported. We then compared these findings with the historic patient data from the five landmark randomized MT trials, the Hermes collaborators (HC). Results: An initial search generated 12 studies but after excluding case reports and multiple reports comprising of the same series of patients, a total of five reports consisting of 51 patients were analyzed. The mean age of patients was 59 years (IQR 36-75), and 40 (78 %) were men. Median NIHSS on presentation was 20 (IQR 10-29). AIS with LVO was the presenting manifestation of COVID-19 in 16 (20%) of patients. Intracranial ICA was the most common site of occlusion found in 27 (53%) of patients with multi-territory occlusion in 10 (20 %). Final recanalization TICI ≥ 2b was achieved in 33 (64%) of patients but reocclusion was noted in 7 (14 %). Modified Rankin score (mRS) 0-2 was reported in 12 (23 %) of patients with 40 % in-hospital mortality. When compared to historic data from HC, COVID -19 patients were younger (59 vs 69 years), presented with a higher median NIHSS score (20 vs 17), and had a higher prevalence of ICA terminus occlusion (53% vs 21% ). Similarly, patient outcomes were poor in the COVID -19 group with mRs 0-2 in (23 % versus 46 %) and mortality (40 % vs 15 %) compared to Hermes group. Conclusion: COVID -19 AIS patients with LVO who underwent MT were younger, had multiple territory occlusions with a propensity for ICA terminus location, and had poor angiographic and clinical outcomes as compared to historic data.

scholarly journals B.04 Distal and asymmetric myasthenia gravis: a case series of 54 patients

2016 ◽  
Vol 43 (S2) ◽  
pp. S10-S10
Author(s):  
AG Florendo-Cumbermack ◽  
MW Nicolle
Keyword(s):  
Myasthenia Gravis ◽  
Clinical Course ◽  
Case Reports ◽  
Delayed Diagnosis ◽  
Case Series ◽  
Retrospective Chart Review ◽  
Individual Case ◽  
Response To Treatment ◽  
Antibody Testing ◽  
Repetitive Nerve Stimulation

Background: Distal/asymmetric presentations of myasthenia gravis (MG) are uncommon and occur in 3-7% of patients with MG. This pattern of weakness is often not recognized as a manifestation of MG, leading to inappropriate investigations, delayed diagnosis and potentially missed opportunities for treatment. Our knowledge about this atypical presentation is limited to small case series and individual case reports. This study therefore aims to expand our understanding by describing the clinical course, diagnosis and treatment of a larger series of patients with this presentation. Methods: We conducted a retrospective chart review of patients with definite MG (either acetylcholine receptor [AChR] or MuSK antibody positive or clear evidence of postsynaptic neuromuscular junction dysfunction on electrodiagnostic studies), who attended the MG Clinic in London. Details of the clinical course, electrodiagnostic studies, antibody testing and response to treatment are reported. Results: 5.9% (54/921) of patients with definite MG had distal/asymmetric limb involvement, 56% at onset and 4% developing more than 10 years later. Males predominated (2:1). Finger extensors were most affected. 83% were AChR antibody positive. 7% had thymomas. On repetitive nerve stimulation most patients showed the most significant decrement distally on the more affected side. Almost all patients improved with treatment. Conclusions: This study expands our understanding of distal/asymmetric presentations of MG.

scholarly journals Practical applications of regulatory requirements for signal detection and communications in pharmacovigilance

2020 ◽  
Vol 11 ◽  
pp. 204209862090961
Author(s):  
Marina A. Malikova
Keyword(s):  
Pharmaceutical Industry ◽  
Health Professionals ◽  
Case Reports ◽  
Individual Case ◽  
Regulatory Requirements ◽  
Practical Applications ◽  
Safety Alert ◽  
Potential Safety ◽  
Post Marketing ◽  
Regulatory Decisions

Pharmacovigilance is a field where communication is crucial, and exchange of information is expected to be done in a timely manner. Information from individual case reports is transmitted from pharmaceutical industry and health professionals to the regulatory authorities. The safety profile of a drug is established by analyzing individual cases and aggregate reports. The cumulative information, obtained from these reports, can be used to assist pharmacovigilance professionals in the detection of potential safety signals by monitoring evolving trends. If there is a message identifying concern as potential safety signal, the transmission of individual case reports, as well as cumulative and aggregate reports will occur from pharmaceutical industry to the regulators; and based on their assessments of causality in relationship to the drug, the regulatory decisions will be made. Once regulators confirming a signal as a possible safety alert have made the decision, the decisions and the reasons must be communicated to health professionals, the pharmaceutical industry, and other parties involved (e.g. clinical trials participants, investigators, consumers and medical professionals at post-marketing stage, etc.).

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