Azithromycin resistant gonococci: a literature review

Abstract Objective Gonorrhea is the second most common sexually transmitted bacterial infection (STI) next to Chlamydia. Untreated cases could results in major complications like pelvic inflammatory disease (PID), ectopic pregnancy, infertility, miscarriage, fetal death and congenital infections. Gonorrhea has been treated with antibiotics for more than eight decades. However, the emergence and spread of antimicrobial resistance (AMR) in gonococcus seriously compromises the management of the disease. The aim of this review was to describe the current developments in the field of azithromycin resistant gonococci. Methods Literatures published in English in the last 10 years were retrieved from PubMed, SCOPUS, Google scholar, Cochrane library and the Google databases using relevant searching terms. Results Gonococcus is capable of using a number of strategies to confer resistance as the bacterium has an extraordinary capacity to alter its genome. So far the accumulated data on the field showed that the world is heading towards a pandemic of extensively drug-resistant (XDR) gonococcus which is now seems to be evolving into a true “superbug”. Hence, in the near future gonorrhea may become untreatable on the international basis unless new drugs become available. An antibiotic resistance in gonococcus has been noted beginning in 1940s against sulfonamides. Since then, resistance has rapidly emerged to penicillins, tetracyclines, macrolides, fluoroquinolones, and cephalosporins. Currently, in most nations, the injectable extended-spectrum cephalosporin (ESC), i.e. ceftriaxone based therapy is the only remaining option for gonorrhea. Based on the WHO and the US-CDC recommendations, countries are increasingly using a combination of cephalosporin and azithromycin for the treatment of gonorrhoea. Azithromycin revolutionized gonoccocal therapy as it shortened treatment time by more than half from 7 to 14 days and improved patient compliance due to high tissue levels and long half-life. However, constantly emerging reports from different parts of the globe showed that N. gonorrhoeae is developing significant level of resistance against azithromycin, and so far more than 33% level of resistance was reported. Two strategies have been commonly implicated in gonococcal resistance against azithromycin: over expression of an efflux pump (due to mutations at mtrR coding region) and decreased antimicrobial affinity (due to mutations in genes encoding the 23S ribosomal subunit). Conclusions With no alternative antimicrobial treatment options for gonorrhoea and only a few new drugs in the development pipeline, it is necessary to monitor drug resistance and optimize treatment regimens regularly. Moreover, investigations for novel drugs should be wired.

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Benznidazole Treatment: Time- and Dose-Dependence Varies with the Trypanosoma cruzi Strain

Pathogens ◽

10.3390/pathogens10060729 ◽

2021 ◽

Vol 10 (6) ◽

pp. 729

Author(s):

Kátia da Silva Fonseca ◽

Luísa Perin ◽

Nívia Carolina Nogueira de Paiva ◽

Beatriz Cristiane da Silva ◽

Thays Helena Chaves Duarte ◽

...

Keyword(s):

Treatment Adherence ◽

Treatment Efficacy ◽

Treatment Time ◽

Standard Dose ◽

Acute Infection ◽

Chronic Phase ◽

Disease Status ◽

Dose Dependence ◽

New Drugs ◽

Treatment Regimens

As the development of new drugs for Chagas disease is not a priority due to its neglected disease status, an option for increasing treatment adherence is to explore alternative treatment regimens, which may decrease the incidence of side effects. Therefore, we evaluated the efficacy of different therapeutic schemes with benznidazole (BNZ) on the acute and chronic phases of the disease, using mice infected with strains that have different BNZ susceptibilities. Our results show that the groups of animals infected by VL-10 strain, when treated in the chronic phase with a lower dose of BNZ for a longer period of time (40 mg/kg/day for 40 days) presented better treatment efficacy than with the standard protocol (100 mg/kg/day for 20 days) although the best result in the treatment of the animals infected by the VL-10 strain was with100 mg/kg/day for 40 days. In the acute infection by the Y and VL-10 strains of T. cruzi, the treatment with a standard dose, but with a longer time of treatment (100 mg/kg/day for 40 days) presented the best results. Given these data, our results indicate that for BNZ, the theory of dose and time proportionality does not apply to the phases of infection.

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Sexually Transmitted Neisseria gonorrhoeae Infections—Update on Drug Treatment and Vaccine Development

Medicines ◽

10.3390/medicines8020011 ◽

2021 ◽

Vol 8 (2) ◽

pp. 11

Author(s):

Amber Jefferson ◽

Amanda Smith ◽

Pius S. Fasinu ◽

Dorothea K. Thompson

Keyword(s):

Neisseria Gonorrhoeae ◽

Vaccine Development ◽

Target Identification ◽

Treatment Options ◽

New Drugs ◽

Effective Vaccine ◽

Sexually Transmitted ◽

Successful Vaccine ◽

Future Success ◽

The Status

Background: Sexually transmitted gonorrhea, caused by the Gram-negative diplococcus Neisseria gonorrhoeae, continues to be a serious global health challenge despite efforts to eradicate it. Multidrug resistance among clinical N. gonorrhoeae isolates has limited treatment options, and attempts to develop vaccines have not been successful. Methods: A search of published literature was conducted, and information extracted to provide an update on the status of therapeutics and vaccine development for gonorrheal infection. Results: Recommended pharmacological treatment for gonorrhea has changed multiple times due to increasing acquisition of resistance to existing antibiotics by N. gonorrhoeae. Only broad-spectrum cephalosporin-based combination therapies are currently recommended for treatment of uncomplicated urogenital and anorectal gonococcal infections. With the reported emergence of ceftriaxone resistance, successful strategies addressing the global burden of gonorrhea must include vaccination. Century-old efforts at developing an effective vaccine against gonorrhea, leading to only four clinical trials, have not yielded any successful vaccine. Conclusions: While it is important to continue to explore new drugs for the treatment of gonorrhea, the historical trend of resistance acquisition suggests that any long-term strategy should include vaccine development. Advanced technologies in proteomics and in silico approaches to vaccine target identification may provide templates for future success.

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Impact of Socioeconomic Status on Prostate Cancer Outcomes Globally: A Protocol for Systematic Review and Meta-analysis

10.21203/rs.3.rs-109558/v1 ◽

2020 ◽

Author(s):

Emmanuel Okechukwu Nna ◽

Bertilla Uzoma Ezeonwu ◽

Dorathy Chinwe Obu ◽

Abdullahi Khalid ◽

Uzoma Vivian Asiegbu ◽

...

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Socioeconomic Status ◽

Treatment Time ◽

Treatment Options ◽

Cochrane Library ◽

Final Report ◽

Cancer Outcomes ◽

Statistical Heterogeneity ◽

The Impact

Abstract BackgroundOne in every four men will be affected by prostate cancer. Choice of treatment depends on factors including grade and stage of the disease, age of the patient, availability of treatment options and socioeconomic status. We aimed to develop a protocol to assess the impact of socioeconomic status on prostate cancer outcomes globally.Methods A search strategy is developed using MeSH, text words, and entry terms. Nine databases will be searched, including PubMed, African Journals Online (AJOL), Google Scholar, Scopus, Cochrane Library, CINAHL, Web of Science, Embase and ResearchGate.Only observational studies, retrievable in the English language will be included. The primary outcome of this study is the socioeconomic status of prostate cancer patients. Secondary outcomes include mortality due to prostate cancer, health related quality of life, prostate cancer recurrence, need for secondary treatment, time to return to work, treatment choice regret and hospice enrollment. Identified studies will be screened and selected based on inclusion criteria. Data items will be managed in Zotero software, Microsoft Excel and CMA software. Both quality scores and the risk of bias for individual studies will be reported. Studies will be assessed for methodological, clinical, and statistical heterogeneity. Funnel Plots will be used for assessing publication bias. DiscussionThis protocol will enable a transparent, reliable and accurate method for assessing the impact of socioeconomic status on the global prostate cancer outcomes. It will allow discussions on outcomes such as mortality due to prostate cancer and how income disparity and availability of treatment options can influence prostate cancer outcomes. The final report of this study will be published in a peer-reviewed journal and the findings will be made available to health authorities.Systematic review RegistrationThis protocol has been registered in PROSPERO, with registration number CRD42020213700

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Multiresistant Neisseria gonorrhoeae: a new threat in second decade of the XXI century

Medical Microbiology and Immunology ◽

10.1007/s00430-019-00651-4 ◽

2019 ◽

Vol 209 (2) ◽

pp. 95-108 ◽

Cited By ~ 5

Author(s):

Beata Młynarczyk-Bonikowska ◽

Anna Majewska ◽

Magdalena Malejczyk ◽

Grażyna Młynarczyk ◽

Sławomir Majewski

Keyword(s):

Neisseria Gonorrhoeae ◽

Clonal Complex ◽

Etiologic Agent ◽

New Drugs ◽

Sexually Transmitted ◽

Treatment Regimens ◽

Resistant Strains ◽

High Level ◽

First Time ◽

Level Resistance

AbstractNeisseria gonorrhoeae is an etiologic agent of gonorrhoea, one of the most common sexually transmitted diseases caused by bacteria. For many years, infections caused by N. gonorrhoeae were considered to be relatively easy to treat; however, resistance has emerged successively to all therapeutic agents used in treatment of the disease, e.g., penicillin, ciprofloxacin or azithromycin. Currently, the global problem is the emergence and a threat of spread of N. gonorrhoeae strains resistant to extended-spectrum cephalosporins (ESC), such as injectable ceftriaxone and oral-used cefixime. Especially, dangerous are multi-resistant strains resistant simultaneously to ESC and azithromycin. Three strains with high-level resistance to azithromycin and resistant to ESC were first time isolated in 2018. Moreover, in 2018, the first ESBL was described in N. gonorrhoeae and that makes the threat of appearing the ESBL mechanism of resistance in N. gonorrhoeae more real, even though the strain was sensitive to ceftriaxone. Molecular typing revealed that variants resistant to ESC occurred also among strains belonging to epidemic clonal complex CC1 (genogroup G1407) distinguished in NG-MAST typing system. The G1407 genogroup, in particular the ST1407 sequence type, is currently dominant in most European countries. The presence of different mechanisms of drug resistance significantly affects clinical practice and force changes in treatment regimens and introduction of new drugs.

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Considering a Potential Role of Linalool as a Mood Stabilizer for Bipolar Disorder

Current Pharmaceutical Design ◽

10.2174/1381612826666200724160742 ◽

2020 ◽

Vol 26 (40) ◽

pp. 5128-5133

Author(s):

Kate Levenberg ◽

Wade Edris ◽

Martha Levine ◽

Daniel R. George

Keyword(s):

Bipolar Disorder ◽

Treatment Options ◽

Mood Stabilizer ◽

Well Being ◽

Epidemiologic Studies ◽

Treatment Regimens ◽

Bipolar Spectrum Disorders ◽

Short And Long Term

Epidemiologic studies suggest that the lifetime prevalence of bipolar spectrum disorders ranges from 2.8 to 6.5 percent of the population. To decrease morbidity and mortality associated with disease progression, pharmacologic intervention is indicated for the majority of these patients. While a number of effective treatment regimens exist, many conventional medications have significant side effect profiles that adversely impact patients’ short and long-term well-being. It is thus important to continue advancing and improving therapeutic options available to patients. This paper reviews the limitations of current treatments and examines the chemical compound Linalool, an alcohol found in many plant species, that may serve as an effective mood stabilizer. While relatively little is known about Linalool and bipolar disorder, the compound has been shown to have antiepileptic, anti-inflammatory, anxiolytic, anti-depressive, and neurotrophic effects, with mechanisms that are comparable to current bipolar disorder treatment options.

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4H-1,3-Benzothiazin-4-one a Promising Class Against MDR/XDR-TB

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190305130809 ◽

2019 ◽

Vol 19 (8) ◽

pp. 567-578 ◽

Cited By ~ 1

Author(s):

Marcus Vinicius Nora de Souza ◽

Thais Cristina Mendonça Nogueira

Keyword(s):

Treatment Time ◽

Public Health Problem ◽

New Drugs ◽

Global Public Health ◽

Synthesis Mechanism ◽

Highly Active ◽

Latent Disease ◽

Resistant Strains ◽

Chemical Class ◽

Global Public Health Problem

Nowadays, tuberculosis (TB) is an important global public health problem, being responsible for millions of TB-related deaths worldwide. Due to the increased number of cases and resistance of Mycobacterium tuberculosis to all drugs used for the treatment of this disease, we desperately need new drugs and strategies that could reduce treatment time with fewer side effects, reduced cost and highly active drugs against resistant strains and latent disease. Considering that, 4H-1,3-benzothiazin-4-one is a promising class of antimycobacterial agents in special against TB-resistant strains being the aim of this review the discussion of different aspects of this chemical class such as synthesis, mechanism of action, medicinal chemistry and combination with other drugs.

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New Drugs and Treatment Regimens

Current Respiratory Medicine Reviews ◽

10.2174/1573398x113099990017 ◽

2013 ◽

Vol 9 (3) ◽

pp. 200-210 ◽

Cited By ~ 20

Author(s):

Derek Sloan ◽

Geraint Davies ◽

Saye Khoo

Keyword(s):

New Drugs ◽

Treatment Regimens

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Efficacy and safety of gout flare prophylaxis and therapy use in people with chronic kidney disease: a Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN)-initiated literature review

Arthritis Research & Therapy ◽

10.1186/s13075-021-02416-y ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Huai Leng Pisaniello ◽

Mark C. Fisher ◽

Hamish Farquhar ◽

Ana Beatriz Vargas-Santos ◽

Catherine L. Hill ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Literature Review ◽

Interleukin 1 ◽

Treatment Options ◽

Cochrane Library ◽

Efficacy And Safety ◽

Clinical Trial Results ◽

Gout Flare

AbstractGout flare prophylaxis and therapy use in people with underlying chronic kidney disease (CKD) is challenging, given limited treatment options and risk of worsening renal function with inappropriate treatment dosing. This literature review aimed to describe the current literature on the efficacy and safety of gout flare prophylaxis and therapy use in people with CKD stages 3–5. A literature search via PubMed, the Cochrane Library, and EMBASE was performed from 1 January 1959 to 31 January 2018. Inclusion criteria were studies with people with gout and renal impairment (i.e. estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) < 60 ml/min/1.73 m2), and with exposure to colchicine, interleukin-1 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids. All study designs were included. A total of 33 studies with efficacy and/or safety analysis stratified by renal function were reviewed—colchicine (n = 20), anakinra (n = 7), canakinumab (n = 1), NSAIDs (n = 3), and glucocorticoids (n = 2). A total of 58 studies reported these primary outcomes without renal function stratification—colchicine (n = 29), anakinra (n = 10), canakinumab (n = 6), rilonacept (n = 2), NSAIDs (n = 1), and glucocorticoids (n = 10). Most clinical trials excluded study participants with severe CKD (i.e. eGFR or CrCl of < 30 mL/min/1.73 m2). Information on the efficacy and safety outcomes of gout flare prophylaxis and therapy use stratified by renal function is lacking. Clinical trial results cannot be extrapolated for those with advanced CKD. Where possible, current and future gout flare studies should include patients with CKD and with study outcomes reported based on renal function and using standardised gout flare definition.

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Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets

Cancers ◽

10.3390/cancers13040909 ◽

2021 ◽

Vol 13 (4) ◽

pp. 909

Author(s):

Krzysztof Kotowski ◽

Jakub Rosik ◽

Filip Machaj ◽

Stanisław Supplitt ◽

Daniel Wiczew ◽

...

Keyword(s):

Current Knowledge ◽

Treatment Options ◽

Protein Structures ◽

New Drugs ◽

Proliferating Cells ◽

Cancer Tissues ◽

The Impact ◽

Rate Limiting ◽

Synthesis And Degradation

Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm. However, the most potent regulator of PFK-1 is fructose-2,6-bisphosphate (F-2,6-BP), the level of which is strongly associated with 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase activity (PFK-2/FBPase-2, PFKFB). PFK-2/FBPase-2 is a bifunctional enzyme responsible for F-2,6-BP synthesis and degradation. Four isozymes of PFKFB (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) have been identified. Alterations in the levels of all PFK-2/FBPase-2 isozymes have been reported in different diseases. However, most recent studies have focused on an increased expression of PFKFB3 and PFKFB4 in cancer tissues and their role in carcinogenesis. In this review, we summarize our current knowledge on all PFKFB genes and protein structures, and emphasize important differences between the isoenzymes, which likely affect their kinase/phosphatase activities. The main focus is on the latest reports in this field of cancer research, and in particular the impact of PFKFB3 and PFKFB4 on tumor progression, metastasis, angiogenesis, and autophagy. We also present the most recent achievements in the development of new drugs targeting these isozymes. Finally, we discuss potential combination therapies using PFKFB3 inhibitors, which may represent important future cancer treatment options.

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The Modern Landscape of Endocrine Therapy for Premenopausal Women with Breast Cancer

Breast Care ◽

10.1159/000439462 ◽

2015 ◽

Vol 10 (5) ◽

pp. 312-315 ◽

Cited By ~ 8

Author(s):

Lorenzo Rossi ◽

Olivia Pagani

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Ovarian Function ◽

Treatment Options ◽

Endocrine Resistance ◽

Premenopausal Women ◽

New Drugs ◽

Fine Tuning ◽

Individual Risk ◽

Ovarian Function Suppression

The optimal endocrine therapy for premenopausal women with early and advanced breast cancer still remains an important and controversial issue. For over 30 years, tamoxifen has been the gold standard in the adjuvant setting. New therapeutic options, such as the addition of ovarian function suppression to oral endocrine therapy (either tamoxifen or aromatase inhibitors), can improve outcomes over tamoxifen alone in well-selected patients. Treatment duration has also been revisited, and extended therapy is becoming a new standard of care, especially in high-risk patients. Endocrine therapy for advanced disease still represents a challenge and a research priority. New drugs and combinations able to overcome endocrine resistance are at the horizon, and their role in premenopausal women should be better elucidated. Side effects and quality of life (including family planning considerations) play an important role in treatment selection and in the patients' treatment adherence and should always be discussed before start of treatment. The paper will specifically focus on how to integrate all new treatment options in the current armamentarium of endocrine therapy of premenopausal women, with the aim of best fine-tuning treatment selections according to the individual risk/benefit evaluation.

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