Treatment Of Chronic Infection Research Articles

CHRONIC INFECTION AND SEVERE MITRAL REGURGITATION: A TRICKY CASE REPORT

Abstract Background Techniques of mitral valve repair has improved in the last decades. Percutaneous approach is now a reliable and safe therapy in those patients with high surgical risk. Of note, the presence of implanted prothesis may increase the risk of endocarditis, especially in those patients experiencing recurrent infection. Case Summary We describe a case of a 75–year–old with medical history of chronic lymphedema. It was characterized by periodical episode (yearly) of cellulitis, with a rapid onset of fever (38.5–39° C), lasting for a few days after paracetamol therapy. Patients had severe mitral valve regurgitation due to prolapse of the posterior leaflet (P2). In December 2022, he had percutaneous edge–to–edge mitral valve. Three months later the patient was admitted to the emergency department of our hospital due to fever without any specific symptoms. The patient was well compensated, normal blood pressure, heart rate and oxygen saturation. He had emocolture which revealed the presence of Staphilococcus lugdunensis. Transesophageal echocardiogram confirmed the presence endocarditis, showing a huge (10x12 mm) vegetation at the level of mitral device (Fig 1 and 2). Patients was then referred to cardiac surgery for urgent mitral valve replacement with mitral bioprothesis (Fig 3). He was treated with ev antibiotic for six weeks after cardiac surgery. Additionally, chronic treatment with amoxicillin 500 mg/day was also prescribed at discharge. After six months follow–up, patients had no signs of endocarditis. Conclusion The management and treatment of chronic infection is of paramount importance to reduce the risk of prothesis infection procedure in patients needing a prothesis implantation. The last European Society of Cardiology guidelines on endocarditis do not provide any recommendation regarding a long–term treatment of patients with high risk of infection (i.e. due to chronic infection) and with an implanted cardiac device/prothesis. We believe this represents an important unmeet need.

Elimination of the hepatitis B virus: A goal, a challenge.

The hepatitis B elimination is a goal proposed by the WHO to be achieved by 2030 through the adoption of synergistic measures for the prevention and chronic HBV infection treatment. Complete cure is characterized by the HBV elimination from the body and is the goal of the chronic hepatitis B treatment, which once achieved, will enable the hepatitis B elimination. This, today, has been a scientific challenge. The difficulty in achieving a complete cure is due to the indefinite maintenance of a covalently closed episomal circular DNA (cccDNA) reservoir and the maintenance and persistence of an insufficient and dysfunctional immune response in chronically infected patients. Among the measures adopted to eliminate hepatitis B, two have the potential to directly interfere with the virus cycle, but with limited effect on HBV control. These are conventional vaccines-blocking transmission and antiviral therapy-inhibiting replication. Vaccines, despite their effectiveness in protecting against horizontal transmission and preventing mother-to-child vertical transmission, have no effect on chronic infection or potential to eliminate the virus. Treatment with antivirals suppresses viral replication, but has no curative effect, as it has no action against cccDNA. Therapeutic vaccines comprise an additional approach in the chronic infection treatment, however, they have only a modest effect on the immune system, enhancing it temporarily. This manuscript aims to address (1) the cccDNA persistence in the hepatocyte nucleus and the immune response dysfunction in chronically infected individuals as two primary factors that have hampered the treatment and HBV elimination from the human body; (2) the limitations of antiviral therapy and therapeutic vaccines, as strategies to control hepatitis B; and (3) the possibly promising therapeutic approaches for the complete cure and elimination of hepatitis B.

Evaluation of topotecan and 10-hydroxycamptothecin on Toxoplasma gondii: Implications on baseline DNA damage and repair efficiency

Toxoplasma gondii is an obligate intracellular parasite in the phylum Apicomplexa that causes toxoplasmosis in humans and animals worldwide. Despite its prevalence, there is currently no effective vaccine or treatment for chronic infection. Although there are therapies against the acute stage, prolonged use is toxic and poorly tolerated. This study aims to explore the potential of repurposing topotecan and 10-hydroxycamptothecin (HCPT) as drugs producing double strand breaks (DSBs) in T. gondii. DSBs are mainly repaired by Homologous Recombination Repair (HRR) and Non-Homologous End Joining (NHEJ). Two T. gondii strains, RHΔHXGPRT and RHΔKU80, were used to compare the drug's effects on parasites. RHΔHXGPRT parasites may use both HRR and NHEJ pathways but RHΔKU80 lacks the KU80 protein needed for NHEJ, leaving only the HRR pathway. Here we demonstrate that topotecan and HCPT, both topoisomerase I venoms, affected parasite replication in a concentration-dependent manner. Moreover, variations in fluorescence intensity measurements for the H2A.X phosphorylation mark (γH2A.X), an indicator of DNA damage, were observed in intracellular parasites under drug treatment conditions. Interestingly, intracellular replicative parasites without drug treatment show a strong positive staining for γH2A.X, suggesting inherent DNA damage. Extracellular (non-replicating) parasites did not exhibit γH2A.X staining, indicating that the basal level of DNA damage is likely to be associated with replicative stress. A high rate of DNA replication stress possibly prompted the evolution of an efficient repair machinery in the parasite, making it an attractive target. Our findings show that topoisomerase 1 venoms are effective antiparasitics blocking T. gondii replication.

Latin American and the Caribbean Code Against Cancer 1st edition: Infections and cancer

About 13% of all cancers around the world are associated with infectious agents, particularly in low-resource settings. The main infectious agents associated with cancer are Helicobacter pylori (H. pylori), that causes gastric cancer, human papillomavirus (HPV) that causes cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancer, hepatitis B and C viruses that cause liver cancer, and human immunodeficiency virus (HIV), associated with cancers of the cervix, Kaposi sarcoma (KS) and non-Hodgkin´s lymphoma. In Latin America and the Caribbean (LAC), about 150,000 cancer cases are caused annually by infections. The LAC Cancer Code Against Cancer consists of a set of 17 evidence-based and individual-level cancer prevention recommendations targeted to the general population, suited to the epidemiological, socioeconomic, and cultural conditions of the region, and tailored to the availability and accessibility of health-care systems. The recommendations with respect to infection-driven malignancies include testing and treating for H. pylori in the context of specific public health programs, vaccination against HPV and Hepatitis B Virus (HBV) and detection and treatment of chronic infections with HBV, Hepatitis C virus (HCV) and HIV, in addition to the promotion of safe sex and use of condoms to prevent sexually transmitted infections (STI). Countries, policy makers, health care systems and individuals should consider the adoption of these recommendations to help reduce the incidence and mortality of infection-related cancers in LAC, to improve quality of life of individuals and reduce the costs of cancer care in the region.

An Example of the Importance of Electronic Health Records from Mogadishu, Somalia: Hepatitis B Prevalence and Co-infections with Hepatitis C

The epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) has been discussed in detail from different aspects around the world. Current epidemiological data has critical importance in the planning and carrying out of public health policies for the prevention of transmission and spread of these infections, and the treatment of chronic infections, and to reduce the burden and mortality associated with complications such as cirrhosis and liver cancer by national health authorities and international health institutions, especially the World Health Organization. Elimination of a social health problem is possible by first raising awareness, then determining the dimensions of the problem, and planning and implementing interventions for a solution. Somalia was in the position of a region where access to diagnosis and treatment for many life-threatening diseases was difficult, aside from the monitoring of public health criteria due to the unstable situations that has continued for more than 40 years. Until recently, basic health parameters and epidemiological predictions in Somalia were monitored through estimates based on data from neighboring countries or on data obtained from small groups from Somalia immigrants settled different parts of the world. However, this situation is changing rapidly. A tertiary education and research hospital established in the capital, Mogadishu, with the coordination of the Türkiye and Somalia governments, and which has become the largest health center in the country today; contributes to understanding the extent of the serious health problems faced by the country by pioneering specialized training and scientific studies, in addition to providing health care. Electronic health records have been kept regularly since 2015 in this hospital, where hundreds of thousands of patients receive treatment or undergo health checks every year and it has been the source of numerous retrospective epidemiological studies some of which have exceeded 100 thousand cases, in different age groups and sub-populations. These studies include human immunodeficiency virus (HIV) prevalence and complications, HCV prevalence and genotype distribution, prevalence and epidemiology of parasitic infections, incidence of tuberculosis and related complications, cancer incidence and distribution, causes of blindness, thyroid diseases, antibiotic resistance profiles, and the epidemiology of various organ-specific diseases. Dozens of studies using the hospital records were included in the scientific literature between 2020 and 2023. In this study, a four-year period between November 2015 and November 2019, HBV serological test results of more than 100,000 different patients are presented. HBsAg and anti-HBs seropositivity for all age groups was found to be 8.1% (9,405/115,946) and 32.7% (25,988/79,410), respectively. When the anti-HCV test results of HBsAg positive patients were examined, the rate of HCV co-infections was found to be 0.9% (82/9,405). HBsAg and anti-HBs seropositivity were significantly higher in males than females (p<0.001). HBV, HCV, and co-infection incidence tended to decrease. Conversely, vaccination rates (especially in children under one year of age) tended to increase. While the comprehensive data presented in this study provide us with important and new information about the prevalence and co-infection rates of viral hepatitis in the country, many topics including HBV genotypes, hepatitis D frequency, access to treatment rates, complication rates, and HBV vaccination rates are still waiting to be researched in Somalia. In the region where it is not possible to carry out field studies, epidemiological data provided by electronic health records have become a country's window to the world.

Outpatient parenteral antimicrobial therapy for leishmaniasis: 13 years' experience at a large UK infectious diseases centre.

Leishmaniasis is a neglected tropical disease that is imported by travellers returning to the UK. Given the prolonged therapy required, outpatient treatment has been proven to be cost-effective and safe. We describe cases of leishmaniasis treated through outpatient parenteral antimicrobial therapy (OPAT) over a 13-y period (March 2006-September 2018) at a large teaching hospital. A total of 26 episodes of leishmaniasis were treated successfully, with a mean saving of 14.2bed-days/episode. Sodium stibogluconate was the most used antileishmanial (92%). Treatment of chronic infections via OPAT is now commonplace and this approach may be considered for other imported infectious diseases.

Combinatorial treatment of mupirocin nanomicelle in insulin-based gel for wound healing in diabetic rats

Abstract Background: Diabetic wounds remain an important clinical challenge over the past few decades. Nanodrug delivery systems play a crucial role in the treatment of chronic infections and wound healing. Objectives: To evaluate the wound healing potential of newly synthesized and characterized mupirocin (MP) nanomicelle (NM) in insulin (I)-based gel (MP-NM-I), utilizing alloxan-induced diabetic rat model. Materials and Methods: MP-NM-I was prepared by solvent evaporation technique, 96 male rats were assigned randomly into eight groups (n = 12): one group is healthy, and the remaining seven groups were diabetic and wounded receiving treatments of gel base, tween 80, I, MP, MP-I, MP-NM, and MP-NM-I, respectively. Rats were sacrificed after 7 and 14 days of wounding. Blood samples were collected for glucose and insulin concentration measurement. Skin biopsies were examined by histological and immunohistochemical analyses. Results: Diabetes was confirmed after a significant increase in blood glucose and a decrease in serum insulin concentrations (P ≤ 0.001). MP-NM– and MP-NM-I–treated groups presented a rapid wound closure (100 ± 0, P ≤ 0.001), and the bacterial growth in these samples was relatively low (P ≤ 0.001). Histological examination established a significant decrease in inflammatory cells (P ≤ 0.001) with a significant elevation in tissue re-epithelialization, fibroblasts, angiogenesis, and collagen fibers (P ≤ 0.001). Immunohistochemical investigation presented a significant decrease in tumor necrosis factor-α, increase in vascular endothelial growth factors, and interleukin-10 scores (P ≤ 0.001). Conclusion: The developed formula of MP-NM with or without insulin is more effective than MP alone for diabetic wound healing in rats, because it accelerated wound closure. Accordingly, the formula might serve as an innovative tool for diabetic wound healing.

Antibiotic use and resistance in a tertiary care hospital: knowledge and attitude among patients of orthopaedic and surgical wards in Malaysia

Abstract Objectives The prevalence of antimicrobial resistance (AMR) is rising globally as well as in Malaysia. AMR can lead to difficulty in the treatment of chronic infection if being neglected. This study aimed to assess the level of knowledge and attitude about antibiotic usage and AMR. Methods A cross-sectional study design was carried out at the Hospital Kuala Lumpur (HKL), Malaysia, where participants were recruited by using the non-probability convenience sampling from the six orthopaedic and four surgical wards. A self-administered questionnaire was used to collect the required data which were then analysed by using SPSS. Key findings A total number of 390 adult Malaysians (286 from orthopaedic wards and 104 from surgical wards) were involved in the study. This study showed that the level of knowledge and attitude about antibiotics among the majority of respondents were moderate. However, their knowledge regarding AMR was very low (i.e. lack of knowledge). In contrast, the majority of them (69.8%) showed a positive attitude towards antibiotics. Statistical analysis of data revealed that the level of knowledge of AMR was significantly associated with gender, age, race, marital status, educational level and knowledge about antibiotic resistance terms (P < 0.05) while respondents’ attitude towards antibiotic usage was significantly associated with gender, race, marital status and education level (P < 0.05). Conclusions It was necessary to formulate and develop strategies to improve the knowledge and awareness about antibiotics and AMR among health professionals. These might help them to improve their skills in delivering health information to the patients through a proper counselling technique.

Improvement of anti-biofilm activities via co-delivery of curcumin and gentamicin in lipid-polymer hybrid nanoparticle

Pseudomonas aeruginosa is the most common pathogen that causes chronic lung infections and recurrence of the disease in cystic fibrosis patients by hiding inside cells and biofilm matrix. Herein, we developed gentamicin and curcumin-loaded lipid-polymer hybrid nanoparticle- (termed CG-HNPs) to evaluate in vitro activities against biofilm-embedded P. aeruginosa and compared with lipid nanoparticles containing the same drugs (CG-Lip). The nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), fluorescence spectroscopy, and ultraviolet-visible (UV-vis) spectroscopy, which demonstrated that HNPs with a diameter of approximately 340 nm were uniform. The optimal CG-HNPs formulation illustrated high encapsulation (∼70%) and controlled release characteristics (gradually released in 72 h). The antibacterial activities of generated nanoparticles are maintained against planktonic and biofilm bacteria and it is effective in damage established biofilms. Besides, HNPs were biocompatible and nontoxic to J774 and HFF cell lines and uptake by the macrophages (J774), which facilitated the killing of intracellular bacteria in macrophages. These results introduced CG-HNPs as a promising antibacterial agent for the treatment of chronic infections and intracellular bacteria due to excellent antibacterial activity.

Hepatitis E, what is the real issue?

Hepatitis E virus (HEV) infection is a worldwide disease and the primary cause of acute viral hepatitis with an estimated 3.3 million symptomatic cases every year and 44,000 related deaths. It is a waterborne infection in the developing countries. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects resulting in significant mortality in pregnant women and patients with cirrhosis. In developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. Parenteral transmission by the transfusion of blood products has been identified as a potential new mode of transmission. HEV can also cause neurological disorders and chronic infections in immunocompromised patients. The progression of acute hepatitis E is usually asymptomatic and resolves spontaneously. Diagnosis is based on both anti-HEV IgM antibodies in serum and viral RNA detection in blood or stools by PCR in immunocompetent patients, while only PCR is validated in immunocompromised individuals. Ribavirin is the only validated treatment in chronic infection. A vaccine has been developed in China.

Bacteriophages: A Potential New Therapeutic Alternate to Antibiotics to Treat Chronic Septic Wounds in Large Animals

Background: Overuse of antibiotics is a major problem in the treatment of chronic infections. The antibiotic treatment is frequently non-curative due to emergence of antibiotic resistance, thus alternative treatment is necessary. The natural ability of pathogens to develop resistance is not only a threat to animal health but also leads to accumulation of antibiotic resistance determinants or resistant bacteria livestock products. Phage therapy has been developed as an alternative therapeutic approach against antibiotic resistance microorganisms.Methods: In present study 150 samples of sewage were collected from livestock farm, NDVSU, Jabalpur (M.P.). Bacteriophages were isolated and characterized from the collected sewage samples. “Cocktail” of the recovered phage lysate isolates (ØVS1, ØVS5, ØVS9 and ØVS27) was prepared for assessment of therapeutic utility of S. aureus phages in chronic septic infections. Therapeutic trial was performed in large animals (cattle and buffalo) at livestock farm, Adhartal, NDVSU, Jabalpur (MP.). Pathogens isolated from chronic septic wounds were showing antibiotic resistance but the bacteria were sensitive to phage lysate. Phage ‘cocktail’ was applied topically over the chronic septic wounds as single dose. Follow up of the cases was done at regular intervals (0, 5 and 10 days) which included clinical examination of wound by appearance, status of discharge and formation of granulation tissue.Result: Six animals showed complete recovery (60%) out of 10 animals from wounds as predicted by progressive healing status of wounds till the formation of granulation tissue within 10 days after phage application. Thus, recovery was much higher than the conventional antibiotic therapy normally used for the treatment of chronic septic wound infections in animals.

Do Mixed-Species Biofilms Dominate in Chronic Infections?-Need for in situ Visualization of Bacterial Organization.

Chronic infections present a serious economic burden to health-care systems. The severity and prevalence of chronic infections are continuously increasing due to an aging population and an elevated number of lifestyle related diseases such as diabetes. Treatment of chronic infections has proven difficult, mainly due to the presence of biofilms that render bacteria more tolerant toward antimicrobials and the host immune response. Chronic infections have been described to harbor several different bacterial species and it has been hypothesized that microscale interactions and mixed-species consortia are present as described for most natural occurring biofilms i.e., aquatic systems and industrial settings, but also for some commensal human biofilms i.e., the mouth microbiota. However, the presence of mixed-species biofilms in chronic infections is most often an assumption based on culture-based methods and/or by means of molecular approaches, such as PCR and sequencing performed from homogenized bulk tissue samples. These methods disregard the spatial organization of the bacterial community and thus valuable information on biofilm aggregate composition, spatial organization, and possible interactions between different species is lost. Hitherto, only few studies have made visual in situ presentations of mixed-species biofilms in chronic infections, which is pivotal for the description of bacterial composition, spatial distribution, and interspecies interaction on the microscale. In order for bacteria to interact (synergism, commensalism, mutualism, competition, etc.) they need to be in close proximity to each other on the scale where they can affect e.g., solute concentrations. We argue that visual proof of mixed species biofilms in chronic infections is scarce compared to what is seen in e.g., environmental biofilms and call for a debate on the importance of mixed-species biofilm in chronic infections.

Identification of a Master Regulator of Differentiation in Toxoplasma

SummaryToxoplasma gondii chronically infects a quarter of the world’s population, and its recrudescence can cause life-threatening disease in immunocompromised individuals and recurrent ocular lesions in the immunocompetent. Acute-stage tachyzoites differentiate into chronic-stage bradyzoites, which form intracellular cysts resistant to immune clearance and existing therapies. The molecular basis of this differentiation is unknown, despite being efficiently triggered by stresses in culture. Through Cas9-mediated screening and single-cell profiling, we identify a Myb-like transcription factor (BFD1) necessary for differentiation in cell culture and in mice. BFD1 accumulates during stress and its synthetic expression is sufficient to drive differentiation. Consistent with its function as a transcription factor, BFD1 binds the promoters of many stage-specific genes and represents a counterpoint to the ApiAP2 factors that dominate our current view of parasite gene regulation. BFD1 provides a genetic switch to study and control Toxoplasma differentiation and will inform prevention and treatment of chronic infections.

Efecto del análogo de L-carnitina, la b-hidroxifosfocarnitina sobre el metabolismo de Nocardia brasiliensis

Objectives: To determine whether β-HFC, in addition to its immunomodulatory effect as a therapeutic alternative in the combat of the mycetoma has an effect on the biochemical activity of N. brasiliensis. Methodology: determination of bacterial growth using N. brasilensis in the presence of β-HFC and biochemical analysis of its metabolism. Contribution: The immunomodulatory function of β-HFC in the treatment of chronic infections has recently been studied but it is not known whether it also has any antimicrobial effect, so in this paper the direct effect of β-HFC in N. brasiliensis will be elucidated in part.

AUTOVACCINATION: EFFECTIVE PERSONIFIED TREATMENT OF CHRONIC INFECTIONS (WHEN ANTIBIOTIC THERAPY IS POWERLESS)

In this article we review and discuss data of the use and mechanisms of action of autovaccines. The idea of autovaccination is that killed microorganisms could be used not only in prevention, but also in the treatment of infections. Autovaccines are prepared individually from strains of microorganisms isolated from the patient. The pathogens are inactivated and then administered in increasing concentrations. Autogenous vaccines permit treatment of infections caused by bacteria against which no preventive vaccine has been available.
 Autovaccine therapy has a long history, it have been used since the beginning of the 20th century to treat chronic infections. From the literature is known, that autovaccines have been used for treatment diseases’ of the skin, bones, joints, digestive organs, genitals, periodontal, eye, ears, nose and respiratory system the history of the half-century use of auto vaccines has shown that they may be a promising alternative in the treatment of chronic infections.
 However from the middle of the 20th century autovaccines have been forgotten because of efficient antibiotic therapies. But now rapid spread of multiresistant bacterial and fungal strains enforces the development of new strategies to combat chronic infections. In view of the variability of the bacterial species, personalized approaches could hold promise for patients with recurrent or chronic infection. Therefore interest to autovaccines returns.
 Autovaccines have been used to treat ongoing chronic infection but their mechanism of action is still unknown. Recently, the results of several studies have been published that examined the effects of autovaccines on the immune system. But published data are quite inconsistent and incomplete. Therefore further research is required in this area.
 So clinical studies from the early 1900s and novel autovaccination approaches suggest an alternative strategy to antibiotic therapy.

Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune Responses.

Extracellular vesicles (EVs) are known to contain unique proteins that reflect the cells of origins. Activated T cells are reported to secrete various EVs. To establish T cell subset-specific biomarkers, we performed proteomic analysis with Th1- and Th2-derived EVs and identified HLA-DR as a Th1-dominated EV membrane protein. We designed a measurement system for CD3+CD4+, CD3+CD8+, and CD3+HLA-DR+ EVs to specifically determine EV subpopulations derived from CD4+, CD8+, and Th1-type T cells, respectively. In vitro analysis showed that CD3+CD4+ EVs and CD3+CD8+ EVs were selectively secreted from activated CD4+ and CD8+ T cells, respectively, and that CD3+HLA-DR+ EVs were actively secreted from not only Th1 but also activated CD8+ T (probably mostly Tc1) cells. To evaluate the clinical usefulness of these EVs, we measured the serum levels in patients with inflammatory diseases, including Epstein-Barr virus (EBV, n = 13) infection, atopic dermatitis (AD, n = 10), rheumatoid arthritis (RA, n = 20), and osteoarthritis (OA, n = 20) and compared the levels with those of healthy adults (n = 20). CD3+CD4+ EVs were significantly higher in all of EBV infection, AD, RA, and OA while CD3+CD8+ EVs were higher in EBV infection, lower in RA, and not different in AD and OA relative to the control. The levels of CD3+HLA-DR+ EVs were markedly higher in EBV infection and significantly lower in AD. The results suggest that these EV subpopulations reflect in vivo activation status of total CD4+, total CD8+, and Th1/Tc1-type T cells, respectively, and may be helpful in T cell-related clinical settings, such as cancer immunotherapy and treatment of chronic infection, autoimmune diseases, and graft-versus-host disease.

Synergy between Synthetic Antimicrobial Polymer and Antibiotics: A Promising Platform To Combat Multidrug-Resistant Bacteria.

The failure of many antibiotics in the treatment of chronic infections caused by multidrug-resistant (MDR) bacteria necessitates the development of effective strategies to combat this global healthcare issue. Here, we report an antimicrobial platform based on the synergistic action between commercially available antibiotics and a potent synthetic antimicrobial polymer that consists of three key functionalities: low-fouling oligoethylene glycol, hydrophobic ethylhexyl, and cationic primary amine groups. Checkerboard assays with Pseudomonas aeruginosa (P.aeruginosa) and Escherichia coli demonstrated synergy between our synthetic antimicrobial polymer and two antibiotics, doxycycline and colistin. Coadministration of these compounds significantly improved the bacteriostatic efficacy especially against MDR P.aeruginosa strains PA32 and PA37, where the minimal inhibitory concentrations (MICs) of polymer and antibiotics were reduced by at least 4-fold. A synergistic killing activity was observed when the antimicrobial polymer was used in combination with doxycycline, killing >99.999% of planktonic and biofilm P.aeruginosa PAO1 upon a 20 min treatment at a polymer concentration of 128 μg mL-1 (4.6 μM) and doxycycline concentration of 64 μg mL-1 (133.1 μM). In addition, this synergistic combination reduced the rate of resistance development in P.aeruginosa compared to individual compounds and was also capable of reviving susceptibility to treatment in the resistant strains.

Microbiological Progress in Patients with Bronchial Infection with Pseudomonas aeruginosa Treated with Nebulised Colistin

Background: Inhaled antibiotics allow the delivery of higher drug concentrations at the site of infection without the systemic adverse effects observed with the use of parenteral or oral antibiotics. These antibiotics have shown to decrease the number of exacerbations, reduce bacterial load or improve pulmonary function in several chronic respiratory conditions. Objectives: The aim of this study was to describe changes in the bacteriology of sputum in patients with chronic bronchial infection with Pseudomonas aeruginosa treated with nebulised colistin. Material and Methods: All patients with chronical infection with P. aeruginosa treated with nebulised colistin attending a day care unit during a 5-year (January 2010 to December 2014) period were included. Repeated-measures t tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalisations. Results: Treatment with colistin was associated with a decrease in the number of ambulatory exacerbations (1.87–1.1, p = 0.007), of hospital exacerbations (1.3–0.7, p = 0.010) and of length of stay (15.7–8.6 days, p = 0.005). There was no linear trend in the proportion of isolate Enterobacteriaceae, gram-positive cocci, Haemophilus influenzae or fungi. Isolation of Enterobacteriaceae within 1 year after the beginning of the treatment with nebulised colistin was associated with an increase in the number of ambulatory exacerbations (incidence rate ratio 1.99, 95% CI 1.05–3.79). Conclusions: Nebulised colistin was effective in the treatment of chronic infection with P. aeruginosa, and no significant changes in the microbiological evolution were observed. Isolation of Enterobacteriaceae within 1 year after the beginning of the treatment with nebulised colistin was associated with an increase in the number of exacerbations.

Identification of a Master Regulator of Differentiation in Toxoplasma

Toxoplasma gondii chronically infects a quarter of the world’s population, and its recrudescence can cause life-threatening disease in immunocompromised individuals and recurrent ocular lesions in the immunocompetent. Chronic stages are established by differentiation of rapidly replicating tachyzoites into slow-growing bradyzoites, which form intracellular cysts resistant to immune clearance and existing therapies. Despite its central role in infection, the molecular basis of chronic differentiation is not understood. Through Cas9-mediated genetic screening and single-cell transcriptional profiling, we identify and characterize a putative transcription factor (BFD1) as necessary and sufficient for differentiation. Translation of BFD1 appears to be stress regulated, and its constitutive expression elicits differentiation in the absence of stress. As a Myb-like factor, BFD1 provides a counterpoint to the ApiAP2 factors which dominate our current view of parasite gene regulation. Overall, BFD1 provides a genetic switch to study and control Toxoplasma differentiation, and will inform prevention and treatment of chronic infection.

Nontuberculous mycobacteria and allergic bronchopulmonary aspergillosisin lung transplant candidate

Airway infections are a key component of cystic fibrosis (CF) lung disease. The approach to common pathogens such as Pseudomonas aeruginosa or Staphilococcus aureus is guided by a significant evidence base, but the treatment of other infections is significant challenge to pharmacotherapy teams. Here we present a specific approach to treatment of chronic infections with non-tuberculous mycobacteria (NTM) anaerobic bacteria and fungi in a 25 year old patient with CF and severely decreased lung function. Also, allergic bronchopulmonary aspegillosis (ABPA) was diagnosed in the patient. Key words: cystic fibrosis, non-tuberculous mycobacteria, allergic bronchopulmonary aspegillosis, antibiotics, systemic steroids