Secondary Infections in Patients with Extremely Severe COVID-19 During ECMO Therapy.

Up to 70% of patients hospitalized for COVID-19 need respiratory support, up to 10% need high-flow oxygen therapy, non-invasive and invasive ventilation. However, standard methods of respiratory support are ineffective in 0.4-0.5% of patients. In case of potentially reversible critical refractory respiratory failure that patients may require ECMO. Management of patients with extremely severe COVID-19 associates with numerous clinical challenges, including critical illness, multiple organ dysfunction, blood coagulation disorders, requiring prolonged ICU stay and care, use of multiple pharmacotherapies including immunosuppressive drugs. Pharmacological suppression of immunity is associated with a significant increase in the risk of secondary bacterial and fungal infections. Currently, data on epidemiology of secondary infections in patients with COVID-19 undergoing ECMO is limited. Aim. To study the prevalence and etiology of secondary infections associated with positive blood cultures in patients with extremely severe COVID-19 requiring ECMO. Materials and methods. A single-center retrospective non-interventional epidemiological study including 125 patients with extremely severe COVID-19 treated with ECMO in April 2020 to December 2021. Results. Out of 700 blood culture tests performed in 125 patients during the study, 250 tests were positive confirming bacteremia/fungemia. Isolated pathogens varied depending on the duration of ECMO: gram-positive bacteria (primarily coagulase-negative staphylococci) dominated from the initiation of ECMO support;increased duration of ECMO associated with an increasing the proportion of pathogens common in ICU (Klebsiella pneumoniae and/or Acinetobacter baumannii with extensively drug resistant and pan-drug resistant phenotypes, and vancomycin-resistant Enterococcus faecium). When ECMO lasted more than 7-14 days, opportunistic pathogens (Candida species, Stenotrophomonas maltophilia, Providencia stuartii, non-diphtheria corynebacteria, Burkholderia species and others) prevailed as etiological agents. Conclusion. Longer duration of ECMO resulted in increasing the rates of infectious complications. In patients undergoing ECMO for more than 14 days, the microbiological landscape becomes extremely diverse, which hampers choosing an empirical antimicrobial therapy. Since potential pathogens causing secondary infections in patients during ECMO are difficult to predict, rapid identification of rare opportunistic pathogens and their sensitivity profile, followed by targeted administration of antimicrobials, seems most beneficial.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

Evolution of tuberculosis diagnostics: From molecular strategies to nanodiagnostics.

Tuberculosis has remained a global concern for public health affecting the lives of people for ages. Approximately 10 million people are affected by the disease and 1.5 million succumb to the disease worldwide annually. The COVID-19 pandemic has highlighted the role of early diagnosis to win the battle against such infectious diseases. Thus, advancement in the diagnostic approaches to provide early detection forms the foundation to eradicate and manage contagious diseases like tuberculosis. The conventional diagnostic strategies include microscopic examination, chest X-ray and tuberculin skin test. The limitations associated with sensitivity and specificity of these tests demands for exploring new techniques like probe-based assays, CRISPR-Cas and microRNA detection. The aim of the current review is to envisage the correlation between both the conventional and the newer approaches to enhance the specificity and sensitivity. A significant emphasis has been placed upon nanodiagnostic approaches manipulating quantum dots, magnetic nanoparticles, and biosensors for accurate diagnosis of latent, active and drug-resistant TB. Additionally, we would like to ponder upon a reliable method that is cost-effective, reproducible, require minimal infrastructure and provide point-of-care to the patients.

Cefiderocol-Based versus Colistin-Based Regimens for Severe Carbapenem-Resistant Acinetobacter baumannii Infections: A Propensity Score-Weighted, Retrospective Cohort Study during the First Two Years of the COVID-19 Pandemic.

BACKGROUND: A large increase in multi-drug-resistant Acinetobacter baumannii, especially carbapenem-resistant strains, occurred during the first two years of the COVID-19 pandemic, posing important challenges in its treatment. Cefiderocol appeared to be a good option for the treatment of Carbapenem-resistant Acinetobacter baumannii (CR-Ab), but to date, the guidelines and evidence available are conflicting. METHODS: We retrospectively included a group of patients with CR-Ab infections (treated with colistin- or cefiderocol-based regimens) at Padua University Hospital (August 2020-July 2022) and assessed predictors of 30-day mortality, and differences in microbiological and clinical treatment. To evaluate the difference in outcomes, accounting for the imbalance in antibiotic treatment allocation, a propensity score weighting (PSW) approach was adopted. RESULTS: We included 111 patients, 68% males, with a median age of 69 years (IQR: 59-78). The median duration of antibiotic treatment was 13 days (IQR:11-16). In total, 60 (54.1%) and 51 (45.9%) patients received cefiderocol- and colistin-based therapy, respectively. Notably, 53 (47.7%) patients had bloodstream infections, while 58 (52.3%) had pneumonia. Colistin was combined in 96.1%, 80.4%, and 5.8% of cases with tigecycline, meropenem, and fosfomycin, respectively. Cefiderocol was combined in 13.3%, 30%, and 18.3% of cases with fosfomycin, tigecycline, and meropenem, respectively. At the baseline, the two treatment groups significantly differed in age (patients treated with colistin were significantly older), the prevalence of diabetes and obesity (more frequent in the group treated with colistin), length of stay (longer in the group receiving cefiderocol), and type of infection (BSI were more frequent in the group receiving cefiderocol). The proportion of patients who developed acute kidney injury was significantly higher in the colistin group. By using PSW, no statistically significant differences emerged for mortality or clinical and microbiological cure between the two groups. No independent predictors were detected for hospital mortality or clinical cure, while for the length of stay, the only selected predictor was age, with a non-linear effect (p-value 0.025 for non-linearity) on the prolongation of hospital stay of 0.25 days (95% CI 0.10-0.39) at increasing ages (calculated over the IQR). CONCLUSIONS: Cefiderocol treatment did not differ in terms of main outcomes and safety profile from colistin-based regimens. More prospective studies with a larger number of patients are required to confirm our results.

Recent Advances in Strategies to Combat Bacterial Drug Resistance: Antimicrobial Materials and Drug Delivery Systems.

Bacterial infection is a common clinical disease. Antibiotics have saved countless lives since their discovery and are a powerful weapon in the fight against bacteria. However, with the widespread use of antibiotics, the problem of drug resistance now poses a great threat to human health. In recent years, studies have investigated approaches to combat bacterial resistance. Several antimicrobial materials and drug delivery systems have emerged as promising strategies. Nano-drug delivery systems for antibiotics can reduce the resistance to antibiotics and extend the lifespan of novel antibiotics, and they allow targeting drug delivery compared to conventional antibiotics. This review highlights the mechanistic insights of using different strategies to combat drug-resistant bacteria and summarizes the recent advancements in antimicrobial materials and drug delivery systems for different carriers. Furthermore, the fundamental properties of combating antimicrobial resistance are discussed, and the current challenges and future perspectives in this field are proposed.

Nanomedicine for drug resistant pathogens and COVID-19 using mushroom nanocomposite inspired with bacteriocin - A review.

Multidrug resistant (MDR) pathogens have become a major global health challenge and have severely threatened the health of society. Current conditions have become worse as a result of the COVID-19 pandemic, and infection rates in the future will rise. It is necessary to design, respond effectively, and take action to address these challenges by investigating new avenues. In this regard, the fabrication of metal NPs utilized by various methods, including green synthesis using mushroom, is highly versatile, cost-effective, eco-compatible, and superior. In contrast, biofabrication of metal NPs can be employed as a powerful weapon against MDR pathogens and have immense biomedical applications. In addition, the advancement in nanotechnology has made possible to modify the nanomaterials and enhance their activities. Metal NPs with biomolecules composite prevent the microbial adhesion and kills the microbial pathogens through biofilm formation. Bacteriocin is an excellent antimicrobial peptide that works well as an augmentation substance to boost the antimicrobial effects. As a result, we concentrate on the creation of new, eco-compatible mycosynthesized metal NPs with bacteriocin nanocomposite via electrostatic, covalent, or non-covalent bindings. The synergistic benefits of metal NPs with bacteriocin to combat MDR pathogens and COVID-19, as well as other biomedical applications, are discussed in this review. Moreover, the importance of the adverse outcome pathway (AOP) in risk analysis of manufactured metal nanocomposite nanomaterial and their future possibilities were also discussed.

New advances in management and treatment of multidrug-resistant Klebsiella pneumoniae.

INTRODUCTION: The management of multidrug-resistant (MDR) Klebsiella pneumoniae (KP) represents a major challenge in the field of infectious diseases. It is associated with a high rate of nosocomial infections with a mortality rate that reaches approximately 50%, even when using an effective antimicrobial therapy. Therefore, combined actions addressing infection control and antibiotic stewardship are required to delay the emergence of resistance. Since new antimicrobial agents targeting MDR-GNB bacteria have been produced during the last years and are now available for physicians to treat MDR, it is fundamental to choose appropriate antimicrobial therapy for K. pneumoniae infection. AREAS COVERED: The PubMed database was searched to review the most significant recent literature on the topic, including data from articles coming from endemic areas and from the current European and American Guidelines. EXPERT OPINION: We explore the most effective strategies for prevention of MDR-KP spread and the currently available treatment options, focusing on comparing old strategies and new compounds. We reviewed data concerning newly developed drugs that could play an important role in the future; we also propose a treatment algorithm that could be useful for physicians in daily clinical practice.

Pseudomonas aeruginosa Bloodstream Infections in SARS-CoV-2 Infected Patients: A Systematic Review.

Bacterial co-infections increase the severity of respiratory viral infections and are frequent causes of mortality in COVID-19 infected subjects. During the COVID-19 period, especially at the beginning of the pandemic, an inappropriate use of broad-spectrum antibiotic treatments has been frequently described, mainly due to prolonged hospitalization, especially in intensive care unit departments, and the use of immune-suppressive treatments as steroids. This misuse has finally led to the occurrence of infections by multi-drug resistant (MDR) bacteria in hospitalized COVID-19 patients. Although different reports assessed the prevalence of Gram-negative infections in COVID-19 infected patients, scarce data are currently available on bloodstream infections caused by Pseudomonas aeruginosa in hospitalized COVID-19 patients. The aim of our systematic review is to describe data on this specific population and to discuss the possible implications that these co-infections could have in the management of COVID-19 pandemics in the future. We systematically analysed the current literature to find all the relevant articles that describe the occurrence of P. aeruginosa bloodstream infections in COVID-19 patients. We found 40 papers that described in detail P. aeruginosa HAIs-BSI in COVID-19 patients, including 756,067 patients overall. The occurrence of severe infections due to MDR bacteria had a significant impact in the management of hospitalized patients with COVID-19 infections, leading to a prolonged time of hospitalization and to a consequent increase in mortality. In the near future, the increased burden of MDR bacteria due to the COVID-19 pandemic might partially be reduced by maintaining the preventive measures of infection control implemented during the acute phase of the COVID-19 pandemic. Finally, we discuss how the COVID-19 pandemic changed the role of antimicrobial stewardship in healthcare settings, according to the isolation of MDR bacteria and how to restore on a large scale the optimization of antibiotic strategies in COVID-19 patients.

Fatal Pyopneumothorax in a COVID-19 Patient.

The COVID-19 pandemic has impacted every aspect of our lives since its start in December 2019. Among various COVID-19 complications, pleural complications are also increasingly reported but rarely from Nepal. Here, we presented a case of pyopneumothorax in a 52-year-old male patient referred from another center and admitted to the ICU of Nepal Armed Police Force Hospital with a diagnosis of severe COVID-19 pneumonia in the background of alcohol withdrawal syndrome with delirium tremens and generalized tonic-clonic seizures. He developed a rapid decline in respiratory status with a right-sided pneumothorax and underwent an immediate needle thoracostomy, followed by chest tube insertion. On the sixth day of admission, he had thick yellowish pus in the chest drain (pyopneumothorax), and despite the rigorous efforts in treatment, he died on the 15th day of admission. Though relatively uncommon, clinicians should consider pleural complications like pneumothorax, pleural effusion, pneumomediastinum, and empyema in patients with impaired immune status. In such patients, we should ensure prompt diagnosis with the earliest intervention and rationale use of antibiotics.

Bloodstream infections in the COVID-19 era: results from an Italian multi-centre study.

BACKGROUND: Correlation between coronavirus disease 2019 (COVID-19) and superinfections has been investigated, but remains to be fully assessed. This multi-centre study reports the impact of the pandemic on bloodstream infections (BSIs). METHODS: This study included all patients with BSIs admitted to four Italian hospitals between 1 January and 30 June 2020. Clinical, demographic and microbiologic data were compared with data for patients hospitalized during the same period in 2019. RESULTS: Among 26,012 patients admitted between 1 January and 30 June 2020, 1182 had COVID-19. Among the patients with COVID-19, 107 BSIs were observed, with an incidence rate of 8.19 episodes per 1000 patient-days. The incidence of BSI was significantly higher in these patients compared with patients without COVID-19 (2.72/1000 patient-days) and patients admitted in 2019 (2.76/1000 patient-days). In comparison with patients without COVID-19, BSI onset in patients with COVID-19 was delayed during the course of hospitalization (16.0 vs 5 days, respectively). Thirty-day mortality among patients with COVID-19 was 40.2%, which was significantly higher compared with patients without COVID-19 (23.7%). BSIs in patients with COVID-19 were frequently caused by multi-drug-resistant pathogens, which were often centre-dependent. CONCLUSIONS: BSIs are a common secondary infection in patients with COVID-19, characterized by increased risk during hospitalization and potentially burdened with high mortality.

Molecular detection of biofilm coding genes in Staphylococcus aureus

In accordance with epidemic COVID-19, the elevated infection rates, disinfectant overuse and antibiotic misuse what led to immune suppression in most of the population in addition to genotypic and phenotypic alterations in the microorganisms, so a great need to reevaluate the genetic determinants that responsible for bacterial community (biofilm) has been raised. A total of 250 clinical specimens were obtained from patients in Baghdad hospitals and streaked on Mannitol salt agar medium. The results revealed that 156 isolates appeared as round yellow colonies, indicating that they were mostly identified as Staphylococcus aureus from 250 specimens. The antibiotic resistance pattern of the isolates for methicillin 37.17% (n=58), Amoxicillin-Clavulanate 58.9% (n=92), chloramphenicol 6.4% (n=10), Tetracyclin 62.8% (n=98), ceftriaxone 53.8% (n=84), Ciprofloxacin 6.4% (n=10), Gentamicin 42.3% (n=66), levofloxacin 28.2% (n=44), Penicillin 33.3% (n=52). The results demonstrated that 49 isolates were multidurg resistance. The biofilm formation ability of MDR was detected and total of 120 S. aureus isolates (76.92 %) were found to be adherent to varied degrees. Only fifty isolates (32.05% of the total) were classified as strong biofilm producers. Twenty-three (14.75%) were moderate producers, and forty seven isolates (30.12%) were found to be weak producers. A total of 36 isolates (23.08%) exhibited no biofilm production. Molecular detection of four biofilm coding genes icaA, icaD, icaR and eno was applied using doublex PCR technique. The current study revealed that 72%, 78%, 70% and 84% of isolates that carried icaA, icaD, icaR and eno genes respectively, eno is the predominant in the Iraqi isolates. © 2022 International Journal of Health Sciences.

Clinical Impact of COVID-19 on Multi-Drug-Resistant Gram-Negative Bacilli Bloodstream Infections in an Intensive Care Unit Setting: Two Pandemics Compared.

Two mutually related pandemics are ongoing worldwide: the COVID-19 and antimicrobial resistance pandemics. This study aims to evaluate the impact of COVID-19 on multi-drug-resistant Gram-negative bacteria (MDR-GN) bloodstream infections (BSIs) in a single intensive care unit (ICU). We conducted a retrospective study including patients admitted to the ICU, reorganized for COVID-19 patients' healthcare, with at least one confirmed MDR-GN BSI during 2019-2020. We compared clinical and microbiological features, incidence density, antibiotic therapy and mortality rate in pre- and during-COVID-19 pandemic periods. We estimated the impact of COVID-19 on mortality by means of univariate Cox regression analyses. A total of 46 patients were included in the study (28 non-COVID-19/18 COVID-19). Overall, 63 BSI episodes occurred (44/19), and non-COVID-19 patients had a higher incidence of MDR-GN BSIs and were more likely to present K. pneumoniae BSIs, while the COVID-19 group showed more A. baumannii BSIs with higher per pathogen incidence. COVID-19 patients presented more critical conditions at the BSI onset, a shorter hospitalization time from BSI to death and higher 30-day mortality rate from BSI onset. COVID-19 and septic shock were associated with 30-day mortality from MDR-GN BSIs, while early active therapy was a protective factor. In conclusion, COVID-19 showed a negative impact on patients with MDR-GN BSIs admitted to the ICU.

Adapting Clofazimine for Treatment of Cutaneous Tuberculosis by Using Self-Double-Emulsifying Drug Delivery Systems.

Although chemotherapeutic treatment regimens are currently available, and considerable effort has been lavished on the development of new drugs for the treatment of tuberculosis (TB), the disease remains deeply intractable and widespread. This is due not only to the nature of the life cycle and extraordinarily disseminated habitat of the causative pathogen, principally Mycobacterium tuberculosis (Mtb), in humans and the multi-drug resistance of Mtb to current drugs, but especially also to the difficulty of enabling universal treatment of individuals, immunocompromised or otherwise, in widely differing socio-economic environments. For the purpose of globally eliminating TB by 2035, the World Health Organization (WHO) introduced the "End-TB" initiative by employing interventions focusing on high impact, integrated and patient-centered approaches, such as individualized therapy. However, the extraordinary shortfall in stipulated aims, for example in actual treatment and in TB preventative treatments during the period 2018-2022, latterly and greatly exacerbated by the COVID-19 pandemic, means that even greater pressure is now placed on enhancing our scientific understanding of the disease, repurposing or repositioning old drugs and developing new drugs as well as evolving innovative treatment methods. In the specific context of multidrug resistant Mtb, it is furthermore noted that the incidence of extra-pulmonary TB (EPTB) has significantly increased. This review focusses on the potential of utilizing self-double-emulsifying drug delivery systems (SDEDDSs) as topical drug delivery systems for the dermal route of administration to aid in treatment of cutaneous TB (CTB) and other mycobacterial infections as a prelude to evaluating related systems for more effective treatment of CTB and other mycobacterial infections at large. As a starting point, we consider here the possibility of adapting the highly lipophilic riminophenazine clofazimine, with its potential for treatment of multi-drug resistant TB, for this purpose. Additionally, recently reported synergism achieved by adding clofazimine to first-line TB regimens signifies the need to consider clofazimine. Thus, the biological effects and pharmacology of clofazimine are reviewed. The potential of plant-based oils acting as emulsifiers, skin penetration enhancers as well as these materials behaving as anti-microbial components for transporting the incorporated drug are also discussed.

Rhamnolipid Nano-Micelles versus Alcohol-Based Hand Sanitizer: A Comparative Study for Antibacterial Activity against Hospital-Acquired Infections and Toxicity Concerns.

Hospital-acquired infections (HAIs) are considered to be a major global healthcare challenge, in large part because of the development of microbial resistance to currently approved antimicrobial drugs. HAIs are frequently preventable through infection prevention and control measures, with hand hygiene as a key activity. Improving hand hygiene was reported to reduce the transmission of healthcare-associated pathogens and HAIs. Alcohol-based hand sanitizers are commonly used due to their rapid action and broad spectrum of microbicidal activity, offering protection against bacteria and viruses. However, their frequent administration has been reported to be associated with many side effects, such as skin sensitivity, skin drying, and cracks, which promote further skin infections. Thus, there is an essential need to find alternative approaches to hand sanitation. Rhamnolipids are glycolipids produced by Pseudomonas aeruginosa, and were shown to have broad antimicrobial activity as biosurfactants. We have previously demonstrated the antimicrobial activity of rhamnolipid nano-micelles against selected drug-resistant Gram-negative (Salmonella Montevideo and Salmonella Typhimurium) and Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae). To the best of our knowledge, the antimicrobial activity of rhamnolipid nano-micelles in comparison to alcohol-based hand sanitizers against microorganisms commonly causing HAIs in Egypt-such as Acinetobacter baumannii and Staphylococcus aureus-has not yet been studied. In the present work, a comparative study of the antibacterial activity of rhamnolipid nano-micelles versus alcohol-based hand sanitizers was performed, and their safety profiles were also assessed. It was demonstrated that rhamnolipid nano-micelles had a comparable antibacterial activity to alcohol-based hand sanitizer, with a better safety profile, i.e., rhamnolipid nano-micelles are unlikely to cause any harmful effects on the skin. Thus, rhamnolipid nano-micelles could be recommended to replace alcohol-based hand sanitizers; however, they must still be tested by healthcare workers in healthcare settings to ascertain their antimicrobial activity and safety.

Bacterial Coinfection and Antibiotic Resistance Profiles among Hospitalised COVID-19 Patients.

While it is reported that COVID-19 patients are more prone to secondary bacterial infections, which are strongly linked to the severity of complications of the disease, bacterial coinfections associated with COVID-19 are not widely studied. This work aimed to investigate the prevalence of bacterial coinfections and associated antibiotic resistance profiles among hospitalised COVID-19 patients. Age, gender, weight, bacterial identities, and antibiotic sensitivity profiles were collected retrospectively for 108 patients admitted to the intensive care unit (ICU) and non-ICU ward of a single center in Saudi Arabia. ICU patients (60%) showed a significantly higher percentage of bacterial coinfections in sputum (74%) and blood (38%) samples, compared to non-ICU. Acinetobacter baumannii (56%) and Klebsiella pneumoniae (56%) were the most prevalent bacterial species from ICU patients, presenting with full resistance to all tested antibiotics except colistin. By contrast, samples of non-ICU patients exhibited infections with Escherichia coli (31%) and Pseudomonas aeruginosa (15%) predominantly, with elevated resistance of E. coli to piperacillin/tazobactam and trimethoprim/sulfamethoxazole. This alarming correlation between multi-drug resistant bacterial coinfection and admission to the ICU requires more attention and precaution with prescribed antibiotics to limit the spread of resistant bacteria and improve therapeutic management.

Genomic New Insights Into Emergence and Clinical Therapy of Multidrug-Resistant Klebsiella pneumoniae in Infected Pancreatic Necrosis.

Infected pancreatic necrosis (IPN) is a key risk factor in the progression of severe acute pancreatitis, and use of antibiotics is one of the main clinical actions. However, early prophylactic or unreasonable use of antibiotics promotes drug resistance in bacteria and also delays optimum treatment. To explore genomic evidence of rational antibiotic use in intensive care units, we isolated Klebsiella pneumoniae from IPN samples that showed the highest positive-culture rate in 758 patients. Based on whole-genome sequencing from eight strains, 42 antibiotic-resistant genes were identified in the chromatin and 27 in the plasmid, which included classic resistance-mechanism factors such as ß-lactamases [16.67% (7/42) in the chromatin and 25.93% (7/27) in the plasmid]. The K. pneumoniae isolates were identified to be resistant to multiple antibiotics used in clinics. In vivo and in vitro, ceftazidime-avibactam (CZA) plus aztreonam (ATM) (2.5:1) showed more significant antibacterial effectiveness than CZA alone. The isolated K. pneumoniae were of three different types according to the resistance phenotypes for CZA and ATM. Those co-harboring bla NDM-5, bla CTX-M-15, bla OXA-1, and bla SHV-187 showed higher resistance to CAZ than bla NDM-5. Those co-harboring bla CTX-M-65, bla SHV-182, and bla TEM-181 were significantly less resistant to ß-lactam than to other extended-spectrum ß-lactamases. However, ß-lactamases were inhibited by avibactam (AVI), except for NDM-5. ATM plus AVI showed a significant inhibitory effect on K. pneumoniae, and the minimum dosage of ATM was < 1 mg/L. In conclusion, we propose that ATM plus AVI could be a major therapy for complex infectious diseases caused by multidrug-resistant K. pneumoniae.

Biodegradable Nanofibrous Membranes for Medical and Personal Protection Applications: Manufacturing, Anti-COVID-19 and Anti-Multidrug Resistant Bacteria Evaluation.

Biodegradable nanofibrous hybrid membranes of polyvinyl alcohol (PVA) with ZnO and CuO nanoparticles were manufactured and characterized, and their anti-COVID-19 and anti-multidrug resistant bacteria activities were also evaluated. The morphological structures of the prepared PVA composites nanofibers were observed by scanning electron microscope (SEM), which revealed a homogenous pattern of the developed nanofibers, with an average fibrous diameter of 200-250 nm. Moreover, the results of the SEM showed that the fiber size changed with the type and the concentration of the metal oxide. Moreover, the antiviral and antibacterial potential capabilities of the developed nanofibrous membranes were tested in blocking the viral fusion of SARS-COV-2, as a representative activity for COVID-19 deactivation, as well as for their activity against a variety of bacterial strains, including multi-drug resistant bacteria (MDR). The results revealed that ZnO loaded nanofibers were more potent antiviral agents than their CuO analogues. This antiviral action was attributed to the fact that inorganic metallic compounds have the ability to extract hydrogen bonds with viral proteins, causing viral rupture or morphological changes. On the other hand, the anti-multi-drug resistant activity of the prepared nanofibers was also evaluated using two techniques; the standard test method for determining the antimicrobial activity of immobilized antimicrobial agents under dynamic contact conditions and the standard test method for determining the activity of incorporated antimicrobial agents in polymeric or hydrophobic materials. Both techniques proved the superiority of the ZnO loaded nanofibers over the CuO loaded fibers. The results of the antiviral and antibacterial tests showed the effectiveness of such nanofibrous formulas, not only for medical applications, but also for the production of personal protection equipment, such as gowns and textiles.

Situational analysis of 10 countries with a high burden of drug-resistant tuberculosis 2 years post-UNHLM declaration: progress and setbacks in a changing landscape.

OBJECTIVES: Globally, drug-resistant tuberculosis (DR-TB) is the leading cause of death globally related to antimicrobial resistance, affecting 500,000 emergent cases annually. In 2018, the first United Nations High-Level Meeting (UNHLM) on tuberculosis declared DR-TB a global public health priority. Bold country targets were established for 2018-2022. This study reviews the DR-TB situation in 2018, and the UNHLM target accomplishments in 10 high-burden countries (HBCs). METHODS: An ecological descriptive analysis of the top 10 DR-TB HBCs (Bangladesh, China, India, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, Russian Federation, and South Africa), which share 70% of the global DR-TB burden, was undertaken, complemented by a cascade-of-care analysis and a survey gathering additional information on key advances and setbacks 2 years after the UNHLM declaration. RESULTS: Most countries are showing historic advances and are on track for the 2018 and 2019 targets. However, according to the cascade-of-care, none of the countries are capable of providing effective care for 50% of the estimated patients. Increasing levels of fluoroquinolone resistance and access to timely susceptibility testing can jeopardize ongoing adoption of shorter, all-oral treatment regimens. The programmatic management of DR-TB in children remains minimal. Achievements for 2020 and beyond may be affected significantly by the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSION: Triggered by the COVID-19 pandemic, there is a global risk of recoil in DR-TB care with long-term consequences in terms of deaths, suffering and wider transmission. Investment to support DR-TB services is more important now than ever to meet the aspirations of the UNHLM declaration.

Clinical Perspectives of Multiple and Extensively Drug-Resistant Typhoid; result from a tertiary care hospital from Pakistan.

INTRODUCTION: Typhoid fever remains a problem in developing countries, including Pakistan. The emergence of multidrug-resistant and, since 2016, of extensively drug-resistant cases is a continuous challenge for health care workers. The COVID-19 pandemic is making management more difficult. METHODOLOGY: In the present study, a total of 52 confirmed cases of typhoid have been studied during 2019. Detailed clinical features, complications and, lab findings were studied. Typhoid culture and sensitivity were recorded and patients were treated accordingly. Patients were asked about risk factors to aim at informing prevention. RESULTS: Out of the 52 having blood culture positive for Salmonella Typhi 47 (90.4%) and Salmonella Paratyphi 5 (9.6%), 4 (7.7%) were sensitive to first-line (Non-resistant), 11 (21.2%) MDR and 37 (71.2%) patient were XDR. One case was resistant to azithromycin. Nausea, vomiting or, abdominal pain was present in 12 (23%), abdominal distension present in 9 (17.3%), abdominal tenderness in 8 (15.4%), hepatomegaly in 10 (19.2%) and, splenomegaly in 22 (42.3%).There were ultrasound abnormalities in 58% of patients and GI complications in 19% of patients. No significant difference was found in clinical findings and complications between resistant and non-resistant cases. Only 23-27% of patients were aware of typhoid prevention and vaccination measures. CONCLUSIONS: The increasing prevalence of resistance and higher degree of complications seen in typhoid fever raises the concern further about prevention and effective infection management in the community as well as clinical settings. Moreover, judicial use of antibiotics is much needed in developing countries like Pakistan.

The silent pandemic: Emergent antibiotic resistances following the global response to SARS-CoV-2.

The ongoing SARS-CoV-2 pandemic has highlighted the importance of the rapid development of vaccines and antivirals. However, the potential for the emergence of antibiotic resistances due to the increased use of antibacterial cleaning products and therapeutics presents an additional, underreported threat. Most antibacterial cleaners contain simple quaternary ammonium compounds (QACs); however, these compounds are steadily becoming less effective as antibacterial agents. QACs are extensively used in SARS-CoV-2-related sanitization in clinical and household settings. Similarly, due to the danger of secondary infections, antibiotic therapeutics are increasingly used as a component of COVID-19 treatment regimens, even in the absence of a bacterial infection diagnosis. The increased use of antibacterial agents as cleaners and therapeutics is anticipated to lead to novel resistances in the coming years.

Ventilator-associated bacterial pneumonia in coronavirus 2019 disease, a retrospective monocentric cohort study.

INTRODUCTION: Severe coronavirus 2019 disease (CoViD-19) may lead to respiratory failure and mechanical ventilation. Therefore, ventilator associated pneumonia (VAP) may complicate the course of the disease. The aim of the current article was to investigate possible predictive factors for bacterial VAP on a retrospective manner, in a cohort of mechanically ventilated CoViD-19 patients. Additionally, determinant factors of lethality were analyzed. METHODS: Medical records of patients hospitalized in the intensive care units (ICU) at the university hospital UZ Brussel during the epidemic were reviewed. VAP was defined following the National Healthcare Safety Network 2017 criteria. Univariate and multivariate logistic regressions analyses were performed. RESULTS: Among the 39 patients included in the study, 54% were diagnosed with bacterial VAP. Case fatality rate was 44%, but 59% of the deceased patients had a do-not-resuscitate status. Multivariate logistic regression for prediction of VAP showed significant differences in duration of ICU hospitalization and in minimal lung compliance. Additional analyses were performed on CoViD-19 patients who were affected by bacterial respiratory superinfection. The responsible pathogens correspond to the commonly found bacteria in VAP. However, 71% of the isolated germs were multi-drug resistant and bacteraemia was reported in 38%. Multivariate analyses for prediction of lethality found significant difference in SOFA score. CONCLUSIONS: Mechanically ventilated CoViD-19 patients might frequently develop VAP. Longer ICU hospitalization was associated with pulmonary superinfection in the current cohort. Moreover, decreased minimal lung compliance was correlated to VAP and higher SOFA score at VAP diagnosis was associated with lethality.