ABSTRACT
SARS-CoV-2 has caused millions of infections and deaths worldwide and case numbers continue to rise. Besides the effect of the virus on key organs - leading to respiratory illness, anosmia, diarrhea, and fever and other complications - delayed inflammatory reactions to hyaluronic acid dermal fillers, mainly in the face, have also been reported to occur after confirmed SARS-CoV-2 infections and in vaccinated individuals. While delayed inflammatory reactions tend to be self-limiting, they should be diagnosed and treated with corticosteroids, hyaluronidase, and/or antibiotics when necessary. The inflammation is generally not severe, yet these complications are classified as serious adverse events by the US Food and Drug Administration. They appear to be delayed type IV hypersensitivity reactions triggered by the immune system in the presence of SARS-CoV-2 or other viruses, such as those causing influenza, although the underlying mechanisms have not been fully elucidated. Because the longevity of dermal fillers is increasing, while the pandemic continues to evolve and new vaccines are under development, the long-term effects on hyaluronic acid fillers and other bioimplant materials should be studied. Physicians must also be encouraged to report these reactions, however mild, to ensure accurate records.
Subject(s)
COVID-19 , Dermal Fillers , Anti-Bacterial Agents , COVID-19/prevention & control , Dermal Fillers/adverse effects , Humans , Hyaluronic Acid/adverse effects , Hyaluronoglucosaminidase/therapeutic use , SARS-CoV-2ABSTRACT
BACKGROUND: The World Health Organization recommends changing the first-line antimicrobial treatment for gonorrhoea when ≥ 5% of Neisseria gonorrhoeae cases fail treatment or are resistant. Susceptibility to ceftriaxone, the last remaining treatment option has been decreasing in many countries. We used antimicrobial resistance surveillance data and developed mathematical models to project the time to reach the 5% threshold for resistance to first-line antimicrobials used for N. gonorrhoeae. METHODS: We used data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales from 2000-2018 about minimum inhibitory concentrations (MIC) for ciprofloxacin, azithromycin, cefixime and ceftriaxone and antimicrobial treatment in two groups, heterosexual men and women (HMW) and men who have sex with men (MSM). We developed two susceptible-infected-susceptible models to fit these data and produce projections of the proportion of resistance until 2030. The single-step model represents the situation in which a single mutation results in antimicrobial resistance. In the multi-step model, the sequential accumulation of resistance mutations is reflected by changes in the MIC distribution. RESULTS: The single-step model described resistance to ciprofloxacin well. Both single-step and multi-step models could describe azithromycin and cefixime resistance, with projected resistance levels higher with the multi-step than the single step model. For ceftriaxone, with very few observed cases of full resistance, the multi-step model was needed to describe long-term dynamics of resistance. Extrapolating from the observed upward drift in MIC values, the multi-step model projected ≥ 5% resistance to ceftriaxone could be reached by 2030, based on treatment pressure alone. Ceftriaxone resistance was projected to rise to 13.2% (95% credible interval [CrI]: 0.7-44.8%) among HMW and 19.6% (95%CrI: 2.6-54.4%) among MSM by 2030. CONCLUSIONS: New first-line antimicrobials for gonorrhoea treatment are needed. In the meantime, public health authorities should strengthen surveillance for AMR in N. gonorrhoeae and implement strategies for continued antimicrobial stewardship. Our models show the utility of long-term representative surveillance of gonococcal antimicrobial susceptibility data and can be adapted for use in, and for comparison with, other countries.
Subject(s)
Gonorrhea , Sexual and Gender Minorities , Male , Humans , Female , Neisseria gonorrhoeae/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Gonorrhea/drug therapy , Gonorrhea/epidemiology , Cefixime/pharmacology , Cefixime/therapeutic use , Ceftriaxone/pharmacology , Ceftriaxone/therapeutic use , Azithromycin/pharmacology , Azithromycin/therapeutic use , Homosexuality, Male , Drug Resistance, Bacterial , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Microbial Sensitivity TestsABSTRACT
INTRODUCTION: Our work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. METHODS: Retrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. RESULTS: Two-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p<0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4-16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1-5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2-5.1, p<0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p<0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). CONCLUSIONS: Superinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.
Subject(s)
COVID-19 , Sepsis , Superinfection , Humans , Retrospective Studies , Tertiary Care Centers , Superinfection/drug therapy , COVID-19/complications , COVID-19/epidemiology , Intensive Care Units , Sepsis/drug therapy , Anti-Bacterial Agents/therapeutic useABSTRACT
Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111-142). The non-fibrillar peptide has membranolytic activity against various bacterial species, while the HBA(111-142) fibrils aggregated bacteria to promote their phagocytotic clearance. Further, HBA(111-142) fibrils selectively inhibited measles and herpes viruses (HSV-1, HSV-2, HCMV), but not SARS-CoV-2, ZIKV and IAV. HBA(111-142) is released from its precursor by ubiquitous aspartic proteases under acidic conditions characteristic at sites of infection and inflammation. Thus, HBA(111-142) is an amyloidogenic AMP that may specifically be generated from a highly abundant precursor during bacterial or viral infection and may play an important role in innate antimicrobial immune responses.
Subject(s)
COVID-19 , Zika Virus Infection , Zika Virus , Humans , Peptides , Amyloid/chemistry , Anti-Bacterial Agents/pharmacology , HemoglobinsABSTRACT
A woman reported decreased vision in the right eye since hospitalization for COVID-19. Vision in the right eye was 6/18 and in the left eye was counting fingers. Her left eye had cataract and right eye was pseudophakic with earlier documented good recovery. In the right eye, she had branch retinal vein occlusion (BRVO) with macular edema documented on optical coherence tomography (OCT). It was suspected that it might be an ocular manifestation of COVID-19 which had not been reported and had worsened. An overdose of antibiotics or remdesivir might also be responsible for the same. She was advised anti-VEGF injections and was kept under treatment.
Subject(s)
COVID-19 , Retinal Vein Occlusion , Humans , Female , Anticoagulants/therapeutic use , Anti-Bacterial Agents/adverse effects , COVID-19 Drug Treatment , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/drug therapy , Vitreous Body , Tomography, Optical Coherence , Intravitreal InjectionsABSTRACT
BACKGROUND: Patients with COVID-19 have a high incidence of acute kidney injury (AKI), which is associated with mortality. The objective of the study was to determine the factors associated with AKI in patients with COVID-19. METHODOLOGY: A retrospective cohort was established in two university hospitals in Bogotá, Colombia. Adults hospitalized for more than 48 h from March 6, 2020, to March 31, 2021, with confirmed COVID-19 were included. The main outcome was to determine the factors associated with AKI in patients with COVID-19 and the secondary outcome was estimate the incidence of AKI during the 28 days following hospital admission. RESULTS: A total of 1584 patients were included: 60.4% were men, 738 (46.5%) developed AKI, 23.6% were classified as KDIGO 3, and 11.1% had renal replacement therapy. The risk factors for developing AKI during hospitalization were male sex (OR 2.28, 95% CI 1.73-2.99), age (OR 1.02, 95% CI 1.01-1.03), history of chronic kidney disease (CKD) (OR 3.61, 95% CI 2.03-6.42), High Blood Pressure (HBP) (OR 6.51, 95% CI 2.10-20.2), higher qSOFA score to the admission (OR 1.4, 95% CI 1.14-1.71), the use of vancomycin (OR 1.57, 95% CI 1.05-2.37), piperacillin/tazobactam (OR 1.67, 95% CI 1.2-2.31), and vasopressor support (CI 2.39, 95% CI 1.53-3.74). The gross hospital mortality for AKI was 45.5% versus 11.7% without AKI. CONCLUSIONS: This cohort showed that male sex, age, history of HBP and CKD, presentation with elevated qSOFA, in-hospital use of nephrotoxic drugs and the requirement for vasopressor support were the main risk factors for developing AKI in patients hospitalized for COVID-19.
Subject(s)
Acute Kidney Injury , COVID-19 , Hypertension , Renal Insufficiency, Chronic , Adult , Humans , Male , Female , Anti-Bacterial Agents/adverse effects , Retrospective Studies , COVID-19/epidemiology , COVID-19/complications , Risk Factors , Hypertension/complications , Acute Kidney Injury/etiology , Renal Insufficiency, Chronic/complications , Hospital MortalityABSTRACT
Objective: To measure sales of antibiotics without a prescription in pharmacies in China in 2017 and 2021, before and during the coronavirus disease 2019 (COVID-19) pandemic, and determine the factors associated with such sales. Methods: We conducted cross-sectional surveys using the simulated patient method in retail pharmacies in 13 provinces in eastern, central and western China in 2017 and 2021. At the pharmacies, the simulated patients (trained medical students) reported that they had mild respiratory tract symptoms and asked for treatment, using a three-stage process: (i) request some treatment; (ii) request antibiotics; (iii) request specific antibiotics. We used multivariable logistic regression analysis to determine factors associated with sale of antibiotics without a prescription. Findings: Of the pharmacies visited in 2017, 83.6% (925/1106) sold antibiotics without a prescription; this figure was 78.3% (853/1090) in 2021 (P-value: 0.002). After excluding pharmacies prohibited from selling antibiotics because of COVID-19, this difference was not significant (83.6% versus 80.9%; 853/1054; P-value: 0.11). Factors significantly associated with selling antibiotics without a prescription in both 2017 and 2019 were: location in central and western China compared with eastern China; being in a township or village compared with in a city; and presence of a counter where antibiotics were dispensed. Conclusion: Although laws became stricter between 2017 and 2021, antibiotic sales without a prescription were still common in pharmacies across China. Existing regulations need to be more strictly enforced, and pharmacy staff and the public should be made more aware of the risks of antibiotic misuse and dangers of antimicrobial resistance.
Subject(s)
Anti-Bacterial Agents , Pharmacies , Humans , Anti-Bacterial Agents/therapeutic use , China , COVID-19/epidemiology , Cross-Sectional Studies , Prescriptions , CommerceABSTRACT
Quaternary ammonium compounds (QACs), a large class of chemicals that includes high production volume substances, have been used for decades as antimicrobials, preservatives, and antistatic agents and for other functions in cleaning, disinfecting, personal care products, and durable consumer goods. QAC use has accelerated in response to the COVID-19 pandemic and the banning of 19 antimicrobials from several personal care products by the US Food and Drug Administration in 2016. Studies conducted before and after the onset of the pandemic indicate increased human exposure to QACs. Environmental releases of these chemicals have also increased. Emerging information on adverse environmental and human health impacts of QACs is motivating a reconsideration of the risks and benefits across the life cycle of their production, use, and disposal. This work presents a critical review of the literature and scientific perspective developed by a multidisciplinary, multi-institutional team of authors from academia, governmental, and nonprofit organizations. The review evaluates currently available information on the ecological and human health profile of QACs and identifies multiple areas of potential concern. Adverse ecological effects include acute and chronic toxicity to susceptible aquatic organisms, with concentrations of some QACs approaching levels of concern. Suspected or known adverse health outcomes include dermal and respiratory effects, developmental and reproductive toxicity, disruption of metabolic function such as lipid homeostasis, and impairment of mitochondrial function. QACs' role in antimicrobial resistance has also been demonstrated. In the US regulatory system, how a QAC is managed depends on how it is used, for example in pesticides or personal care products. This can result in the same QACs receiving different degrees of scrutiny depending on the use and the agency regulating it. Further, the US Environmental Protection Agency's current method of grouping QACs based on structure, first proposed in 1988, is insufficient to address the wide range of QAC chemistries, potential toxicities, and exposure scenarios. Consequently, exposures to common mixtures of QACs and from multiple sources remain largely unassessed. Some restrictions on the use of QACs have been implemented in the US and elsewhere, primarily focused on personal care products. Assessing the risks posed by QACs is hampered by their vast structural diversity and a lack of quantitative data on exposure and toxicity for the majority of these compounds. This review identifies important data gaps and provides research and policy recommendations for preserving the utility of QAC chemistries while also seeking to limit adverse environmental and human health effects.
Subject(s)
COVID-19 , Disinfectants , Humans , Quaternary Ammonium Compounds/chemistry , Pandemics , Anti-Bacterial AgentsABSTRACT
OBJECTIVES: To investigate the levels of MDR in the predominant serotypes of invasive Streptococcus pneumoniae isolated in Canada over a 10âyear period. METHODS: All isolates were serotyped and had antimicrobial susceptibility testing performed, in accordance with CLSI guidelines (M07-11 Ed., 2018). Complete susceptibility profiles were available for 13â712 isolates. MDR was defined as resistance to three or more classes of antimicrobial agents (penicillin MIC ≥2 mg/L defined as resistant). Serotypes were determined by Quellung reaction. RESULTS: In total, 14â138 invasive isolates of S. pneumoniae were tested in the SAVE study (S. pneumoniae Serotyping and Antimicrobial Susceptibility: Assessment for Vaccine Efficacy in Canada), a collaboration between the Canadian Antimicrobial Resistance Alliance and Public Health Agency of Canada-National Microbiology Laboratory. The rate of MDR S. pneumoniae in SAVE was 6.6% (902/13â712). Annual rates of MDR S. pneumoniae decreased between 2011 and 2015 (8.5% to 5.7%) and increased between 2016 and 2020 (3.9% to 9.4%). Serotypes 19A and 15A were the most common serotypes demonstrating MDR (25.4% and 23.5% of the MDR isolates, respectively); however, the serotype diversity index increased from 0.7 in 2011 to 0.9 in 2020 with a statistically significant linear increasing trend (Pâ<â0.001). In 2020, MDR isolates were frequently serotypes 4 and 12F in addition to serotypes 15A and 19A. In 2020, 27.3%, 45.5%, 50.5%, 65.7% and 68.7% of invasive MDR S. pneumoniae were serotypes included in the PCV10, PCV13, PCV15, PCV20 and PPSV23 vaccines, respectively. CONCLUSIONS: Although current vaccine coverage of MDR S. pneumoniae in Canada is high, the increasing diversity of serotypes observed among the MDR isolates highlights the ability of S. pneumoniae to rapidly evolve.
Subject(s)
Pneumococcal Infections , Streptococcus pneumoniae , Humans , Serogroup , Pneumococcal Infections/microbiology , Anti-Bacterial Agents/pharmacology , Canada/epidemiology , Microbial Sensitivity Tests , Serotyping , Pneumococcal VaccinesABSTRACT
Background: Antimicrobial resistance is a serious threat to public health globally. It is a slower-moving pandemic than COVID-19, so we are fast running out of treatment options. Purpose: Thus, this study was designed to search for an alternative biomaterial with broad-spectrum activity for the treatment of multidrug-resistant (MDR) bacterial and fungal pathogen-related infections. Methods: We isolated Streptomyces species from soil samples and identified the most active strains with antimicrobial activity. The culture filtrates of active species were purified, and the bioactive metabolite extracts were identified by thin-layer chromatography (TLC), preparative high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentrations (MICs) of the bioactive metabolites against MDR bacteria and fungi were determined using the broth microdilution method. Results: Preliminary screening revealed that Streptomyces misakiensis and S. coeruleorubidus exhibited antimicrobial potential. The MIC50 and MIC90 of S. misakiensis antibacterial bioactive metabolite (ursolic acid methyl ester) and antifungal metabolite (tetradecamethylcycloheptasiloxane) against all tested bacteria and fungi were 0.5 µg/ml and 1 µg/mL, respectively, versus S. coeruleorubidus metabolites: thiocarbamic acid, N,N-dimethyl, S-1,3-diphenyl-2-butenyl ester against bacteria (MIC50: 2 µg/ml and MIC90: 4 µg/mL) and fungi (MIC50: 4 µg/ml and MIC90: 8 µg/mL). Ursolic acid methyl ester was active against ciprofloxacin-resistant strains of Streptococcus pyogenes, S. agalactiae, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovars, colistin-resistant Aeromonas hydrophila and K. pneumoniae, and vancomycin-resistant Staphylococcus aureus. Tetradecamethylcycloheptasiloxane was active against azole- and amphotericin B-resistant Candida albicans, Cryptococcus neoformans, C. gattii, Aspergillus flavus, A. niger, and A. fumigatus. Ursolic acid methyl ester was applied in vivo for treating S. aureus septicemia and K. pneumoniae pneumonia models in mice. In the septicemia model, the ursolic acid methyl ester-treated group had a significant 4.00 and 3.98 log CFU/g decrease (P < 0.05) in liver and spleen tissue compared to the infected, untreated control group. Lung tissue in the pneumonia model showed a 2.20 log CFU/g significant decrease in the ursolic acid methyl ester-treated group in comparison to the control group. The haematological and biochemical markers in the ursolic acid methyl ester-treated group did not change in a statistically significant way. Moreover, no abnormalities were found in the histopathology of the liver, kidneys, lungs, and spleen of ursolic acid methyl ester-treated mice in comparison with the control group. Conclusion: S. misakiensis metabolite extracts are broad-spectrum antimicrobial biomaterials that can be further investigated for the potential against MDR pathogen infections. Hence, it opens up new horizons for exploring alternative drugs for current and reemerging diseases.
Subject(s)
Anti-Infective Agents , COVID-19 , Methicillin-Resistant Staphylococcus aureus , Pneumonia , Sepsis , Mice , Animals , Staphylococcus aureus , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/pharmacology , Bacteria , Fungi , Microbial Sensitivity Tests , Pneumonia/drug therapy , Klebsiella pneumoniae , Sepsis/drug therapyABSTRACT
Objective: To analyse trends and patterns in inpatient antibacterial use in China's tertiary and secondary hospitals between 2013 and 2021. Methods: The analysis involved quarterly data from hospitals covered by China's Center for Antibacterial Surveillance. We obtained information on hospital characteristics (e.g. province, a de-identified hospital code, hospital level and inpatient days) and antibacterial characteristics (e.g. generic name, drug classification, dosage, administration route and usage volume). We quantified antibacterial use as the number of daily defined doses per 100 patient-days. The analysis took into account the World Health Organization's (WHO's) Access, Watch, Reserve classification of antibiotics. Findings: Between 2013 and 2021, overall antibacterial use in inpatients decreased significantly from 48.8 to 38.0 daily defined doses per 100 patient-days (P < 0.001). In 2021, the variation between provinces was almost twofold: 29.1 daily defined doses per 100 patient-days in Qinghai versus 55.3 in Tibet. The most-used antibacterials in both tertiary and secondary hospitals throughout the study period were third-generation cephalosporins, which comprised around one third of total antibacterial use. Carbapenems entered the list of most-used antibacterial classifications in 2015. The most frequently used antibacterials in WHO's classification belonged to the Watch group: usage increased significantly from 61.3% (29.9/48.8) in 2013 to 64.1% (24.4/38.0) in 2021 (P < 0.001). Conclusion: Antibacterial use in inpatients decreased significantly during the study period. However, the rising proportion of last-resort antibacterials used is concerning, as is the large gap between the proportion of antibacterials used belonging to the Access group and WHO's global target of no less than 60%.
Subject(s)
Anti-Bacterial Agents , Inpatients , Humans , Anti-Bacterial Agents/therapeutic use , Hospitals , China/epidemiologyABSTRACT
OBJECTIVE: To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. DESIGN: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. SETTING: Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. PARTICIPANTS: Women (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics. INTERVENTIONS: Participants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment. MAIN OUTCOME MEASURES: Primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator's global assessment (IGA) for treatment success; and adverse reactions. RESULTS: From 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported. CONCLUSIONS: Spironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne. TRIAL REGISTRATION: ISRCTN12892056.
Subject(s)
Acne Vulgaris , Spironolactone , Adult , Humans , Female , Spironolactone/adverse effects , Quality of Life , Wales , Acne Vulgaris/drug therapy , Acne Vulgaris/complications , Anti-Bacterial Agents/therapeutic use , Double-Blind Method , Immunoglobulin A , Treatment OutcomeABSTRACT
Respiratory tract infections are a common cause of morbidity and mortality globally. The current paper aims to treat this respiratory disorder. Therefore, we elucidated the phytochemical profile of Euphorbia milii flowers and isolated chlorogenic acid (CGA) for the first time. The electrospraying technique was utilized to prepare CGA nanoparticles in polyvinyl alcohol (PVA)/PLGA polymeric matrix. Complete in vitro characterizations were performed to determine particle size, polydispersity index (PDI), zeta potential, loading efficiency (LE), scanning electron microscopy and in vitro release study. The optimum formula (F2) with a particle size (454.36 ± 36.74 nm), a surface charge (-4.56 ± 0.84 mV), % of LE (80.23 ± 5.74), an initial burst (29.46 ± 4.79) and % cumulative release (97.42 ± 4.72) were chosen for further activities. In the murine lung infection model, PVA/PLGA NPs loaded with CGA (F2) demonstrated in vivo antibacterial activity against Pseudomonas aeruginosa. Using a plaque assay, the in vitro antiviral activity was investigated. The F2 exhibited antiviral activity against coronavirus (HCoV-229E) and (Middle East respiratory syndrome coronavirus (MERS-CoV), NRCEHKU270). The IC50 of F2 against HCoV-229E and MERS-CoV was 170 ± 1.1 and 223 ± 0.88 µg/mL, respectively. The values of IC50 of F2 were significantly lower (p < .05) than that of free CGA. Therefore, the encapsulation of CGA into electrospray PVA/PLGA NPs would be a promising tool as an antimicrobial agent.
Subject(s)
Middle East Respiratory Syndrome Coronavirus , Nanoparticles , Mice , Animals , Polyvinyl Alcohol/chemistry , Antiviral Agents , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Chlorogenic Acid/pharmacology , Pseudomonas aeruginosa , Anti-Bacterial Agents/pharmacology , Lung , Nanoparticles/chemistryABSTRACT
Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe hypersensitivity reaction. Up-to-date treatment is based on withdrawal of medication, supportive care, and immunosuppression using high-dose corticosteroid (CS) therapy. However, evidence-based data are lacking regarding second-line therapy for steroid-resistant or steroid-dependent patients. Objectives: We hypothesize that the interleukin (IL)-5 axis plays a critical role in the pathophysiology of DRESS; hence, inhibition of this signaling pathway could offer a potential therapy for steroid-dependent and/or steroid-resistant cases, and it may offer an alternative to CS therapy in certain patients more prone to CS toxicity. Methods: Herein, we collected worldwide data on DRESS cases treated with biological agents targeting the IL-5 axis. We reviewed all cases indexed in PubMed up to October 2022 and performed a total analysis including our center experience with two additional novel cases. Results: A review of the literature yielded 14 patients with DRESS who were treated with biological agents targeting the IL-5 axis as well as our two new cases. Reported patients are characterized by a female-to-male ratio of 1:1 and a mean age of 51.8 (17-87) years. The DRESS-inducing drugs, as expected from the prospective RegiSCAR study, were mostly antibiotics (7/16), as follows: vancomycin, trimethoprim-sulfamethoxazole, ciprofloxacin, piperacillin-tazobactam, and cefepime. DRESS patients were treated with anti-IL-5 agents (mepolizumab and reslizumab) or anti-IL-5 receptor (IL-5R) biologics (benralizumab). All patients have clinically improved under anti-IL-5/IL-5R biologics. Multiple doses of mepolizumab were needed to achieve clinical resolution, whereas a single dose of benralizumab was often sufficient. Relapse was noted in one patient receiving benralizumab treatment. One patient receiving benralizumab had a fatal outcome, although mortality was probably related to massive bleeding and cardiac arrest due to coronavirus disease 2019 (COVID-19) infection. Conclusion: Current treatment guidelines for DRESS are based on case reports and expert opinion. Understanding the central role of eosinophils in DRESS pathogenicity emphasizes the need for future implementation of IL-5 axis blockade as steroid-sparing agents, potential therapy to steroid-resistant cases, and perhaps an alternative to CS treatment in certain DRESS patients more prone to CS toxicity.
Subject(s)
Drug Hypersensitivity Syndrome , Eosinophilia , Interleukin-5 , Female , Humans , Male , Middle Aged , Anti-Bacterial Agents/therapeutic use , COVID-19/complications , Drug Hypersensitivity Syndrome/diagnosis , Drug Hypersensitivity Syndrome/drug therapy , Drug Hypersensitivity Syndrome/etiology , Eosinophilia/drug therapy , Eosinophilia/complications , Prospective Studies , Interleukin-5/metabolismABSTRACT
Patients with extracorporeal membrane oxygenation (ECMO) support do frequently receive broad-spectrum antibiotics, due to the high frequency of infection by multidrug resistant microorganisms. The extracorporeal circuit can alter the pharmacokinetics (PK) of administered drugs, and in the case of antibiotics this may lead to treatment failure. Cefiderocol is a new cephalosporin that exhibits excellent in vitro activity against many multidrug-resistant (MDR) microorganisms, but there is no published data about the modifications of its PK in patients with ECMO support. Herein we report the results of a pharmacokinetic investigation of cefiderocol in a critically ill patient receiving extracorporeal respiratory support.
Subject(s)
Extracorporeal Membrane Oxygenation , Humans , Extracorporeal Membrane Oxygenation/methods , Anti-Bacterial Agents/therapeutic use , Cephalosporins/therapeutic use , MonobactamsABSTRACT
BACKGROUND: During the initial stages of the coronavirus disease 2019 (COVID-19) pandemic, the administration of antibiotics to patients was prevalent in numerous countries. Despite this, the rising threat of antimicrobial resistance (AMR) presents a significant public health concern. The escalation of AMR has been exacerbated by the ongoing COVID-19 pandemic. Against this backdrop, the primary aim of this study was to conduct a bibliometric and visual analysis of research pertaining to the use of antibiotics in COVID-19. METHODS: This study examined documents indexed in Scopus between 2020 and 2022. To visualize the trends and hotspots of research related to antibiotics and COVID-19, as well as collaborative networks, the researcher utilized version 1.6.18 of the VOSviewer software. Scopus data were analysed to extract information on the types of publications, annual research output, countries, institutions, funding agencies, journals, citations, and highly cited references. Microsoft Excel 2019 was used to process and organize the extracted data. RESULTS: This study analysed 1137 documents related to COVID-19 and antibiotics and found that the number of publications increased from 130 in 2020 to 527 in 2022. These publications included 777 (68.34%) articles and 205 (18.03%) reviews. The top five countries in terms of scientific production were the United States (n = 231; 20.32%), the United Kingdom (n = 156; 13.72%), China (n = 101; 8.88%), India (n = 100; 8.8%), and Italy (n = 63; 5.54%), and the leading institutions were Imperial College London (n = 21; 1.85%), University of Oxford (n = 20; 1.76%), and University College London (n = 15; 1.32%). The National Natural Science Foundation of China provided funding for the highest number of articles (n = 48; 4.22%), followed by the National Institutes of Health (n = 32; 2.81%). The most productive journals were Antibiotics (n = 90; 7.92%), Journal of Antimicrobial Chemotherapy (n = 30; 2.64%), and Infection Control and Hospital Epidemiology (n = 26; 2.29%). Finally, the research hotspots identified in this study were 'antimicrobial stewardship during the COVID-19 outbreak' and 'implications of the COVID-19 pandemic on the emergence of antimicrobial resistance.' CONCLUSIONS: This is the first bibliometric analysis of COVID-19-related research on antibiotics. Research was carried out in response to global requests to increase the fight against AMR and awareness of the issue. More restrictions on the use of antibiotics are urgently needed from policy makers and authorities, more so than in the current situation.
Subject(s)
Anti-Bacterial Agents , COVID-19 , Humans , Anti-Bacterial Agents/therapeutic use , Pandemics , Drug Resistance, Bacterial , China/epidemiologyABSTRACT
Subdural empyema refers to the collection of purulent material in the subdural space and the most source of it is bacterial meningitis in infants while sinusitis and otitis media in older children. It has been very recently reported that coronaviruses (CoV) exhibit neurotropic properties and may also cause neurological diseases. CoV-related complications as hypercoagulability with thrombosis and associated inflammation, catastrophic cerebral venous sinus thrombose sand bacterial-fungal superinfections have been well documented in adult patients. Hereby, we describe 15-year-old and 12-year-old female children with subdural empyema after SARS-CoV2. The patients presented limitation of eye in the outward gaze, impaired speech, drowsiness, fever, vomiting and they also were tested positive for COVID-19. MRI indicated subdural empyema and surgical interventions were needed to relieve intracranial pressure and drain pus after receiving broad spectrum antibiotics treatments. The microbiological analysis of abscess material revealed Streptococcus constellatus which is extremely rare in an immunocompetent child and the patients received appropriate IV antibiotic therapy. Eventually, patients became neurologically intact. Pediatric patients with CoV infections should be closely monitored for neurological symptoms. Further research and more data on the correlation between CoV infections would provide better recognition and treatment options in an efficient manner in children.
Subject(s)
COVID-19 , Empyema, Subdural , Infant , Adult , Female , Humans , Child , Empyema, Subdural/etiology , Empyema, Subdural/surgery , SARS-CoV-2 , RNA, Viral , COVID-19/complications , Abscess/drug therapy , Anti-Bacterial Agents/therapeutic useABSTRACT
BACKGROUND: The World Health Organization targeted trachoma for global elimination as a public health problem by 2030. Reaching elimination thresholds by the year 2030 in the Republic of South Sudan will be a considerable challenge, as the country currently has many counties considered hyper-endemic (> 30% trachomatous inflammation-follicular [TF]) that have yet to receive interventions. Evidence from randomized trials, modeling, and population-based surveys suggests that enhancements may be needed to the standard-of-care annual mass drug administration (MDA) to reach elimination thresholds in a timely manner within highly endemic areas. We describe a protocol for a study to determine the cost and community acceptability of enhanced antibiotic strategies for trachoma in South Sudan. METHODS: The Enhancing the A in SAFE (ETAS) study is a community randomized intervention costing and community acceptability study. Following a population-based trachoma prevalence survey in 1 county, 30 communities will be randomized 1:1 to receive 1 of 2 enhanced MDA interventions, with the remaining communities receiving standard-of-care annual MDA. The first intervention strategy will consist of a community-wide MDA followed by 2 rounds of targeted treatment to children ages 6 months to 9 years, 2 weeks and 4 weeks after the community MDA. The second strategy will consist of a community-wide biannual MDA approximately 6 to 8 months apart. The costing analysis will use a payer perspective and identify the total cost of the enhanced interventions and annual MDA. Community acceptability will be assessed through MDA coverage monitoring and mixed-methods research involving community stakeholders. A second trachoma-specific survey will be conducted 12 months following the original survey. DISCUSSION: ETAS has received ethical clearance and is expected to be conducted between 2022 and 2023. Results will be shared through subsequent manuscripts. The study's results will provide information to trachoma programs on whether enhanced interventions are affordable and acceptable to communities. These results will further help in the design of future trachoma-specific antibiotic efficacy trials. Enhanced MDA approaches could help countries recover from delays caused by conflict or humanitarian emergencies and could also assist countries such as South Sudan in reaching trachoma elimination as a public health problem by 2030. TRIAL REGISTRATION: This trial was registered on December 1st, 2022 (clinicaltrails.org: NCT05634759).