Pregnancy Outcomes in Women with Sickle Cell Disease in Ireland: A Retrospective Review

Background: Sickle cell disease (SCD) is one of the most common single gene disorders worldwide and is characterised by significant morbidity and early mortality.[1] Pregnancy in SCD is associated with an increased risk of maternal and foetal complications.[2,3] The 2011 RCOG and the 2021 BSH guidelines[5,6] on the management of pregnancy in SCD have provided the basis for best practice care in the UK over the past decade and is the guidance which we follow in Ireland. To date, there is no published data on outcomes for pregnant women with SCD in Ireland. The number of Irish patients with SCD has risen over the past 20 years. Without a national database, the exact prevalence is not known but currently there are at least 600 adults and children with SCD in Ireland, whose population is just over 5 million.[4] Aims: Our study assesses outcomes of pregnant patients with SCD from 2015 to 2022. Our aims were to: * Assess adherence to current guidelines * Assess pregnancy outcomes and maternal complications * Assess transfusion rates amongst our patient cohort. Method(s): This is a retrospective cohort study. We do not have a directly matched cohort, but have compared our findings to published data on Irish pregnancy outcomes from the Irish Maternity Indicator System National Report and have correlated our findings with studies of women with SCD who were managed in UK centres.[8,9,10] Results: We reviewed outcomes of 29 pregnancies in 19 women over a 7-year period. The median age was 29 (range 20-41) and the predominant maternal sickle genotype was HbSS (65.5%). Before conception, 55.2% of cases had pre-existing complications of SCD, including acute chest syndrome (ACS), pulmonary hypertension (PHTN) and prior stroke. In accordance with current guidelines, 100% of women (n=29) were prescribed folic acid, penicillin, and aspirin prophylaxis. 51.7% (n=15) of women had documented maternal complications during pregnancy, including ACS (34%), vaso-occlusive crisis (34%), gestational diabetes (10%), VTE (3%) and UTI (3%). Two women (7%) developed Covid-19 pneumonitis despite vaccination. There was one case of maternal bacteraemia (3%). 65.5% of cases (n=19) required blood transfusion during pregnancy. One woman was already on a blood transfusion programme for disease modification prior to pregnancy. In 6 cases (20.6%), a transfusion programme was commenced during pregnancy due to prior pregnancy complications or intrauterine growth restriction. During pregnancy, 27.6% (n=8) of women required emergency red cell exchange for ACS. Prior studies have suggested that between 30% and 70% of pregnant women with SCD require at least one blood transfusion during pregnancy.[8,9,10] By comparison, only 2.6% of the Irish general obstetric population required transfusion during pregnancy.[7] 20.6% (n=6) of births were preterm at <37 weeks' gestation. There was one live preterm birth (3%) at <34 weeks and one intrauterine death (3%) at 23 weeks' gestation. Similar to UK data[9], 31% of women required critical care stay (n=9) during pregnancy, in comparison with 1.44% nationwide in 2020.[7] Conclusion(s): It is well established that pregnancy in SCD is high risk, and despite adherence to current guidelines, we have shown very high rates of critical care admission, significant transfusion requirement and hospital admissions. Our findings are comparable to published UK outcomes and they further support the need for a comprehensive specialist care setting for this patient cohort.

We should be learning as much from failure as success

'You do not know what you will find, you may set out to find one thing and end up discovering something entirely different'-Alexander Fleming As the pace at which medicine is advancing continues to accelerate, haematologists will increasingly find themselves practising unfamiliar medicine and using novel treatments. Whilst most scientific breakthroughs hopefully lead to an overall improvement in quality of life and prognosis, it is imperative that enough attention is paid to the shortcomings of new treatments and adverse events. The recent COVID-19 pandemic is a stark reminder of the cyclical nature of history and the need for healthcare professionals to utilise lessons learnt by our predecessors. Fleming and the discovery of penicillin highlights how mistakes in practice can sometimes lead to unexpected but useful revelations. The use of thalidomide as a treatment for hyperemesis gravidarum in the 1960s devastatingly lead to birth defects in thousands of people. Today, the repurposing of thalidomide, through lateral thinking and further study, has contributed to significant improvements in the prognosis of patients with Multiple Myeloma.1 Mortality following allogenic stem cell transplant continues to decrease overtime as knowledge surrounding complications and how to manage these improves, despite the fact that patients receiving stem cell transplants are becoming increasingly complex.2 These examples from history demonstrate the merit in studying adverse events and undesired outcomes. National reviews of patient health records indicate that errors currently occur in 10% of hospital admissions.3 With new treatments and more complex patients this will likely increase. It is estimated that voluntary reporting by healthcare professionals of such events only occurs 70% of the time.3 History should be used to guide essential changes in attitudes towards error reporting and help to create an ethos where 'failings' are more willingly recognised as a tool to guide improvement and innovation.

The effect of hydroxychloroquine in COVID-19 patients who did not receive corticosteroids

Background and Objective: At the beginning of the pandemic, Hydroxychloroquine (HCQ) was one of the most widely used drugs prescribed to patients admitted to hospitals with coronavirus disease 2019 (COVID-19). We try to find the effect of HCQ on the severity and mortality of patients who did not receive corticosteroids. Methods: In this retrospective study, patients with COVID-19 disease were collected from February 20, 2020, to July 21, 2020, at Rouhani Hospital in Babol. Patients were followed up until December 6, 2021. In this study, 170 patients in case and control groups were studied. We used logistic and COX regression models to explore the effects of drugs. Data were analyzed by SPSS version 22. Findings: The use of HCQ did not affect mortality (p=0.46, 95%CI= 0.63 to 2.71, OR= 1.31) and final severity (p= 0.75, 95%CI= 0.59 to 2.06, OR= 1.10) at admission time. However, azithromycin remained in the final model but did not have a significant effect (P= 0.08, HR= 0.28, 95%CI= 0.06 to 0.18). Heparin use was not associated with severity improvement (p= 0.06, 95%CI= 0.97 to 2.81, HR= 1.65), while ceftriaxone remained a factor affecting severity in the model (p = 0.03, 95% CI= 0.29 to 0.95, HR = 0.52). Conclusion: In this study, HCQ harmed mortality admission time and was ineffective in the long term. The use of ceftriaxone compared to other drugs showed protective effects against the mortality hospitalization time. Heparin is not recommended without considering the risk of bleeding in COVID-19 patients.

Copper(II) Schiff base complex derived from salen ligand: structural investigation, Hirshfeld surface analysis, anticancer and anti-SARS-CoV-2.

This work deals with the synthesis and characterization of copper(II) complex [Cu(salen)(H2O)](1) of salen-type Schiff base ligand derived from the condensation of 5-bromo-2-hydroxy-3-methoxybenzaldehyde and ethylenediamine in EtOH. This complex was characterized by different spectroscopic and physicochemical methods. Single crystal X-ray crystallography study revealed that Cu(II) in complex (1) is five-coordinate and adopts a distorted square pyramidal geometry. A DFT calculation was employed to evaluate the optimized electronic structure, HOMO-LUMO, energy gap, and global parameters. A detailed structural and non-covalent interaction on the complex is investigated by single crystal structure analysis and computational approaches. The strength of the interaction and 3D topology of the crystal packing are visualized through an energy framework. Hirshfeld surface and 2D fingerprint plots have been explored in the crystal structure of the complex. The anticancer properties of copper(II) complex was studied against the selected cancerous cell lines of breast cancer, cervical cancer, colon cancer and hepatocellular carcinoma. Additionally, molecular docking and MD simulations was performed on the complex to predict the binding mode and interactions between the ligand and the main protease of the SARS-CoV-2 (PDB ID: 7CBT and 7D1M). The molecular docking calculations of the complex (1) with SARS-CoV-2 virus revealed the binding energy of -8.1 kcal/mol and -7.5 kcal/mol with an inhibition constant of 3.245 µM and 2.318 µM at inhibition binding site of receptor towards 7CBT and 7D1M main protease (Mpro), respectively. Besides this, molecular docking results (-7.6 kcal/mol, 3.196 µM) towards Escherichia coli PBP2 targets (PDB ID: 6G9S) was also studied. Communicated by Ramaswamy H. Sarma.

Clostridium Difficillae Infection in Post-Covid Patients

Intro: The ongoing pandemic caused by the SARS-CoV-2 virus has brought many new insights into medicine. During the first months of the pandemic, when there were no comprehensive guidelines for precise antimicrobial therapy, empirical overuse of broad-spectrum antibiotics was observed. Which resulted in the development of clostidium infection in certain cases. In our report, we address 83 cases of clostridial colitis in post-covid patients from 3/2020 to 3/2021 and their specific therapy. Method(s): Retrospective analysis of risk factors for clostridial infection and therapy of clostridial colitis. Finding(s): In the period 3/2020-3/2021, 9617 patients were diagnosed with SARS-CoV-2 virus infection in our hospital, of which 1247 were hospitalized. In 83 cases, clostridial colitis occurred during or after the covid infection had resolved. Mortality in this group was 17%, which corresponds to 14 patients. Previous empirical administered antiobiotics in COVID-19 infection contributed to the development of clostridial colitis in case of 22 patients (27%) by clarithromycin, in 14 pacients (17%) by penicillins and by 3rd generation cephalosporins in 9 patients (11%). The average duration of therapy with broad-spectrum antibiotics was 15.63 days (+-8.99). Other risk factors we observed are: PPI use (25%), active malignant disease (10%), previous glucocorticoid therapy (22%). Vancomycin was used in clostridial infection therapy in 47% (39), metronidazole in 31% (25) and fidaxonicin in 7% (6). In the group, we observed recurrence of clostridium difficile infection in 14% of patients and FMT was performed in 6 patients. Conclusion(s): This study shows a higher percentage of clostridial infection in cases of long-term therapy with broad-spectrum antibiotics. It also points to the effect of specific antimicrobial therapy for infection caused by the bacterium Clostridium difficile and the possibility of using fecal bacteriotherapy.Copyright © 2023

Syphilis: "The Great Imitator" Presenting as Acute Hepatitis

Introduction: Syphilis is a multi-systemic disease caused by spirochete Treponema pallidum. Very rarely, it can affect the liver and cause hepatitis. Since most cases of hepatitis are caused by viral illnesses, syphilitic hepatitis can be missed. Here, we present a case of syphilitic hepatitis in a 35-year-old male. Case Description/Methods: Patient was a 35-year-old male who presented to the hospital for jaundice and mild intermittent right upper quadrant abdominal pain. His medical history was only significant for alcohol abuse. His last drink was 4 weeks ago. He was sexually active with men. On exam, hepatomegaly, mild tenderness in the right upper quadrant, jaundice, and fine macular rash on both hands and feet were noted. Lab tests revealed an ALT of 965 U/L, AST of 404 U/L, ALP of 1056 U/L, total bilirubin of 9.5 mg/dL, direct bilirubin of 6.5 mg/dL, INR of 0.96, and albumin of 2.0 g/dL. Right upper quadrant ultrasound showed an enlarged liver but was negative for gallstones and hepatic vein thrombosis. MRI of the abdomen showed periportal edema consistent with hepatitis without any gallstones, masses, or common bile duct dilation. HIV viral load and Hepatitis C viral RNA were undetectable. Hepatitis A & B serologies were indicative of prior immunization. Hepatitis E serology and SARS-CoV-2 PCR were negative. Ferritin level was 177 ng/mL. Alpha-1-antitrypsin levels and ceruloplasmin levels were normal. Anti-Smooth muscle antibody titers were slightly elevated at 1:80 (Normal < 1:20). Anti-Mitochondrial antibody levels were also slightly elevated at 47.9 units (Normal < 25 units). RPR titer was 1:32 and fluorescent treponemal antibody test was reactive which confirmed the diagnosis of syphilis. Liver biopsy was then performed which showed presence of mixed inflammatory cells without any granulomas which is consistent with other cases of syphilitic hepatitis. Immunohistochemical stain was negative for treponemes. Patient was treated with penicillin and did have Jarisch-Herxheimer reaction. ALT, AST, ALP, and total bilirubin down trended after treatment. Repeat tests drawn exactly 1 month post treatment showed normal levels of ALT, AST, ALP, and total bilirubin (Figure). Discussion(s): Liver damage can occur in syphilis and can easily be missed because of the non-specific nature of presenting symptoms. In our patient, the fine macular rash on both hands and feet along with history of sexual activity with men prompted us to test for syphilis which ultimately led to diagnosis and treatment in a timely manner. (Figure Presented).

Antibiotics in Paediatrics: A Boon or a Bane?

Antibiotics play an essential role in antimicrobial therapy. Among all the medications in children, the most commonly prescribed therapy is antibiotics and is currently the indispensable means to cure transmissible diseases. Several categories of antibiotics have been introduced into clinical practice to treat microbial infections. Reducing the unnecessary use of antibiotics is a global need and priority. This article aims to provide better knowledge and understanding of the impact of the early use of antibiotics. This article highlights the proper use of antibiotics in chil-dren, detailing how early and inappropriate use of antibiotics affect the gut microbiome during normal body development and consequently affect the metabolism due to diabetes mellitus, obe-sity, and recurrence of infections, such as UTI. Several new antibiotics in their development stage, newly marketed antibiotics, and some recalled and withdrawn from the market are also briefly discussed in this article. This study will help future researchers in exploring the latest information about antibiotics used in paediatrics.Copyright © 2023 Bentham Science Publishers.

Outcomes of coblation tonsillectomy versus bipolar electrocautery tonsillectomy in pediatric population

Background: Bipolar electrocautery tonsillectomy has been the preferred technique for many otolaryngologists, yet coblation tonsillectomy is gaining popularity in the current practice. This study aims at comparing both techniques in terms of pain, bleeding, and healing. Result(s): A total of 120 patients were randomly divided into two equal groups. Overall mean pain score associated with coblation tonsillectomy was statistically less than that caused by bipolar electrocautery throughout the follow-up period (p < 0.001). The difference in pain duration was statistically longer for the bipolar group. The incidence of postoperative hemorrhage-both reactionary and secondary-was statistically higher in the bipolar group. Coblation tonsillectomy showed statistically shorter duration of healing (p < 0.001). Conclusion(s): Coblation tonsillectomy is associated with less pain severity and shorter pain duration, fewer bleeding incidents, and more prompt healing.Copyright © 2022, The Author(s).

Detection of blaZ and mecA genes and antimicrobial susceptibility in Staphylococcus aureus colonizing multipurpose boxes of dentistry students

Cross-contamination between patient and dentist is a real threat that has not been adequately studied. Staphylococcus aureus, through its characteristic genetic plasticity, has managed to develop multiple virulence and antibiotic resistance proteins. The antibiotic susceptibility profile and the presence of the blaZ and mecA genes that encode resistance to penicillin and methicillin, respectively, were analyzed in strains isolated from multipurpose boxes used by dental students at the Catholic University of Cuenca. These boxes are used to transport instruments and material. From the universe of study (249 boxes) 139 samples were obtained from boxes of the students who accepted and signed a consent to participate. Eight strains of S. aureus were identified, of which, through antibiogram analysis, it was found that seven were resistant to penicillin and two strains resistant to cefoxitin (MRSA strains). In molecular analysis, the mecA gene was identified in two strains, while the blaZ gene was found in all of them. It was concluded that the rate of S. aureus found in this study was low due to various factors, possibly including increased vigilance and cleanliness due to the COVID-19 pandemic during the study. © FUNPEC-RP www.funpecrp.com.br.

Consumption of systemic antibiotics in the Russian Federation in 2017-2021.

Objective. To assess level and the structure of systemic antibiotic consumption in Russia over the period 2017 to 2021. Materials and methods. Data were collected and analysed in compliance with the standard protocol of the World Health Organization Regional Office for Europe by the means of ATC/DDD methodology for J01 group - antibacterials for systemic use. Consumption was calculated for outpatients and inpatients separately as a number of DDDs per 1000 inhabitants per day (DID) for the main classes of antibiotics and the agents with the highest or the most diverse consumption levels for the given period of time, and was based on the data of wholesale purchases and public tenders. Results. Antibiotic consumption in Russia in 2017, 2018, 2019, 2020, and 2021 was 16.6 DID, 14.3 DID, 14.8 DID, 19 DID, and 15.7 DID respectively. Penicillins, macrolides and lincosamides, and quinolones had the highest levels of consumption in outpatients. Prominent increase in outpatient consumption of antibacterials in 2020 was related to three agents: azithromycin, levofloxacin and ceftriaxone. Cephalosporins (mainly III-V generations), quinolones and penicillins had the highest levels of consumption in inpatients. Hospital consumption of meropenem, tigecycline, and vancomycin increased and amikacin and ciprofloxacin decreased over the duration of the study. Conclusions. Levels of systemic antibiotic consumption in Russia for the period 2017 to 2019 were relatively low and consistent with the average means for European Union and European Economic Area countries. The steep increase in consumption in 2020 was probably due to the wide use of antibiotics for the management of COVID-19 patients. The results of the study can be of value for the development of targeted national antibiotic stewardship programs and awareness campaigns as well as for the analysis of trends of emergence and spread of antibiotic resistance.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

SG-APSIC1096: Changes in resistance patterns of "ESKAPE” pathogens to azithromincin and levofloxacin in Yogyakarta

Objectives: Bacterial coinfection occurred in 3.5% of COVID-19 patients, and secondary bacterial infection occurred in 14.3% of patients. In Indonesia, one of the guidelines for COVID-19 therapy is to administer azithromycin 500 mg per 24 hours for mild and moderate cases and azithromycin 500 mg per 24 hours and levofloxacin 750 g per 24 hours for severe cases with suspected secondary bacterial infection. At the beginning of the pandemic, many antibiotics were used, even without proven or suspected bacterial infection. We sought to determine changes in the resistance of "ESKAPE” bacteria (ie, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp) to the antibiotics levofloxacin and azithromycin prior to and during the COVID-19 pandemic. Methods: The study was conducted retrospectively by examining the culture and sensitivity test results of "ESKAPE” bacteria to levofloxacin and azithromycin antibiotics in 2019 (before the pandemic) and April 2020–April 2021 (during the pandemic) in 4 hospitals in Yogyakarta. The number of samples represents all cultures completed within the specified period to detect antibiotic sensitivity patterns. Results: In a top referral hospital, resistance to levofloxacin and azithromycin increased significantly for E. faecium and P. aeruginosa, but at a private hospital, an increase in resistance to azithromycin and levofloxacin occurred for A. baumannii and for Enterobacter spp and resistance to levofloxacin increased significantly. At an academic hospital, there was a considerable decrease in S. aureus and E. faecium resistance to levofloxacin and azithromycin. At the government hospital, S. aureus, K. pneumoniae, P. aeruginosa, Acinetobacter baumannii, and Enterobacter spp developed resistance to levofloxacin. Conclusions: Resistance to azithromycin and levofloxacin by different ESKAPE bacteria increased on average during the COVID-19 pandemic.

Antibiotic Use in Acute Upper Respiratory Tract Infections

Upper respiratory tract infections are responsible for millions of physician visits in the United States annually. Although viruses cause most acute upper respiratory tract infections, studies show that many infections are unnecessarily treated with antibiotics. Because inappropriate antibiotic use results in adverse events, contributes to antibiotic resistance, and adds unnecessary costs, family physicians must take an evidence-based, judicious approach to the use of antibiotics in patients with upper respiratory tract infections. Antibiotics should not be used for the common cold, influenza, COVID-19, or laryngitis. Evidence supports antibiotic use in most cases of acute otitis media, group A beta-hemolytic streptococcal pharyngitis, and epiglottitis and in a limited percentage of acute rhinosinusitis cases. Several evidence-based strategies have been identified to improve the appropriateness of antibiotic prescribing for acute upper respiratory tract infections.Copyright © 2022 American Academy of Family Physicians.

Clinico-Epidemiological Profile of Cutaneous Adverse Drug Reactions at Rural Tertiary Care Centre

Background: Cutaneous adverse drug reactions (CADRs), also known as toxidermia, are skin manifestations resulting from systemic drug administration and it constituted 10%-30% among all reported adverse drug reactions (ADRs). These reactions range from mild morbilliform drug rash to much more severe reactions. Material(s) and Method(s): A retrospective observational study was conducted at dermatology outpatient department of rural based tertiary care center for a duration of 03 years from August 2019 to July 2022, a total of 211 patients who had been clinically diagnosed or were suspected to have drug reactions were studied. Result(s): In this observation there was male preponderance (59.72%) and majority of patients were in their 3rd and 4th decade (40.28%) with maculopapular drug rash (33.17%) being most common clinical profile of CADRs, followed by urticaria (23.70%). Less frequently seen CADRs were acneiform eruptions (21), hair Loss (9), photodermatitis (9), generalised pruritus (7), erythroderma (2), pityriasis rosea (2), Stevens Johnson Syndrome-Toxic Epidermal Necrolysis (SJS-TEN) (4), lichenoid drug eruptions (3), Vasculitis (1) and pustular drug eruption (1). The most common group of drugs causing CADRs were antibiotics (40.28%), followed by NSAIDs (28.43%). Conclusion(s): Cutaneous Adverse Drug Reactions (CADRs) are price we pay for the benefits of modern drug therapy;knowledge of these reactions is important for treating physician as prompt recognition and treatment can prove lifesaving.Copyright © 2022 Academic Medicine and Pharmacy

Identification of Multi Drug Resistant Bacteria from Drinking Water Samples - A Microbial Survey

Antimicrobial resistance may result from rising resistance patterns of commercially available antibiotics, which is one of the most serious threats to global health and should not be overlooked while the world is focused on the COVID-19 disaster. Waterborne resistant bacteria have been shown to be capable of spreading to people in a lot of circumstances, particularly crowded places in urban living environment with heavy human behavior, such as drinking in public systems and swimming pools. Four hundred drinking water samples were collected from different zones in district Lahore, Pakistan. Multidrug resistance bacterial strains of waterborne pathogens have been isolated and characterized on the basis of colony characteristics, microscopic visuality and biochemical tests. The outcomes of this project revealed that Staphylococcus aureus was (26%), Escheria coli was (45%), Salmonella typhi (15%), Shigella dysenteriae (10%) and Enterococcus faecalis (4%) in district Lahore, Pakistan. These multidrug resistance bacteria showed high resistant patterns against amoxicillin, penicillin, streptomycin, tetracycline, erythromycin, gentamycin, amikacin whereas susceptible for chloramphenicol, cefixime, ofloxacin and ciprofloxacin. The prevalence of associated risk factors such as polluted drinking water (32%), children<5year age (22%), adults >45year age (18%), excessive use of antibiotics (8%), health status of individual (5%), smoking habits (6%), and emotional variables (6%) were observed in this research. These investigations have demonstrated infectious bacterial contamination in surface and groundwater, which caused significant bowel syndrome.Copyright © 2022 Indian Veterinary Assocaition. All rights reserved.

Virtually supported penicillin allergy de-labelling during COVID-19.

BACKGROUND: Penicillin allergy is a commonly listed medication allergy despite rare overall incidence. Many patients erroneously have this label, which has personal, health, and societal costs. Penicillin allergy delabelling requires an oral challenge, which can be a rate limiting step in the de-labeling process; this is even more relevant with the reduction of in-person visits during the COVID-19 pandemic. OBJECTIVE: To identify the utility and broader applicability of using a virtually supported platform, initially adopted given COVID-19 restrictions, to expedite penicillin oral provocation challenge and penicillin de-labeling in patients at low to moderate risk of immediate hypersensitivity reaction and based on shared decision making. METHODS: Patients in Vancouver catchment area were referred for penicillin allergy and virtually assessed by the consulting allergist between July 2020 and April 2021. Those deemed appropriate for oral challenge based on the allergist consultant were offered the option of a virtual oral provocation challenge to oral amoxicillin in a subsequent virtual visit. Patients who agreed and were consented underwent a virtually supervised oral amoxicillin challenge during the second virtual visit. Findings are summarized in this case series. RESULTS: Twenty-three patients, both adult and pediatric, ranging from no to significant co-morbidities were consented and underwent the virtual challenge. One hundred percent of patients were successful with no reaction after an hour post virtual oral provocation challenge with amoxicillin. CONCLUSION: Virtual medicine is likely to remain in the allergist's practice. Virtually supported penicillin allergy delabelling, based on shared decision making and risk stratification, presents another pathway for penicillin allergy delabelling.

Distribution of Multidrug-Resistant Invasive Serotypes of Streptococcus pneumoniae during the Period 2007-2021 in Madrid, Spain.

After the systematic use of conjugate vaccines, the invasive pneumococcal disease (IPD) was included into the Madrid Notifiable Diseases Surveillance System through an Epidemiological Surveillance Network. Furthermore, Streptococcus pneumoniae was included in the Spanish Plan of Antibiotic Resistance. The aim of this study was to analyse the multidrug-resistant (MDR) phenotype distribution among invasive strains of Streptococcus pneumoniae isolated during 2007-2021 from usually sterile clinical samples in Madrid, Spain. A total number of 7133 invasive pneumococcal isolates were studied during the period from February 2007 to December 2021. Serotyping was characterised using the Pneumotest-Latex and by the Quellung reaction. Antibiotic susceptibility testing to penicillin (PEN), erythromycin (ERY), and levofloxacin (LVX) was performed using the E-test according to the EUCAST guidelines and breakpoints. Combination of non-susceptibility to PEN at standard dosing regimen (PNSSDR), resistance to ERY (ERYR) and to LVX (LVXR) was considered to be multidrug-resistant at standard dosing regimen of penicillin (MRPSDR), whereas the combination of resistance to PEN (PENR), ERYR, and LVXR was considered multidrug-resistant (MDR). The number of MDRPSDR and or MDR strains in the entire population (n = 7133) during the complete period (2007-2021) were 51 (0.7%) and 6 (0.1%), respectively. All MDRPSDR and/or MDR strains belonged to nine serotypes: 19A (n = 13), 15A (n = 12), 9V (n = 12), 14 (n = 7), 24F (n = 3), 15F (n = 1), 19F (n = 1), 6B (n = 1) and 6C (n = 1). Only two serotypes (9V and 19A) were found among MDR strains, and most of them (5/6) belonged to serotype 9V. Only 12.4% of the strains typified as serotype 9V were MDRPSDR and only 5.2% as MDR. The levels of pneumococcal MDRPSDR and/or MDR in this study were low and all six MDR strains were isolated between 2014 and 2018. These results reinforce the importance of monitoring the evolution of non-susceptible serotypes including those with MDR in the coming years, especially after the introduction of new conjugate vaccines of a broader spectrum.

Macrophage membrane-biomimetic adhesive polycaprolactone nanocamptothecin for improving cancer-targeting efficiency and impairing metastasis

The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. Numerous synthetic nanoparticles have been developed for pharmaceutical delivery and cancer treatment. However, only a limited number of nanotherapies have enter clinical trials or are clinically approved. Systemically administered nanotherapies are likely to be sequestered by host mononuclear phagocyte system (MPS), resulting in suboptimal pharmacokinetics and insufficient drug concentrations in tumors. Bioinspired drug-delivery formulations have emerged as an alternative approach to evade the MPS and show potential to improve drug therapeutic efficacy. Here we developed a biodegradable polymer-conjugated camptothecin prodrug encapsulated in the plasma membrane of lipopolysaccharide-stimulated macrophages. Polymer conjugation revived the parent camptothecin agent (e.g., 7-ethyl-10-hydroxy-camptothecin), enabling lipid nanoparticle encapsulation. Furthermore, macrophage membrane cloaking transformed the nonadhesive lipid nanoparticles into bioadhesive nanocamptothecin, increasing the cellular uptake and tumor-tropic effects of this biomimetic therapy. When tested in a preclinical murine model of breast cancer, macrophage-camouflaged nanocamptothecin exhibited a higher level of tumor accumulation than uncoated nanoparticles. Furthermore, intravenous administration of the therapy effectively suppressed tumor growth and the metastatic burden without causing systematic toxicity. Our study describes a combinatorial strategy that uses polymeric prodrug design and cell membrane cloaking to achieve therapeutics with high efficacy and low toxicity. This approach might also be generally applicable to formulate other therapeutic candidates that are not compatible or miscible with biomimetic delivery carriers. © 2022 The Authors

Massive empyema due to Lactococcus garvieae

Introduction Lactococcus garvieae, a zoonotic pathogen, may rarely infect humans through the consumption of fish. Documented manifestations of L. garvieae infection in humans include infective endocarditis, prosthetic joint infections, liver abscesses, peritoneal dialysis-associated peritonitis, osteomyelitis, meningitis, infective spondylodiscitis, acalculous cholecystitis, and urinary tract infection. Case report An 87-year-old female was hospitalized for coffee-ground emesis secondary to acute gastritis after eating cooked fish. One week after her discharge, she developed new-onset confusion and was returned to the hospital. Chest computed tomography revealed total consolidation of the left lung and a multiloculated left pleural effusion. The patient required intubation and direct admission to the intensive care unit. Pleural fluid and blood cultures grew L. garvieae, which was susceptible to ceftriaxone, penicillin, and vancomycin. Despite intensive antibiotic therapy and supportive care for thirteen days, the patient remained in irreversibl e shock, and the family opted for comfort care. Conclusions Heretofore unreported, this case demonstrates that L. garvieae can cause bronchopneumonia and empyema. Copyright © GERMS 2022.

Tsukamurella and mycobacterium tuberculosis pneumonia co-infection

Case Report: Tsukamurella species are aerobic, partially acid fast saprophytes commonly isolated from soil and water. They are opportunistic pathogens known to infect multiple organs and can contribute to significant pathologies such as bacteremia, peritonitis, and respiratory tract infections. Moreover, Tsukamurella shares certain characteristic properties to Mycobacterium tuberculosis and Actinomyces species, including the acid fast stain, which can contribute to misdiagnosis of patients. A 68 year old female patient presented to the ED for shortness of breath, fatigue, and weight loss for 6 months. The patient's past medical history includes pulmonary fibrosis, type 2 diabetes, coronary artery disease with stent, hyperlipidemia, hypertension, and M. tuberculosis infection when she was 3 years old in Finland. On admission, labs revealed thrombocytosis (reactive 555 000/microL), leukocytosis (14 450/microL), and microcytic anemia (9.4 microg/dl). Moreover, C reactive protein was elevated and procalcitonin was normal (0.06 microg/l);a COVID-19 PCR was negative. An X-ray revealed severe patchy and interstitial infiltrates throughout both lungs with parenchymal scarring and pleural thickening in the periphery of the left mid-lung zone with multifocal pneumonia. Blood and sputum cultures were performed under the impression of pneumonia, and treatment with azithromycin and ceftriaxone was started. A M. tuberculosis infection was suspected due to a positive AFS. Further chest CT suggested multifocal pneumonia within the left lung in addition to apparent cavitary lesions versus bulla, a chronic interstitial lung disease with traction bronchiectasis, calcified right lower lung nodule, and calcified hilar lymph nodes suggesting a history of granulomatosis diseases. A bronchoscopy with Bronchoalveolar lavage was performed. The initial sputum specimen direct smear showed acid-fast stain positive with Actinomyces growth, and Penicillin G was added to the treatment. Samples were sent to the state department lab, and biopsy revealed granulomatous inflammation negative for malignant cells. One month later, the patient's sputum culture showed Tsukamurella for High-performance liquid chromatography (HPLC). Moreover, a rifampicin sensible M. tuberculosis complex by NAA was also positive six weeks later. The patient was started on a complete TB regimen and continued in the outpatient pulmonology clinic with the addition of levofloxacin for three months and rifampicin substituted for rifabutin. As demonstrated in the case above, a Tsukamurella infection can present similarly to a Mycobacterium infection. Patients may be misdiagnosed or potentially be co-infected. Our patient was further tested and appropriately treated for Tsukamurella after further extensive diagnostic screenings. Due to a high rate of missed cases, it is important to keep Tsukamurella infection on the differential diagnosis as the patient presentation may initially appear to be a Mycobacterium or other pulmonary infection. Copyright © 2023 Southern Society for Clinical Investigation.