Acute Lymphoblastic Leukemia Presenting as Pituitary Apoplexy: A Case Report and Review of the Literature

Thrombocytopenia as a precipitating factor for pituitary apoplexy (PA) is very rare event. There are only five reported cases of PA secondary to thrombocytopenia caused by underlying haematological malignancy. Herein, we report a case of 60-year-old male presenting with acute-onset headache, bilateral vision loss, and ptosis. Computed tomography and magnetic resonance imaging revealed findings indicative of pituitary adenoma with apoplexy. He was noted to have thrombocytopenia, and bone marrow evaluation revealed precursor B-lineage CALLA-positive acute lymphoblastic leukemia. Accordingly, he was started on dexamethasone and vincristine but succumbed to Acinetobacter baumanii-related hospital-acquired pneumonia two weeks after initiation of chemotherapy. We performed a literature search and found five cases of pituitary apoplexy secondary to haematological malignancy-related thrombocytopenia. The usual age of presentation was in the 6th to 7th decade, and there was slight male preponderance. The underlying pituitary adenoma was either nonfunctioning or a prolactinoma, and in majority, the apoplexy event occurred after the diagnosis of haematological malignancy. The platelet counts at the time of PA were less than 30 × 109/L in all, and the malignancy subtypes were acute or chronic myeloid leukemia and chronic lymphoid leukemia. The current case highlights the importance of careful evaluation for the cause of thrombocytopenia in a case of PA.

ĐẶC ĐIỂM LÂM SÀNG VÀ CẬN LÂM SÀNG ÁP XE TRUNG THẤT DO THỦNG THỰC QUẢN ĐIỀU TRỊ TẠI BỆNH VIỆN VIỆT ĐỨC

Đặt vấn đề: Áp xe trung thất (AXTT) là nhiễm khuẩn nặng, nguy cơ tử vong cao, nguyên nhân do bệnh lý nhiễm khuẩn miệng, họng, đặc biệt liên quan đến tổn thương thực quản (TQ). Mục đích nghiên cứu chúng tôi mô tả một số đặc điểm lâm sàng và cận lâm sàng giúp cho chẩn đoán bệnh. Đối tượng và phương pháp nghiên cứu: Nghiên cứu tiến cứu các trường hợp chẩn đoán AXTT do tổn thương TQ được điều trị tại Bệnh viện Việt Đức từ 1/2016 đến 10/2019, bao gồm các trường hợp tử vong và nặng về. Chẩn đoán theo tiêu chuẩn của Estrera (1983), phân loại theo Endo S (1999). Kết quả: Tổng số có 40 trường hợp, tuổi trung bình: 48,5 ± 17,74 tuổi, nam giới chiếm 82,5 %. Nguyên nhân tổn thương TQ do chấn thương chiếm 70%, chủ yếu hóc xương; do bệnh lý 30%, trong đó hội chứng Boerhaave chiếm 62,5%. Vị trí tổn thương hay gặp nhất ở 1/3 trên (TQ cổ) chiếm 65%, TQ ngực (1/3 giữa) chiếm 15 %, và TQ ngực (1/3 dưới) 20%. Phân độ theo Endo: type I 28 bệnh nhân chiếm 70%, không có type IIa, type IIb có 12 trường hợp, chiếm 30%. Dấu hiệu lâm sàng chính: nuốt đau 35%, đau ngực 42,5%, sốt và khó thở 75%. Khám tại chỗ: Đau máng cảnh 47,5%, mất lọc cọc thanh quản – cột sống 52,5%, tràn khí dưới da 50%. Hình ảnh X quang: CLVT có độ nhạy và đặc hiệu cao, 54,6% hình ảnh thâm nhiễm, 50% hình khí hơi trung thất (type I); Ổ giảm tỷ trọng ở trung thất 100%, mủ màng phổi 83,3%, hơi khí trung thất 100% (type II). 25/40 trường hợp phân lập được vi khuẩn/nấm (62,5%). Vi khuẩn Gram (+) phổ biến Streptococcus species (44%) Enterococcus faecalis (24%) Vi khuẩn Gram (-) phổ biến Acinetobacter Baumanii (24%) Klebsiella pneumonie (12%), Pseudomonas aeruginosa (8%). Nấm: Phân lập được 6/24 chiếm 25%. Kết luận: Áp xe trung thất do tổn thương thực quản là biến chứng nhiễm khuẩn nặng, cần được chẩn đoán sớm để có thái độ xử lý kịp thời. Nghiên cứu đặc điểm AXTT do tổn thương TQ qua những dấu hiệu điển hình trên lâm sàng, X quang cũng như vi khuẩn giúp cho phẫu thuật viên đưa ra chiến lược điều trị sớm và phù hợp.

Reducing Biofilm Infections in Burn Patients’ Wounds and Biofilms on Surfaces in Hospitals, Medical Facilities and Medical Equipment to Improve Burn Care: A Systematic Review

Biofilms in burns are major problems: bacterial communities rapidly develop antibiotic resistance, and 60% of burn mortality is attributed to biofilms. Key pathogens are Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and multidrug-resistant Acinetobacter baumanii. Purpose: identify current and novel interventions to reduce biofilms on patients’ burns and hospital surfaces and equipment. Medline and Embase were searched without date or language limits, and 31 possible interventions were prioritised: phages, nano-silver, AgSD-NLs@Cur, Acticoat and Mepilex silver, acetic acid, graphene-metal combinations, CuCo2SO4 nanoparticles, Chlorhexidene acetate nanoemulsion, a hydrogel with moxifloxacin, carbomer, Chitosan and Boswellia, LED light therapy with nano-emodin or antimicrobial blue light + Carvacrol to release reactive oxygen species, mannosidase + trypsin, NCK-10 (a napthalene compound with a decyl chain), antimicrobial peptide PV3 (includes two snake venoms), and polypeptides P03 and PL2. Most interventions aimed to penetrate cell membranes and reported significant reductions in biofilms in cfu/mL or biofilm mass or antibiotic minimal inhibitory concentrations or bacterial expression of virulence or quorum sensing genes. Scanning electron microscopy identified important changes in bacterial surfaces. Patients with biofilms need isolating and treating before full admission to hospital. Cleaning and disinfecting needs to include identifying biofilms on keyboards, tablets, cell phones, medical equipment (especially endoscopes), sinks, drains, and kitchens.

Effect of Ocimum Sanctum Bio Compounds against csuE Gene Protein of Acinetobacter baumanii

Background: Acinetobacter baumannii is a Gram-negative bacillus that is aerobic, pleomorphic and non-motile. Multi-drug resistance and biofilm formation contributes to the virulence and pathogenicity of the bacterium. Among many virulence factors, csuE is critical for initiation and assembly, showing much homology to type 1 and P pili. With much propensity of drug resistance, in recent years alternative medications have spurred renewed interest in targeting potent pathogens. Ocimum sanctum, also known as holy basil or tulsi possess various bio-active properties and can be used as alternative medicine to treat systemic ailments. Aim: This study was aimed to analyze the drug-ligand interactions between csuE protein of A. baumannii and the bio-compounds from O.sanctum using in-silico docking analysis. Material and Methods: csuE protein was retrieved and optimisation of protein was done. Ligands were selected and were assessed for drug likeness using molinspiration parameters. Further the compounds were subjected for docking analysis and the interacted molecules were visualized for binding energy and hydrogen bonds. Results: Out of the 9 compounds of Ocimum sanctum, benzofuran showed good interaction with csuE protein of Acinetobacter baumannii with a least docking energy of -5.31Kcal/Mol. Conclusion: The present study recommends benzofuran as the potent candidate for novel drug design to treat the infections caused by A.baumannii upon further evaluations for its safety and immunological response.

Molecular detection of blaOXA-23gene and blaOXA-51 gene in carbapenem resistant strains of Acinetobacterbaumannii in patients with ventilator associated pneumonia at tertiary care hospital

Objective: To evaluate carbapenem resistance and to detect blaOXA-23 and blaOXA-51 genes in carbapenem-resistant acinetobacter baumanii isolates recovered from patients having pneumonia secondry to ventilation. Methods: The cross-sectional study was conducted from July 2017 to June 2018 at the Department of Microbiology, University of Health Sciences, Lahore, Pakistan, and comprised endotracheal aspirates / tracheobroncheal lavage samples from patients irrespective of age and gender who developed pneumonia after being on the ventilator for 48 hrs at the Combined Military Hospital, and Jinnah Hospital, Lahore. The samples were inoculated on MacConkey and blood agar and aerobically incubated at a temperature of 370C for 18-24 hours. The isolated organisms were further assessed by standard morphological, cultural and biochemical profile. Antibiotic susceptibility was done by Kirby-Bauer disc diffusion method. Carbapenem-resistant acinetobacter baumannii were checked for carbapenemase production using Modified Hodge Test. Conventional polymerase chain reaction and agarose gel electrophoreses were performed to detect blaOXA-23 and blaOXA-51 genes. Data was analysed using SPSS 17. Results: Out of 157 samples, 92(58.6%) yielded growth of bacteria, and, among them, 39(42.4%) were identified as acinetobacter baumannii. All (100%) acinetobacter baumannii cases showed resistance to carbapenem, were producing carbapenemase enzyme, and were positive for blaOXA-51 gene. The blaOXA-23 gene was amplified in 38(97.4%) isolates. Conclusion: BlaOXA-23 gene appeared to be the major cause of carbapenem resistance. Continuous...

A Prospective Study on Neonatal Sepsis in a Tertiary Hospital, Nepal

About 20 % of neonates develop sepsis and among them approximately 1% die due to sepsis-related causes. Bacterial pathogens are the commonest cause of neonatal sepsis which is either early-onset (<72 hours of age) or late-onset (>72 hours). Little is known about the epidemiology and antimicrobial susceptibility pattern of sepsis causing bacterial pathogens in Nepal. A prospective study was carried out among neonates suspected to have sepsis and admitted to Tribhuwan University Teaching Hospital from January to December 2016. Clinical suspicion of sepsis was made based on clinical findings and laboratory parameters, later confirmed by isolation of organisms in blood culture. Drug resistance pattern of Gram-positive and Gram-negative bacteria were studied by standard methods. Meropenem resistant Gram-negative bacteria were processed for the detection of β-lactamases and resistant genes were detected by X-pert Carba-R (Cepheid) Assays. Of 372 neonates with clinically suspected sepsis, 132 (35.4%) had blood culture positivity, with 47% early-onset and 53% late-onset sepsis. Coagulase-negative Staphylococcus aureus (CONS) was the most common (37.9%) etiological agent followed by Klebsiella pneumoniae (12.9%). Of all 132 isolates, 81 (61.3%) were Gram-positive of which 22 (27.2%) were multi-drug resistant (MDR), three (3.7%) were methicillin-resistant S. aureus (MRSA), and 14 (17.2%) were methicillin-resistant CoNS; and 50 (37.8%) were Gram-negative of which 26 (52%) were MDR and 29 (58%) were resistant to β-lactamases. The blaKPC gene was detected in four isolates of K. pneumoniae, two of E. coli, one ABC (Acinetobacter baumanii complex), and one Enterobacter aerogenes whereas blaNDM gene was detected in one isolate of K. pneumoniae, two of E. coli, two Pseudomonas aeruginosa, one Acinetobacter baumanii complex, and one Enterobacter aerogenes. Overall mortality due to sepsis-related causes was 7.6% (10 of 132). One-third of clinically suspected neonatal sepsis cases were culture positive. Late-onset sepsis was more common than early onset. CoNS was the predominant bacterial isolate followed by Klebsiella pneumoniae, with high rates of multi-drug resistance.

Rational prioritization strategy allows the design of macrolide derivatives that overcome antibiotic resistance

Antibiotic resistance is a major threat to global health; this problem can be addressed by the development of new antibacterial agents to keep pace with the evolutionary adaptation of pathogens. Computational approaches are essential tools to this end since their application enables fast and early strategical decisions in the drug development process. We present a rational design approach, in which acylide antibiotics were screened based on computational predictions of solubility, membrane permeability, and binding affinity toward the ribosome. To assess our design strategy, we tested all candidates for in vitro inhibitory activity and then evaluated them in vivo with several antibiotic-resistant strains to determine minimal inhibitory concentrations. The predicted best candidate is synthetically more accessible, exhibits higher solubility and binding affinity to the ribosome, and is up to 56 times more active against resistant pathogens than telithromycin. Notably, the best compounds designed by us show activity, especially when combined with the membrane-weakening drug colistin, against Acinetobacter baumanii, Pseudomonas aeruginosa, and Escherichia coli, which are the three most critical targets from the priority list of pathogens of the World Health Organization.

1278. Testing the Synergistic Effect of Ceftazidime-Avibactam Plus Aztreonam on Metallobetalactamase-Producing Non-Fermenting Gram-negative Bacteria

Background Metallo-betalactamases (MBL) are rapidly becoming a more widespread form of antimicrobial resistance. MBL are class B betalactamases that use zinc rather than serine in their active site and are only inactivated by monobactams, such as aztreonam. Unfortunately, most MBL-producing organisms also produce aztreonam-inactivating beta-lactamases. Synergy between ceftazidime-avibactam and aztreonam is well documented for MBL-producing Enterobacteriaceae but has not been tested extensively in non-fermenting Gram-negative bacteria. This study evaluates the susceptibilities of non-fermenting Gram-negative bacteria via E-test to this combination in vitro, in order to provide support for use to treat infections from these organisms. Methods The antibiotic combination ceftazidime-avibactam+aztreonam was tested against a total of 33 isolates, including MBL-producing Pseudomonas aeruginosa, Pseudomonas putida, and the intrinsically aztreonam resistant Acinetobacter baumanii using the E-test method. MBL-producing Enterobacteriaceae were included as positive controls. All isolates were also tested against ceftazidime alone, aztreonam alone, and ceftazidime-avibactam. Bacterial isolates were procured from the Multidrug-resistant organism Repository & Surveillance Network at the Walter Reed Army Institute of Research. Antimicrobial resistance genes were previously identified by whole genome sequencing Results Of 13 Pseudomonas spp. isolates tested, 9 were resistant, 3 were intermediate, and 1 was susceptible to aztreonam. Synergistic testing of ceftazidime-avibactam+aztreonam reduced the MIC of 4 Pseudomonas isolates by 1-2 doubling dilutions. While Acinetobacter spp. are usually considered intrinsically resistant to aztreonam, synergistic testing of ceftazidime-avibactam+aztreonam reduced the MIC of all 12 isolates tested by 1 to 3 doubling dilutions. Conclusion The ability of ceftazidime-avibactam+aztreonam to reduce the MICs of Acinetobacter baumanii and MBL-producing Pseudomonas aeruginosa is a potentially promising therapeutic option when faced with growing antimicrobial resistance. Disclosures All Authors: No reported disclosures

The Immunomodulatory Activity in vitro of NDV ZG1999HDS in Comparison to NDV La Sota

ABSTRACT. The immunotherapies, as a modern therapeutic approach, get an attention because of theirs&rsquo; promise to treat a large number of different medical disorders. Immunomodulation effects of low titres (10 HA/ml) of NDV (Newcastle Disease Virus) ZG1999HDS or La Sota were tested on TLT (Human macrophage cell line) bound to PBMC (Peripheral Blood Mononuclear Cells). During the immunomodulation, the amount of NO, H2O2, lysozym and induced antibacterial activity against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) and against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) were analysed. In addition, the cytokine secretion, IL-1&alpha;, IL-2, IL-4, GM-CSF, TNF-&alpha;, IFN-&alpha; and IFN-&alpha; were evaluated. Firstly, the TLT cells are activated through the NDV ZG1999HDS or La Sota binding, followed by the NO &ldquo;burst&rdquo; and H2O2 and lysozyme level increase. Secondly, after the binding to the TLT cells and interaction with the PBMCs, the decrease of GM-CSF, and an increase of TNF &ndash; &alpha; and IFN &ndash; &gamma; were found. Simultaneously, the decrease of pro &ndash; inflammatory cytokine IFN-&alpha; and the differentially increase of IL-1&alpha;, IL-2 and IL-4 were recorded. During the induction of the antibacterial response, against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) the effect was one third higher with NDV ZG1999HDS compared to La Sota. Antibacterial response against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) was not so clear. In general, NDV ZG1999HDS or La Sota activated TLT cells, further bound to PBMC; the ZG1999HDS is stronger immunomodulator than La Sota.

P006 MICROBIOLOGY OF CHRONIC MESH INFECTION

Aim Mesh infection represents a significant concern due to its terrible consequences. Mesh sinus, infected seromas, mesh extrusion, and mesh-related enteric fistulas are common complications associated with synthetic mesh. This study aimed to review the microbiota of mesh infection in a series of 100 patients submitted to mesh explantation. Material and Methods We reviewed the charts of patients presenting with a history of mesh infection lasting six months or more after mesh placement. All patients submitted to further abdominal wall repair with complete removal of the infected mesh and presenting a positive culture were included. The microbiota analysis was based on positive cultures obtained from the fluids and tissues surrounding the mesh or a positive culture of the mesh itself. Microorganisms were divided into gram-positive or gram-negative, aerobic or anaerobic, and fungi. Results Pure aerobic gram-positive cultures were encountered in 50% of the patients, followed by a combination of aerobic gram-positive/gram-negative (9%) and pure gram-negative cultures (6%). Anaerobes were recovered from 31% of patients. Fungi were recovered from 6%. Staphylococcus aureus was identified in 64% of cultures, with methicillin-resistant Staphylococcus aureus present in 42% and methicillin-sensitive Staphylococcus aureus in 22%. Among aerobic gram-negative infections, six (17%) were caused by multi-resistant bacteria, including Pseudomonas aeruginosa, Proteus mirabilis, Acinetobacter baumanii, Klebsiella pneumoniae complex, and Enterobacter cloacae complex. Conclusions Pure Staphylococcus aureus infections, occurring in 29%, accounted for most single bacterial infections. Gram-negative infections and anaerobes were commonly encountered in polymicrobial infections. Most fungi cultures occurred in patients with enteric fistulas.