Bacterial Infections and Mycoses Commons^™

Identifying Constraints For Hospital Infection Control Management Via Mckinsey 7s Framework In Pakistan, Shagufta Perveen, Shifa Salman Habib

Community Health Sciences

Background: In Pakistan, structured guidelines for hospital infection control and prevention are deficient in most public sector facilities. There is dearth of literature available on management of hospital-care acquired infections and related issues. This study aims to understand infection control management as a proxy measure for quality of health care provided at a public sector tertiary care hospital in Karachi, Pakistan. In this study, we identify barriers to implementation of infection control measures and highlight key areas for quality improvement.
Methods: A cross sectional study was carried out in 2008 using qualitative research methods. In-depth interviews were conducted with hospital …

Emergence Of Fluoroquinolone Resistance Among Drug Resistant Tuberculosis Patients At A Tertiary Care Facility In Karachi, Pakistan, Syed Mohammad Asad Zaidi, Abdul Haseeb, Shifa Salman Habib, Amyn Malik, Saira Khowaja, Nausheen Saifullah, Nadeem Rizvi

Community Health Sciences

Background: Pakistan is classified as one of the high multi-drug resistant tuberculosis (MDR-TB) burden countries. A poorly regulated private sector, over-prescription of antibiotics and self-medication has led to augmented rates of drug-resistance in the country. Pakistan's first national anti-tuberculosis drug resistance survey identified high prevalence of fluoroquinolone resistance among MDR-TB patients. Further institutional evidence of fluoroquinolone drug-resistance can support re-evaluation of treatment regimens as well as invigorate efforts to control antibiotic resistance in the country.
Findings: In this study, data for drug-susceptibility testing (DST) was retrospectively analyzed for a total of 133 patients receiving MDR-TB treatment at the Chest Department …

The Feoabc Locus Of Yersinia Pestis Likely Has Two Promoters Causing Unique Iron Regulation, Lauren O'Connor, Jacqueline D. Fetherston, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The FeoABC ferrous transporter is a wide-spread bacterial system. While the feoABC locus is regulated by a number of factors in the bacteria studied, we have previously found that regulation of feoABC in Yersinia pestis appears to be unique. None of the non-iron responsive transcriptional regulators that control expression of feoABC in other bacteria do so in Y. pestis. Another unique factor is the iron and Fur regulation of the Y. pestis feoABC locus occurs during microaerobic but not aerobic growth. Here we show that this unique iron-regulation is not due to a unique aspect of the Y. pestis …

Colonization Density Of The Upper Respiratory Tract As A Predictor Of Pneumonia-Haemophilus Influenzae, Moraxella Catarrhalis, Staphylococcus Aureus, And Pneumocystis Jirovecii., Daniel E Park, Henry C Baggett, Stephen R C Howie, Qiyuan Shi, Nora L Watson, W Abdullah Brooks, Perch Study Group

Epidemiology Faculty Publications

Background.

There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. Methods.

In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Antibiotic Prophylaxis Is Associated With Subsequent Resistant Infections In Children With An Initial Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae Infection., Sibani Das, Amanda L. Adler, Arianna Miles-Jay, Matthew P. Kronman, Xuan Qin, Scott J. Weissman, C A. Burnham, Alexis Elward, Jason G. Newland, Rangaraj Selvarangan, Kaede V. Sullivan, Theoklis Zaoutis, Danielle M. Zerr

Manuscripts, Articles, Book Chapters and Other Papers

The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged species, resistance determinants, and fumC-fimH (E. coli) or tonB (Klebsiella pneumoniae) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 …

Aspergillus Fumigatus Trehalose-Regulatory Subunit Homolog Moonlights To Mediate Cell Wall Homeostasis Through Modulation Of Chitin Synthase Activity, Arsa Thammahong, Alayna K. Caffrey-Card, Sourabh Dhingra, Joshua J. Obar, Robert Cramer

Dartmouth Scholarship

Trehalose biosynthesis is found in fungi but not humans. Proteins involved in trehalose biosynthesis are essential for fungal pathogen virulence in humans and plants through multiple mechanisms. Loss of canonical trehalose biosynthesis genes in the human pathogen Aspergillus fumigatus significantly alters cell wall structure and integrity, though the mechanistic link between these virulence-associated pathways remains enigmatic. Here we characterize genes, called tslAand tslB, which encode proteins that contain domains similar to those corresponding to trehalose-6-phosphate phosphatase but lack critical catalytic residues for phosphatase activity. Loss of tslA reduces trehalose content in both conidia and mycelia, impairs cell wall …

Ticked Off: An Analysis Of The Inadequate Diagnosis And Treatment Of Lyme Disease, Virginia P. Yoder

Senior Honors Theses

Lyme disease is the most common vector-borne disease in the United States and has a high prevalence among people in the northeast. Lyme disease can be a debilitating illness if not diagnosed early, and can lead to long-term health problems for many patients. This thesis serves as a review of scientific literature on Lyme disease, with the prevalence, symptomology, the bacterial mechanism of infection, the diagnostic process, transmission, and treatment therapies. Further research and development could lead to better primary care for those suffering with Lyme disease.

Filamentous Fungal Carbon Catabolite Repression Supports Metabolic Plasticity And Stress Responses Essential For Disease Progression, Sarah R. Beattie, Kenneth Mark, Arsa Thammahong, Laure Nicolas Annick Ries, Sourabh Dhingra, Alayna Caffrey-Carr, Chao Cheng

Dartmouth Scholarship

Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A. fumigatus requires a carbon catabolite repression (CCR) mediated genetic network to support in vivo fungal fitness and disease progression. While CCR as mediated by the transcriptional repressor CreA is …

Chagas, Enfermedad Olvidada: Una Perspectiva Histórica De La Prevención Y Control Del Chagas En La Provincia De Salta, Argentina (1909 – 2017) \ Chagas, A Forgotten Disease: A Historical Perspective On The Prevention And Control Of Chagas In Salta Province, Argentina (1909 – 2017), Tara Shea

Independent Study Project (ISP) Collection

El Chagas es una enfermedad vectorial más conocida en zonas rurales de América Latina y en Argentina es endémica en la región noroeste del país (MSAL, 2017). Designada una enfermedad tropical desatendida (Neglected Tropical Disease, NTD) por la OMS, la crónica del Chagas desde su “hallazgo casual” en 1909 siempre se trató de abandono (INP, 2017; MSF, 2012; OMS, 2017; Reyes López, 2009; Stamboulian, 2015; Zabala, 2009). En toda la Argentina se identifican 1.600.000 casos y 7.300.000 personas expuestas al Chagas, dando el país una de las tasas chagásicas más altas del mundo (Bär, 2015; MSAL, 2017).1

El modo de …

Abordajes De Nuevos Tratamientos Para La Enfermedad De Chagas Y Su Potencial Aplicación En Pacientes Desde Las Perspectivas De Los Profesionales En La Ciudad Autónoma De Buenos Aires, Argentina / Approaches To New Treatments For Chagas Disease And Their Potential Application In Patients From The Perspectives Of Professionals In The Autonomous City Of Buenos Aires, Argentina, Chelsea Hipwell

Independent Study Project (ISP) Collection

Más de cien años después del descubrimiento de la enfermedad de Chagas, esta enfermedad desatendida sigue afectando más de 6 millones de personas en Latinoamérica, de las cuales 1.5 millones son de Argentina. Al día de hoy, solo existen dos medicamentos para tratar esta enfermedad. El presente proyecto se basa sobre un estudio exploratorio de los desafíos de tratar la enfermedad de Chagas en sus distintas fases y los abordajes actuales para nuevos tratamientos.

Los objetivos de este trabajo fueron los siguientes: en primer lugar, estudiar el contexto socio-económico en que existe esta enfermedad y las implicaciones de este contexto …

Hemophagocytic Lymphohistiocytosis Associated With Anaplasmosis, T Johnson, M Brown, M Rabbat, Jihad Slim

NYMC Faculty Publications

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome characterized by unregulated macrophage and T-lymphocyte activation resulting in cytokine overproduction and subsequent histiocytic phagocytosis. Variant infections, particularly viruses have been postulated as the inciting factor for this potentially fatal disease. Herein, we will report a case of HLH associated with anaplasmosis.

Complex Multimodality Central Airway Management Of Aspergillus Pseudomembranous Tracheobronchitis, S Dhillon, M Saoud, Kassem Harris

NYMC Faculty Publications

A 69-year-old woman developed central airway obstruction due to invasive Aspergillus infection resulting in pseudomembranous tracheobronchitis (PTB). Several challenges were encountered in the airway management of this patient including her having relatively smaller airways which were more prone to obstruction by pseudomembranes and made airway interventions difficult. The patient had clinical deterioration in spite of antifungal therapy and bronchoscopic debridement. The multimodality airway techniques included the use of smaller biliary balloons for dilatation, using a hybrid stent to slowly dilate and maintain patency of right main stem and finally the insertion of right secondary carina peripheral Y stent, which resulted …

Enhanced Control Of Mycobacterium Tuberculosis Extrapulmonary Dissemination In Mice By An Arabinomannan-Protein Conjugate Vaccine, R Prados-Rosales, L Carreno, T Cheng, C Blanc, B Weinrick, Aharona Glatman-Freedman, A Casadevall, S Hung, A Tripathi, J Xu, Aharona Glatman-Freedman, W Jacobs Jr., J Chan, S Porcelli, J Achkar, A Casadevall

NYMC Faculty Publications

Currently there are a dozen or so of new vaccine candidates in clinical trials for prevention of tuberculosis (TB) and each formulation attempts to elicit protection by enhancement of cell-mediated immunity (CMI). In contrast, most approved vaccines against other bacterial pathogens are believed to mediate protection by eliciting antibody responses. However, it has been difficult to apply this formula to TB because of the difficulty in reliably eliciting protective antibodies. Here, we developed capsular polysaccharide conjugates by linking mycobacterial capsular arabinomannan (AM) to either Mtb Ag85b or B. anthracis protective antigen (PA). Further, we studied their immunogenicity by ELISA and …

Outpatient Parenteral Antimicrobial Therapy In Pediatric Medicaid Enrollees., Jennifer Goldman, Troy Richardson, Jason G. Newland, Brian R. Lee, Jeffrey S. Gerber, Matt Hall, Matthew Kronman, Adam L. Hersh

Manuscripts, Articles, Book Chapters and Other Papers

Background: Outpatient parenteral antimicrobial therapy (OPAT) is overused in cases where highly bioavailable oral alternatives would be equally effective. However, the scope of OPAT use for children nationwide is poorly understood. Our objective was to characterize OPAT use and clinical outcomes for a large population of pediatric Medicaid enrollees treated with OPAT.

Methods: We analyzed the Truven MarketScan Medicaid claims database between 2009 and 2012. An OPAT episode was identified by capturing children with claims data indicating home infusion therapy for an intravenous antimicrobial. We characterized OPAT use by describing patient demographics, diagnoses, and antimicrobials prescribed. We categorized an antimicrobial …

Plasmid Diversity And Phylogenetic Consistency In The Lyme Disease Agent Borrelia Burgdorferi, Sherwood R. Casjens, Eddie B. Gilcrease, Marija Vujadinovic, Emmanuel F. Mongodin, Benjamin J. Luft, Steven E. Schutzer, Claire M. Fraser, Wei-Gang Qiu

Publications and Research

Background: Bacteria from the genus Borrelia are known to harbor numerous linear and circular plasmids. We report here a comparative analysis of the nucleotide sequences of 236 plasmids present in fourteen independent isolates of the Lyme disease agent B. burgdorferi.

Results: We have sequenced the genomes of 14 B. burgdorferi sensu stricto isolates that carry a total of 236 plasmids. These individual isolates carry between seven and 23 plasmids. Their chromosomes, the cp26 and cp32 circular plasmids, as well as the lp54 linear plasmid, are quite evolutionarily stable; however, the remaining plasmids have undergone numerous non-homologous and often duplicative recombination …

Epidemiological Investigation Of Candida Species Causing Bloodstream Infection In Pediatric Small Bowel Transplant Recipients, Mallory J. Suhr, João Carlos Gomes-Neto, Nabaraj Banjara, Diana F. Florescu, David F. Mercer, Peter C. Iwen, Heather E. Hallen-Adams

Department of Food Science and Technology: Faculty Publications

Small bowel transplantation (SBT) can be a life-saving medical procedure. However, these recipients experience high risk of bloodstream infections caused by Candida. This research aims to characterize the SBT recipient gut microbiota over time following transplantation and investigate the epidemiology of candidemia in seven pediatric patients. Candida species from the recipients’ ileum and bloodstream were identified by internal transcribed spacer sequence and distinguished to strain by multilocus sequence typing and randomly amplified polymorphic DNA. Antifungal susceptibility of bloodstream isolates was determined against nine antifungals. Twenty-two ileostomy samples harbored at least one Candida species. Fungemia were caused by Candida parapsilosis …

What Are The Barriers And Facilitators To Nurses’ Utilization Of A Nurse Driven Protocol (Ndp) For Indwelling Urinary Catheter (Iuc) Removal?, Brenda Clark

Interprofessional Research and Innovations Council

What are the barriers and facilitators to Nurses’ utilization of a Nurse Driven Protocol (NDP) for Indwelling Urinary Catheter (IUC) removal?

By Brenda Clark, BSN, RN, CMSRN

Background: Urinary tract infections (UTIs) are recognized as a major cause of morbidity and mortality in hospitalized patients; 80% of UTIs are related to using indwelling urinary catheters.

Reducing these infections is recognized as a National Patient Safety Goal (NPSG) by the Joint Commission; the American Nurses Association (ANA) has classified catheter associated urinary tract infections (CAUTIs) as one of the nurse-sensitive indicators that reflect the quality of nursing care. Centers for Medicare …

Mucosal Fluid Glycoprotein Dmbt1 Suppresses Twitching Motility And Virulence Of The Opportunistic Pathogen Pseudomonas Aeruginosa, Jianfang Li, Matteo E. O. Metruccio, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition …

Human Tear Fluid Reduces Culturability Of Contact Lens-Associated Pseudomonas Aeruginosa Biofilms But Induces Expression Of The Virulence-Associated Type Iii Secretion System, Yvonne T. Wu, Connie Tam, Lucia S. Zhu, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Purpose

The type III secretion system (T3SS) is a significant virulence determinant for Pseudomonas aeruginosa. Using a rodent model, we found that contact lens(CL)-related corneal infections were associated with lens surface biofilms. Here, we studied the impact of human tear fluid on CL-associated biofilm growth and T3SS expression.

Methods

P. aeruginosa biofilms were formed on contact lenses for up to 7 days with or without human tear fluid, then exposed to tear fluid for 5 or 24 h. Biofilms were imaged using confocal microscopy. Bacterial culturability was quantified by viable counts, and T3SS gene expression measured …

Fluoride Varnish Application In The Pediatric Population, Ellen Gnaedinger

Doctor of Nursing Practice (DNP) Projects

Purpose: The United States (U.S.) has a persistent problem of dental caries in primary teeth with a greater prevalence of dental caries found in minority and poor children. The majority of children in the U.S. experience dental caries in their primary teeth by age eight. This problem could be addressed by primary care providers applying fluoride varnish (FV) to children's teeth starting at the age of primary tooth eruption. The causes of dental caries in children’s primary teeth are multifactorial and therefore require multiple interventions. Around the world providers are utilizing FV as an effective and easily administered strategy. This …

Life-Threatening Hypercalcemia During Prodrome Of Pneumocystis Jiroveci Pneumonia In An Immunocompetent Infant, Judith Sebestyen Vansickle, Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Severe hypercalcemia in infants is usually attributed to genetic etiologies and less commonly to acquired ones. An 8-week-old girl presented with failure to thrive, mild respiratory distress, and life-threatening hypercalcemia (23.5 mg/dL). Serum 1,25(OH)2-D) level was elevated and parathyroid hormone undetectable. Evaluation for genetic mutations and malignant etiologies of hypercalcemia was negative. Treatment with intravenous hydration, loop diuretic, and calcitonin failed to correct the hypercalcemia, which was subsequently controlled with bisphosphonate therapy. Due to progressive respiratory deterioration, a bronchopulmonary lavage was done on day 17 of her hospitalization disclosing Pneumocystis jiroveci infection. The subsequent immunological investigation showed no abnormalities. She …

Mc-Ppea As A New And More Potent Inhibitor Of Clp-Induced Sepsis And Pulmonary Inflammation Than Fk866., Peixin Huang, Mark W Lee, Keivan Sadrerafi, Daniel P. Heruth, Li Q. Zhang, Dev Maulik, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Our previous study indicated that overexpression of nicotinamide phosphoribosyltransferase (NAMPT) aggravated acute lung injury, while knockdown of NAMPT expression attenuated ventilator-induced lung injury. Recently, we found that meta-carborane-butyl-3-(3-pyridinyl)-2E-propenamide (MC-PPEA, MC4), in which the benzoylpiperidine moiety of FK866 has been replaced by a carborane, displayed a 100-fold increase in NAMPT inhibition over FK866. Here, we determined the effects of MC4 and FK866 on cecal ligation and puncture (CLP) surgery-induced sepsis in C57BL/6J mice. MC4 showed stronger inhibitory effects than FK866 on CLP-induced mortality, serum tumor necrosis factor α (TNFα) levels, pulmonary myeloperoxidase activity, alveolar injury, and interleukin 6 and interleukin1β messenger …