Aggressive Infection Research Articles

Coronavirus disease (COVID-19) Associated mucormycosis (CAM)

The currently prevalent COVID-19 infection, its line of treatment, resultant immunosuppression, and pre-existing comorbidities have made patients exposed to secondary infections including mucormycosis. Mucormycosis is a rare but in invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities which include diabetes mellitus, organ transplant, immunosuppressive corticosteroid therapy. The maxilla rarely undergoes necrosis due to its rich vascularity. Rare but not uncommon is the incidence of mucormycosis associated maxillary osteomyelitis occurring post COVID-19 infection. Fungal osteomyelitis is a life-threatening infection which may further spread from maxilla to the nose and paranasal sinuses within the orofacial region. It is an aggressive infection that needs to be addressed promptly to prevent fatal consequences.

Increased sensitivity of Aggregatibacter actinomycetemcomitans to human serum is mediated by induction of a bacteriophage.

Aggregatibacter actinomycetemcomitans, a Gram-negative oral pathobiont causing aggressive periodontitis and systemic infections, demonstrates serum resistance. We have identified a dsDNA-tailed bacteriophage, S1249, which was found to convert from this microorganism inducible by human serum into a lytic state to kill the bacterium. This phage demonstrated active transcripts when exposed to human serum: 20% of genes were upregulated more than 10-fold, and 45% of them were upregulated 5-10-fold when the bacterium was grown in the presence of human serum compared to without the presence of human serum. Transcriptional activation when grown in equine serum was less pronounced. This phage demonstrated a tail with inner rigid tubes and an outer contractile sheath, features of Myoviridae spp. Further characterization revealed that the lysogenized integration of the phage in the chromosome of A. actinomycetemcomitans occurred between the genes encoding cold-shock DNA-binding domain-containing protein (csp) and glutamyl-tRNA synthetase (gltX). Both phage DNA integrated lysogeny and nonintegrated pseudolysogeny were identified in the infected bacterium. A newly generated, lysogenized strain using this phage displayed similar attributes, including 63% growth inhibition compared to its isogenic phage-free strain when in the presence of human serum. Our data suggest that bacteriophage S1249 can be induced in the presence of human serum and enters the lytic cycle, which reduces the viability of infected bacteria in vivo.

Application of Dehydrated Amniotic Membrane Allografts in Advanced Diabetic Foot Ulceration: Case Report and Review of Literature

The management of diabetic foot ulcers (DFUs) presents challenges to even the most experienced wound-care providers. Because of the chronic, non-healing nature of many DFUs, advances in the treatment and care of this disease process are particularly relevant. This case study aims to report the efficacy of the application of dehydrated amniotic membrane allograft (DAMA) to a diabetic foot ulcer. The patient in this study is a 44-year-old male who presented with an aggressive infection on his right foot, which resulted in an open wound of 18-month duration. This patient received weekly applications of dual-layer DAMA over seven weeks. Upon examination at the initial application, the wound was classified as a Wagner grade 3 with necrosis of the underlying muscle. Upon inspection at the final visit, the wound was closed entirely. The results that were shown include improvements in the size, depth, edges, necrotic tissue amount, and epithelization of the wound. This case study demonstrates that the application of DAMA has the potential to augment the body’s natural DFU healing response; however, future nonrandomized and randomized controlled trials are needed to establish its efficacy further.

Increased iron uptake in the bladder wall of racemose cysts of Taenia solium

Racemose neurocysticercosis is an aggressive infection caused by the aberrant expansion and proliferation of the bladder wall of the Taenia solium cyst within the subarachnoid spaces of the human brain. The parasite develops and proliferates in a microenvironment with low concentrations of growth factors and micronutrients compared to serum. Iron is important for essential biological processes, but its requirement for racemose cyst viability and proliferation has not been studied. The presence of iron in the bladder wall of racemose and normal univesicular T. solium cysts was determined using Prussian blue staining. Iron deposits were readily detected in the bladder wall of racemose cysts but were not detectable in the bladder wall of univesicular cysts. Consistent with this finding, the genes for two iron-binding proteins (ferritin and melanotransferrin) and ribonucleotide reductase were markedly overexpressed in the racemose cyst compared to univesicular cysts. The presence of iron in the bladder wall of racemose cysts may be due to its increased metabolic rate due to proliferation.

COVID-19-A Qualitative Orthopaedic Nurse Perspective.

In response to a March 2020, New York State mandate, our elective surgery center began a physical and operational transformation to provide inpatient care to COVID-19 patients. Research study aims included (1) a description of the orthopaedic nurses' experience during the pandemic, and (2) tactics used to cope with related stress. Researchers used a descriptive, qualitative design to achieve study aims. During April to December 2020, nine nurses responded to seven open-ended, study prompts asking them to journal their thoughts about the pandemic. The majority (66%) of participants were experienced nurses and all provided direct patient care. Nurses provided 51 journal entries that generated 12 themes, which encapsulated their experience living through the pandemic: (1) Whirlwind, (2) War, (3) Control, (4) Death and Dying, (5) Staying Safe, (6) Loss, (7) Looking for Meaning, (8) Whatever It Takes, (9) Adaptability and Resilience, (10) What I Have Learned, (11) The New Normal, and (12) When Will This Be Over? Orthopaedic nurses in this study pivoted to the needs of patients requiring them to draw on all their training and resources. Nurses described the enormity and taxing nature of the viral threat and their ability to manage their well-being while caring for patients and loved ones, amidst social distancing and need for aggressive infection control. Support from peers and leadership were paramount factors in nurse coping. Positive thinking and personal resilience were considered essential. Most participants described personal growth; however, decreased participation in journal responses overtime, suggested emotional strain. Future studies should examine nurses' observations about the impact of changes to their practice brought on by the pandemic, and reliance on technology.

Clinical Study of Septal Deviation and Its Association with Sinusitis

Introduction: Aim: To establish association between Septal deviation and sinusitis along with the clinical profile of Chronic Rhinosinusitis in Deviated nasal septum. Methodology: A cross sectional study of 50 patients attending ENT department of VIMS, Bellary with symptoms of chronic rhinosinusitis were included. Nasal trauma, Nasal polyposis, Septal perforation, Allergic rhinitis, Aggressive fungal infections, Odontogenic sinusitis, Neoplasia, Patients <15 yrs of age, Immunodeficiency and mucociliary disorders, Prior history of nasal or sinus surgery, Other anatomic abnormalities were excluded. Included patients underwent detailed clinical examination, Diagnostic nasal endoscopy, X-ray or computed tomography of Paranasal sinuses. Results: Among 50 patients with chronic rhinosinusitis, 36 patients were found to have Deviated nasal septum. Male preponderance was observed in both sinusitis and septal deviation population. Bilateral maxillary sinus (28%) was the most common presentation in CTPNS. We found that significant association was found between anterior and posterior ethmoid sinusitis with Left sided S shaped obstructed or impacted type of deviated nasal septum. Conclusion: Chronic rhinosinusitis is most common rhinological problem encountered worldwide which has greater propensity to cause morbidity. Deviated nasal septum can be associated with significant sinonasal disease, especially a S-shaped obstructed and impacted type of DNS which showed statistically significant correlation with sinus disease in our study. Also, DNS to left, in general, was associated with higher incidence of sinuses disease than central and DNS to right. This study brings to light various presentations of DNS implicated in causation of chronic sinusitis which will influence the treatment decisions and also reduce the morbidity caused by it. Keywords: Chronic Rhinosinusitis (CRS), Deviated nasal septum (DNS)

Clinical epidemiology of carbapenem-resistant Enterobacterales in the Greater Houston region of Texas: a 6-year trend and surveillance analysis

ObjectivesCarbapenem-resistant Enterobacterales (CRE) remain an urgent public health priority in the United States. CRE poses a major threat to patients in healthcare and a potential risk to the community. This study examined the epidemiological trends, clinical, and microbiological data of CRE in the Greater Houston region of Texas. MethodsA multi-institutional retrospective observational study was conducted using surveillance data collected from 2015 to 2020. Predictors of incidence rates of CRE were determined by a negative binomial regression fit using a generalized estimation equation. ResultsOver a 6-year period, 4236 CRE cases were reported, of which Klebsiella pneumoniae accounted for 84.8%. The results show a steady increase in CRE cases, with a sharp rise since 2018. The majority of carbapenemase-producing Enterobacterales were Klebsiella pneumoniae carbapenemase (KPC)-producing (77.2%), followed by other rare carbapenemases, which includes OXA-48, NDM, IMP, VIM, coproduction of KPC with OXA-48, KPC with NDM, and NDM with OXA-48. Acute care hospitals (ACH) accounted for 68.5% of the source of CRE cases. The incidence rate of CRE cases reported from ACH and long-term acute care (LTAC) facilities was 1.16 times that of long-term care facilities (adjusted rate ratio [ARR] = 1.16, 95% confidence interval [CI]:1.04–1.30). The incidence rate of CRE among patients with indwelling devices was 15% (ARR = 0.85, 95% CI: 0.79–0.92) lower than that of patients without indwelling devices. ConclusionThe rise in the rate of CRE cases despite aggressive infection prevention and control strategies in the region is alarming. Evaluating and improving the current infection control strategies may be warranted.

Structural Mimicry in Microbial and Antimicrobial Amyloids.

The remarkable variety of microbial species of human pathogens and microbiomes generates significant quantities of secreted amyloids, which are structured protein fibrils that serve diverse functions related to virulence and interactions with the host. Human amyloids are associated largely with fatal neurodegenerative and systemic aggregation diseases, and current research has put forward the hypothesis that the interspecies amyloid interactome has physiological and pathological significance. Moreover, functional and molecular-level connections between antimicrobial activity and amyloid structures suggest a neuroimmune role for amyloids that are otherwise known to be pathological. Compared to the extensive structural information that has been accumulated for human amyloids, high-resolution structures of microbial and antimicrobial amyloids are only emerging. These recent structures reveal both similarities and surprising departures from the typical amyloid motif, in accordance with their diverse activities, and advance the discovery of novel antivirulence and antimicrobial agents. In addition, the structural information has led researchers to postulate that amyloidogenic sequences are natural targets for structural mimicry, for instance in host-microbe interactions. Microbial amyloid research could ultimately be used to fight aggressive infections and possibly processes leading to autoimmune and neurodegenerative diseases.

Extent of craniofacial fungal osteomyelitis in a ketoacidotic patient may predict optic nerve involvement: A case report.

IntroductionMucormycosis is an opportunistic mycosis common in poorly-controlled insulin dependent diabetic patients particularly with ketoacidosis. Fungal osteomyelitis is a life-threatening condition affectation of the nose and paranasal sinuses within the orofacial region.Presentation of caseWe present a 63-year-old diabetic male patient with maxillary mucormycotic osteomyelitis threatening his better seeing eye and review the clinical symptoms, relevant imaging, and management.DiscussionWe highlight a rare pattern of craniofacial fungal bone infection with maxillary and orbital involvement that ultimately spared the optic nerve. This case report offers the clinician a review of important clinical and diagnostic findings that can help direct the need for orbital exenteration.ConclusionMaxillary mucormycotic osteomyelitis is an aggressive infection that needs to be addressed promptly to prevent fatal consequences.

Black Fungus Mutilating COVID-19 Pandemic in India: Facts and Immunological Perspectives

While the world is still struggling with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, an aggressive and rare fungal infection which is commonly ascribed as the black fungus has emerged as a new medical challenge in India. India had already experienced the devastating consequences of the COVID-19 and, being a rare “opportunistic” fungal infection, black fungus infection has severely complicated the post-COVID-19 recoveries. Together with the uncertain treatment modalities at the beginning of the pandemic, indiscriminate use of a plethora of medications has driven the surging cases of black fungus-associated complications. Moreover, low oxygen, high iron levels, and prolonged hospitalization with mechanical ventilators created a superlative condition for contracting black fungus infection. The disease mainly spreads through the respiratory tract and erodes facial structures. Since mucormycosis specifically attacks immunosuppressed patients, the disease started spreading rapidly, with an average mortality rate of 54 %. Common symptoms include blackening over the nose, blurred or double vision, breathing difficulties, chest pain and hemoptysis. Although not contagious, the outcome of the disease is often very frightful. If the infection disseminates systematically, the risk of affecting the vital organs such as the spleen and heart is substantially high. We have tried to provide an epidemiological overview of black fungus infection in India. We focused on drawing a comprehensive fact check of the current situation through an immunological perspective to better understand the infection as a major co-infection in patients affected by COVID-19 and its impact on India's fight against the COVID-19 pandemic.

Head and neck necrotizing fasciitis: the importance of negative pressure wound therapy with literature review

BackgroundNecrotizing fasciitis is an aggressive infection of the soft tissues and subcutaneous fascia. The involvement of the head and neck region is very rare but carries significant mortality. Negative pressure wound therapy (NPWT) became very popular in treating complicated wounds.Case presentationWe present a case of necrotizing fasciitis in cervical region. After surgical debridement, a NPWT device was applied. NPWT provides advantages compared to conventional debridement and drainage.ConclusionThis method is recommended as an adjuvant tool in treating necrotizing fasciitis in head and neck region because it helps to eradicate infection, provides comfort to the patient and facilitates wound healing.

Sodium Citrate Alleviates Virulence in Pseudomonas aeruginosa.

The development of bacterial resistance is an insistent global health care issue, especially in light of the dwindled supply of new antimicrobial agents. This mandates the development of new innovative approaches to overcome the resistance development obstacle. Mitigation of bacterial virulence is an interesting approach that offers multiple advantages. Employing safe chemicals or drugs to mitigate bacterial virulence is an additive advantage. In the current study, the in vitro antivirulence activities of citrate were evaluated. Significantly, sodium citrate inhibited bacterial biofilm formation at sub-MIC concentrations. Furthermore, sodium citrate decreased the production of virulence factors protease and pyocyanin and diminished bacterial motility. Quorum sensing (QS) is the communicative system that bacterial cells utilize to communicate with each other and regulate the virulence of the host cells. In the present study, citrate in silico blocked the Pseudomonas QS receptors and downregulated the expression of QS-encoding genes. In conclusion, sodium citrate showed a significant ability to diminish bacterial virulence in vitro and interfered with QS; it could serve as a safe adjuvant to traditional antibiotic treatment for aggressive resistant bacterial infections such as Pseudomonas aeruginosa infections.

Vaccination as protection against particularly dangerous infections and infectious processes that create Рublic health emergencies of international importance

The article presents a brief history of epidemics (pandemics) and vaccination in the most aggressive and widespread infections, currently representing Public health emergencies of international importance. Data on measures to combat them are provided.

Mucormycosis: A comparative update between conventional and molecular diagnosis strategies.

Mucormycosis is an opportunistic, aggressive, and angioinvasive fungal infection associated with a high mortality rate as it disseminates and infects the whole body if not treated early. Most conventional diagnostic methods require time and may also generate false-negative reports due to the several lacunae associated. On the other hand, molecular methods are rapid, reliable, and can be applied to different biological samples, such as fresh tissue, formalin-fixed paraffin-embedded blocks, serum, and urine. Mucorales are angio-invasive, and many studies have found the circulating fungal DNA (a non-invasive form of DNA) in the blood and urine of the patient. In addition, with the increase in the usage of steroid drugs in this COVID scenario, the rate of mucormycosis infection has taken a sudden rise. In light of this situation, there is an imperative need to diagnose these infections at the earliest.

Time-serial expression of toll-like receptor 4 signaling during polymicrobial sepsis in rats.

Sepsis caused by aggressive infection is a severe clinical problem with an increasing incidence worldwide. Toll-like receptors and their common adapter myeloid differentiation factor 88 (MyD88) can activate immune responses by recognizing a foreign microbe’s product. This study aimed to identify the different time expression of TLR four signaling pathway in an experimental rodent model of polymicrobial sepsis. A randomized animal study was investigated in rats with septic peritonitis induced by cecal ligation and puncture (CLP). The expressions of MyD88-dependent pathway biomarkers, including MyD88, nuclear factor-κB (NF-κB), and serum tumor necrosis factor-α (TNF-α), were analyzed and compared to the sham controls at the different time points after CLP surgery. CLP-induced sepsis increased liver MyD88 mRNA expression and protein expression compared to the control groups at 2 h after surgery. The MyD88 mRNA and protein expressions in rats with CLP-induced sepsis marked increased at 4 and 6 h, and their NF-κB activities and serum TNF-α levels also increased at 4 h after CLP surgery (both p < .05). The different serial expression of MyD88-ependent pathway during sepsis may be used as biomarkers during sepsis. These results may provide further helpful information for using pro-inflammatory biomarkers of innate immunity such as MyD88 and TNF-α in clinical sepsis or related abdominal surgical emergency in the future.

Survival in rhino-orbito-cerebral mucormycosis: An international, multicenter ID-IRI study

BackgroundMucormycosis is an emerging aggressive mold infection. This study aimed to assess the outcome of hospitalized adults with rhino-orbito-cerebral mucormycosis (ROCM). The secondary objective was to identify prognostic factors in this setting. MethodsThis study was an international, retrospective, multicenter study. Patients’ data were collected from 29 referral centers in 6 countries. All qualified as “proven cases” according to the EORTC/MSGERC criteria. ResultsWe included 74 consecutive adult patients hospitalized with ROCM. Rhino-orbito-cerebral type infection was the most common presentation (n = 43; 58.1%) followed by rhino-orbital type (n = 31; 41.9%). Twenty (27%) had acquired nosocomial bacterial infections. A total of 59 (79.7%) patients (16 in combination) received appropriate antifungal treatment with high-doses of liposomal amphotericin B. Fifty-six patients (75.7%) underwent curative surgery. Thirty-five (47.3%) required intensive care unit admission (27; 36.5% under mechanical ventilation). Hospital survival was 56.8%, being reduced to 7.4% in patients with invasive mechanical ventilation. A multivariate binary backward logistic regression model identified confusion at admission (OR 11.48), overlapping hospital-acquired infection (OR 10.27), use of antifungal treatment before diagnosis (OR 10.20), no surgical debridement (OR 5.92), and the absence of prior sinusitis (OR 6.32) were independently associated with increased risk for death. ConclusionToday, ROCM still has high mortality rate. Improving source control, rational therpy, and preventing nosocomial infections may improve survival in this severe infection.

MALIGNANT OTITIS EXTERNA – OUR EXPERIENCE

Objective: In this study, we aim to find out different symptoms and treatment outcomes of patients who are diagnosed with malignant otitis externa according to Levenson’s criteria, attending ENT OPD in a tertiary care hospital. Methods: This is a prospective study, conducted over 18 months from August 2018 to February 2020 in the Department of ENT, GITAM Institute of Medical Sciences and Research, Visakhapatnam. Patients typically presented with nocturnal otalgia, persistent otorrhea, hearing loss, and aural fullness. Consent from patients for participation in the study has been taken. Complete history and thorough clinical examination were made, along with relevant investigations. Results: Out of the 15 patients selected, MOE is more common in males (60%) than females (40%). The most common organism isolated is Pseudomonas aeruginosa. Nocturnal otalgia was the presenting complaint in all the patients. The age group commonly affected with MOE is 60−75 years. Facial nerve palsy is seen among 46% of the patients. Dry moping and application of betadine wick after the scrapping of granulations and reasonable glycemic control was helpful in-patient recovery in 50% of the cases. Conclusion: Malignant otitis externa (MOE) is an aggressive infection representing a life-threatening condition. In our patients, a prolonged topical and oral antibiotic treatment and strict control of glycemic levels permitted to control the disease, but the surgical approach by debridement of granulations appeared essential for the resolution of the disease.

Proliferative cells in racemose neurocysticercosis have an active MAPK signalling pathway and respond to metformin treatment

Racemose neurocysticercosis is an aggressive infection caused by the aberrant expansion of the cyst form of Taenia solium within the subarachnoid spaces of the human brain and spinal cord, resulting in the displacement of the surrounding host tissue and chronic inflammation. We previously demonstrated that the continued growth of the racemose bladder wall is associated with the presence of mitotically active cells but the nature and control of these proliferative cells are not well understood. Here, we demonstrated by immunofluorescence that the racemose cyst has an active mitogen-activated protein kinases (MAPK) signalling pathway that is inhibited after treatment with metformin, which reduces racemose cell proliferation in vitro, and reduces parasite growth in the murine model of Taenia crassiceps cysticercosis. Our findings indicate the importance of insulin receptor-mediated activation of the MAPK signalling pathway in the proliferation and growth of the bladder wall of the racemose cyst and its susceptibility to metformin action. The antiproliferative action of metformin may provide a new therapeutic approach against racemose neurocysticercosis.

Emergence of mucormycosis following second wave of COVID-19 pandemic and possible risk factors in a hilly state of North India

Background: Mucormycosis is a rare, highly aggressive fungal infection affecting the rhino-orbital, respiratory, gastrointestinal or cutaneous systems and is caused by a group of moulds called mucoromycetes belonging to order Mucorales and has been associated with corona pandemic. The aim of the study was to assess the emerging trends of mucormycosis following second wave of Corona pandemic and possible risk factors in a hilly state of North India.Methods: It was a retrospective data analysis study where the information’s were gathered from various sources in state of Himachal Pradesh. After detection of 1st case, data was collected from May 2021 to July 2021. Since objective and authentic data was released by different agencies daily, so the state profile of mucormycosis cases was taken as per information available from newspapers, various state websites and analysed for various parameters.Results: The current study conducted in state of Himachal Pradesh showed that Hamirpur was the worst hit district with affected population 0.002%, with case fatality rate 57%. While male mortality was more (60%) as compared to female mortality (40%).Conclusions: This study showed that underlying risk factors for mucormycosis were COVID-19 infection, un-controlled diabetes, steroid and oxygen use.

From SARS-CoV-2 infection to COVID-19 morbidity: an in silico projection of virion flow rates to the lower airway via nasopharyngeal fluid boluses

Background: While the nasopharynx is initially the dominant upper airway infection site for SARS-CoV-2, the physiologic mechanism launching the infection at the lower airway is still not well-understood. Based on the rapidity of infection progression to the lungs, it has been hypothesized that the nasopharynx may be acting as the primary seeding zone for subsequent contamination of the lower airway via aspiration of virus-laden boluses of nasopharyngeal fluids. Methodology: To examine the plausibility of the aspiration-driven mechanism, we have computationally tracked the inhalation process in three anatomic airway reconstructions and have quantified the nasopharyngeal liquid volume transmitted to the lower airspace during each aspiration. Results: Extending the numerical trends on aspiration volume to earlier records on aspiration frequencies indicates a total aspirated nasopharyngeal liquid volume of 0.3 – 0.76 ml/day. Subsequently, for mean sputum viral load, our modeling projects that the number of virions reaching the lower airway will range over 2.1×106 – 5.3×106 /day; for peak viral load, the corresponding number hovers between 7.1×108 – 1.8×109. Conclusions: The virion transmission findings fill in a key piece of the mechanistic puzzle on the systemic progression of SARS-CoV-2, and subjectively point to health conditions like dysphagia, with proclivity to increased aspiration, as some of the potential underlying risk factors for aggressive lung infections.