Immune-compromised Patients Research Articles

Ethyl Isothiocyanate as a Novel Antifungal Agent Against Candida albicans.

In the recent years, occurrence of candidiasis has increased drastically which leads to significant mortality and morbidity mainly in immune compromised patients. Glucosinolate(GLS) derivatives are reported to have antifungal activities. Ethyl isothiocyanate (EITC) and its antifungal activity and mechanism of action is still unclear against Candida albicans. The present workwas designed to get a mechanistic insight in to the anti-Candida efficacy of EITC through invitro and in vivo studies. EITC inhibited C. albicans planktonic growth at 0.5mg/ml and virulence factors like yeast to hyphal form morphogenesis (0.0312mg/ml), adhesion to polystyrene surface (0.0312mg/ml) and biofilm formation (developing biofilm at 2mg/ml and mature biofilm at 0.5mg/ml) effectively. EITC blocked ergosterol biosynthesis and arrested C. albicans cells at S-phase. EITC caused ROS-dependent cellular death and nuclear or DNA fragmentation. EITC at 0.0312mg/ml concentration regulated the expression of genes involved in the signal transduction pathway and inhibited yeast to hyphal form morphogenesis by upregulating TUP1, MIG1, and NRG1 by 3.10, 5.84 and 2.64-fold, respectively and downregulating PDE2 and CEK1 genes by 15.38 and 2.10-fold, respectively. EITC has showed haemolytic activity at 0.5mg/ml concentration. In vivo study in silk worm model showed that EITC has toxicity to C. albicans at 0.5mg/ml concentration. Thus, from present study we conclude that EITC has antifungal activity and to reduce its MIC and toxicity, combination study with other antifungal drugs need to be done. EITC and its combinations might be used as alternative therapeutics for the prevention and treatment of C. albicans infections.

Phenotypic identification of Candida species and relative expression of candida drug resistance (CDR1) gene in fluconazole resistant and sensitive Candida albicans

ABSTRACT:
 Background and objective:
 Candida albicans belongs to the genus Candida. It is a commensal yeast in healthy individuals and can cause wide variety of infections in immune-compromised patients. The aim of the present study was to observe the frequency of Candida species, resistant profile of C. albicans against fluconazole and over-expression of CDR1 gene in both fluconazole resistant and sensitive C. albicans.
 Methodology:
 A total number of 206 Candida species were collected on Sabouraud Dextrose agar from Jinnah hospital Lahore. The isolates were re-confirmed by using various microbiological techniques like wet preparation, Gram stain and Germ tube test. Identification upto the species level was done by APIC 20AUX. Antifungal susceptibility profile of C. albicans against fluconazole was determined by broth microdilutiom method. Real Time PCR was performed on both the sensitive and resistant C. albicans to observe the role of CDR1 gene against fluconazole resistance. Results:
 
 tropicals was the most common species with the frequency of 66 (32.0%) followed by C. albicans 41(19.9), C. glabrata 24 (11.7%), C. lusitaniae 14 (6.8%) and other less common species. The majority of infected patients were females (59.2%) than males (41%). Antifungal susceptibility testing showed that 80% C. albicans were sensitive to fluconazole. Results of gene expression showed that CDR1 gene play a major role towards fluconazole resistance in C.albicans.Conclusion: Fluconazole was found to be effective in treating infections caused by C. albicans. 
 
 Keywords: Candida albicans, Candida Drug Resistant Gene 1, Polymerase Chain Reaction, Candida Tropicalis, Candida glabrata, and Candida lusitaniae

Model of Pulmonary Co-Infection of Aspergillus and Pseudomonas in Immunocompetent Mice

Co-infection with Pseudomonas (Pa) and Aspergillus (Af) commonly occurs in the airways of immune-compromised patients or in cystic fibrosis and frequently results in more severe outcomes than mono-infection. We affixed both pathogens to agar beads, separately (Af beads, Pa beads) or on the same bead (AfPa beads) and infected immunocompetent mice, an in vivo Af-Pa interaction model. Endotracheal administration was superior to intranasal, allowing larger beads to be administered resulting in longer lung residence. The CFU of the Af beads, diameter 150–250 µm, were detectable for ≤21 days. Af-bead-infected mice cleared the Af infection more than mice infected with AfPa beads, but Af clearance was the same with a combination of beads (Af beads + Pa beads). Pa-infected mice had more Pa clearance in the presence of Af than with Pa beads alone. In vitro studies supported our conclusion that the close proximity of Af and Pa (on AfPa beads) was disadvantageous for Af, whereas a larger distance (Af + Pa beads) was not. We demonstrated that the interaction between Pseudomonas and Aspergillus during co-infection can be studied in immunocompetent mice. The mutual inhibition of Af and Pa in vivo appears to be dependent on their proximity. We review the literature relating to animal models of infection with Af, Pa, or both.

Treatment of Refractory Adenovirus (ADV) Infections Using Adv-Specific Cytotoxic T-Lymphocytes (CTLs) in Children, Adolescents and Young Adults (CAYA) Post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT), Solid Organ Transplantation (SOT), or with Primary Immunodeficiency (PID)

Background: AlloHSCT induces long-term, cure in CAYA with malignant and non-malignant disorders, including those with primary immunodeficiencies (PID). However, post-transplant complications secondary to immunosuppression and slow or delayed immune reconstitution remains a cause of morbidity and mortality amongst AlloHSCT recipients (Satwani/Cairo, BBMT, 2009). Major complications include refractory viral infections, most importantly adenovirus (ADV), which is secondary to absent or decreased adenovirus specific T-cell immunity which occurs due to delayed immune reconstitution and/or continued immunosuppression (George/Cairo, BJH, 2012). The use of virus-specific (vs) CTLs in immunocompromised patients offer an opportunity to restore temporary virus specific immunity. From the Viral Cytotoxic T-Lymphocyte Consortium (VIRCTLC), we present safety and efficacy results on immune compromised, AlloHSCT, or SOT patients treated with familial ADV specific CTLs. Objective: Determine the safety and efficacy of familial ADV specific CTLs for the treatment of refractory systemic ADV infections. Design/Methods: Patient were deemed eligible if they had a history of AlloHSCT, SOT, or PID and had evidence of ADV infections refractory to anti-viral agents. Refractory ADV infection was defined by increasing serum RT-PCR DNA (by 1 log) after 7 days or persistent quantitative RT-PCR DNA copies after 14 days of appropriate anti-viral therapy, and/or known resistance/intolerance to anti-viral agents. Related donors were required to be matched ≥3 HLA (A, B, or DRB1) loci and have an adequate T-cell response to viral specific MACS ADV PepTivators®. We chose a direct selection method to facilitate more rapid generation of cellular products in a point of care setting (and with 14 hrs eligibility determination). Peripheral blood mononuclear cells were collected from eligible family donors using non-mobilized apheresis. vsCTLs were isolated using the CliniMACS ® Prodigy following stimulation with viral specific MACS® GMP PepTivator® AdV5 Hexon, generously provided by Miltenyi Biotec®. ADV specific CTLs were enriched using a Cytokine Capture System (CCS). CD4+ and CD8+ vsCTLs were quantified by flow cytometry (Feuchtinger et al, Blood, 2010). The target cell dose was 0.5x10 4 CD3+ cells/kg (recipient weight) for haploidentical related donors and 2.5x10 4 CD3+ cells/kg for matched related donors. Repeated doses were permitted every 2 weeks to a maximum of doses in the absence of a complete response (CR) and adverse events. The following were used to define response: CR - undetected ADV PCR, partial response (PR) - at least one log decrease from baseline, progressive disease (PD) - at least one log increase from baseline, and patients with stable disease. Results: Fifteen patients were enrolled: 10 females and 5 males; aged 1-19 years. All patients were post-AlloHSCT. All vsCTL donors were haploidentical: 8 were the original HSCT donors and 7 were third party donors (5 maternal, 2 paternal). The mean number of ADV CTL infusions was 3.7 (range: 1-16). One patient with underlying aplastic anemia had progressive disease complicated by increased adenoviral load despite 5 infusions of vsCTLs. Patient received FDA approval for additional CTLs, totaling 16 doses. Thirteen patients achieved CR as defined and 2 achieved PR. The overall response (OR) was 100% and the CR was 88%. The average time to OR was 33 days (range 6-112 days) and time to CR was 34 days (range 6-112 days). Day 100 and 365 overall survival (OS) post-HSCT was 86.1% (CI95: 49.4-95.7) and 70.5% (CI95: 38.9-87.8), respectively (Figure 1). For patients who achieved CR, the Day 100 OS post AlloHSCT was 83.9% (CI95: 55.0-94.3) and Day 365 post AlloHSCT was 74.6% (CI95: 39.8-91.1). Day 100 and 365 probability of ADV related mortality was 0% (Figure 2). One patient developed acute grade 2 skin GVHD possibly related to infusion, which resolved. Conclusion: Our preliminary data demonstrate that haploidentical ADV specific CTLs manufactured by direct selections using the CCS with the CliniMACS® Prodigy and ADV specific peptivators are safe, well-tolerated, and efficacious in patients with refractory/persistent ADV infections after AlloHSCT. Manufacturing is rapid, reproducible, and effective. Accrual is ongoing. This research is supported by FDA RO1006301A1.

Acute Pyelonephritis management through Ayurveda - A Case Study

The role of Diet, Drugs and Medical attention is very important specially for Elderly People, most probably they were neglected because they need assistance. Modern Science enriched with Antibiotics which are not advisable for a long duration to Elderly, Diabetic & Immune compromised Patients. Even, in Elderly people the Organs are Fragile and most of the Drugs become contraindicated, in such condition Ayurveda is inevitable. Ayurveda explained Tryoupasthambha, Dinacharya, Rutucharya, Aaharaniyama and “Swasthasya Swasthya Rakshnaam Aaturasya Vikara Prsamanaam[1]” (prevention is better than cure) to preserve the health of healthy individual right from Childhood. Ayurveda plays a crucial role in promoting healthy Body and step forward in treating the disease based on Ayurvedic principles, where there is no role of antibiotics. Here is a case neglecting diet, physical activity and medical attention finally alighted to Diabetes, near prostate obstruction, upper urinary tract infection which agonized him severely. This condition according to Ayurveda~Vrukkavikara, Mutravaha Srotovikara, Vasti Vikara. All the protocols of Ayurveda Deepana, Paachna, Srotosodhana, Mutrala, Kapha Vatahara, Vata Anulomama, Pittasama Chikitsa, Krimihara Chikitsa Sutra are followed and treated with Chitrakadi Vati, Gokshuradi Kwatha, Diet, Physical exercise and Barley water.

Monocyte distribution width as an early predictor of short-term outcome in adult patients with sepsis.

Monocyte distribution width (MDW) is a quantitative measurement of monocyte anisocytosis and has been proposed as an efficient marker for early sepsis detection. This study aimed to assess the prognostic potential of MDW in septic patients. In this study, a total of 252 adult septic patients were enrolled. Demographic, clinical, and laboratory finding including MDW and traditional inflammatory biomarkers detected at three time points (day 1, day 3 and day 6) after admission were collected and compared between 28-day survivors and non-survivors. Receiver operating characteristic (ROC) curves, Kaplan-Meier survival curve and Cox regression analyses were performed to assess and compare their predictive values. Group-based trajectory modeling was applied to identify MDW trajectory endotypes. Basic characteristics and 28-day outcomes were compared between the trajectories. ROC curve analysis showed that MDW levels measured on day 3 after admission (D3-MDW) had moderate prognostic value and was independently associated with 28-day mortality in patients with sepsis. A D3-MDW value of 26.20 allowed discrimination between survivors and non-survivors with a sensitivity of 77.8 % and a specificity of 67.6 %. However, the prognostic accuracy of D3-MDW was diminished in immune-compromised patients and patients who already received antibiotics before admission. Group-based trajectory modeling indicated that excessively elevated and delayed decreased MDW levels during the first week after admission inversely correlated with prognosis. MDW values detected on day 3 after admission and its kinetic change might be potential markers for predicting short-term outcome in adult septic patients.

Synthesis, Antifungal Ergosterol Inhibition, Antibiofilm Activities, and Molecular Docking on β-Tubulin and Sterol 14-Alpha Demethylase along with DFT-Based Quantum Mechanical Calculation of Pyrazole Containing Fused Pyridine-Pyrimidine Derivatives.

Multidrug-resistant fungal infections have become much more common in recent years, especially in immune-compromised patients. Therefore, researchers and pharmaceutical professionals have focused on the development of novel antifungal agents that can tackle the problem of resistance. In continuation to this, a novel series of pyrazole-bearing pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives (4a-4o) have been developed. These compounds have been screened against Candida albicans, Aspergillus niger, and Aspergillus clavatus. The synthesized compounds were characterized by well-known spectroscopic techniques, i.e., IR, 1H NMR, 13C NMR, and mass spectrometry. In vitro antifungal results revealed that compound 4n showed activity against C. albicans having MIC value of 200 μg/mL. To know the plausible mode of action, the active derivatives were screened for anti-biofilm and ergosterol biosynthesis inhibition activities. The compounds 4h, 4j, 4k, and 4n showed greater ergosterol biosynthesis inhibition than the control DMSO. To comprehend how molecules interact with the receptor, studies of molecular docking of 4k and 4n have been performed on the homology-modeled protein of β-tubulin. The molecular docking revealed that the active compounds 4h, 4j, 4k, 4l, and 4n interacting with the active site amino acid of sterol 14-alpha demethylase (PDB ID: 5v5z) indicate one of the possible modes of action of ergosterol inhibition activity. The synthesized compounds 4c, 4e, 4h, 4i, 4j, 4k, 4l, and 4n inhibited biofilm formation and possessed the potential for anti-biofilm activity. DFT-based quantum mechanical calculations were carried out to optimize, predict, and compare the vibration modes of the molecule 4a.

Prosthetic joint infection in the hip and knee

Prosthetic joint infection (PJI) is one of the worst complications of joint arthroplasty with an incidence of around 1% following primary arthroplasty, 3% following aseptic revision, and 20% following septic revision. It can occur following direct inoculation, haematogenous or contiguous spread. The majority of PJIs are secondary to bacterial infection although fungal PJI may be seen in multiply operated or immune compromised patients. Risk factors for PJI include patient, pathology and procedure-related factors which, where possible, should be optimized prior to surgery. The diagnosis of PJI remains a challenge and is based on patient history, clinical examination, laboratory tests, and imaging studies. No diagnostic assessment is 100% accurate with various diagnostic criteria used clinically. Investigation and treatment of PJI should be guided by a multi-disciplinary team. Surgical treatment remains the gold standard with the aim of eradicating infection. During surgery the causative organism is sought through a rigorous standardized tissue sampling technique. Surgical approaches including debridement, antibiotics and implant retention (DAIR), single-stage revision, two-stage revision, excision arthroplasty, arthrodesis and amputation. The approach used is tailored to the individual patient with the optimum surgical strategy being one that successfully eradicates the infection, but at the same time minimizes morbidity to the patient.

Imaging spectrum in rhino-orbito-cerebral mucormycosis: a cross-sectional study.

Rhino-orbital-cerebral mucormycosis (ROCM) is a life-threatening condition caused by a saprophytic fungus that predominately affecting immune-compromised patients. Early diagnosis of ROCM is of utmost importance to start the treatment as early as possible to prevent early and horrible complications of the disease. This retrospective study evaluated the imaging findings of 21 patients with biopsy and KOH mount-based evidence of invasive ROCM. The imaging was obtained from a Siemens Magnetom Amira 1.5T system with a strength of 1.5T or more. The spectrum of findings was evaluated for the sites of involvement, signal intensity, contrast characteristics, necrotic component as well as orbital, infratemporal, and intracranial extensions, especially cavernous sinuses, Meckel's cave, and the brain parenchyma. The mean age of the patients was 55.8±10.9 years and included 71% male. All the patients were positive for COVID-19 and the majority were diabetic. MRI showed predominant involvement of the maxillary sinus (17, 81%) and the ethmoidal sinus (15, 71.4%). The orbital extension was present in 18 cases (86%). T1-weighted imaging showed iso to low signal intensity in involved sinuses in the majority of the patients (9, 42.9%). Heterogeneously high signal intensity was observed in T2-weighted and short tau inversion recovery images in all the patients. Heterogenous contrast enhancement was present in 20 (95.2%) patients. The imaging spectrum of ROCM is variable. Multiplanar MRI with postcontrast images is a very useful complementary tool to the clinical evaluation to assess the extent of disease and its complications, which has a high mortality. Clinicians and radiologists should be aware of the imaging spectrums of ROCM.

Assessment of Awareness and Approach Regarding Antibiotic Prescription and Resistance among Different Level of Dental Students in a Tertiary Care Dental College, Karachi

OBJECTIVE: To evaluate the awareness and approach of dental students regarding antibiotic prescription and its resistance due to irrational use of antibiotics. Antibiotic resistance is spreading alarmingly throughout the world, including developed countries. The common causes of antibiotic resistance include over prescription, incomplete treatment and inappropriate self medication.Among different causes of antimicrobial resistance, irrational use of antibiotic is the most prominent one. METHODOLOGY: After approved by the Institutional Ethics Committee of Ziauddin University this cross-sectional study was conducted from 1st April, 2020 to 30th July,2020 at Ziauddin University. Third and final year dental students as well as house officers were enrolled and the computed sample size was 133 to which 5% non-response rate was added, therefore total 139 dental students were approached. Non-probability convenience sampling technique was used. A self- designed, self administered questionnaire was prepared to collect the demographic data and information regarding the prescription pattern of antibiotics amongst study subjects. All questions in the questionnaire were close ended. The questionnaire comprised information pertaining to demographic characteristics, standard guideline for antibiotic prescriptions, antibiotic stewardship and resistance, improper prescription and its consequences. The dental students were briefed about the purpose of the study and the significance of participation and a written informed consent was obtained from them. The awareness of dental students regarding antibiotics was the outcome factor. The data was analyzed by using SPSS version 22. RESULTS: Out of total 139 dental students majority (79.1%)were familiar to standard antibiotic prescription guidelines .(87.8%) responded amoxicillin is beta lactam, for probability of antibiotic abuse and antibiotics aid in recovery of infections majority showed awareness (92.1% and 84.9% respectively). Almost equal students inquire recent antibiotic course prior to prescription (90.6%) as well as take extra caution prescribing antibiotic in immune compromised patients (89.9%). CONCLUSION: This study concluded that majority of the dental students had good awareness regarding antibiotics and factors related to it, as participants responded positively to the 70% of awareness - based questions. KEYWORDS: Awareness. Antibiotics, Resistance, Prescription, Dental Students

Evidence supporting the use of therapeutic drug monitoring of ganciclovir in transplantation.

This review describes current knowledge of ganciclovir (GCV) and valganciclovir (ValGCV) pharmacokinetic/pharmacodynamic characteristics, highlighting the likely contribution from host genetic factors to interpatient variability. The evidence and challenges surrounding optimization of drug dosing through therapeutic drug monitoring (TDM) are examined, with recommendations made. Pharmacokinetic studies of current dosing guidelines have shown high interindividual and intraindividual variability of GCV concentrations. This is sometimes associated with a slow decline in cytomegalovirus (CMV) viral load in some transplant recipients. A high incidence of GCV-associated myelosuppression has limited the use of this drug in the transplant setting. Patient groups identified to benefit from GCV TDM include pediatric patients, cystic fibrosis with lung transplantation, obese with kidney transplantation, and patients with fluctuating renal function or on hemodialysis. The emergence of refractory resistant CMV, particularly in immune compromised patients, highlights the importance of appropriate dosing of these antivirals. Host genetic factors need to be considered where recently, two host genes were shown to account for interpatient variation during ganciclovir therapy. Therapeutic Drug Monitoring has been shown to improve target antiviral-level attainment. The use of TDM may guide concentration-based dose adjustment, potentially improving virological and clinical outcomes. However, evidence supporting the use of TDM in clinical practice remains limited and further study is needed in the transplant cohort. Further studies examining novel biomarkers are needed to guide target concentrations in prophylaxis and treatment. The use of TDM in transplant recipients is likely to improve the clinical efficacy of current antivirals and optimize outcomes in transplant recipients.

In Silico Identification of Cadmium Binding Protein and its Secreted Metalloproteins in Stenotrophomonas maltophilia

Background: Stenotrophomonas maltophilia is a pathogenic bacteria that causes serious infectious complications in humans, especially in immune-compromised patients. Stenotrophomonas maltophilia is a gram-negative bacterium that is multidrug-resistant. Objective: The purpose of the study is to understand the diverse cellular and biological functions of cadmium-binding metalloproteins and to predict their role in pathogenicity, regulation, and growth. Methodology: Different in silico approaches were used to check the Functional Annotation, Subcellular Localization, Gene Ontology, and Bacterial toxin prediction have been used to identify the cellular and biological function of Cd-binding metalloproteins in Stenotrophomonas maltophilia. Results: Identified 116 Cd-binding proteins from the whole proteome sequence and functional domain, family, localization, and toxicity were also studied. Conclusion: The outcomes revealed that this study could be used in understanding the 116 cadmiumbinding proteins from the whole proteome sequence. This study shows the survival, growth, and pathogenicity of the bacteria.

Novel Chewable Gum Sticks for The Treatment of Oral Candidiasis

Beeswax is used in medicine from ancient times treatment od oral candidacies is possible by formulation of chewable gum sticks consisting natural hydrophobic wax with anti-fungal drug clotrimazole. Gum sticks are smooth and compatible in oral cavity. Develop safe stable and instant release dosage form offers opportunity for treating immune compromised patients and maintaining their good oral health.

Immune Checkpoint Inhibitors in Advanced Cutaneous Squamous Cell Carcinoma: Real-World Experience from a Canadian Comprehensive Cancer Centre.

Immune checkpoint inhibitors (ICI) cemiplimab and pembrolizumab have revolutionized the treatment of advanced cutaneous squamous cell carcinoma (cSCC). We aimed to evaluate the effectiveness and safety of ICI in a real-world cSCC population, including patients with conditions that would exclude clinical trial participation. In this single-center, retrospective cohort study, we included all non-trial patients with advanced cSCC treated with ICI between 2017 and 2022. We evaluated investigator-assessed best overall response (BOR) and immune-related adverse events (irAEs). We correlated survival outcomes with age, performance status, immune status and irAEs. Of the 36 patients identified, the best overall response (BOR) to ICI was a partial response (PR) in 41.7%, a complete response (CR) in 27.8%, and stable disease in (SD) 13.9%. The progression-free survival (PFS) rate for 1 year was 58.1%; the median PFS was 21.3 months (95% CI 6.4-NE). The 1-year overall survival (OS) was 76.7%, and the median OS was 38.6 months (95% CI 25.4-NE). Immune-compromised patients, ECOG performance 2-3, and age ≥ 75 years were not significantly associated with PFS or OS. IrAE grades 3-4 were seen in 13.9% of patients. In our Canadian experience with real-world patients, ICI was an effective and safe treatment for advanced cSCC patients. Patients achieved great benefits with ICI regardless of age, immune status or ECOG performance status. We acknowledge the small sample size and retrospective methodology as the main limitations of our study.

A case of concomitant leukemoid reaction and mucormycosis in a patient with severe COVID-19 infection

Abstract Objectives Leukemoid Reaction (LR) signifies leukocytosis characterized by mature neutrophils. The incidence of LR is about 1 % among hospitalized patients. Mucormycosis is a rare, aggressive, fatal fungal infection that afflicts immune-compromised patients. This study discusses the case of concomitant leukemoid reaction and mucormycosis in a patient with severe COVID-19 infection. Case presentation A 45-year-old female patient was presented to the hospital with confirmed SARS-CoV-2 and was given supplemental oxygen and placed on mechanical ventilation. Her skin biopsy revealed non-septate hyphae with wide-angle branching. Her blood tests also revealed the presence of LR. Conclusions Severe COVID-19 infection causes new-onset hyperglycemia, which can lead to metabolic acidosis, toxic metabolite accumulation in the body due to renal failure, the release of stress hormones and inflammatory cytokines, and the occurrence of secondary bacterial and opportunistic fungal infections. The study has shown that LR in severe COVID-19 may be associated with severe infections (bacterial or fungal) and other pathophysiological changes in the body.

Chryseobacterium Bloodstream Infection in a Case of Non-Hodgkins Lymphoma: An Emerging Pathogen Complicating Clinical Management in Cancer Patients

Over the past decade, novel pathogens causing infections in patients have been identified. Chryseobacterium is one such emerging pathogen that is frequently reported in hospitalized patients. Case reports of bloodstream infections, and pneumonia due to Chryseobacterium spp in cancer patients from different parts of the world are drawing the attention of the clinical community to this bacterium as an emerging threat in patients with malignancies. Besides its propensity to cause serious infection to the immune-compromised patients, the antibiotic-resistant trait is posing a serious challenge, further complicating the clinical management of malignancies. We report a similar experience with the bacterium causing bloodstream infection in a patient with Non-Hodgkin lymphoma. The new automated identification systems have enabled us to identify these relatively uncommon pathogens in our clinical setting and also recognize their role in causing infection in hospitalized patients. Besides the difficulties in the treatment of these antibiotic-resistant pathogens, detecting their source within the healthcare setup remains a challenge for medical professionals.

Study of Frequency, Epidemiology of Nosocomial Infections in Healthcare Centres.

Infections are frequent complications of hospitalization. Nosocomial infections or healthcare associated infections or hospital acquired infections are endogenous or exogenous infections which a patient acquires either during hospitalization or soon after discharge from the hospital. Hospitals and hospital-like settings tend to gather many sick under one roof and hence, serve as a reservoir of numerous infectious agents. These overcrowded healthcare settings with inability to maintain hygienic conditions are threat not only to the patients but also to the healthcare workers. Increasing population of immune-compromised patients including the aged-ones, unsafe medical care, surgical procedure, injections, transplants are some of the major causes of spread of nosocomial infections. Nosocomial infections have severe adverse effects. It leads to emotional stress, functional disability and even death in certain cases. Mortality caused by nosocomial infections in India is more than any other form of accidental death. It also prolongs the hospital stays and adds to the economic burden of managing the underlying disease. The active cooperation of the Healthcare workers for better implementation of the existing preventive and control measures along with the technical advances will contribute much to fight against the nosocomial infections.

A temperature-dependent virus-binding assay reveals the presence of neutralizing antibodies in human cytomegalovirus gB vaccine recipients' sera.

Human cytomegalovirus (HCMV) remains an important cause of mortality in immune-compromised transplant patients and following congenital infection. Such is the burden, an effective vaccine strategy is considered to be of the highest priority. The most successful vaccines to date have focused on generating immune responses against glycoprotein B (gB) - a protein essential for HCMV fusion and entry. We have previously reported that an important component of the humoral immune response elicited by gB/MF59 vaccination of patients awaiting transplant is the induction of non-neutralizing antibodies that target cell-associated virus with little evidence of concomitant classical neutralizing antibodies. Here we report that a modified neutralization assay that promotes prolonged binding of HCMV to the cell surface reveals the presence of neutralizing antibodies in sera taken from gB-vaccinated patients that cannot be detected using standard assays. We go on to show that this is not a general feature of gB-neutralizing antibodies, suggesting that specific antibody responses induced by vaccination could be important. Although we can find no evidence that these neutralizing antibody responses are a correlate of protection in vivo in transplant recipients their identification demonstrates the utility of the approach in identifying these responses. We hypothesize that further characterization has the potential to aid the identification of functions within gB that are important during the entry process and could potentially improve future vaccine strategies directed against gB if they prove to be effective against HCMV at higher concentrations.

Achromobacter Hepatic Abscess Several Months After Laparoscopic Cholecystectomy: A Case Report and Review of Literature

Achromobacter xylosoxidans is a rare pathogen that causes opportunistic and nosocomial infections in immune-compromised patients. After a cholecystectomy, dropped stones can serve as nidus for abscess formation. We describe a rare case of hepatic abscess caused by Achromobacter xylosoxidans in a 40-year-old immune-competent woman who had a laparoscopic cholecystectomy 9 months previously.

In silico Prediction and Evaluation of Human Parainfluenza Virus-3 CD4+ T Cell Epitopes.

Human parainfluenza viruses type 3 (HPIV-3) through bronchiolitis and pneumonia is a common cause of lower respiratory tract infections. It is the main cause of hospitalization of infants and young children and also one of the main causes of morbidity and mortality in immuno-compromised and transplant patients. Despite many efforts, there is currently no specific anti-HPIV-3 drug or approved vaccine to prevent and control the virus. Identification of HPIV-3 epitopes with the capability of binding to human leukocyte antigen (HLA) class II molecules can be helpful in designing new vaccine candidates against HPIV-3 infection, and also can be useful for the in vitro stimulation and proliferation of HPIV-3-specific T cells for transplant and immunocompromised patients. To predict and comprehensively evaluate CD4+T cell epitope (HLA-II binders) from four main HPIV-3 antigens. In the present work, we predicted and comprehensively evaluated CD4+T cell epitope (HLA-II binders) from four main HPIV-3 antigens, including fusion protein (F), hemagglutininneuraminidase (HN), nucleocapsid (N) and matrix (M) proteins using bio- and immunoinformatics software. The toxicity, allergenicity, Blast screening and population coverage of the predicted epitopes were evaluated. The binding ability of the final selected epitopes was evaluated via a docking study. After several filtering steps, including blast screening, toxicity and allergenicity assay, population coverage and docking study, 9 epitopes were selected as candidate epitopes. The selected epitopes showed high population coverage and docking studies revealed a significantly higher binding affinity for the final epitopes in comparison with the negative control peptides. The final selected epitopes could be useful in designing vaccine candidates and for the treatment of immune-compromised individuals and patients with transplantation.