Burkholderia cepacia complex as a cause of community acquired bacteremia in a young immuncompetent male.

Burkholderia cepacia complex (BCC) is a well-recognized cause of nosocomial infections. We describe here a young healthy male who presented with fever and chest pain with ECG changes of acute pericarditis. Two sets of blood cultures at separate timings grew gram negative bacilli identified as BCC by molecular methods. The patient responded to intravenous ceftazidime despite high ceftazidime MIC's. The source of infection was probably contaminated nasal spray/nasal saline wash which he used after a balloon sinoplasty procedure one month ago. Issues related to accurate identification and susceptibility testing of BCC are also discussed.

Preventing Risks of Infections and Medication Errors in IV therapy (PRIME): a patient safety initiative.

BACKGROUND: Two major avoidable reasons for adverse events in hospital are medication errors and intravenous therapy-induced infections or complications. Training for clinical staff and compliance to patient safety principles could address these. METHODS: Joint Commission International (JCI) consultants created a standardised, 6-month training programme for clinical staff in hospitals. Twenty-one tertiary care hospitals from across south-east Asia took part. JCI trained the clinical consultants, who trained hospital safety champions, who trained nursing staff. Compliance and knowledge were assessed, and monthly audits were conducted. RESULTS: There was an overall increase of 29% in compliance with parameters around medication preparation and vascular access device management. CONCLUSION: The programme improved safe practice around preparing medications management and managing vascular access devices. The approach could be employed as a continuous quality improvement initiative for the prevention of medication errors and infusion-associated complications.

A co-infection of Pneumocystis jirovecii and Lophomonas blattarum causing pneumonia in a patient with adenocarcinoma of lung.

Patients with lung cancer suffer frequent infections which not only thwart the effect of oncological treatment but also affect overall survival. We present a fatal case where coinfection of Pneumocystis jirovecii and Lophomonas blattarum caused pneumonia in a patient with advanced and treated metastatic adenocarcinoma of lung. Cytomegalovirus (CMV) PCR was positive for the patient. Newer pathogens are not only emerging but also there is an increase in incidence of coinfections. Pneumonia due to coinfection of Pneumocystis jirovecii and Lophomonas blattarum is rare and unusual and requires high degree of suspicion and skill for the diagnosis.

Blocking common γ chain cytokine signaling ameliorates T cell-mediated pathogenesis in disease models.

The common γ chain (γc; IL-2RG) is a subunit of the interleukin (IL) receptors for the γc cytokines IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. The lack of appropriate neutralizing antibodies recognizing IL-2RG has made it difficult to thoroughly interrogate the role of γc cytokines in inflammatory and autoimmune disease settings. Here, we generated a γc cytokine receptor antibody, REGN7257, to determine whether γc cytokines might be targeted for T cell-mediated disease prevention and treatment. Biochemical, structural, and in vitro analysis showed that REGN7257 binds with high affinity to IL-2RG and potently blocks signaling of all γc cytokines. In nonhuman primates, REGN7257 efficiently suppressed T cells without affecting granulocytes, platelets, or red blood cells. Using REGN7257, we showed that γc cytokines drive T cell-mediated disease in mouse models of graft-versus-host disease (GVHD) and multiple sclerosis by affecting multiple aspects of the pathogenic response. We found that our xenogeneic GVHD mouse model recapitulates hallmarks of acute and chronic GVHD, with T cell expansion/infiltration into tissues and liver fibrosis, as well as hallmarks of immune aplastic anemia, with bone marrow aplasia and peripheral cytopenia. Our findings indicate that γc cytokines contribute to GVHD and aplastic anemia pathology by promoting these characteristic features. By demonstrating that broad inhibition of γc cytokine signaling with REGN7257 protects from immune-mediated disorders, our data provide evidence of γc cytokines as key drivers of pathogenic T cell responses, offering a potential strategy for the management of T cell-mediated diseases.

A case of Kytococcus schroeteri prosthetic valve endocarditis in a patient with COVID-19 infection.

64 years old male presented fever, gastrointestinal symptoms, COVID-19 infection with bioprosthetic mitral in situ, cardio embolic stroke 2 years ago. The 2 D ECHO showed a vegetation indicating infective endocarditis. Three paired blood cultures grew Kytococcus schroeteri. The organism was sensitive to Vancomycin, Teicoplanin, Gentamycin and Linezolid. Patient had multiorgan dysfunction which further deteriorated into failure, disseminated intravascular coagulation resulting into death of the patient.

The Prevalence and Antimicrobial Susceptibility Pattern of Gram-Positive Pathogens: Three-Year Study at a Tertiary Care Hospital in Mumbai, India.

Introduction The growing resistance pattern of the gram-positive pathogens along with a steady increase in minimum inhibitory concentration of the currently available antibiotics have led to an increase in morbidity and mortality rates in India. This study aims to access the shifting antibiotic susceptibility paradigm of the gram-positive pathogens in various infections at a tertiary care center. Methods This is a 3-year retrospective observational study which was performed from January 2016 to December 2018 at a tertiary care hospital in Mumbai. All clinically significant gram-positive cocci isolated from a variety of clinical specimens were studied for their prevalence and antimicrobial susceptibility. Results Out of 4,428 gram-positive isolates, Staphylococcus aureus (35.3%) was the commonly encountered pathogen, followed by Enterococcus spp. (32.1%) and coagulase-negative Staphylococcus (CoNS) (25.7%). S. aureus was majorly isolated from skin and soft tissue infections (60.3%), followed by patients with respiratory tract infections (18.2%) and blood stream infections (13%). Among S. aureus , particularly methicillin-resistant S. aureus (MRSA), prevalence increased from 29.5% in 2016 to 35.1% in 2018, with an overall prevalence of 33.6%. All S. aureus isolates were 100% sensitive toward vancomycin, linezolid, tigecycline, and teicoplanin. However, the CoNS isolates showed a higher resistance rate with reduced susceptibility toward linezolid and teicoplanin. High prevalence of resistance was observed across gram-positive isolates with commonly used antibiotics such as ciprofloxacin, levofloxacin, and erythromycin. While the prevalence of linezolid-resistant enterococcus (LRE) was 3.6%, vancomycin (VRE) and teicoplanin resistance among the enterococcus species was as high as 7.7% and 7.5%, respectively. Conclusion Rising methicillin resistance among the Staphylococcal species (MRSA and MR-CoNS) along with reduced susceptibility toward currently available anti-MRSA agents is a matter of serious concern as it limits the therapeutic options for treating multidrug resistant (MDR) gram-positive infections.

In silico Study and Solvent-free one-pot Synthesis of Tetrahydropyrimidine derivatives by Mechanochemistry Approach for Targeting Human Neutrophil Elastase against Lung Cancer.

BACKGROUND: Pyrimidine derivative has evinced its biological importance in targeting lung cancer by inhibiting neutrophil elastase. METHODS: All THPM derivatives were synthesized by the grindstone method at ambient temperature followed by molecular docking study for efficient binding interaction of THPM compounds by targeting human neutrophil elastase (HNE) (PDB ID: 5A0A) and In-silico ADMET study using PkCSM. Moreover, all synthesized compounds were characterized by spectroscopy techniques and screened for anti-cancer activity using in vitro HNE assay kit. RESULTS: We reported a one-pot solvent-free mechanochemical approach for synthesizing tetrahydropyrimidine (THPM) derivatives from various aromatic aldehydes, ethyl cyanoacetate, and urea followed by in silico study and evaluation against human neutrophil elastase (HNE) for treatment of lung cancer. We calibrated the best molecules that bound to specific targets more efficiently using a molecular docking approach and provided the desired efficacy. In-silico ADMET studies revealed that all best-scored compounds had drug-like characteristics for potential use as human neutrophil elastase inhibitors (HNE) in lung cancer treatment. Additionally, the in vitro studies revealed that compounds 1, 2, and 8 show potent HNE inhibitory activity for lung cancer treatment. CONCLUSION: In a nutshell, the tetrahydropyrimidine (THPM) scaffold and its derivatives may serve as potential HNE inhibitors for the development of a promising anti-cancer agent.

Post coronavirus disease- 19 invasive renal and gastrointestinal mucormycosis.

A 68-year-old female patient who was treated with anti-viral, steroids and biologics for coronavirus disease- 19 (COVID- 19) infection presented to our facility following right abdominal and flank pain since a week. Initially attributed to pancreatitis and right sided pyelonephritis, it was diagnosed as mucormycosis on KOH mount following CT-guided renal biopsy. She underwent right total nephrectomy and Whipple's surgery followed by Isavuconazole and liposomal Amphotericin B. This is a rare presentation of renal and gastrointestinal mucormycosis in a patient without diabetes mellitus following COVID- 19 infection. High suspicion and early diagnosis help in timely treatment of this life-threatening infection.

In vitro activity of Ceftazidime-Avibactam and its comparators against Carbapenem resistant Enterobacterales collected across India: results from ATLAS surveillance 2018 to 2019.

ATLAS (Antimicrobial Testing Leadership and Surveillance) detects trends in multi-drug resistance longitudinally over time. In the present study, the in vitro activity of ceftazidime-avibactam and comparators was analyzed against Escherichia coli (n = 458) and Klebsiella pneumoniae (n = 455)  isolates obtained from 9 centers across India. The overall susceptibility to ceftazidime-avibactam was observed to be 72% among K. pneumoniae isolates and 87% among E. coli isolates. Among the tested carbapenem resistant isolates, 51% of CR-K. pneumoniae and 24% of CR-E. coli were susceptible to ceftazidime- avibactam. OXA-48 like was identified in 52% of the K. pneumoniae isolates followed by co-production of NDM with OXA-48 like in 27%. NDM was predominantly identified in 68% of the E. coli isolates followed by OXA-48 like in 24% isolates. The findings suggest that ceftazidime- avibactam is a reasonable alternative to standard therapy for management of carbapenem resistant Enterobacterales infections particularly with K. pneumoniae and E. coli with the OXA-48 like genotype.

The implementation and outcome of a 2-year prospective audit and feedback based antimicrobial stewardship program at a private tertiary care hospital.

PURPOSE: Antimicrobial resistance has emerged as a major public health problem in India. Hence effective antimicrobial stewardship programs (AMSP) are needed. We report the design, implementation and results of a prospective audit and feedback based AMSP at a private tertiary care hospital. METHODS: During the study period - January 2018 to December 2019 - the prescription of restricted antimicrobials required the filling of a justification form which was reviewed by the antimicrobial stewardship committee (AMSC) at 48-72 â€‹h. Patients in whom the restricted antimicrobial was stopped earlier than 48 â€‹h were not applicable for review. The eligible prescriptions were judged as justified/unjustified by AMSC based on the patient's clinical and previous antimicrobial history, course, results of investigations/cultures, guidelines and communicated to the treating team. Compliance to the recommendations of the AMSC was measured. Days of therapy for each restricted antimicrobial/1000 patient days was calculated. Colistin resistance rates in pathogens causing central line associated blood stream infections (CLABSI) were compared with previous years. RESULTS: A total of 2397 restricted antimicrobials in 1366 patients were prescribed in the study period of which 1801 prescriptions were applicable for review (75%). Overall, 1.4% of admitted patients were prescribed restricted antimicrobials. The total days of therapy with restricted antimicrobials was 41/1000 patient days. The AMSC committee adjudged 12.5% of prescriptions as unjustified and recommendations for de-escalation were accepted in 89%. There was no significant difference in the study outcomes between 2018 and 2019. CONCLUSION: The prospective audit and feedback component of AMSP provided insight into the use of restricted antimicrobials at our hospital. This component should be considered by hospitals for inclusion in their AMSP program on an ongoing basis even if limited to a few drugs and in few areas of the hospital.

An unusual cause of fever and jaundice.

A 52 year old previously healthy woman from Mumbai presented with fever and jaundice of 10 days duration. At admission, she was jaundiced with tachycardia, tachypnea, hypoxia, hypotension, conjunctival congestion and mild erythematous flush over the skin. She had very high WBC counts and CRP's with direct hyperbilirubinemia and azotemia. Investigations for infectious causes of fever were negative. RT-PCR for SARS-CoV-2 in the nasopharynx was negative. However her SARS-CoV-2 antibodies were reactive. She also had echocardiographic and biochemical evidence of cardiac dysfunction. The diagnosis of Multisystem inflammatory syndrome-Adult (MIS-A) was thus established. She rapidly improved with intravenous immunoglobulin (2 gm/kg) and high dose steroids.

No correlation between Ct values and severity of disease or mortality in patients with COVID 19 disease.

There are several reports of Ct values of RT PCR assays for COVID 19 being associated with disease severity and infectivity. We studied the correlation between Ct values and disease severity and mortality at our hospital . All patients with RT PCR diagnosed COVID 19 illness admitted at the study site and for whom Ct values were available were included in the study. The patients with mild disease had significantly lower Ct values than patients with severe disease but had also been tested significantly earlier in the illness than those with severe disease. The patients who died had significantly lower Ct values than patients who survived but here again they had significantly shorter duration of symptoms before testing. We therefore recommend that the time of testing since onset of symptoms should be controlled for while correlating Ct values with disease severity.

Six-year study on peripheral venous catheter-associated BSI rates in 262 ICUs in eight countries of South-East Asia: International Nosocomial Infection Control Consortium findings.

BACKGROUND: Short-term peripheral venous catheter-associated bloodstream infection rates have not been systematically studied in Asian countries, and data on peripheral venous catheter-associated bloodstream infections incidence by number of short-term peripheral venous catheter days are not available. METHODS: Prospective, surveillance study on peripheral venous catheter-associated bloodstream infections conducted from 1 September 2013 to 31 May 2019 in 262 intensive care units, members of the International Nosocomial Infection Control Consortium, from 78 hospitals in 32 cities of 8 countries in the South-East Asia Region: China, India, Malaysia, Mongolia, Nepal, Philippines, Thailand, and Vietnam. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System. RESULTS: We followed 83,295 intensive care unit patients for 369,371 bed-days and 376,492 peripheral venous catheter-days. We identified 999 peripheral venous catheter-associated bloodstream infections, amounting to a rate of 2.65/1000 peripheral venous catheter-days. Mortality in patients with peripheral venous catheter but without peripheral venous catheter-associated bloodstream infections was 4.53% and 12.21% in patients with peripheral venous catheter-associated bloodstream infections. The mean length of stay in patients with peripheral venous catheter but without peripheral venous catheter-associated bloodstream infections was 4.40 days and 7.11 days in patients with peripheral venous catheter and peripheral venous catheter-associated bloodstream infections. The microorganism profile showed 67.1% were Gram-negative bacteria: Escherichia coli (22.9%), Klebsiella spp (10.7%), Pseudomonas aeruginosa (5.3%), Enterobacter spp. (4.5%), and others (23.7%). The predominant Gram-positive bacteria were Staphylococcus aureus (11.4%). CONCLUSIONS: Infection prevention programs must be implemented to reduce the incidence of peripheral venous catheter-associated bloodstream infections.

Current Drug Repurposing Strategies for Rare Neurodegenerative Disorders.

Rare diseases are life-threatening or chronically debilitating low-prevalent disorders caused by pathogenic mutations or particular environmental insults. Due to their high complexity and low frequency, important gaps still exist in their prevention, diagnosis, and treatment. Since new drug discovery is a very costly and time-consuming process, leading pharmaceutical companies show relatively low interest in orphan drug research and development due to the high cost of investments compared to the low market return of the product. Drug repurposing-based approaches appear then as cost- and time-saving strategies for the development of therapeutic opportunities for rare diseases. In this article, we discuss the scientific, regulatory, and economic aspects of the development of repurposed drugs for the treatment of rare neurodegenerative disorders with a particular focus on Huntington's disease, Friedreich's ataxia, Wolfram syndrome, and amyotrophic lateral sclerosis. The role of academia, pharmaceutical companies, patient associations, and foundations in the identification of candidate compounds and their preclinical and clinical evaluation will also be discussed.

Predominance of multidrug-resistant Gram-negative organisms as cause of surgical site infections at a private tertiary care hospital in Mumbai, India.

Background: This study aims to study the incidence, microbial aetiology and antimicrobial susceptibility of surgical site infections (SSIs) at a private tertiary care hospital in Mumbai, India, and compare it with previously published data from the same institute as well as literature. Methods: This is a prospective observational study done over 6 years (January 2013-December 2018) at a 750-bed private multi-specialty hospital in Mumbai, India, among all patients undergoing clean and clean-contaminated surgeries. Standard guidelines for preventing, diagnosing and classifying SSIs were followed. The incidence rates of SSI (overall and specialty specific), microbial aetiology and antibiotic susceptibility of SSI were calculated and expressed as percentages. Results: A total of 55,553 patients underwent clean and clean-contaminated surgeries during the study period. The overall SSI rate was 1.0% (555 cases). The SSI rate in clean surgeries was 0.97% and in clean-contaminated surgeries was 1.03%. Sixty-five per cent of SSIs were due to Gram-negative bacilli, 30% were due to Gram-positive cocci and 4% were due to Candida. Klebsiella pneumoniae (19%), Escherichia coli (17%), Pseudomonas aeruginosa (13%), Staphylococcus aureus(12%) and Enterococcus (10%) were the top five organisms. The overall susceptibility rate of the Gram-negative isolates to beta-lactam-beta-lactamase inhibitor combinations was 60% and carbapenems was 73%. The prevalence of methicillin resistance in S. aureus was 44% and coagulase-negative Staphylococcus was 84%. The crude mortality rate was 1%. Conclusions: Although the SSI rate is comparable to established international benchmarks, the predominance of multidrug-resistant Gram-negative organisms is a matter of serious concern.

Prevalence of COVID-19 antibodies in healthcare workers at the peak of the pandemic in Mumbai, India: A preliminary study.

Healthcare worker (HCW) infections due to COVID-19 are of serious consequence. Testing for antibodies against COVID-19 in HCWs has been previously recommended. We conducted a serosurvey in HCWs at a private hospital in Mumbai which is treating COVID patients. A total of 244 HCWs were tested. The prevalence of infection in asymptomatic HCWs was 4.3% and in previously symptomatic untested HCWs was 70%. We recommend that HCWs with a previous history of COVID symptoms who were not tested/tested negative by reverse transcription-polymerase chain reaction should be tested for antibodies at least 2 weeks after onset of symptoms.

Reorienting Nurturing Care for Early Childhood Development during the COVID-19 Pandemic in Kenya: A Review.

In Kenya, millions of children have limited access to nurturing care. With the Coronavirus disease 2019 (COVID-19) pandemic, it is anticipated that vulnerable children will bear the biggest brunt of the direct and indirect impacts of the pandemic. This review aimed to deepen understanding of the effects of COVID-19 on nurturing care from conception to four years of age, a period where the care of children is often delivered through caregivers or other informal platforms. The review has drawn upon the empirical evidence from previous pandemics and epidemics, and anecdotal and emerging evidence from the ongoing COVID-19 crisis. Multifactorial impacts fall into five key domains: direct health; health and nutrition systems; economic protection; social and child protection; and child development and early learning. The review proposes program and policy strategies to guide the reorientation of nurturing care, prevent the detrimental effects associated with deteriorating nurturing care environments, and support the optimal development of the youngest and most vulnerable children. These include the provision of cash transfers and essential supplies for vulnerable households and strengthening of community-based platforms for nurturing care. Further research on COVID-19 and the ability of children's ecology to provide nurturing care is needed, as is further testing of new ideas.