Identifying risk factors for blood culture negative infective endocarditis: An international ID-IRI study.

Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE. Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI). The study analysing one of the largest case series ever reported was conducted across 41 centers in 13 countries. We analysed the database to determine the predictors of BCNE using univariate and logistic regression analyses. Results: Blood cultures were negative in 101 (11.65 %) of 867 patients. We disclosed that as patients age, the likelihood of a negative blood culture significantly decreases (OR 0.975, 95 % CI 0.963-0.987, p < 0.001). Additionally, factors such as rheumatic heart disease (OR 2.036, 95 % CI 0.970-4.276, p = 0.049), aortic stenosis (OR 3.066, 95 % CI 1.564-6.010, p = 0.001), mitral regurgitation (OR 1.693, 95 % CI 1.012-2.833, p = 0.045), and prosthetic valves (OR 2.539, 95 % CI 1.599-4.031, p < 0.001) are associated with higher likelihoods of negative blood cultures. Our model can predict whether a patient falls into the culture-negative or culture-positive groups with a threshold of 0.104 (AUC±SE = 0.707 ± 0.027). The final model demonstrates a sensitivity of 70.3 % and a specificity of 57.0 %. Conclusion: Caution should be exercised when diagnosing endocarditis in patients with concurrent cardiac disorders, particularly in younger cases.

Factors affecting mortality in COVID-19-associated pulmonary aspergillosis: An international ID-IRI study.

Background: This study aimed to identify factors that influence the mortality rate of patients with coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA). Methods: In this cross-sectional study, data from 23 centers across 15 countries, spanning the period of March 2020 to December 2021, were retrospectively collected. The study population comprised patients who developed invasive pulmonary aspergillosis while being treated for COVID-19 in the intensive care unit. Cox regression and decision tree analyses were used to identify factors associated with mortality in patients with CAPA. Results: A total of 162 patients (males, 65.4 %; median age: 64 [25th-75th: 54.0-73.8] years) were included in the study, of whom 113 died during the 90-day follow-up period. The median duration from CAPA diagnosis to death was 12 (25th-75th: 7-19) days. In the multivariable Cox regression model, an age of ≥65 years (hazard ratio [HR]: 2.05, 95 % confidence interval [CI]: 1.37-3.07), requiring vasopressor therapy at the time of CAPA diagnosis (HR: 1.80, 95 % CI: 1.17-2.76), and receiving renal replacement therapy at the time of CAPA diagnosis (HR: 2.27, 95 % CI: 1.35-3.82) were identified as predictors of mortality. Decision tree analysis revealed that patients with CAPA aged ≥65 years who received corticosteroid treatment for COVID-19 displayed higher mortality rates (estimated rate: 1.6, observed in 46 % of patients). Conclusion: This study concluded that elderly patients with CAPA who receive corticosteroids are at a significantly higher risk of mortality, particularly if they experience multiorgan failure.

Factors influencing mortality in COVID-19-associated mucormycosis: The international ID-IRI study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first 3 months post-COVID-19 diagnosis. Data collected through the ID-IRI included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29 ± 13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis. Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age (hazard ratio [HR] = 1.06, [P < .001]), rituximab use (HR = 21.2, P = .05), and diabetic ketoacidosis (HR = 3.58, P = .009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR = 8.81, P < .001). The utilization of rituximab and diabetic ketoacidosis, along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Over a third of patients who developed mucormycosis after COVID-19 died. Older people, those on specific immunosuppressive treatments, and those with diabetic ketoacidosis had a higher risk of death. However, undergoing surgery as part of treatment significantly improved survival.

Burden of bacterial antimicrobial resistance in low-income and middle-income countries avertible by existing interventions: an evidence review and modelling analysis.

National action plans enumerate many interventions as potential strategies to reduce the burden of bacterial antimicrobial resistance (AMR). However, knowledge of the benefits achievable by specific approaches is needed to inform policy making, especially in low-income and middle-income countries (LMICs) with substantial AMR burden and low health-care system capacity. In a modelling analysis, we estimated that improving infection prevention and control programmes in LMIC health-care settings could prevent at least 337 000 (95% CI 250 200-465 200) AMR-associated deaths annually. Ensuring universal access to high-quality water, sanitation, and hygiene services would prevent 247 800 (160 000-337 800) AMR-associated deaths and paediatric vaccines 181 500 (153 400-206 800) AMR-associated deaths, from both direct prevention of resistant infections and reductions in antibiotic consumption. These estimates translate to prevention of 7·8% (5·6-11·0) of all AMR-associated mortality in LMICs by infection prevention and control, 5·7% (3·7-8·0) by water, sanitation, and hygiene, and 4·2% (3·4-5·1) by vaccination interventions. Despite the continuing need for research and innovation to overcome limitations of existing approaches, our findings indicate that reducing global AMR burden by 10% by the year 2030 is achievable with existing interventions. Our results should guide investments in public health interventions with the greatest potential to reduce AMR burden.

Long COVID in Pakistan: a cross-sectional analysis of health and psychosocial outcomes.

According to the World Health Organization-led Delphi consensus, long COVID corresponds to the occurrence of symptoms beyond twelve weeks after the onset of acute COVID-19 illness that cannot be explained by alternate diagnosis. This cross-sectional study aimed to analyse the impacts of long COVID on general health and psychosocial well-being. For this study, the participants were interviewed either face to face or via telephone, and their responses were recorded on a questionnaire capturing information on demographics, COVID-19 status, duration of symptoms and long COVID symptoms. The psychosocial impacts of the pandemic were assessed using scales like Short Mood and feeling questionnaire (sMFQ), Warwick-Edinburgh Mental Well-being Scale (WEMWBS), Generalized Anxiety Disorder Assessment (GAD-7) and Perceived Stress Scale (PSS). Regression analysis was conducted to analyse the predictors of long COVID. A total of 300 participants were interviewed, of which 155 (52%) had COVID-19 illness. Of these 54 (35%) had persistent symptoms for a period of more than 12 weeks classified as long COVID. Muscle problems and fatigue were the most frequent (14.7%) symptoms encountered, followed by breathing problems (12.6%) and cognitive issues (12.6%). The symptoms of decrease in appetite and confusion or disorientation during the initial phase of the infection were associated with long COVID. The majority of the participants (83.3%) had moderate level of perceived stress, while moderate to severe levels of stress were observed in 17.3% of the individuals. Moreover, a high level of positive mental well-being was also observed. This study highlights the need for further research into the clinical aspects and implications of long COVID in Pakistan and emphasizes the importance of ongoing support for affected individuals.

Case of Carbapenem-Resistant Salmonella Typhi Infection, Pakistan, 2022.

Salmonella Typhi infection in a patient in Pakistan initially responded to standard treatment but failed to respond to subsequent treatment. The first strain was susceptible to carbapenems and azithromycin; subsequent strains harbored the NDM-5 gene. Treatment with a combination of intravenous meropenem and colistin was successful. Carbapenem-resistant Salmonella Typhi emergence will hinder treatment.

Self-reported antibiotic stewardship and infection control measures from 57 intensive care units: An international ID-IRI survey.

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.

International Multicentre Study of Candida auris Infections.

Background:Candida auris has emerged globally as a multi-drug resistant yeast and is commonly associated with nosocomial outbreaks in ICUs. Methods: We conducted a retrospective observational multicentre study to determine the epidemiology of C. auris infections, its management strategies, patient outcomes, and infection prevention and control practices across 10 centres from five countries. Results: Significant risk factors for C. auris infection include the age group of 61-70 years (39%), recent history of ICU admission (63%), diabetes (63%), renal failure (52%), presence of CVC (91%) and previous history of antibiotic treatment (96%). C. auris was commonly isolated from blood (76%). Echinocandins were the most sensitive drugs. Most common antifungals used for treatment were caspofungin (40%), anidulafungin (28%) and micafungin (15%). The median duration of treatment was 20 days. Source removal was conductedin 74% patients. All-cause crude mortality rate after 30 days was 37%. Antifungal therapy was associated with a reduction in mortality (OR:0.27) and so was source removal (OR:0.74). Contact isolation precautions were followed in 87% patients. Conclusions:C. auris infection carries a high risk for associated mortality. The organism is mainly resistant to most azoles and even amphotericin-B. Targeted antifungal therapy, mainly an echinocandin, and source control are the prominent therapeutic approaches.

Vector-borne and zoonotic infections and their relationships with regional and socioeconomic statuses: An ID-IRI survey in 24 countries of Europe, Africa and Asia.

BACKGROUND: In this cross-sectional, international study, we aimed to analyze vector-borne and zoonotic infections (VBZI), which are significant global threats. METHOD: VBZIs' data between May 20-28, 2018 was collected. The 24 Participatingcountries were classified as lower-middle, upper-middle, and high-income. RESULTS: 382 patients were included. 175(45.8%) were hospitalized, most commonly in Croatia, Egypt, and Romania(P = 0.001). There was a significant difference between distributions of VBZIs according to geographical regions(P < 0.001). Amebiasis, Ancylostomiasis, Blastocystosis, Cryptosporidiosis, Giardiasis, Toxoplasmosis were significantly more common in the Middle-East while Bartonellosis, Borreliosis, Cat Scratch Disease, Hantavirus syndrome, Rickettsiosis, Campylobacteriosis, Salmonellosis in Central/East/South-East Europe; Brucellosis and Echinococcosis in Central/West Asia; Campylobacteriosis, Chikungunya, Tick-borne encephalitis, Visceral Leishmaniasis, Salmonellosis, Toxoplasmosis in the North-Mediterranean; CCHF, Cutaneous Leishmaniasis, Dengue, Malaria, Taeniasis, Salmonellosis in Indian Subcontinent; Lassa Fever in West Africa. There were significant regional differences for viral hemorrhagic fevers(P < 0.001) and tick-borne infections(P < 0.001), and according to economic status for VBZIs(P < 0.001). The prevalences of VBZIs were significantly higher in lower-middle income countries(P = 0.001). The most similar regions were the Indian Subcontinent and the Middle-East, the Indian Subcontinent and the North-Mediterranean, and the Middle-East and North-Mediterranean regions. CONCLUSIONS: Regional and socioeconomic heterogeneity still exists for VBZIs. Control and eradication of VBZIs require evidence-based surveillance data, and multidisciplinary efforts.

Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey.

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.

Outcome of upper respiratory tract infections in healthy children: Antibiotic stewardship in treatment of acute upper respiratory tract infections.

OBJECTIVE: The objective of the study was to assess the outcome of upper respiratory tract infections (URTI) in healthy children. METHODS: This descriptive study was conducted on 314 children aged 3-36 months in the paediatric outpatient clinic and emergency department with symptoms of URTI (fever, cough, rhinorrhoea) for ≤5 days. Patient's demographics, clinical features, laboratory data and outcome were recorded. Follow up phone calls were made to parents on day 7 (response 93.6%) and day 14 (response 94.6%) to record outcome. RESULTS: A total of 314 children with URTIs were included. Majority (57.6%) were males and <1year of age (40%). Common manifestations of URTI were fever (89%), cough (79%), rhinorrhoea (62%), pharyngitis (79%) and conjunctivitis (46%). More than half (53%) had history of contact with URTI in a family member. Mean duration of symptoms was 2.7±1.3 days. Majority (93%) of children were given supportive treatment and only 6.7% received antibiotics initially. Most of children (76%) recovered within one week and 91.8% within two weeks with supportive care only. Only 4% children were hospitalized and 12% required follow up visit of which 16% needed oral antibiotics. Complications or deaths did not occur. CONCLUSIONS: Majority of URTIs in healthy children resolved with supportive treatment and do not require antibiotics. Antibiotic stewardship in simple URTIs should be practiced using awareness and advocacy campaigns.

Kawasaki disease: Clinico-laboratory spectrum and outcome in a cohort of children treated at a tertiary care hospital in Islamabad, Pakistan.

OBJECTIVE: To describe the demographics; clinical, laboratory, echocardiographic findings; treatment and outcome in a cohort of children with Kawasaki disease in a tertiary care hospital. METHODS: This is a descriptive, observational, retrospective cohort study conducted at Shifa International Hospital, Islamabad, from January 2013-June 2019. Children who met the criteria for Kawasaki disease according to the American Heart Association and American Academy of Pediatrics guidelines were included. RESULTS: A total of 25 children who met the criteria of Kawasaki disease were included. Their mean age was 43 months (4-150 months). Majority (76%) were males. Eighteen (72%) had complete Kawasaki disease and 7 (28%) had incomplete Kawasaki disease. Fever (> five days) was present in 20 (80%) patients. Eight patients (32%) had echocardiographic changes, out of which two patients (25%) had complete Kawasaki disease and six patients (75%) had incomplete Kawasaki disease. Intravenous immunoglobulin was given to all patients. Fifteen children (60%) received intravenous immunoglobulin within 10 days of fever. None required a second dose. All patients received high dose aspirin at diagnosis which was reduced to antiplatelet dose after resolution of fever for ≥48hrs. Eighteen patients (72%) came for regular follow up. Follow up at 6 months showed complete resolution of echocardiographic changes in six patients (75%), 1 (12.5%) was lost to follow up and one (12.5%) child had persistent coronary artery dilatation. CONCLUSION: Complete KD was present in 72% of our cohort of children. Coronary artery abnormalities were present in one third of these children, at younger age and more common in those with incomplete KD but recovered in most.

The Lancet Infectious Diseases Commission on antimicrobial resistance: 6 years later.

In 2013, a Lancet Infectious Diseases Commission described the state of antimicrobial resistance worldwide. Since then, greater awareness of the public health ramifications of antimicrobial resistance has led to national actions and global initiatives, including a resolution at the high-level meeting of the UN General Assembly in 2016. Progress in addressing this issue has ranged from a ban on irrational drug combinations in India to commitments to ban colistin as a growth promoter in animals, improve hospital infection control, and implement better antimicrobial stewardship. Funds have been mobilised, and regulatory barriers to new antibiotic development have been relaxed. These efforts have been episodic and uneven across countries, however. Sustained funding for antimicrobial resistance and globally harmonised targets to monitor progress are still urgently needed. Except for in a few leading countries, antimicrobial resistance has not captured the sustained focus of national leaders and country-level actors, including care providers.

Recurrent aseptic meningitis: A rare clinical presentation of Sjogren's syndrome.

Sjogren's syndrome most commonly presents with dry eyes, dry mouth, joint pain and fatigue. However, recurrent aseptic meningitis, reported as the most uncommon initial symptom, was the presenting feature in our case. We present the case of a 19-year-old female with recurrent episodes of aseptic meningitis. She presented with fever, headache, vomiting and photophobia. Neurological examination showed neck stiffness. Fundoscopy was normal. On two previous occasions her cerebrospinal fluid analysis was consistent with meningitis; however, it was normal at this presentation. Review of system revealed history of fatigue and sicca symptoms since early childhood. Autoimmune workup showed antinuclear antibodies with a titer of 1:400 and positive anti SSA (Ro) antibodies that led to the diagnosis of Sjogren's syndrome. She responded well to intravenous steroids, followed by oral prednisolone and hydroxychloroquine. To conclude, diagnosis of Sjogren's syndrome may also be considered in a patient presenting with recurrent aseptic meningitis.

Portraying infective endocarditis: results of multinational ID-IRI study.

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).

Leukocyte adhesion defect: An uncommon immunodeficiency.

Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency disorder with autosomal recessive inheritance which is characterized by presence of a defect of phagocytic function resulting from a lack of leukocyte cell surface expression of b2 integrin molecules (CD11 and CD18) that are essential for chemotaxis. The classic symptoms of the disease are failure of separation of the umbilical cord and recurrent bacterial infections, which continue throughout life. We describe here two cases of infants who presented with characteristic history of recurrent infections, delayed separation of umbilical cord and marked leukocytosis.

Neurobrucellosis: A report of two cases.

Neurobrucellosis is a rare complication of brucellosis, a common zoonosis with multisystem involvement. Its clinical presentation is quite heterogeneous and diagnosis requires a high index of suspicion in patients from endemic areas. We present two cases of neurobrucellosis with widely varying clinical involvement from a tertiary center in Pakistan. Our case report emphasizes that neurobrucellosis should be considered in evaluation of patients with unexplained neurological symptoms..