Background: Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most lifethreatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis. Methods: A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intentionto-treat population). The trial was registered at clinicaltrials.gov (NCT04521309). Findings: Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54 §13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087À1.272), arm II (RR, 0.5; 95% CI, 0.171À1.463), arm III (RR, 0.167; 95% CI, 0.024À1.145), and arm IV (RR, 0.667; 95% CI, 0.268À1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127À400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study. Interpretation: Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression. Funding: Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).

Background An outbreak of Candida auris began globally in 2014 including Pakistan and since then it has emerged as a nosocomial multi-drug resistant pathogen. The aim of this study was to assess the clinical spectrum and outcome of patients, from a single center in Pakistan, in whom C. auris was isolated. Methods A retrospective study was conducted on 92 patients; ≥16 years with at least one culture positive for C. auris, at the Aga Khan University Hospital Karachi, Pakistan from Sept 2014-Mar 2017.Demographics, clinical history, management and outcome were studied. A logistic regression model was used to identify the risk factors for mortality. Results We identified 92 patients with C. auris (193 isolates), of whom 52.2% were males. Mean age was 54.14 ± 20.4 years. Positive cultures were obtained after a median hospital stay of 14 days. Most patients had a history of surgery (57.6%), antibiotic use (95.6%), ICU stay (44.6%), indwelling lines (88.04%) and isolation of another multi-resistant organism (52.2%).Most patients were symptomatic (70.7%). Amongst these, 38 had candidemia while 27 had non-candidemia infections. Sites of infection included central lines (35), urinary tract (19), peritonitis (4), nosocomial ventriculitis (1), empyema (1), fungal keratitis (1) otitis externa (1) and surgical site (1). Fluconazole resistance was 100% while 28.5 and 7.9% were Voriconazole and Amphotericin resistant respectively. Overall crude mortality was 42.4% while 14-day mortality was 31.5%. Both infected and colonized cases shared similar mortality (46.2% vs 33.3%; p -value = 0.25). Among infected cases mortality was high in candidemia compared to non-candidemia (60.5% vs 25.9%) in which deaths related to C. auris were 34.2% vs 22.2% respectively. On multivariate analysis candidemia (AOR 4.2, 95% CI: 1.09–16.49; p-value = 0.037) was associated with greater mortality with source control being the only protective factor for mortality (AOR 0.22, 95% CI: 0.05–0.92; p-value0.038] while ICU stay, rapidity of blood culture clearance, DM, malignancy and MDR co-infection had no impact. Conclusion Patients with C.auris from a single center in Pakistan have a wide clinical spectrum with line associated infection being the predominant site of infection. Candidemia leads to high mortality while source control improves outcome.

Candida auris has emerged as a nosocomial multi-drug resistant pathogen. This study aimed to compare the risk factors and outcomes of C. auris candidemia patients with non-C. auris candidemia, at a single center in Pakistan. A retrospective study compared 38 C. auris with 101 non-C. auris (36 C. albicans, 38 C. tropicalis, and 27 C. parapsilosis) candidemia patients between September 2014 and March 2017 at the Aga Khan University Hospital, Pakistan. Demographics, clinical history, management and outcomes were studied. Prior history of surgery (adjusted odds ratio [aOR] 4.9, 95% confidence interval [CI]: 1.4–17.5), antifungals exposure (aOR 38.3, 95% CI: 4.1–356) and prior MDR bacteria isolation (aOR 5.09, 95% CI: 1.6–15.9) were associated with C. auris candidemia. On survival analysis both groups of patients had similar outcome in terms of mortality (62.6% vs. 52.54%, hazard ratio [HR] 1.45, 95% CI: 0.84–2.4, P-value = .17) and microbiological failure rates (42.3% vs. 32.2%, HR 0.65, 95% CI: 0.35–1.2, P-value = .17) however, C. auris patients had a higher mean hospital stay (36.32 days vs. 14.8 days, P-value = <.001) and higher >15-day in-hospital stay from positive culture (HR 2.68, 95% CI: 1.1–6.3, P-value = .025). Antifungal susceptibility was different, with C. auris more often resistant to voriconazole (29.6% vs. 0%) and amphotericin (3.7 vs. 0%); though no echinocandin resistance was detected in either group. As opposed to other Candida species, C. auris candidemia occurred after nosocomial exposure, and its source was most commonly an indwelling line. Although these patients had a higher in-hospital stay, but there was no excess mortality when compared to other Candida species.

Ralstonia species are Gram-negative bacilli that have increasingly been recognized as emerging nosocomial pathogens, particularly in immunocompromised hosts. Ralstonia pickettii is the most clinically important pathogen from the Ralstonia genus. Nosocomial outbreaks of Ralstonia pickettii infections brought about by the use of contaminated medical solutions, including saline, sterile water, as well as disinfectants, have been reported. There have been case reports of invasive infections with variable presentations. Here, we describe three cases of Ralstonia pickettii bacteremia during a period of one year in a tertiary care hospital in Karachi, Pakistan. The first case was a 76-year-old male, known case of type 2 diabetes mellitus (DM), hypertension, and amyotrophic lateral sclerosis, who presented with complaints of burning micturition, hematuria, and fever. The patient had a history of multiple hospital admissions in the recent past. His blood culture was found to be positive for Ralstonia pickettii. A computed tomography scan of the kidneys, ureter, and bladder (CT KUB) was suggestive of pyelonephritis. The patient improved on intravenous meropenem. The second case was a 47-year-old man, who was admitted with a gunshot injury to the neck, resulting in complete cervical cord resection and mild hydrocephalus with intraventricular hemorrhage. The patient had a prolonged intensive care unit (ICU) stay, which was complicated by ventilator-associated pneumonia with Acinetobacter and central line-associated bloodstream infection (CLABSI) with Ralstonia pickettii. He was treated with meropenem and colistin but continued to deteriorate and expired. The third case was a 46-year-old lady, known case of end-stage renal disease (ESRD), who was admitted with prosthetic valve endocarditis. She had a prolonged hospital stay complicated by CLABSI with Ralstonia pickettii, improved on meropenem, but later died due to fungemia. Ralstonia pickettii is an emerging cause of nosocomial infection in patients, particularly those with a prolonged hospital stay, and can cause invasive and severe infections.

Introduction: In Pakistan, the first case of COVID-19 was reported in February of 2020, cases peaked in June, and by January 2021, approximately 500,000 confirmed cases and over 10,000 deaths have been reported. There is a lack of data in Pakistan of the demographics, clinical characteristics, and outcome of patients with COVID-19 pneumonia, particularly those with severe illness, which we aim to assess. Methods: This is a single-centered, observational study conducted at the COVID unit of the Shaheed Mohtarma Benazir Bhutto Institute of Trauma in Karachi, Pakistan. A manual medical record review of patients admitted from April 24, 2020 to August 24, 2020 was conducted, and all patients with polymerase chain reaction (PCR) positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) with moderate, severe, and critical COVID-19 pneumonia were included. Results: Of 299 patients, the median age was 60 years (50-65). Males accounted for 221 (73.9%). Most common symptoms were shortness of breath seen in 270 (90.3%) and fever in 225 (75.3%) patients. Diabetes mellitus (51.2%) and hypertension (50.3%) were the predominant co-morbidities. COVID disease was categorized on admission as moderate in 68 (22.7%), severe in 151 (50.5%), and critical in 80 (26.8%) patients. Survival analysis was done in 252 patients, all of whom received steroids, while tocilizumab was administered to 111 (44%) patients. Hundred (39.7%) patients received non-invasive ventilation (NIV), while 57 (22.6%) were placed on mechanical ventilation. Overall, 95 (37.7%) patients died. Factors associated with mortality included older age with those above 60 years more likely to die (odds ratio [OR]: 1.925; 95% CI: 1.148-3.228; pvalue: 0.009), presence of co-morbidities (OR 1.843; 95% CI: 0.983-3.456; p value: 0.070), development of cytokine release syndrome (CRS) (73 [56.2%] vs 57 [43.8%], p value: <0.001), acute kidney injury (31 [81.6%] vs 7 [18.4%], p value: <0.001), cardiac complications (12 [75%] vs 4 [25%], p value: 0.002), and sepsis (29 [87.9%] vs 4 [12.1%], p value: <0.001). Non-survivors were more likely to develop acute respiratory distress syndrome (ARDS), having been placed on NIV and mechanical ventilation. Laboratory parameters at final outcome found that in non-survivors, median total leukocyte count, C-reactive protein (CRP), neutrophil lymphocyte ratio (NLR), and lactate dehydrogenase (LDH) were higher, while absolute lymphocyte count and platelet counts were lower which were found to be statistically significant compared to survivors. Conclusion: In this study of patients with severe COVID-19 pneumonia at a public sector hospital in Karachi, Pakistan, most were males, and the average age was 60 years. Mortality was high, and associated factors included older age, presence of comorbid conditions, and the development of ARDS, CRS, and sepsis.