Co-prevalent infections in adults with HIV-associated cryptococcal meningitis are associated with an increased risk of death: a nested analysis of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) cohort

Background: HIV-associated cryptococcal meningitis accounts for 15% of AIDS related deaths globally. In sub-Saharan Africa, acute mortality ranges from 24% to 100%. In addition to the mortality directly associated with cryptococcosis, patients with HIV-associated cryptococcal meningitis are at risk of a range of opportunistic infections (OIs) and hospital acquired nosocomial infections (HAIs). The attributable mortality associated with co-prevalent infections in cryptococcal meningitis has not been evaluated. Methods: As part of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) trial, consecutive HIV-positive adults with cryptococcal meningitis were randomised to one of five anti-fungal regimens and followed up until 10-weeks. We conducted a retrospective case note review of ACTA participants recruited from Queen Elizabeth Central Hospital in Blantyre, Malawi to describe the range and prevalence of OIs and HAIs diagnosed, and the attributable mortality associated with these infections. Results: We describe the prevalence of OIs and HAIs in 226 participants. Baseline median CD4 count was 29 cell/mm3, 57% (129/226) were on anti-retroviral therapy. 56% (127/226) had at least one co-prevalent infection during the 10-week study period. Data were collected for 187 co-prevalent infection episodes. Suspected blood stream infection was the commonest co-prevalent infection diagnosed (34/187, 18%), followed by community-acquired pneumonia (32/187, 17%), hospital-acquired pneumonia (13/187, 7%), pulmonary tuberculosis (12/187, 6%) and confirmed blood stream infections (10/187, 5%). All-cause mortality at 10-weeks was 35% (80/226), diagnosis of an OI or HAI increased the risk of death at 10 weeks by nearly 50% (HR 1.48, 95% CI 1.01-2.17, p=0.04). Conclusion: We demonstrate the high prevalence and broad range of OIs and HAIs occurring in patients with HIV-associated cryptococcal meningitis. These co-prevalent infections are associated with a significantly increased risk of death. Whether a protocolised approach to improve surveillance and proactive treatment of co-prevalent infections would improve cryptococcal meningitis outcomes warrants further investigation.

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Recurrent thrombosis of an arteriovenous fistula as a complication of COVID-19 in a chronic hemodialysis patient: A case report

The Journal of Vascular Access ◽

10.1177/11297298211000881 ◽

2021 ◽

pp. 112972982110008

Author(s):

Joao Pedro Teixeira ◽

Sara A Combs ◽

Jonathan G Owen

Keyword(s):

Arteriovenous Fistula ◽

Hemodialysis Patient ◽

Blood Stream Infection ◽

Blood Stream ◽

Chronic Hemodialysis ◽

Risk Of Death ◽

Catheter Directed Thrombolysis ◽

Intravenous Heparin ◽

Increased Risk ◽

End Stage

Patients with end-stage kidney disease are at increased risk of death from coronavirus disease 2019 (COVID-19). In addition, severe COVID-19 has been associated with an increased risk of arterial and venous thromboses. In this report, we describe the case of a hemodialysis patient who developed an otherwise-unexplained thrombosis of an arteriovenous fistula during a symptomatic COVID-19 infection. Despite prompt treatment with three technically successful thrombectomies along with systemic intravenous heparin and two rounds of catheter-directed thrombolysis with tissue plasminogen activator, the fistula rapidly re-thrombosed each time and he required tunneled dialysis catheter placement. He subsequently required admission for hypoxemia from COVID-19 pneumonia and ultimately developed a catheter-related blood stream infection that likely contributed to his death. As the fistula had been previously well functioning and no angiographic explanation for the thrombosis was found, we speculate in this case the recurrent thromboses were related to the hypercoagulable state characteristic of severe COVID-19. Interventionalists performing hemodialysis access procedures should be aware of the prothrombotic state associated with COVID-19 and should consider it when deliberating how to best plan and approach access interventions in patients with symptomatic COVID-19.

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Hospital Acquired Blood Stream Infection in an Adult Intensive Care Unit: a Retrospective Case Series

10.21203/rs.3.rs-136463/v1 ◽

2020 ◽

Author(s):

Jeffrey Harte ◽

Germander Soothill ◽

Jack Samuel ◽

Laurence Sharifi ◽

Mary White

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Blood Stream Infection ◽

Case Series ◽

Blood Stream ◽

Apache Ii Score ◽

Invasive Procedures ◽

Retrospective Case ◽

Retrospective Case Series ◽

Hospital Acquired

Abstract Introduction: Hospital acquired blood stream infections are a common and serious complication in critically ill patients. Methods: A retrospective case series was undertaken investigating the incidence and causes of bacteraemia on an intensive care unit with a high proportion of postoperative cardiothoracic surgical and oncology patients. Results: 405 eligible patients were admitted to the intensive care unit over the course of nine months. 12 of these patients developed a unit acquired blood stream infection. The average Acute Physiology And Chronic Health Evaluation II (APACHE II) score of patients, who developed bacteraemia was greater than those who did not (19.8 versus 16.8 respectively). The risk of developing bacteraemia was associated with intubation and higher rates of invasive procedures. The mortality rate amongst the group of patients that developed bacteraemia was 33%. There was a higher proportion of Gram-negative bacteria isolated on blood cultures than in intensive care units reported in other studies.Conclusion: Critical care patients are at risk of secondary bloodstream infection. This study highlights the importance of measures to reduce the risk of infection in the intensive care setting particularly in patients who have undergone invasive procedures.

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Cytomegalovirus Viremia Associated With Increased Mortality in Cryptococcal Meningitis in Sub-Saharan Africa

Clinical Infectious Diseases ◽

10.1093/cid/ciz864 ◽

2019 ◽

Vol 71 (3) ◽

pp. 525-531 ◽

Cited By ~ 1

Author(s):

Caleb Skipper ◽

Mark R Schleiss ◽

Ananta S Bangdiwala ◽

Nelmary Hernandez-Alvarado ◽

Kabanda Taseera ◽

...

Keyword(s):

Cryptococcal Meningitis ◽

Opportunistic Infections ◽

Survival Rates ◽

Hazard Ratio ◽

Sub Saharan Africa ◽

Persons Living With Hiv ◽

Median Plasma ◽

Sub Saharan ◽

Immunodeficiency Syndrome ◽

Living With Hiv

Abstract Background Cryptococcal meningitis and tuberculosis are both important causes of death in persons with advanced human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Cytomegalovirus (CMV) viremia may be associated with increased mortality in persons living with HIV who have tuberculosis. It is unknown whether concurrent CMV viremia is associated with mortality in other AIDS-related opportunistic infections. Methods We prospectively enrolled Ugandans living with HIV who had cryptococcal meningitis from 2010–2012. Subsequently, we analyzed stored baseline plasma samples from 111 subjects for CMV DNA. We compared 10-week survival rates among those with and without CMV viremia. Results Of 111 participants, 52% (58/111) had detectable CMV DNA (median plasma viral load 498 IU/mL, interquartile range [IQR] 259–2390). All samples tested were positive on immunoglobin G serology. The median CD4+ T cell count was 19 cells/µL (IQR 9–70) and did not differ by the presence of CMV viremia (P = .47). The 10-week mortality rates were 40% (23/58) in those with CMV viremia and 21% (11/53) in those without CMV viremia (hazard ratio 2.19, 95% confidence interval [CI] 1.07–4.49; P = .03), which remained significant after a multivariate adjustment for known risk factors of mortality (adjusted hazard ratio 3.25, 95% CI 1.49–7.10; P = .003). Serum and cerebrospinal fluid cytokine levels were generally similar and cryptococcal antigen-specific immune stimulation responses did not differ between groups. Conclusions Half of persons with advanced AIDS and cryptococcal meningitis had detectable CMV viremia. CMV viremia was associated with an over 2-fold higher mortality rate. It remains unclear whether CMV viremia in severely immunocompromised persons with cryptococcal meningitis contributes directly to this mortality or may reflect an underlying immune dysfunction (ie, cause vs effect). Clinical Trials Registration NCT01075152.

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Low birth weight, very low birth weight and extremely low birth weight in African children aged between 0 and 5 years old: a systematic review

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174416000131 ◽

2016 ◽

Vol 7 (4) ◽

pp. 408-415 ◽

Cited By ~ 6

Author(s):

M. E. Tchamo ◽

A. Prista ◽

C. G. Leandro

Keyword(s):

Systematic Review ◽

Birth Weight ◽

Low Birth Weight ◽

Very Low Birth Weight ◽

Neurodevelopmental Outcome ◽

Sub Saharan Africa ◽

Extremely Low Birth Weight ◽

Risk Of Death ◽

African Children ◽

Increased Risk

Low birth weight (LBW<2500), very low birth weight (VLBW<1500), extremely low birth weight (ELBW<1500) infants are at high risk for growth failure that result in delayed development. Africa is a continent that presents high rates of children born with LBW, VLBW and ELBW particularly sub-Saharan Africa. To review the existing literature that explores the repercussions of LBW, VLBW and ELBW on growth, neurodevelopmental outcome and mortality in African children aged 0–5 years old. A systematic review of peer-reviewed articles using Academic Search Complete in the following databases: PubMed, Scopus and Scholar Google. Quantitatives studies that investigated the association between LBW, VLBW, ELBW with growth, neurodevelopmental outcome and mortality, published between 2008 and 2015 were included. African studies with humans were eligible for inclusion. From the total of 2205 articles, 12 articles were identified as relevant and were subsequently reviewed in full version. Significant associations were found between LBW, VLBW and ELBW with growth, neurodevelopmental outcome and mortality. Surviving VLBW and ELBW showed increased risk of death, growth retardation and delayed neurodevelopment. Post-neonatal interventions need to be carried out in order to minimize the short-term effects of VLBW and ELBW.

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772. Effect of Selective Digestive Decontamination Using Oral Colistin on HAI Rates and All-Cause Mortality Among Cardiovascular Surgery Patients - A Single Centre Experience from India

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.969 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S483-S483

Author(s):

Sneha R ◽

Arun Wilson ◽

Anup R Warrier ◽

Shilpa Prakash ◽

Reima Elizabeth ◽

...

Keyword(s):

Blood Stream Infection ◽

Tertiary Care ◽

Blood Stream ◽

Selective Digestive Decontamination ◽

Care Hospital ◽

Intervention Period ◽

All Cause Mortality ◽

Study Participants ◽

Hospital Acquired ◽

Interventional Group

Abstract Background Hospital acquired infections affect the morbidity and mortality of ICU patients considerably. Selective digestive decontamination (SDD) is defined as the prophylactic application of topical, non-absorbable antimicrobials in the oropharynx and stomach, with the goal of eradicating potentially pathogenic microorganisms but preserving the protective anaerobic microbiota. SDD has been applied in trials among critically ill patients and found to be effective in reducing HAI. Methods This cohort study was conducted in our cardiothoracic vascular surgery ICU of a tertiary care hospital, where patients were given oral colistin syrup (100mg 6th hourly for 5 days) in the immediate post op during the intervention period. We compared the clinical and microbiological outcomes of patients before (5 months, pre-intervention arm) and after (5 months, intervention arm) the implementation of SDD (Oral colistin syrup). Results A total of 78 patients were included in the interventional arm with a mean age of 58.7 years whereas the pre-interventional group consisted of 94 study participants with a median age of 57.5 years. 11 out of 94 had positive respiratory sample culture (11.7%) in the preintervention group which mandated antibiotic therapy for HAP compared to one culture positive in the interventional period (OR 0.0980, 95% CI: 0.0124 to 0.777 and P=0.0279). One patient had blood stream infection in the pre-intervention period compared to none in the intervention phase. All-cause mortality in the pre-interventional group was 7.44% (7 in 94) vs 1.28% (1 in 78) in the interventional group (OR 0.1614, 95% CI: 0.0194 to 1.3416, P= 0.0914). Adverse events (nausea, vomiting & loose stools) were observed in a total of 24 study patients, but necessitated withdrawal of regimen only in nine patients. Conclusion An SDD regimen of Colistin alone in Cardiac Surgery patients resulted in statistically significant reduction in incidence of Hospital Acquired Pneumonia, along with a reduction in all-cause mortality (though not statistically significant). Disclosures All Authors: No reported disclosures

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Impact of Early Corticosteroids on 60-day Mortality in Critically Ill Patients with COVID-19: A Multicenter Cohort Study of the OUTCOMEREA Network

10.21203/rs.3.rs-293856/v1 ◽

2021 ◽

Author(s):

Claire Dupuis ◽

Etienne de Montmollin ◽

Niccolò Buetti ◽

Dany Goldgran-Toledano ◽

Jean Reignier ◽

...

Keyword(s):

Invasive Mechanical Ventilation ◽

Bloodstream Infections ◽

Survival Models ◽

Multicenter Cohort Study ◽

Reactive Protein ◽

Risk Of Death ◽

Increased Risk ◽

Study Population ◽

High Doses ◽

Hospital Acquired

Abstract ObjectivesIn severe COVID-19 pneumonia, the appropriate timing and dosing of corticosteroids(CS) is not known. Patient subgroups for which CS could be more beneficial also need appraisal. The aim of this study was to assess the effect of early CS in COVID-19 pneumonia patients admitted to the ICU on the occurrence of 60-day mortality, ICU-acquired-bloodstream infections(ICU-BSI), and hospital-acquired pneumonia and ventilator-associated pneumonia(HAP-VAP).MethodsWe included patients with COVID-19 pneumonia admitted to 11 ICUs belonging to the French OutcomeReaTM network from January to May 2020. We used survival models with ponderation with inverse probability of treatment weighting (IPTW). Inflammation was defined as Ferritin >1000 µg/l or D-Dimers >1000 µg/l or C-Reactive Protein >100 mg/dL.ResultsThe study population comprised 302 patients having a median age of 61.6(53-70) years of whom 78.8% were male and 58.6% had at least one comorbidity. The median SAPS II was 33(25-44). Invasive mechanical ventilation was required in 34.8% of the patients. Sixty-six (21.8%) patients were in the Early-CS-subgroup. Most of them (n=55, 83.3%) received high doses of steroids. Overall, 60-day mortality was 29.4%. The risks of 60-day mortality (IPTWHR =0.88;95% CI 0.55 to 1.39, p=0.58), ICU-BSI and HAP-VAP were similar in the two groups. Importantly, early CS treatment was associated with a lower mortality rate in patients aged 60 years or more (IPTWHR, 0.51;95% CI, 0.29 – 0.91; p=0.02). But, CS was associated with an increased risk of death for the patients younger than 60 years without inflammation on admission (IPTWHR =8.17;95% CI, 1.76, 37.85; p=0.01).ConclusionFor patients with COVID-19 pneumonia, early CS treatment was not associated with patient survival. Interestingly, inflammation and age can significantly influence the effect of CS.

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Presentation and outcome of COVID-19 in HIV patients with high viral loads and opportunistic infections: a case series

Ghana Medical Journal ◽

10.4314/gmj.v54i4s.20 ◽

2020 ◽

Vol 54 (4s) ◽

pp. 121-124

Author(s):

Yasmine O. Hardy ◽

Divine A. Amenuke ◽

Kojo A. Hutton-Mensah ◽

David R. Chadwick ◽

Rita Larsen-Reindorf

Keyword(s):

Opportunistic Infections ◽

Severe Disease ◽

Case Series ◽

Standard Of Care ◽

Sub Saharan Africa ◽

People Living With Hiv ◽

Viral Loads ◽

Increased Risk ◽

Negative Clinical Outcome ◽

The Impact

Coronavirus disease 2019 (COVID-19) is especially severe in patients with underlying chronic conditions, with increased risk of mortality. There is concern that people living with HIV (PLWH), especially those with severe immunosuppression, and COVID-19 may have severe disease and a negative clinical outcome. Most studies on COVID-19 in PLWH are from Asia, Europe and America where population dynamics, antiretroviral treatment coverage and coexisting opportunistic infections may differ from that in sub-Saharan Africa. We report on the clinical profile and outcome of three cases of PLWH co-infected with SARS-CoV-2. They all presented with fever, cough and breathlessness and also had advanced HIV infection as evidenced by opportunistic infections, high HIV viral loads and low CD4 counts. The patients responded favourably to the standard of care and were discharged home. Our findings suggest that PLWH with advanced immunosuppression may not necessarily have an unfavourable disease course and outcome. However, case-controlled studies with a larger population size are needed to better understand the impact of COVID-19 in this patient population.

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Cardiac Microlesions Form During Severe Bacteremic Enterococcus faecalis Infection

10.1101/2020.01.14.906669 ◽

2020 ◽

Author(s):

Armand O. Brown ◽

Kavindra V. Singh ◽

Melissa R. Cruz ◽

Karan Gautam Kaval ◽

Liezl E. Francisco ◽

...

Keyword(s):

Immune Response ◽

Enterococcus Faecalis ◽

Pneumococcal Disease ◽

Blood Stream Infection ◽

Blood Stream ◽

Virulence Determinants ◽

C Elegans ◽

Bond Forming ◽

Hospital Acquired ◽

Pro Inflammatory Cytokines

AbstractEnterococcus faecalis is a significant cause of hospital-acquired bacteremia. Herein, the discovery is reported that cardiac microlesions form during severe bacteremic E. faecalis infection in mice. The cardiac microlesions were identical in appearance to those formed by Streptococcus pneumoniae during invasive pneumococcal disease (IPD). However, E. faecalis does not encode the virulence determinants implicated in pneumococcal microlesion formation. Rather, disulfide bond forming protein DsbA was found to be required for E. faecalis virulence in a C. elegans model and was necessary for efficient cardiac microlesion formation. Furthermore, E. faecalis promoted cardiomyocyte apoptotic and necroptotic cell death at sites of microlesion formation. Additionally, loss of DsbA caused an increase in pro-inflammatory cytokines unlike the wild-type strain, which suppressed the immune response. In conclusion, we establish that E. faecalis is capable of forming cardiac microlesions and identify features of both the bacterium and the host response that are mechanistically involved.SUMMARYThis work presents the observation of cardiac microlesion formation during severe blood stream infection with Enterococcus faecalis in mice. Moreover, we identify the contribution of a novel enterococcal virulence determinant in modulating microlesion formation and the host immune response.

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Hospital-Acquired Blood Stream Infection in an Adult Intensive Care Unit

Critical Care Research and Practice ◽

10.1155/2021/3652130 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Jeffrey Harte ◽

Germander Soothill ◽

John Glynn David Samuel ◽

Laurence Sharifi ◽

Mary White

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Mortality Rate ◽

Blood Stream Infection ◽

Case Series ◽

Blood Stream ◽

Apache Ii Score ◽

Invasive Procedures ◽

Adult Intensive Care Unit ◽

Hospital Acquired

Background. Hospital-acquired blood stream infections are a common and serious complication in critically ill patients. Methods. A retrospective case series was undertaken investigating the incidence and causes of bacteraemia in an adult intensive care unit with a high proportion of postoperative cardiothoracic surgical and oncology patients. Results. 405 eligible patients were admitted to the intensive care unit over the course of nine months. 12 of these patients developed a unit-acquired blood stream infection. The average Acute Physiology And Chronic Health Evaluation II (APACHE II) score of patients who developed bacteraemia was greater than that of those who did not (19.8 versus 16.8, respectively). The risk of developing bacteraemia was associated with intubation and higher rates of invasive procedures. The mortality rate amongst the group of patients that developed bacteraemia was 33%; this is in contrast to the mortality rate in our unit as 27.2%. There was a higher proportion of Gram-negative bacteria isolated on blood cultures (9 out of 13 isolates) than in intensive care units reported in other studies. Conclusion. Critical-care patients are at risk of secondary bloodstream infection. This study highlights the importance of measures to reduce the risk of infection in the intensive-care setting, particularly in patients who have undergone invasive procedures.

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Biomarkers Associated with Death After Initiating Treatment for Tuberculosis and HIV in Patients with Very Low CD4 Cells

Pathogens and Immunity ◽

10.20411/pai.v3i1.235 ◽

2018 ◽

Vol 3 (1) ◽

pp. 46 ◽

Cited By ~ 1

Author(s):

Fred Richard Sattler ◽

Daniel Chelliah ◽

Xingye Wu ◽

Alejandro Sanchez ◽

Michelle A. Kendall ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

C Reactive Protein ◽

Retrospective Case ◽

Reactive Protein ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Treatment Naïve ◽

Low Bmi

Background: The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death.Methods: We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3. The case-cohort sample consisted of 51 randomly selected participants, whose stored plasma was tested for C-reactive protein, cytokines, chemokines, and nutritional markers. Cox proportional hazards models were used to assess the association of nutritional, inflammatory, and immunomodulatory markers for survival.Results: The case-cohort sample was similar to the 282 participants within the parent cohort with CD4 < 50 cells/mm3. In the case cohort, 7 (14%) had BMI < 16.5 (kg/m2) and 17 (33%) had BMI 16.5-18.5(kg/m2). Risk of death was increased per 1 IQR width higher of log10 transformed level of C-reactive protein (adjusted hazard ratio (aHR) = 3.42 [95% CI = 1.33-8.80],P = 0.011), interferon gamma (aHR = 2.46 [CI = 1.02-5.90], P = 0.044), MCP-3 (3.67 [CI = 1.08-12.42], P = 0.037), and with IL-15 (aHR = 2.75 [CI = 1.08-6.98], P = 0.033) and IL-17 (aHR = 3.99 [CI = -1.06-15.07], P = 0.041). BMI, albumin, hemoglobin, and leptin levels were not associated with risk of death.Conclusions: Unlike patients only infected with M. tuberculosis for whom malnutrition and low BMI increase the risk of death, this relationship was not evident in our dually infected patients. Risk of death was associated with significant increases in markers of global inflammation along with soluble biomarkers of innate and adaptive immunity.

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