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The European Respiratory Journal Apr 2022Ventilator-associated pneumonia (VAP) is a leading infectious cause of morbidity in critically ill patients, yet current guidelines offer no indications for follow-up... (Observational Study)
Observational Study
BACKGROUND
Ventilator-associated pneumonia (VAP) is a leading infectious cause of morbidity in critically ill patients, yet current guidelines offer no indications for follow-up cultures. We aimed to evaluate the role of follow-up cultures and microbiological response 3 days after diagnosing VAP as predictors of short- and long-term outcomes.
METHODS
We performed a retrospective analysis of a cohort prospectively collected from 2004 to 2017. VAP was diagnosed based on clinical, radiographical and microbiological criteria. For microbiological identification, a tracheobronchial aspirate was performed at diagnosis and repeated after 72 h. We defined three groups when comparing the two tracheobronchial aspirate results: persistence, superinfection and eradication of causative pathogens.
RESULTS
157 patients were enrolled in the study, among whom microbiological persistence, superinfection or eradication was present in 67 (48%), 25 (16%) and 65 (41%), respectively, after 72 h. Those with superinfection had the highest mortalities in the intensive care unit (p=0.015) and at 90 days (p=0.036), while also having the fewest ventilator-free days (p=0.019). Multivariable analysis revealed shock at VAP diagnosis (OR 3.43, 95% CI 1.25-9.40), isolation at VAP diagnosis (OR 2.87, 95% CI 1.06-7.75) and hypothermia at VAP diagnosis (OR 0.67, 95% CI 0.48-0.95, per +1°C) to be associated with superinfection.
CONCLUSIONS
Our retrospective analysis suggests that VAP short- and long-term outcomes may be associated with superinfection in follow-up cultures. Follow-up cultures may help guide antibiotic therapy and its duration. Further prospective studies are necessary to verify our findings.
Topics: Humans; Intensive Care Units; Pneumonia, Ventilator-Associated; Prospective Studies; Respiration, Artificial; Retrospective Studies; Superinfection
PubMed: 34475230
DOI: 10.1183/13993003.00620-2021 -
PloS One 2017HIV superinfection describes the sequential infection of an individual with two or more unrelated HIV strains. Intersubtype superinfection has been shown to cause a...
HIV superinfection describes the sequential infection of an individual with two or more unrelated HIV strains. Intersubtype superinfection has been shown to cause a broader and more potent heterologous neutralizing antibody response when compared to singly infected controls, yet the effects of intrasubtype superinfection remain controversial. Longitudinal samples were analyzed phylogenetically for pol and env regions using Next-Generation Sequencing and envelope cloning. The impact of CRF02_AG intrasubtype superinfection was assessed for heterologous neutralization and antibody binding responses. We compared two cases of CRF02_AG intrasubtype superinfection that revealed complete replacement of the initial virus by superinfecting CRF02_AG variants with signs of recombination. NYU6564, who became superinfected at an early time point, exhibited greater changes in antibody binding profiles and generated a more potent neutralizing antibody response post-superinfection compared to NYU6501. In contrast, superinfection occurred at a later time point in NYU6501 with strains harboring significantly longer V1V2 regions with no observable changes in neutralization patterns. Here we show that CRF02_AG intrasubtype superinfection can induce a cross-subtype neutralizing antibody response, and our data suggest timing and/or superinfecting viral envelope characteristics as contributing factors. These results highlight differential outcomes in intrasubtype superinfection and provide the first insight into cases with CRF02_AG, the fourth most prevalent HIV-1 strain worldwide.
Topics: Antibodies, Neutralizing; Antibody Formation; Epitopes; Female; HIV Infections; HIV-1; Humans; Phylogeny; Pregnancy; Recombination, Genetic; Superinfection; Viral Load; env Gene Products, Human Immunodeficiency Virus; pol Gene Products, Human Immunodeficiency Virus
PubMed: 28288209
DOI: 10.1371/journal.pone.0173705 -
The New England Journal of Medicine Nov 2016
Topics: Anti-Retroviral Agents; Carcinoma, Hepatocellular; HIV Infections; HIV Seropositivity; HIV-1; Humans; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; RNA, Viral; Superinfection; Viral Load
PubMed: 27806218
DOI: 10.1056/NEJMc1603850 -
Cold Spring Harbor Perspectives in... Jul 2015Hepatitis D is caused by the hepatitis D virus (HDV), a unique RNA pathogen that requires the hepatitis B surface antigen (HBsAg) to infect. Hepatitis D is transmitted... (Review)
Review
Hepatitis D is caused by the hepatitis D virus (HDV), a unique RNA pathogen that requires the hepatitis B surface antigen (HBsAg) to infect. Hepatitis D is transmitted by the parenteral route. The main susceptible group is patients with chronic HBsAg infection who become superinfected with the virus. Hepatitis D occurs throughout the globe, but control of hepatitis B virus (HBV) in the last two decades has consistently diminished the circulation of HDV in industrialized countries. However, hepatitis D remains a medical issue for injecting drug users (IDUs), as well as immigrants from endemic HDV areas, who are reintroducing the infection in Europe.
Topics: Drug Users; Europe; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans; Superinfection
PubMed: 26134842
DOI: 10.1101/cshperspect.a021576 -
Journal of Virology Sep 2017Understanding whether the neutralizing antibody (NAb) response impacts HIV-1 superinfection and how superinfection subsequently modulates the NAb response can help...
Understanding whether the neutralizing antibody (NAb) response impacts HIV-1 superinfection and how superinfection subsequently modulates the NAb response can help clarify correlates of protection from HIV exposures and better delineate pathways of NAb development. We examined associations between the development of NAb and the occurrence of superinfection in a well-characterized, antiretroviral therapy (ART)-naive, primary infection cohort of men who have sex with men. Deep sequencing was applied to blood plasma samples from the cohort to detect cases of superinfection. We compared the NAb activity against autologous and heterologous viruses between 10 participants with intrasubtype B superinfection and 19 monoinfected controls, matched to duration of infection and risk behavior. Three to 6 months after primary infection, individuals who would later become superinfected had significantly weaker NAb activity against tier 1 subtype B viruses ( = 0.003 for SF-162 and = 0.017 for NL4-3) and marginally against autologous virus ( = 0.054). Lower presuperinfection NAb responses correlated with weaker gp120 binding and lower plasma total IgG titers. Soon after superinfection, the NAb response remained lower, but between 2 and 3 years after primary infection, NAb levels strengthened and reached those of controls. Superinfecting viruses were typically not susceptible to neutralization by presuperinfection plasma. These observations suggest that recently infected individuals with a delayed NAb response against primary infecting and tier 1 subtype B viruses are more susceptible to superinfection. Our findings suggest that within the first year after HIV infection, a relatively weak neutralizing antibody response against primary and subtype-specific neutralization-sensitive viruses increases susceptibility to superinfection in the face of repeated exposures. As natural infection progresses, the immune response strengthens significantly in some superinfected individuals. These findings will inform HIV vaccine design by providing testable correlates of protection from initial HIV infection.
Topics: Adult; Antibodies, Neutralizing; California; Case-Control Studies; HIV Antibodies; HIV Envelope Protein gp120; HIV Infections; HIV-1; Humans; Immunoglobulin G; Male; Neutralization Tests; Superinfection; Young Adult
PubMed: 28615205
DOI: 10.1128/JVI.00475-17 -
Cureus May 2024Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis mainly involving the ear, nose, and upper and lower airways. Diagnosis is based on clinical...
Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis mainly involving the ear, nose, and upper and lower airways. Diagnosis is based on clinical manifestations, positive antineutrophil cytoplasmic antibodies (ANCA) serology, and histopathological findings. We report a case of inflammatory polyarthralgia with a high titer of rheumatoid factor (RF), which was revealed to be GPA after extensive diagnosis workup. However, the disease was complicated by superinfections, which delayed and limited immunosuppressive treatment. Methotrexate was at last initiated with antibiotic prophylaxis, and there was significant clinical improvement. This case underlines the importance of an adequate diagnosis workup and the difficulties that often arise when other entities are present.
PubMed: 38894781
DOI: 10.7759/cureus.60606 -
Pancreatology : Official Journal of the... Apr 2022SARS-CoV-2 can cause acute pancreatitis (AP) and SARS-CoV-2 superinfection can occur in patients with AP during prolonged hospitalisation. Our objective was to...
BACKGROUND
SARS-CoV-2 can cause acute pancreatitis (AP) and SARS-CoV-2 superinfection can occur in patients with AP during prolonged hospitalisation. Our objective was to characterize SARS-CoV-2 related AP and study the impact of SARS-CoV-2 superinfection on outcomes in AP.
METHODS
In this multicentre prospective study, all patients with AP and SARS-CoV-2 infection between August 2020 and February 2021 were divided into two groups: SARS-CoV-2-related AP and superadded SARS-CoV-2 infection in patients with AP. The two groups were compared with each other and the whole cohort was compared with a non-COVID AP cohort.
RESULTS
A total of 85 patients with SARS-CoV-2 and AP (SARS-CoV-2-related AP; n = 18 and AP with SARS-CoV-2 superadded infection; n = 67) were included during the study period. They had a higher mortality [28 (32.9%) vs. 44 (19.1%), aOR 2.8 (95% CI, 1.5-5.3)] than 230 propensity matched non-COVID AP patients. Mortality in SARS-CoV-2 and AP patients was due to critical COVID. SARS-CoV-2-related- AP (n = 18) had a higher but statistically insignificant mortality than SARS-CoV-2 superinfection in AP [8/18 (44.4%) vs 20/67 (29.8%), p = 0.24]. On multivariable analysis, infection with SARS-CoV-2 (aHR 2.3; 95% CI, 1.43.7) was a predictor of in-hospital mortality in addition to organ failure (OF) in patients with AP.
CONCLUSION
Patients with AP and SARS-CoV-2 infection had a higher mortality than matched non-COVID AP patients which was largely attributable to the severity of COVID-19. SARS-CoV-2 related AP had higher OF and in-hospital mortality.
Topics: Acute Disease; COVID-19; Humans; Pancreatitis, Chronic; Prospective Studies; SARS-CoV-2; Superinfection
PubMed: 35131169
DOI: 10.1016/j.pan.2022.01.008 -
Mucosal Immunology Sep 2019Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary...
Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary pathogens of interest. IL-22 promotes S. aureus and S. pneumoniae host defense in the lung through epithelial integrity and induction of antimicrobial peptides and is inhibited by the soluble decoy receptor IL-22-binding protein (IL-22BP). Little is known about the effect of the IL-22/IL-22BP regulatory pathway on lung infection, and it has not been studied in the setting of super-infection. We exposed wild-type and IL-22BP mice to influenza A/PR/8/34 for 6 days prior to infection with S. aureus (USA300) S. pneumoniae. Super-infected IL-22BP mice had decreased bacterial burden and improved survival compared to controls. IL-22BP mice exhibited decreased inflammation, increased lipocalin 2 expression, and deletion of IL-22BP was associated with preserved epithelial barrier function with evidence of improved tight junction stability. Human bronchial epithelial cells treated with IL-22Fc showed evidence of improved tight junctions compared to untreated cells. This study revealed that IL-22BP mice are protected during influenza, bacterial super-infection, suggesting that IL-22BP has a pro-inflammatory role and impairs epithelial barrier function likely through interaction with IL-22.
Topics: Animals; Bacterial Infections; Bacterial Load; Blood-Air Barrier; Carrier Proteins; Disease Models, Animal; Gene Expression; Interleukins; Leukocyte Count; Male; Mice; Mice, Knockout; Monocytes; Orthomyxoviridae Infections; Permeability; Protein Binding; Staphylococcus aureus; Streptococcus pneumoniae; Superinfection; Tight Junctions; Interleukin-22
PubMed: 31296910
DOI: 10.1038/s41385-019-0188-7 -
JCI Insight Apr 2018Secondary bacterial respiratory infections are commonly associated with both acute and chronic lung injury. Influenza complicated by bacterial pneumonia is an effective...
Secondary bacterial respiratory infections are commonly associated with both acute and chronic lung injury. Influenza complicated by bacterial pneumonia is an effective model to study host defense during pulmonary superinfection due to its clinical relevance. Multiprotein inflammasomes are responsible for IL-1β production in response to infection and drive tissue inflammation. In this study, we examined the role of the inflammasome during viral/bacterial superinfection. We demonstrate that ASC-/- mice are protected from bacterial superinfection and produce sufficient quantities of IL-1β through an apoptosis-associated speck-like protein containing CARD (ASC) inflammasome-independent mechanism. Despite the production of IL-1β by ASC-/- mice in response to bacterial superinfection, these mice display decreased lung inflammation. A neutrophil elastase inhibitor blocked ASC inflammasome-independent production of IL-1β and the IL-1 receptor antagonist, anakinra, confirmed that IL-1 remains crucial to the clearance of bacteria during superinfection. Delayed inhibition of NLRP3 during influenza infection by MCC950 decreases bacterial burden during superinfection and leads to decreased inflammatory cytokine production. Collectively, our results demonstrate that ASC augments the clearance of bacteria, but can also contribute to inflammation and mortality. ASC should be considered as a therapeutic target to decrease morbidity and mortality during bacterial superinfection.
Topics: Animals; CARD Signaling Adaptor Proteins; Disease Models, Animal; Furans; Heterocyclic Compounds, 4 or More Rings; Humans; Indenes; Inflammasomes; Influenza, Human; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Interleukin-1; Staphylococcal Infections; Staphylococcus aureus; Sulfonamides; Sulfones; Superinfection
PubMed: 29618653
DOI: 10.1172/jci.insight.97470 -
AIDS (London, England) Sep 2014To determine and compare the rates of HIV superinfection and primary HIV infection in high-risk female sex workers (FSWs) in Kampala, Uganda. (Comparative Study)
Comparative Study
OBJECTIVE
To determine and compare the rates of HIV superinfection and primary HIV infection in high-risk female sex workers (FSWs) in Kampala, Uganda.
DESIGN
A retrospective analysis of individuals who participated in a clinical cohort study among high-risk FSWs in Kampala, Uganda.
METHODS
Plasma samples from HIV-infected FSWs in Kampala, Uganda were examined with next-generation sequencing of the p24 and gp41 HIV genomic regions for the occurrence of superinfection. Primary HIV incidence was determined from initially HIV-uninfected FSWs from the same cohort, and incidence rate ratios were compared.
RESULTS
The rate of superinfection in these women (7/85; 3.4/100 person-years) was not significantly different from the rate of primary infection in the same population (3.7/100 person-years; incidence rate ratio = 0.91, P = 0.42). Seven women also entered the study dual-infected (16.5% either dual or superinfected). The women with any presence of dual infection were more likely to report sex work as their only source of income (P = 0.05), and trended to be older and more likely to be widowed (P = 0.07).
CONCLUSIONS
In this cohort of FSWs, HIV superinfection occurred at a high rate and was similar to that of primary HIV infection. These results differ from a similar study of high-risk female bar workers in Kenya that found the rate of superinfection to be significantly lower than the rate of primary HIV infection.
Topics: Adult; Age Factors; Cohort Studies; Disease Progression; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Incidence; Retrospective Studies; Sex Workers; Sexual Partners; Superinfection; Uganda; Viral Load
PubMed: 25265078
DOI: 10.1097/QAD.0000000000000365