-
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 -
Cureus Mar 2022The prevalence, incidence, and characteristics of bacterial infections in patients infected with severe acute respiratory syndrome coronavirus 2 are not well understood... (Review)
Review
The prevalence, incidence, and characteristics of bacterial infections in patients infected with severe acute respiratory syndrome coronavirus 2 are not well understood and have been raised as an important knowledge gap. Therefore, our study focused on the most common opportunistic infections/secondary infections/superinfections in coronavirus disease 2019 (COVID-19) patients. This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Eligible studies were identified using PubMed/Medline since inception to June 25, 2021. Studies meeting the inclusion criteria were selected. Statistical analysis was conducted in Review Manager 5.4.1. A random-effect model was used when heterogeneity was seen to pool the studies, and the result was reported as inverse variance and the corresponding 95% confidence interval. We screened 701 articles comprising 22 cohort studies which were included for analysis. The pooled prevalence of opportunistic infections/secondary infections/superinfections was 16% in COVID-19 patients. The highest prevalence of secondary infections was observed among viruses at 33%, followed by bacteria at 16%, fungi at 6%, and 25% among the miscellaneous group/wrong outcome. Opportunistic infections are more prevalent in critically ill patients. The isolated pathogens included Epstein-Barr virus, , , , , and invasive pulmonary aspergillosis. Large-scale studies are required to better identify opportunistic/secondary/superinfections in COVID-19 patients.
PubMed: 35505698
DOI: 10.7759/cureus.23687 -
World Journal of Gastroenterology Jul 2022Acute pancreatitis (AP) is one of the most common gastrointestinal diseases and remains a life-threatening condition. Although AP resolves to restitutio ad integrum in... (Review)
Review
Acute pancreatitis (AP) is one of the most common gastrointestinal diseases and remains a life-threatening condition. Although AP resolves to restitutio ad integrum in approximately 80% of patients, it can progress to necrotizing pancreatitis (NP). NP is associated with superinfection in a third of patients, leading to an increase in mortality rate of up to 40%. Accurate and early diagnosis of NP and associated complications, as well as state-of-the-art therapy are essential to improve patient prognoses. The emerging role of endoscopy and recent trials on multidisciplinary management of NP established the "step-up approach". This approach starts with endoscopic interventions and can be escalated to other interventional and ultimately surgical procedures if required. Studies showed that this approach decreases the incidence of new multiple-organ failure as well as the risk of interventional complications. However, the optimal interventional sequence and timing of interventional procedures remain controversial. This review aims to summarize the indications, timing, and treatment outcomes for infected NP and to provide guidance on multidisciplinary decision-making.
Topics: Acute Disease; Drainage; Endoscopy, Gastrointestinal; Humans; Pancreatitis, Acute Necrotizing
PubMed: 36158258
DOI: 10.3748/wjg.v28.i27.3383 -
Open Forum Infectious Diseases Sep 2022Identification of bacterial coinfection in patients with coronavirus disease 2019 (COVID-19) facilitates appropriate initiation or withholding of antibiotics. The...
Detection of Viral Infection and Bacterial Coinfection and Superinfection in Coronavirus Disease 2019 Patients Presenting to the Emergency Department Using the 29-mRNA Host Response Classifier IMX-BVN-3: A Multicenter Study.
BACKGROUND
Identification of bacterial coinfection in patients with coronavirus disease 2019 (COVID-19) facilitates appropriate initiation or withholding of antibiotics. The Inflammatix Bacterial Viral Noninfected (IMX-BVN) classifier determines the likelihood of bacterial and viral infections. In a multicenter study, we investigated whether IMX-BVN version 3 (IMX-BVN-3) identifies patients with COVID-19 and bacterial coinfections or superinfections.
METHODS
Patients with polymerase chain reaction-confirmed COVID-19 were enrolled in Berlin, Germany; Basel, Switzerland; and Cleveland, Ohio upon emergency department or hospital admission. PAXgene Blood RNA was extracted and 29 host mRNAs were quantified. IMX-BVN-3 categorized patients into very unlikely, unlikely, possible, and very likely bacterial and viral interpretation bands. IMX-BVN-3 results were compared with clinically adjudicated infection status.
RESULTS
IMX-BVN-3 categorized 102 of 111 (91.9%) COVID-19 patients into very likely or possible, 7 (6.3%) into unlikely, and 2 (1.8%) into very unlikely viral bands. Approximately 94% of patients had IMX-BVN-3 unlikely or very unlikely bacterial results. Among 7 (6.3%) patients with possible (n = 4) or very likely (n = 3) bacterial results, 6 (85.7%) had clinically adjudicated bacterial coinfection or superinfection. Overall, 19 of 111 subjects for whom adjudication was performed had a bacterial infection; 7 of these showed a very likely or likely bacterial result in IMX-BVN-3.
CONCLUSIONS
IMX-BVN-3 identified COVID-19 patients as virally infected and identified bacterial coinfections and superinfections. Future studies will determine whether a point-of-care version of the classifier may improve the management of COVID-19 patients, including appropriate antibiotic use.
PubMed: 36111173
DOI: 10.1093/ofid/ofac437 -
Cureus Oct 2022Bacterial and fungal coinfections including the emergence of antimicrobial resistance are well-recognized in the era of coronavirus disease 2019 (COVID-19) infections....
Bacterial and fungal coinfections including the emergence of antimicrobial resistance are well-recognized in the era of coronavirus disease 2019 (COVID-19) infections. We present three cases of (EM), superinfections in COVID-19 patients admitted between the period of April 2021 and May 2021. All cases were intubated; had central venous catheters, had received prior antibiotics and antivirals as well as dexamethasone as part of severe COVID-19 management. Only one patient received anakinra. EM isolates were resistant to most available antibiotics and patients infected with it had poor treatment outcomes.
PubMed: 36407258
DOI: 10.7759/cureus.30337 -
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 -
Hepatology Communications May 2023HDV, a satellite of HBV, is responsible for the most severe form of human viral hepatitis, for which curative therapy is still awaited. Both HBV and HDV use the hepatic...
BACKGROUND AND AIMS
HDV, a satellite of HBV, is responsible for the most severe form of human viral hepatitis, for which curative therapy is still awaited. Both HBV and HDV use the hepatic transporter of bile acids (ie, Na+-taurocholate cotransporting polypeptide) to enter hepatocytes. We have previously shown that ligands of the farnesoid-X-receptor alpha (FXR), a master regulator of bile acids metabolism, inhibit HBV replication. Here we asked whether FXR ligands can also control HDV infection.
APPROACH AND RESULTS
In vitro HDV monoinfections or HDV/HBV coinfections and superinfections were performed in differentiated HepaRG cells (dHepaRG) and primary human hepatocytes. Following treatment with FXR ligands, HDV RNAs and antigens were analyzed by RT-qPCR, northern blot, immunofluorescence, and western blot. Virus secretion was studied by RNA quantification in supernatants, and the infectivity of secreted HDV particles was measured by reinfection of naive HuH7.5-Na+-taurocholate cotransporting polypeptide cells. In HDV/HBV superinfection models, a 10-day treatment with FXR ligand GW4064 decreased intracellular HDV RNAs by 60% and 40% in dHepaRG cells and primary human hepatocytes, respectively. Both HDV genomic and antigenomic RNAs were affected by treatment, which also reduced the amount of intracellular delta antigen. This antiviral effect was also observed in HDV monoinfected dHepaRG cells, abolished by FXR loss of function, and reproduced with other FXR ligands. In HBV/HDV coinfected dHepaRG cells, HDV secretion was decreased by 60% and virion-specific infectivity by >95%.
CONCLUSIONS
FXR ligands both inhibit directly (ie, independently of anti-HBV activity) and indirectly (ie, dependently of anti-HBV activity) the replication, secretion, and infectivity of HDV. The overall anti-HDV activity was superior to that obtained with interferon-α, highlighting the therapeutic potential of FXR ligands in HDV-infected patients.
Topics: Humans; Hepatitis B virus; Ligands; Bile Acids and Salts; Virion; Taurocholic Acid; Peptides
PubMed: 37058078
DOI: 10.1097/HC9.0000000000000078 -
Microbiology Spectrum Oct 2022Staphylococcus aureus can complicate preceding viral infections, including influenza virus. A bacterial infection combined with a preceding viral infection, known as...
Staphylococcus aureus can complicate preceding viral infections, including influenza virus. A bacterial infection combined with a preceding viral infection, known as superinfection, leads to worse outcomes than a single infection. Most of the pulmonary infection literature focuses on the changes in immune responses to bacteria between homeostatic and virally infected lungs. However, it is unclear how much of an influence bacterial virulence factors have in single or superinfection. Staphylococcal species express a broad range of cell wall-anchored proteins (CWAs) that have roles in host adhesion, nutrient acquisition, and immune evasion. We screened the importance of these CWAs using mutants lacking individual CWAs in both bacterial pneumonia and influenza superinfection. In bacterial pneumonia, the lack of individual CWAs leads to various decreases in bacterial burden, lung damage, and immune infiltration into the lung. However, the presence of a preceding influenza infection partially abrogates the requirement for CWAs. In the screen, we found that the uncharacterized CWA S. aureus surface protein D (SasD) induced changes in both inflammatory and homeostatic lung markers. We further characterized a SasD mutant (sasD A50.1) in the context of pneumonia. Mice infected with sasD A50.1 have decreased bacterial burden, inflammatory responses, and mortality compared to wild-type S. aureus. Mice also have reduced levels of interleukin-1β (IL-1β), likely derived from macrophages. Reductions in IL-1β transcript levels as well as increased macrophage viability point at differences in cell death pathways. These data identify a novel virulence factor for S. aureus that influences inflammatory signaling within the lung. Staphylococcus aureus is a common commensal bacterium that can cause severe infections, such as pneumonia. In the lung, viral infections increase the risk of staphylococcal pneumonia, leading to combined infections known as superinfections. The most common virus associated with S. aureus pneumonia is influenza, and superinfections lead to worse patient outcomes than either infection alone. While there is much known about how the immune system differs between healthy and virally infected lungs, the role of bacterial virulence factors in single and superinfection is less understood. The significance of our research is identifying bacterial components that play a role in the initiation of lung injury, which could lead to future therapies to prevent pulmonary single or superinfection with S. aureus.
Topics: Mice; Animals; Humans; Superinfection; Influenza, Human; Staphylococcus aureus; Interleukin-1beta; Mice, Knockout; Pneumonia, Staphylococcal; Staphylococcal Infections; Lung; Pneumonia, Bacterial; Cell Wall; Virulence Factors; Membrane Proteins
PubMed: 36040164
DOI: 10.1128/spectrum.01645-22