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Journal of Medical Virology, Accepted Article.
Anai García Fariñas, Nivaldo Linares-Pérez, Andrew Clark, María Eugenia Toledo-Romaní, Nathalie El Omeiri, Martha C. Marrero Araújo, Isabel Pilar Gonzálvez, Gilda Toraño Peraza, Alicia Reyes Jiménez, Lena López Ambrón, the Cuban Pneumococcal Vaccine Working Group
Streptococcus pneumoniae is an important cause of severe bacterial infections in young children and the elderly (Valenzuela et al., 2009). In Cuba, high rates of nasopharyngeal colonization have been reported in children
Microbial dysbiosis has been found preceding necrotizing enterocolitis (NEC) in preterm infants; thus, we aimed to investigate whether there is evidence that neonates with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) positive stool cultures are at higher risk for NEC at the NICU.
We included very preterm inborn infants of ≤ 32 weeks of gestational age being fecal carriers of ESBL-E and compared them with 1:1 matched (gestational age, birth weight, gender and year) controls tested negative for ESBL-E in the stool between 2005 and 2016. An association with NEC was defined as the first detection of ESBL-E before or at the time of definite diagnosis of NEC.
During the study period, we diagnosed 217 infants with a total of 270 ESBL-E. We identified ten different species with ESBL-producing Klebsiella oxytoca being the most common one (46%) followed by Klebsiella pneumoniae (19%), and Citrobacter freundii (17%). Ten out of 217 infants had any kind of NEC in the case group compared to two of the controls (p
Lemyze, Malcolm; Courageux, Nathan; Maladobry, Thomas; Arumadura, Clothilde; Pauquet, Philippe; Orfi, Annis; Komorowski, Matthieu; Mallat, Jihad; Granier, Maxime
To investigate patients’ characteristics, management, and outcomes in the critically ill population admitted to the ICU for severe acute respiratory syndrome coronavirus disease 2019 pneumonia causing an acute respiratory distress syndrome.
Retrospective case-control study.
A 34-bed ICU of a tertiary hospital.
The first 44 coronavirus disease 2019 acute respiratory distress syndrome patients were compared with a historical control group of 39 consecutive acute respiratory distress syndrome patients admitted to the ICU just before the coronavirus disease 2019 crisis.
Measurements and Main Results:
Obesity was the most frequent comorbidity exhibited by coronavirus disease 2019 patients (n = 32, 73% vs n = 11, 28% in controls; p < 0.001). Despite the same severity of illness and level of hypoxemia at admission, coronavirus disease 2019 patients failed more high flow oxygen via nasal cannula challenges (n = 16, 100% vs n = 5, 45% in controls; p = 0.002), were more often intubated (n = 44, 100% vs n = 22, 56% in controls; p < 0.001) and paralyzed (n = 34, 77% vs n = 3, 14% in controls; p < 0.001), required higher level of positive end-expiratory pressure (15 vs 8 cm H2O in controls; p < 0.001), more prone positioning (n = 33, 75% vs n = 6, 27% in controls; p < 0.001), more dialysis (n = 16, 36% vs n = 3, 8% in controls; p = 0.003), more hemodynamic support by vasopressors (n = 36, 82% vs n = 22, 56% in controls; p = 0.001), and had more often a prolonged weaning from mechanical ventilation (n = 28, 64% vs n = 10, 26% in controls; p < 0.01) resulting in a more frequent resort to tracheostomy (n = 18, 40.9% vs n = 2, 9% in controls; p = 0.01). However, an intensive management requiring more staff per patient for positioning coronavirus disease 2019 subjects (6 [5–7] vs 5 [4–5] in controls; p < 0.001) yielded the same ICU survival rate in the two groups (n = 34, 77% vs n = 29, 74% in controls; p = 0.23).
In its most severe form, coronavirus disease 2019 pneumonia striked preferentially the vulnerable obese population, evolved toward a multiple organ failure, required prolonged mechanical ventilatory support, and resulted in a high workload for the caregivers.
The authors have disclosed that they do not have any potential conflicts of interest.
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Copyright © by 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Atkinson A, Zwahlen M, Barger D, et al.
AbstractBackgroundUsing data from the COHERE collaboration, we investigated whether primary prophylaxis for Pneumocystis Pneumonia (PcP) might be withheld in all patients on antiretroviral therapy with suppressed plasma HIV RNA (≤ 400c/mL) irrespective of CD4 count.MethodsWe implemented an established causal inference approach whereby observational data is used to emulate a randomised trial. Patients taking PcP prophylaxis were eligible for the emulated trial if their CD4 count was ≤ 200 cells/µL in line with existing recommendations. We compared the following two strategies for stopping prophylaxis: i.) when CD4 count was above 200 cells/µL for more than 3 months, or ii.) when the patient was virologically suppressed (two consecutive HIV RNA ≤ 400c/mL). Patients were artificially censored if they did not comply with these stopping rules. We estimated the risk of primary PcP in patients on ART, using the hazard ratio to compare the stopping strategies by fitting a pooled logistic model, including inverse probability weights to adjust for the selection bias introduced by the artificial censoring.Results4’813 patients (10’324 person years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as endpoint, the adjusted hazard ratio (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared to the existing guidelines (aHR 0.8 with 95% CI [0.6, 1.1], p = 0.2).ConclusionsThe study suggests that primary PcP prophylaxis might be safely withheld in confirmed ART-virologically suppressed patients, regardless of their CD4 count.
de Oliveira L, Shioda K, Valenzuela M, et al.
AbstractBackgroundPneumococcal conjugate vaccines (PCVs) are recommended for use in pediatric immunization programs worldwide. Few data are available on their effect against mortality. We present a multi-country evaluation of the population-level impact of PCVs against death due to pneumonia in children
Elevated Staphylococcus aureus and oral bacterial concentrations are known to correlate with pneumonia hospitalization in nursing home residents. However, the effects of a professional oral care intervention on these factors remain unclear. The aims of this quasi-experimental study were to compare bacterial concentrations in saliva and sputum, oral health status, distribution of Staphylococcus aureus, and pneumonia status before and after a professional oral care intervention.
A purposive sample of residents from two nursing homes was divided into an intervention group that received a weekly professional oral care intervention and a control group. Oral bacterial concentration was determined by real-time polymerase chain reaction. The Staphylococcus aureus distribution was determined by bacterial culture and matrix-assisted laser desorption/ionization–time of flight mass spectrometry. After data collection, a statistical analysis was performed to evaluate the effect of the intervention.
Most residents were unconscious (80%), and most had a history of pneumonia (76%). Baseline demographic data did not significantly differ between the two groups. After the intervention, the intervention group had significant improvements in plaque index (1.66 ± 0.78 vs. 0.94 ± 0.64, p
Cheung, C. H. P., Dulyayangkul, P., Heesom, K. J., Avison, M. B.
Colistin resistance in Klebsiella pneumoniae is predominantly caused by mutations that increase expression of the arn (also known as pbg or pmrF) operon. Expression is activated by the PhoPQ and PmrAB two-component systems. Constitutive PhoPQ activation occurs directly by mutation or following loss of MgrB. PhoPQ may also cross-activate PmrAB via the linker protein PmrD. Using proteomics, we show that MgrB loss causes a wider proteomic effect than direct PhoPQ activation, suggesting additional targets for MgrB. Different mgrB mutations cause different amounts of Arn protein production, which correlated with colistin MIC. Disruption of phoP in an mgrB mutant had a reciprocal effect to direct activation of PhoQ in a wild-type background, but the regulated proteins showed almost total overlap. Disruption of pmrD or pmrA slightly reduced Arn protein production in an mgrB mutant, but production was still high enough to confer colistin resistance; disruption of phoP conferred wild-type Arn production and colistin MIC. Activation of PhoPQ directly, or through mgrB mutation did not significantly activate PmrAB or PmrC production but direct activation of PmrAB by mutation did, and also activated Arn production and conferred colistin resistance. There was little overlap between the PmrAB and PhoPQ regulons. We conclude that under the conditions used for colistin susceptibility testing, PhoPQ-PmrD-PmrAB cross-regulation is not significant and that independent activation of PhoPQ or PmrAB is the main reason that Arn protein production increases above the threshold required for colistin resistance.
Poirel, L., Vuillemin, X., Juhas, M., Masseron, A., Bechtel-Grosch, U., Tiziani, S., Mancini, S., Nordmann, P.
KPC-50 is a KPC-3 variant identified from a Klebsiella pneumoniae clinical isolate recovered in Switzerland in 2019. As compared to KPC-3, KPC-50 shows i) a three amino-acid insertion (Glu-Ala-Val) between amino acids 276 and 277 amino acid sequence, (ii) an increased affinity to ceftazidime, (iii) a decreased sensitivity to avibactam, explaining the ceftazidime-avibactam resistance, and (iv) associated to a sharp reduction of its carbapenemase activity.
Venu M. Konala,
Pavani Reddy Garlapati,
Mohamed A. Merghani,
Journal of Medical Virology, EarlyView.
Sukbin Jang, Ji-Young Rhee
Since the COVID-19 outbreak started in China, most deaths occur in the elderly or people with underlying diseases. The pathogenesis of COVID-19 is still not well understood why the viral infections lead to respiratory failure with a high mortality rate(Gao et al., 2020). An excessive immune response contributes to COVID-19 pathogenesis and lethality(Gao et al., 2020, Jin et al., 2020). Recently, complement suppression may represent a therapeutic approach to treat COVID-19(Gao et al., 2020).
Di Wu, Jianyun Lu, Lan Cao, Xiaowei Ma, Qun Liu, Yanhui Liu, Zhoubin Zhang
The pandemic of Corona Virus Disease 2019 (COVID-19) is becoming a worldwide disaster. According to the WHO, more than 4 248 389 cases were reported and 294 046 deaths were conformed globally as of 14 May, 2020(WHO, 2020). It has been reported that humans may be more likely to be infected with different types of viruses through respiratory transmission. Here we report the protective effect to pneumonia while fighting against COVID-19.
Anke Huss, Laura A.N. Derks, Dick J.J. Heederik, Inge M. Wouters
Legionella is a bacterial species able to cause influenza-like illness (Pontiac fever) or severe pneumonia (Legionnaires Disease, LD). We assessed Legionella presence and concentration in composting facilities in the Netherlands.
Glick H, Miyazaki T, Hirano K, et al.
AbstractBACKGROUNDPneumonia is a common and serious illness in the elderly with poorly characterized long-term impact on health-related quality of life (HRQoL). The Japanese Goto Epidemiology Study is a prospective, active, population-based surveillance study of adults with X-ray/CT-scan–confirmed community-onset pneumonia, assessing the HRQoL outcome quality-adjusted life years (QALYs). Here we report QALY scores and losses among a subset of participants in the Goto Study.METHODSQALYs were derived from responses to the Japanese version of the EuroQol-5D-5L health-state classification instrument at days 0, 7, 15, 30, 90, 180 and 365 after pneumonia diagnosis from participants enrolled from June 2017 to May 2018. We used patients as their own controls, calculating comparison QALYs by extrapolating EuroQol-5D-5L scores for Day −30 accounting for mortality and changes in scores with age.RESULTSOf 405 participants, 85% were aged ≥65 years, 58% were male, and 69% were hospitalized for clinical and radiological confirmed pneumonia. Compliance with interviews by either patients or proxies was 100%. Adjusted EuroQol-5D-5L scores were 0.759 at day −30, 0.561 at diagnosis, 0.702 by day 180 and .689 by day 365. Average scores at all time points remained below the average day −30 scores (P ≤ .001). Pneumonia resulted in a mean adjusted loss of 0.13 QALYs (~47.5 quality-adjusted days lost) at 365 days (P
Andrew M. Parrott, Jun Shi, Justin Aaron, Daniel A. Green, Susan Whittier, Fann Wu
The ‘hypervirulent’ variant of Klebsiella pneumoniae (hvKp) is a predominant cause of community-acquired pyogenic liver abscess in Asia, and is an emerging pathogen in Western countries. hvKp infections have demonstrated ‘metastatic’ dissemination in immunocompetent hosts, an unusual mode of infection associated with severe complications. Two cases alerted us to the possible presence of hvKp at our hospital, both involving elderly Hispanic males who presented with recurrent fever, bacteremia, epigastric pain, and liver abscesses/phlegmon, thus prompting an assessment of hvKp prevalence.
Mycoplasma pneumoniae (M. pneumoniae) is one of the most common causes of community acquired pneumonia (CAP). Establishing an early diagnosis of M. pneumoniae pneumonia in patients with acute respiratory distress syndrome (ARDS) may have important therapeutic implications.
We describe diagnosis and management of M. pneumoniae pneumonia induced ARDS in a case series of adults and youth hospitalized with radiographically confirmed CAP prospectively enrolled in an observational cohort study in two university teaching hospitals, from November 2017 to October 2019.
In all 10 patients, early and rapid diagnosis for severe M. pneumoniae pneumonia with ARDS was achieved with polymerase chain reaction (PCR) or metagenomic next-generation sequencing (mNGS) testing of samples from the lower respiratory tract or pleural effusion. The average PaO2/FiO2 of all patients was 180 mmHg. Of the 10 cases, 4 cases had moderate ARDS (100 mmHg ≤ PaO2/FiO2
Sohn, Annette H.; Lumbiganon, Pagakrong; Kurniati, Nia; Lapphra, Keswadee; Law, Matthew; Do, Viet Chau; Van Nguyen, Lam; Truong, Khanh Huu; Wati, Dewi Kumara; Ounchanum, Pradthana; Puthanakit, Thanyawee; Sudjaritruk, Tavitiya; Ly, Penh Sun; Yusoff, Nik Khairulddin Nik; Fong, Sieu Moy; Mohamed, Thahira Jamal; Nallusamy, Revathy; Kumarasamy, Nagalingaswaran; Kariminia, Azar
To implement a standardized cause of death (CoDe) reporting and review process in order to systematically disaggregate causes of HIV-related deaths in a cohort of Asian children and adolescents.
Death-related data were retrospectively and prospectively assessed in a longitudinal regional cohort study.
Children under routine HIV care at sites in Cambodia, India, Indonesia, Malaysia, Thailand, and Vietnam between 2008–2017 were followed. Causes of death were reported and then independently and centrally reviewed. Predictors were compared using competing risks survival regression analyses.
Among 5918 children, 5523 (93%; 52% male) had ever been on combination antiretroviral therapy (cART). Of 371 (6.3%) deaths, 312 (84%) occurred in those with a history of cART (crude all-cause mortality 9.6 per 1000 person-years; total follow-up time 32,361 person-years). In this group, median age at death was 7.0 (2.9–13) years; median CD4 count was 73 (16–325) cells/mm3. The most common underlying causes of death were pneumonia due to unspecified pathogens (17%), tuberculosis (16%), sepsis (8.0%), and AIDS (6.7%); 12% of causes were unknown. These clinical diagnoses were further grouped into AIDS-related infections (22%) and non-infections (5.8%), and non-AIDS-related infections (47%) and non-infections (11%); with 12% unknown, 2.2% not reviewed. Higher CD4 count and better weight-for-age z-score were protective against death.
Our standardized cause of death assessment provides robust data to inform regional resource allocation for pediatric diagnostic evaluations and prioritization of clinical interventions, and highlight the continued importance of opportunistic and non-opportunistic infections as causes of death in our cohort.
Correspondence to Annette H. Sohn, MD TREAT Asia/amfAR, Exchange Tower, 388 Sukhuvmit Road, Suite 2104, Klongtoey, Bangkok, Thailand 10110. Tel: +66 2 663 7561; e-mail: firstname.lastname@example.org
Received 12 February, 2020
Revised 21 April, 2020
Accepted 27 April, 2020
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com).
Copyright © 2020 Wolters Kluwer Health, Inc.
Xuemei Yang, Ning Dong, Edward Wai-Chi Chan, Rong Zhang, Sheng Chen
Klebsiella pneumoniae has an exceptional ability to acquire exogenous resistance-encoding and hypervirulence-encoding genetic elements. In this review we trace the key evolutionary routes of plasmids involved in the dissemination of such elements; we observed diverse, but convergent, evolutionary paths that eventually led to the emergence of conjugative plasmids which simultaneously encode carbapenem resistance and hypervirulence. One important evolutionary feature of these plasmids is that they contain a wide range of transposable elements that enable them to undergo frequent genetic transposition, resulting in plasmid fusion and presumably better adaptation of the plasmid to the bacterial host.
Physicist turned ecologist and UK Chief Scientific Adviser. He was born in Sydney, NSW, Australia, on Jan 8, 1936, and died of pneumonia in Oxford, UK, on April 28, 2020, aged 84 years.
Rueckel, Johannes; Kunz, Wolfgang G.; Hoppe, Boj F.; Patzig, Maximilian; Notohamiprodjo, Mike; Meinel, Felix G.; Cyran, Clemens C.; Ingrisch, Michael; Ricke, Jens; Sabel, Bastian O.
Interpretation of lung opacities in ICU supine chest radiographs remains challenging. We evaluated a prototype artificial intelligence algorithm to classify basal lung opacities according to underlying pathologies.
Retrospective study. The deep neural network was trained on two publicly available datasets including 297,541 images of 86,876 patients.
One hundred sixty-six patients received both supine chest radiograph and CT scans (reference standard) within 90 minutes without any intervention in between.
Measurements and Main Results:
Algorithm accuracy was referenced to board-certified radiologists who evaluated supine chest radiographs according to side-separate reading scores for pneumonia and effusion (0 = absent, 1 = possible, and 2 = highly suspected). Radiologists were blinded to the supine chest radiograph findings during CT interpretation. Performances of radiologists and the artificial intelligence algorithm were quantified by receiver-operating characteristic curve analysis. Diagnostic metrics (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) were calculated based on different receiver-operating characteristic operating points. Regarding pneumonia detection, radiologists achieved a maximum diagnostic accuracy of up to 0.87 (95% CI, 0.78–0.93) when considering only the supine chest radiograph reading score 2 as positive for pneumonia. Radiologist’s maximum sensitivity up to 0.87 (95% CI, 0.76–0.94) was achieved by additionally rating the supine chest radiograph reading score 1 as positive for pneumonia and taking previous examinations into account. Radiologic assessment essentially achieved nonsignificantly higher results compared with the artificial intelligence algorithm: artificial intelligence-area under the receiver-operating characteristic curve of 0.737 (0.659–0.815) versus radiologist’s area under the receiver-operating characteristic curve of 0.779 (0.723–0.836), diagnostic metrics of receiver-operating characteristic operating points did not significantly differ. Regarding the detection of pleural effusions, there was no significant performance difference between radiologist’s and artificial intelligence algorithm: artificial intelligence-area under the receiver-operating characteristic curve of 0.740 (0.662–0.817) versus radiologist’s area under the receiver-operating characteristic curve of 0.698 (0.646–0.749) with similar diagnostic metrics for receiver-operating characteristic operating points.
Considering the minor level of performance differences between the algorithm and radiologists, we regard artificial intelligence as a promising clinical decision support tool for supine chest radiograph examinations in the clinical routine with high potential to reduce the number of missed findings in an artificial intelligence–assisted reading setting.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http:/journals.lww.com/ccmjournal).
Drs. Rueckel, Hoppe, Patzig, Notohamiprodjo, Ingrisch, and Ricke received support for article research from Siemens Healthcare GmbH (analyzed algorithm as part of a research collaboration). Drs. Kunz and Sabel’s institution received funding from Siemens Healthineers. Dr. Notohamiprodjo received funding from Siemens (speaker’s bureau). Dr. Meinel received funding from Agfa-Gevaert Healthcare GmbH (consulting). Dr. Cyran received funding from Goetz Partner Ltd (speaker’s bureau) and Sandoz (consulting).
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Copyright © by 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Chandrashekar, A., Liu, J., Martinot, A. J., McMahan, K., Mercado, N. B., Peter, L., Tostanoski, L. H., Yu, J., Maliga, Z., Nekorchuk, M., Busman-Sahay, K., Terry, M., Wrijil, L. M., Ducat, S., Martinez, D. R., Atyeo, C., Fischinger, S., Burke, J. S., Slein, M. D., Pessaint, L., Van Ry, A., Greenhouse, J., Taylor, T., Blade, K., Cook, A., Finneyfrock, B., Brown, R., Teow, E., Velasco, J., Zahn, R., Wegmann, F., Abbink, P., Bondzie, E. A., Dagotto, G., Gebre, M. S., He, X., Jacob-Dolan, C., Kordana, N., Li,
An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.
Maria Chiara Pelle,
Francesco Saverio Costanzo,
Enrico Maria Trecarichi,
IDTM UMG COVID‐19 Group
Yang, Xiao; Cai, Shuhan; Luo, Yun; Zhu, Fangfang; Hu, Ming; Zhao, Yan; Zheng, Ruiqiang; Li, Xuyan; Hu, Bo; Peng, Zhiyong
Severe acute respiratory distress syndrome is complicated with coronavirus disease 2019 and extracorporeal membrane oxygenation support may be necessary in severe cases. This study is to summarize the clinical features, extracorporeal membrane oxygenation characteristics, and outcomes of patients with severe acute respiratory syndrome coronavirus 2 pneumonia received extracorporeal membrane oxygenation.
Descriptive study from two hospitals.
The ICUs from university hospitals.
Patients with severe acute respiratory syndrome coronavirus 2 pneumonia received mechanical ventilation, including those underwent extracorporeal membrane oxygenation from Zhongnan Hospital of Wuhan University and Wuhan Pulmonary Hospital from January 8, 2020, to March 31, 2020.
Measurements and Main Results:
Clinical records, laboratory results, ventilator parameters, and extracorporeal membrane oxygenation-related data were abstracted from the medical records. One-hundred twenty-nine critically ill patients with severe acute respiratory syndrome coronavirus 2 pneumonia were admitted to ICU of the two referral hospitals. Fifty-nine patients received mechanical ventilation and 21 of them received extracorporeal membrane oxygenation support (fourteen from Zhongnan hospital and seven from Wuhan pulmonary hospital). Compared to mechanical ventilation patients without extracorporeal membrane oxygenation support, there was a tendency of decline in mortality but with no significant difference (no-extracorporeal membrane oxygenation group 24/38 [63.2%] vs extracorporeal membrane oxygenation group 12/21 [57.1%]; p = 0.782). For those patients with extracorporeal membrane oxygenation, 12 patients died and nine survived by April 7, 2020. Among extracorporeal membrane oxygenation patients, the PaCO2 prior to extracorporeal membrane oxygenation was lower (54.40 mm Hg [29.20–57.50 mm Hg] vs 63.20 mm Hg [55.40–72.12 mm Hg]; p = 0.006), and pH prior to extracorporeal membrane oxygenation was higher (7.38 [7.28–7.48] vs 7.23 [7.16–7.33]; p = 0.023) in survivors than nonsurvivors.
Extracorporeal membrane oxygenation might be an effective salvage treatment for patients with severe acute respiratory syndrome coronavirus 2 pneumonia associated with severe acute respiratory distress syndrome. Severe CO2 retention and acidosis prior to extracorporeal membrane oxygenation indicated a poor prognosis.
Drs. Yang and Cai contributed equally to the first authorship.
This work was supported by the National Natural Science Foundation (grants 81772046 and 81971816 to Dr. Peng) and the Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China (2020ZX09201007 to Dr. Peng).
Dr. Zhao received support for article research from Hubei Clinical Research Center for Emergency and Resuscitation, Hubei Emergency and Critical Mobile Extracorporeal Membrane Oxygenation (ECMO) Support Center, and the Emergency and Critical Care Mobile ECMO Support Center of Zhongnan Hospital of Wuhan University. Dr. Peng received support for article research from the Chinese National Natural Science Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest.
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Copyright © by 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Falcone M, Daikos G, Tiseo G, et al.
AbstractBackgroundIn vitro data support the use of combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI), but clinical studies are lacking. The aim of our study was to compare the outcome of patients with bloodstream infections (BSIs) due to MBLs-producing Enterobacterales treated either with CAZ-AVI plus ATM or other active antibiotics (OAAs).MethodsProspective observational study including patients admitted to three hospitals in Italy and Greece. The primary outcome measure was the 30-day all-cause mortality. Secondary outcomes were clinical failure at day 14 and length of stay (LOS) after BSI diagnosis. Cox regression analysis including a propensity score (PS) for receiving CAZ-AVI plus ATM was performed to evaluate primary and secondary outcomes. A PS-based matched analysis was also performed.ResultsWe enrolled 102 pts with BSI, 82 had infections caused by NDM-producing (79 K.pneumoniae and 3 E.coli) and 20 by VIM-producing (14 K.pneumoniae, 5 Enterobacter spp, 1 M.morganii) strains. The 30-day mortality rate was 19.2% in CAZ-AVI/ATM group vs 44% in OAAs group (p=0.007). The PS-adjusted analysis showed that the use of CAZ-AVI/ATM was associated with lower 30-day mortality (HR 0.37, 95% CI 0.13-0.74, p=0.01), lower clinical failure at day 14 (HR 0.30, 95% CI 0.14-0.65, p=0.002) and shorter LOS (sHR 0.49, 95% CI 0.30-0.82, p=0.007). The PS-matched analysis confirmed these findings.ConclusionsCAZ-AVI/ATM combination offers therapeutic advantage compared to OAAs for patients with BSI due to MBL-producing Enterobacterales. Further studies are warranted.
To date, very little information is available concerning the relationship between acanthosis nigricans (AN) and infection with human immunodeficiency virus type 1 (HIV-1).
Herein, we report the case of a middle-aged man admitted for fever and progressively worsening dyspnea in the context of an opportunistic pneumonia and firstly diagnosed with acquired immunodeficiency syndrome (AIDS). At the time of diagnosis, physical examination revealed the presence of a palpable, hyperpigmented skin lesion on the left areola with surface desquamation and velvety texture consistent with AN. Of note, the most common primary etiologies related to AN were excluded and the complete regression of the skin lesion was observed once antiretroviral therapy was started.
This is the second report of AN found in patients with AIDS and apparently responsive to prolonged antiretroviral treatment. Possible explanations of this association are still not completely understood, probably related to virus-induced changes in lipid metabolism. Our experience suggests that HIV testing should always be considered in the setting of apparently idiopathic AN.
The aim of the study was to identify the pathogens, in addition to bordetella pertussis (B. pertussis), which cause pertussis-like syndrome in children and to compare clinical presentation between those with B. pertussis and pertussis-like syndrome.
A cross-sectional analysis was conducted from March 2016 to September 2018. In total, 281 children with suspected pertussis infections were enrolled in this study. Multi-pathogen detection was performed.
In total, 281 children were enrolled including 139 males and 142 females. Among them, 149 (53.0%) were B. pertussis positive, and 72 (15.6%) children tested positive for other pathogens. Mycoplasma pneumoniae (MP, 27 cases) was the most common causative pathogen in pertussis-like syndrome, followed by human rhinovirus (HRV, 23 cases), Streptococcus pneumoniae (SP, 13 cases), Haemophilus influenzae (HI, 12 cases) and parainfluenza virus 3 (Pinf-3, 9 cases). Children in the B. pertussis group had a higher rate of vaccination and longer hospital stay (P
Venditti, C., Butera, O., Proia, A., Rigacci, L., Mariani, B., Parisi, G., Messina, F., Capone, A., Nisii, C., Di Caro, A.
Extended-spectrum beta-lactamases (ESBLs) and carbapenemases are among the most important causes of resistance in Enterobacterales, often leading to healthcare-associated infections that result in high morbidity and mortality (1-3)....
Zilberberg, M. D., Nathanson, B. H., Sulham, K., Shorr, A. F.
Background: In the face of increasing rates of antimicrobial resistance in complicated urinary tract infections (cUTI), clinicians need to understand cross-resistance patterns among commonly encountered pathogens.Methods: We performed a multicenter, retrospective cohort study in the Premier database of approximately 180 hospitals, 2013-2018. Using an ICD-9/10-based algorithm we identified all adult patients hospitalized with cUTI and included those with a positive blood or urine culture. We examined the microbiology and susceptibilities to common cUTI antimicrobials (3rd generation cephalosporin [C3], fluoroquinolones [FQ], trimethoprim-sulfamethoxazole [TMP/SMX], fosfomycin [FFM], and nitrofurantoin [NFT]) singly and in groups of two.Results: Among 28,057 organisms from 23,331 patients, the 3 most common pathogens were E. coli (41.0%, C3R 15.1%), K. pneumoniae (12.1%, C3R 13.2%), and P. aeruginosa (11.0%, C3R 12.0%). E. coli was most frequently resistant to FQ (43.5%) and least to NFT (6.7%). K. pneumoniae was most frequently resistant to NFT (60.8%) and least to FFM (0.1%). P. aeruginosa was most frequently resistant to FQ (34.4%) and least to TMP/SMX (4.2%). Of the C3R E. coli, 87.1% were also FQR, 63.7% TMP/SMX-R, and 13.3% NFTR. C3R K. pneumoniae had a 76.5% chance of being FQR, 78.1% TMP/SMZ-R, and 77.6% NFTR. C3R P. aeruginosa coexisted with FQR in 47.3%, TMP/SMZ-R in 18.9%, and NFTR in 28.7%.Conclusions: Among the most common pathogens isolated from hospitalized patients with cUTI, the rates of single resistance to common treatments and of cross-resistance to these regimens are substantial. Knowing the patterns of cross-resistance may help clinicians tailor empiric therapy more precisely.
Daniel Overhoff, Thomas Walter, Joachim Gruettner, Sonja Janssen, Julia Riffel, Ursula Hoffmann, Stefan O Schoenberg, Philipp Riffel
Gabriel Rainisch, Eduardo A. Undurraga, Gerardo Chowell
On December 31, 2019, the regional office of the World Health Organization (WHO) was notified of a cluster of pneumonia cases of unknown origin associated with a market in Wuhan, China (Zhu et al., 2020). A novel coronavirus (SARS-COV-2) was identified as the cause of the infections (Zhu et al., 2020) and has since spread worldwide. As of May 7, 2020, more than 3.6 million cases of COVID-19 (illness caused by SARS-COV-2) have been reported in 184 countries and territories, including ∼250,000 deaths (Dong et al., 2020, World Health Organization, 2020).
AbstractDecember 2019 saw the emergence of a new epidemic of pneumonia of varying severity, called COVID-19, caused by a newly identified coronavirus, SARS-CoV-2. No therapeutic option is available to treat this infection that has already killed more than 235,000 people worldwide. This Viewpoint summarizes the strong scientific arguments supporting the use of alisporivir, a non-immunosuppressive analogue of cyclosporine A with potent cyclophilin inhibition properties that has reached Phase 3 clinical development, for the treatment of COVID-19. They include the strong cyclophilin dependency of the lifecycle of many coronaviruses, including SARS-CoV and MERS-CoV, and preclinical data showing strong antiviral and cytoprotective properties of alisporivir in various models of coronavirus infection, including SARS-CoV-2. Alisporivir should be tested without delay on both virological and clinical endpoints in patients with or at-risk of severe forms of SARS-CoV-2 infection.
Benedikt Huttner, Bernadette Cappello, Graham Cooke, Sumanth Gandra, Stephan Harbarth, Monica Imi, Mark Loeb, Marc Mendelson, Lorenzo Moja, Céline Pulcini, Mike Sharland, Evelina Tacconnelli, Mei Zeng, Nicola Magrini
American Journal of Respiratory and Critical Care Medicine, Volume 201, Issue 10, Page 1315-1316, May 15, 2020.
Joshua P. Metlay, Grant W. Waterer
American Journal of Respiratory and Critical Care Medicine, Volume 201, Issue 10, Page 1316-1317, May 15, 2020.
At present, there is no definitive antiviral treatment for coronavirus disease 2019 (COVID-19). We describe our early experience with remdesivir in four critically ill COVID-19 patients. Patients received a 200 mg loading dose, followed by 100 mg daily intravenously for up to 10 days. All patients had been previously treated with other antivirals before remdesivir initiation. One patient experienced a torsade de pointes requiring cardiac resuscitation and one died due to multiple organ failure. Three patients showed biochemical signs of liver injury. Lymphocyte count increased in all patients soon after remdesivir initiation. Nasal swab SARS-CoV-2 RNA became negative in three of four patients after 3 days of therapy. We observed an in vivo virological effect of remdesivir in four critically ill, COVID-19 patients, coupled with a significant burden of adverse events. Although limited by the low number of subjects studied, our preliminary experience may be relevant for clinicians treating COVID-19.
Dong Chen, Feng Tang, Shushu Lu, Qifa Song
We thank Danilo Buonsenso and colleagues for their excellent suggestion in response to our observational cohort study.1 We think that defining the moderate clinical type of coronavirus disease 2019 (COVID-19) severity should be based on what the presence of pneumonia means in the progression of COVID-19 and what classifying measures are more practical for clinicians. COVID-19 was initially understood as pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Now, after the reporting of a great number of mild and asymptomatic cases of COVID-19 (the so-called iceberg phenomenon that is common for most infectious diseases) and the institution of RT-PCR as a diagnostic standard, radiological examination seems less important as a diagnostic tool than it used to be.
Danilo Buonsenso, Niccolò Parri, Cristina De Rose, Piero Valentini, Gemelli-pediatric COVID-19 team
In their Article, Haiyan Qiu and colleagues1 described 36 children with coronavirus disease 2019 (COVID-19) using the Chinese classification for paediatric COVID-19 severity: asymptomatic infection, mild disease, moderate disease, severe disease, and critical illness.2 Herein, we focus on the definition of moderate disease. This definition is based on clinical criteria (pneumonia with fever and cough in the absence of signs of hypoxaemia), radiological criteria (because “some cases may have no clinical signs and symptoms, but chest CT shows lung lesions, which are subclinical”), or both.
David A Kass, Priya Duggal, Oscar Cingolani
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 was first reported in China in late December, 2019, and has since evolved into a global pandemic. As of April 29, 2020, COVID-19 has been confirmed in more than 3 million individuals in 185 countries and regions, with an overall mortality rate of more than 6%.1 Severe disease involves bilateral interstitial pneumonia requiring intensive care unit (ICU) ventilatory support and can evolve into adult respiratory distress syndrome with high mortality.
Sungchan Kim, Yong Dam Jeong, Jong Hyuk Byun, Giphil Cho, Anna Park, Jae Hun Jung, Yunil Roh, Sooyoun Choi, Ibrahim Malik Muhammad, Il Hyo Jung
In December 2019, people in Wuhan, China began to contract pneumonia, and the cause was unknown. The condition was similar to viral pneumonia, as confirmed by clinical presentation. On January 7, 2020, it was confirmed that the cause of the pneumonia was a new coronavirus. Thereafter, this was named the 2019 novel coronavirus disease-COVID-19. Notably, COVID-19 induces mild symptoms that are similar to those induced by other respiratory infections. However, particularly, it affects older people with comorbidity and can result in fatal respiratory diseases (Chen et al., 2020).
Adriana Calderaro, Maria Cristina Arcangeletti, Flora De Conto, Mirko Buttrini, Paolo Montagna, Sara Montecchini, Francesca Ferraglia, Federica Pinardi, Carlo Chezzi
A novel coronavirus was initially detected in Wuhan (China) starting from December 2019 in patients with severe pneumonia of unknown origin (Chen and Yu, 2020). Genome sequencing allowed to classify the virus into the subgenus Sar-becovirus of the genus Betacoronavirus; it was termed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the illness it causes as coronavirus disease 2019 (COVID-19). On March 11, 2020 the World Health Organization declared SARS-CoV-2 pandemic, considering the over 118,000 cases of the coronavirus illness in over 110 countries around the world (World Health Organization, 2020).
X. Wu et al.
C. Duployez et al.
R. A. Bonnin et al.
De Oliveira, D. M. P., Forde, B. M., Kidd, T. J., Harris, P. N. A., Schembri, M. A., Beatson, S. A., Paterson, D. L., Walker, M. J.
Antimicrobial-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. The acquisition of antimicrobial resistance genes by ESKAPE pathogens has reduced the treatment options for serious infections, increased the burden of disease, and increased death rates due to treatment failure and requires a coordinated global response for antimicrobial resistance surveillance. This looming health threat has restimulated interest in the development of new antimicrobial therapies, has demanded the need for better patient care, and has facilitated heightened governance over stewardship practices.
Antibiotic resistance is an emerging problem caused due to antibiotic use. In countries with high rates of infectious diseases, antibiotic resistance is a frequent cause of mortality. The aim was to analyse antibiotic prescribing practices between 2008 and 2017 in a teaching (TH) and a non-teaching (NTH) hospital, as typical hospitals of low- and middle-income countries, and to compare antibiotic prescribing for severe infectious indications for which empiric antibiotic treatment is recommended.
Data from adult patients registered at two Indian private-sector hospitals with one of the following indications: epiglottitis, pneumonia, peritonitis, pyelonephritis, cellulitis, erysipelas, septic arthritis, endocarditis, meningitis or sepsis; were included and analysed. Antibiotic prescription data was analyzed using the World Health Organization’s (WHO) Anatomical Therapeutic Chemical classification system and the Defined Daily Doses. Chi-square and linear regression were used to compare the data between groups. Time series analyses were conducted using linear regression. P-values
Zeng H, Xu C, Fan J, et al.
This study describes results of IgM and IgG antibody testing from throat swabs of newborns born to mothers with COVID-19 pneumonia.
Influenza is a major cause of morbidity and mortality worldwide. Following the 2009 pandemic, there was widened interest in studying influenza burden in all regions. However, since data from the World Health Organization (WHO) Middle East and North Africa (MENA) region remain limited, we aimed to contribute to the understanding of influenza burden in Lebanon.
A retrospective chart review extending over a period of 8 seasons from Jan 1st, 2008 till June 30th, 2016 at a tertiary care center in Beirut was performed. All cases confirmed to have influenza based on rapid antigen detection or/and polymerase chain reaction on a respiratory sample were included for analysis. Data on epidemiology, clinical presentation, complications, antiviral use and mortality were collected for analysis.
A total of 1829 cases of laboratory-confirmed influenza were identified. Average annual positivity rate was 14% (positive tests over total requested). Both influenza A and B co-circulated in each season with predominance of influenza A. Influenza virus started circulating in December and peaked in January and February. The age group of 19–50 years accounted for the largest proportion of cases (22.5%) followed by the age group of 5–19 years (18%). Pneumonia was the most common complication reported in 33% of cases. Mortality reached 3.8%. The two extremes of age (
Aye, S. M., Galani, I., Yu, H., Wang, J., Chen, K., Wickremasinghe, H., Karaiskos, I., Bergen, P. J., Zhao, J., Velkov, T., Giamarellou, H., Lin, Y.-W., Tsuji, B., Li, J.
Resistance to polymyxin antibiotics is increasing. Without new antibiotic classes, combination therapy is often required. We systematically investigated bacterial killing with polymyxin-based combinations against multidrug-resistant (including polymyxin-resistant), carbapenemase-producing Klebsiella pneumoniae. Mono, double and triple combination therapies were compared to identify the most efficacious treatment using static time-kill studies (24h, six isolates), an in vitro pharmacokinetic/pharmacodynamic model (IVM; 48h, two isolates), and the mouse thigh infection model (24h, six isolates). In static time-kill studies, all monotherapies (polymyxin B/rifampicin/amikacin/meropenem/minocycline) were ineffective. Initial bacterial killing was enhanced with various polymyxin B-containing double combinations, however substantial regrowth occurred in most cases by 24h. Most polymyxin B-containing triple combinations provided greater and more sustained killing than double combinations. Standard dosage regimens of polymyxin B (2.5 mg/kg/d), rifampicin (600 mg/12-hourly) and amikacin (7.5 mg/kg/12-hourly) were simulated in the IVM. Against isolate ATH 16, no viable bacteria were detected across 5-25h with triple therapy, with regrowth to ~2-log10 CFU/mL occurring at 48h. Against isolate BD 32, rapid initial killing of ~3.5-log10 CFU/mL at 5h was followed by a slow decline to ~2-log10 CFU/mL at 48h. In infected mice, polymyxin B monotherapy (60 mg/kg/d) was generally ineffective. With triple therapy (polymyxin B 60 mg/kg/d, rifampicin 120 mg/kg/d, and amikacin 300 mg/kg/d), at 24h there was an ~1.7-log10 CFU/thigh reduction compared to the starting inoculum for all six isolates. Our results demonstrate that the polymyxin B/rifampicin/amikacin combination significantly enhanced in vitro and in vivo bacterial killing, providing important information for the optimization of polymyxin-based combinations in patients.
Gebremariam, T., Zhang, L., Alkhazraji, S., Gu, Y., Youssef, E. G., Tong, Z., Kish-Trier, E., Bajji, A., de Araujo, C. V., Rich, B., French, S. W., Li, D. Y., Mueller, A. L., Odelberg, S. J., Zhu, W., Ibrahim, A. S.
The rise in multidrug resistant (MDR) organisms portends a serious global threat to the healthcare system with nearly untreatable infectious diseases, including pneumonia and its often fatal sequelae, acute respiratory distress syndrome (ARDS) and sepsis. Gram-negative bacteria (GNB) including Acinetobacter baumannii, Pseudomonas aeruginosa, and carbapenemase-producing Klebsiella pneumoniae (CPKP), are among the World Health Organization and National Institutes of Health's high priority MDR pathogens for targeted development of new therapies. Here we show that stabilizing the host's vasculature by genetic deletion or pharmacological inhibition of the small GTPase ADP-ribosylation factor 6 (ARF6) increases survival rates of mice infected with A. baumannii, P. aeruginosa, CPKP pneumonia. We show that pharmacological inhibition of ARF6-GTP phenocopies endothelial-specific Arf6 disruption in enhancing survival of mice with A. baumannii pneumonia, suggesting that inhibition is on target. Finally, we show that the mechanism of protection elicited by these small molecule inhibitors is by restoration of vascular integrity disrupted by GNB lipopolysaccharide (LPS) activation of TLR4/MyD88/ARNO/ARF6 pathway. By targeting the host's vasculature with small molecule inhibitors of ARF6 activation, we circumvent microbial drug resistance and provide a potential alternative/adjunctive treatment for emerging and re-emerging pathogens.
coronavirusCOVID-19pregnancypneumoniaSARS-CoV-2fetusintrauterine transmissionemerging infectionmaternal infectioncase-control study
Northern European Conference on Travel Medicine (NECTM) 2020
Mødet udskudt på grund af COVID-19
3.06.2020 - 5.06.2020
ASM Microbe 2020
Aflyst på grund af COVID-19
18.06.2020 - 22.06.2020
Ph.d. forsvar ved Kristina Langholz Kristensen
International AIDS Conference (AIDS) 2020
6.07.2020 - 10.07.2020
International Liver Congress (ILC) 2020
27.08.2020 - 29.08.2020
COVID-19 retningslinje (2020)
National handlingsplan for antibiotika til mennesker (2017)
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
Unusual dermatomycoses caused by Nannizzia nana : the geophilic origin of human infections
1.06.2020Latest Results for Infection
Drusen in dense deposit disease: not just age-related macular degeneration
The health-related determinants of politics
Cost-effectiveness of transitional US plans for universal health care
Towards more balanced representation in Lancet Commissions
Hvad mener Professor Jens Lundgren om artiklen"Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV."?
Hvorfor anbefaler Professor Troels Lillebæk artiklen"The global prevalence of latent tuberculosis: a systematic review and meta-analysis."?
Hvad mener Professor Lars Østergaard om artiklen"Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial."?
Hvad mener Professor Thomas Benfield om artiklen"Oral versus Intravenous Antibiotics for Bone and Joint Infection."?
Hvorfor anbefaler Professor Niels Obel artiklen"Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis."?
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