Background Septic shock with neutropenia can progress rapidly and have a very high mortality. Research Question: How do delays of initial pathogen-appropriate empiric antimicrobial therapy relative to onset of hypotension affect hospital survival in adult neutropenic patients with septic shock? Study Design and Methods: Retrospective data was collected from eligible cases occurring from July 1989 to June 2018 in 32 academic and community hospitals in Canada, the United States, and Saudi Arabia. Results Out of the 508 patients with neutropenic septic shock, 65.7% (334) received appropriate empiric antimicrobial therapy after the onset of persistent hypotension. Survival in this group was 28.4%. The median time to effective antimicrobial therapy from the onset of persistent hypotension was 6.49 hours (IQR: 2.35–13.46 hours). Patients treated within the first 2 hours of hypotension onset experienced the best survival at 60.0%; survival dropped to 42.3% between 2–4 hours delay while delays beyond 4 hours show a marked increase in mortality particularly beyond 18 hours. A significant association was identified between delays in antimicrobial initiation relative to the initial documentation of persistent/recurrent sepsis-related hypotension and increased hospital mortality, with an adjusted odds ratio of 1.161 per hour of delay (95% CI: 1.052–1.281; p = 0.003). In multivariate analysis, it was the second strongest correlate to outcome after severity of illness. Sensitivity analysis further demonstrated that the adverse effects of delayed antimicrobial treatment were consistent across various subgroups, including different types of infections and pathogen groups. Overall hospital survival stood at 27.0%, while ICU survival was 35.8%. Conclusions Initiation of pathogen-appropriate antimicrobials within the first hours of documented hypotension in neutropenic septic shock patients significantly reduces mortality, with delays in treatment leading to progressively higher mortality rates. These findings emphasize the critical importance of timely antimicrobial intervention to reduce mortality in this high-risk patient population.

BACKGROUND:The optimal thromboprophylaxis among critically ill adults with COVID-19 is uncertain. OBJECTIVES:To determine the effectiveness and safety of intermediate-dose heparin compared with standard low-dose thromboprophylaxis. METHODS:In an ongoing adaptive platform trial (randomized embedded multifactorial adaptive platform for community-acquired pneumonia), critically ill patients with COVID-19 were randomized to intermediate-dose heparin or standard low-dose thromboprophylaxis. Interventions were continued in hospital for up to 14 days. The primary endpoint was organ support-free days (OSFDs), an ordinal outcome combining in-hospital survival and the number of days free of intensive care unit-based respiratory or cardiovascular organ support through 21 days. The primary analysis was an adjusted Bayesian hierarchical cumulative logistic model. An odds ratio (OR) > 1.0 represents an improved outcome with intermediate-dose heparin. RESULTS:Between April 27, 2021 and November 25, 2023, 1255 critically ill adults with COVID-19 were enrolled from 78 sites in 15 countries, of whom 1254 completed follow-up (n = 572 intermediate-dose, n = 682 low-dose). Enrollment was terminated prior to reaching a prespecified statistical trigger due to declining case numbers and slow recruitment. Median age was 59 years, and 36.7% were female (n = 461/1255). The probability that intermediate-dose heparin improved OSFDs was 73.5% (OR, 1.06; 95% credible interval, 0.87, 1.30), which did not meet the prespecified superiority threshold of 99%. Hospital survival was 77.1% (441/572) and 76.7% (523/682) in the intermediate- and low-dose heparin groups, respectively (median adjusted OR, 1.14; 95% credible interval, 0.86, 1.52). Major bleeding occurred in 10 of 572 (1.7%) and 14 of 682 (2.1%) patients receiving intermediate and standard low doses, respectively. CONCLUSION:Intermediate-dose heparin did not improve OSFDs or survival compared with standard thromboprophylaxis in critically ill patients with COVID-19. (ClinicalTrials.gov number: CT02735707).

RATIONALE Necrotizing fasciitis is an aggressive, progressive soft tissue infection leading to septic shock, requiring immediate intervention to control infection. While delays in antibiotic therapy and surgical source control increase mortality, the benefits of very early intervention, particularly within the first 24 hours, are unclear. This study evaluated the impact of timely antibiotic and surgical interventions on patient outcomes. METHODS We used the previously published Cooperative Antimicrobial Therapy of Septic Shock (CATSS)database, which includes ICU patients in Canada, the United States, and Saudi Arabia from July1, 1989, to June 30, 2018. This study focused on adult septic shock with necrotizing fasciitis. The primary outcome was in-hospital survival. Univariate logistic regression identified factors associated with in-hospital survival, followed by survival analysis to adjust for relevant clinical variables. We included demographic variables, illness severity, delay in appropriate antibiotic treatment, and source control timing (relative to hypotension onset). RESULTS In this retrospective study, 178 cases of septic shock from necrotizing fasciitis were analyzed. Survivors had lower APACHE II scores (21.8 vs 28.8), were younger (54.2 vs 60.9), and had lower lactate levels (3.6 vs 7.2 mg/dL). Each hour of delay in appropriate antibiotics and source control increased death risk, with hazard ratios of 1.03 (95% CI: 1.02-1.04) and 1.01 (95% CI: 1.00-1.02)per hour, respectively. Diabetic patients had more than twice the death risk (Hazard Ratio: 2.39).Patients receiving antibiotics within 3 hours and source control within 6 hours had higher survival rates (83%) versus those with antibiotics delayed over 6 hours and source control delayed beyond24 hours (10%). [Figure 1] CONCLUSIONS Timely antibiotics and prompt source control improve survival in necrotizing fasciitis-related septic shock. Even slight delays increased mortality, especially when both treatments were delayed. Risk factors such as older age, higher APACHE II scores, elevated lactate, and diabetes worsened mortality. Fast, coordinated care is essential to improve outcomes in these patients. Impact of Timing of Empiric Antibiotic Therapy and Surgical Intervention on Septic Shock Associated Necrotizing Fasciitis

Rationale: Pneumonia-associated septic shock (PaSS) is a leading cause of ICU mortality. This study aims to explore the impact of timing of appropriate antibiotic administration relative to the onset of persistent/recurrent hypotension on the outcomes in patients with (PaSS). Methods: A retrospective cohort study was conducted during periods from July 1989 to June 2018 across hospitals in the United States, Canada, and Saudi Arabia. This analysis includes 4,111 septic shock patients having pneumonia identified as the primary cause of infection. Univariate analysis was performed to evaluate the effect of delayed antibiotic treatment on survival to hospital discharge. Additionally, multivariable logistic regression was performed to identify variables associated with increased mortality in relation to antimicrobial delay. Results: Of the 4,111 patients identified with PaSS, 2,977 (72.4%) received appropriate antimicrobial therapy only after the onset of recurrent or persistent hypotension. In this subgroup, delayed initiation of appropriate antimicrobials was strongly correlated with in-hospital mortality (adjusted odds ratio [OR] 1.08 per hour delay, 95% [CI] 1.078-1.102, p < 0.0001). When effective antimicrobials were administered within the first hour post-hypotension onset, the patient survival rate was shown to be 76.4%, with each additional hour of delay up to 6 hours linked to an average reduction in in-hospital survival of approximately 5.9% per hour. After multivariate analysis including a selection of epidemiologic/therapeutic variables, the time to initiation of pathogen-appropriate antimicrobial therapy was demonstrated to be the most significant independent predictor of in-hospital mortality outcome. Conclusion: For adult patients with PaSS, delays in appropriate antimicrobial administration were associated with significant decreases in survival. Despite these results, only 59.2% of PaSS patients in this cohort received appropriate antimicrobial therapy within the first six hours following hypotension onset. Early recognition and treatment measures are central to improved outcomes in PaSS.

Rationale: Previous studies have demonstrated that prompt antibiotic treatment is associated with improved outcomes in septic shock. However, the precise impact of the timeliness of appropriate of initial antimicrobials in the subset of septic shock patients with neutropenia is not well defined. This study aims to evaluate the relationship between antibiotic timing and patient mortality in neutropenic septic shock. Methods: A retrospective cohort study was conducted for periods between July 1989 toJune 2018 in 29 academic and community hospitals in Canada, the United States, and Saudi Arabia. The primary outcome of this study was in-hospital mortality. Logistic regression was used to evaluate the association between antimicrobial timing in relation to the onset of persistent/recurrent hypotension with mortality, while multivariable regression analyses were performed to adjust for confounding factors, including clinical and treatment variables. Results: Among the 508 adult septic shock patients with neutropenia assessed, the overall mortality rate was 27.0%. The median time to effective antimicrobial administration from the onset of hypotension was 6.33 hours (IQR: 2.7-15.75 hours). Mortality risk was lowest, at 32.3%, for patients who received antibiotics within the first 2 hours. Delays in antibiotic administration were significantly associated with increased mortality, with an adjusted ratio of 1.045 per hour of delay (95% CI: 1.035-1.056; p < 0.0001). Compared to the 1st hrs, delays of >4-6 hrs were associated with increased mortality (p<0.001)(Fig 1).Delays extending beyond 24 hours were associated with a substantial increase in mortality risk, reaching 98.4% (p < 0.001). Conclusions: Delays in appropriate antibiotic treatment are strongly associated with increased mortality in septic shock patients with neutropenia. Figure 1: The association between delayed antimicrobial initiation and risk of mortality, demonstrates a significantly higher mortality rate for patients treated after delays of 4-6 hours compared to those treated within the first hour of hypotension.

Rationale: Candida-associated septic shock is associated with a very high mortality rate. Initiating early, appropriate antifungal therapy is central to survival. Few studies have assessed the relationship between antifungal treatment delay and mortality rates in this group. This study explores the effect of delay in initiation of antifungal therapy following the onset of persistent/recurrent hypotension on mortality rates in patients with Candida-associated septic shock. Methods: This retrospective cohort study included 850 adults with culture-confirmed Candida-associated septic shock, conducted in 29 hospitals across Canada, the U.S., and Saudi Arabia from July 1989 to June 2018. Univariate analysis assessed delay effects on in hospital survival, while multivariate regression evaluated adjusted odds of mortality per hour of delay, with subgroup analyses by infection type, fungemia status, and APACHE II scores. Results: Among 850 patients, 589 (69.2%) received antifungal therapy after hypotension onset. Each hour of delay increased mortality risk, with an adjusted OR of 1.045 (95% CI: 1.035-1.056, p < 0.0001). Patients treated within 2 hours had an 85.7% hospital survival rate. Beyond this 2-hour window, the survival rate decreased by an average of 3.70% each hour, demonstrating a rapid reduction in survival probability with increasing delays. Delays of 12–24 hours resulted in a 38.5% hospital survival rate, dropping sharply to around 0.1% for delays over 36 hours. Results of multivariate analysis, which included the APACHE II score and epidemiologic/therapeutic variables, demonstrated that the time to initiate appropriate antifungal therapy emerged as the single strongest independent predictor of outcomes. Conclusion: This study highlights the critical impact of early antifungal therapy in Candida-associated septic shock. In our cohort, only 20% of patients received effective antifungal therapy within six hours of hypotension onset. Measures to improve early recognition are needed. Figure 1: Mortality risk (adjusted odds ratio) increases with delays in effective antifungal therapy. Bars show 95% confidence intervals. Elevated death risk is evident by 4-6 hours post-hypotension and continues rising beyond 36 hours.

Pseudomonas aeruginosa is the most frequently isolated opportunistic Gram-negative bacilli from recurrent otitis and chronic suppurative skin infections of canines.Chronic infections are mainly due to the development of various resistance mechanisms, of which production of extended spectrum beta lactamases (ESBLs) is the most important.Therefore, the present study was carried out to detect the ESBLs production from Pseudomonas aeruginosa (P.aeruginosa) isolates of canines.A total of ninety-seven samples (n=97) were collected from otitis and pyoderma cases of canines.On microscopic, cultural and biochemical examination, 35 isolates were assumed to be P. aeruginosa.All 35 isolates were confirmed as P. aeruginosa by Polymerase Chain Reaction (PCR) using species-specific 16S rRNA primers that yielded a specific amplicon of 956 bp size.Phenotypic screening of ESBLs production was performed by employing Phenotypic Screening Test (PST), which suggested all isolates as "Suspect ESBLs producers".Twenty one isolates (21/35, 60%) were confirmed as ESBL producers based on the results of Double Disk Synergy Test (DDST).The genetic determinants of ESBLs were detected by using multiplex PCR (mPCR) which revealed the prevalence of bla TEM gene to be 20% (7/35), bla OXA to be 31.42%(11/35) and bla SHV to be 25.71% (9/35).

RATIONALE: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care facilities have implemented systems aimed at detecting and responding to such patients. OBJECTIVES: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients. PANEL DESIGN: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based clinical practice guidelines. METHODS: We generated actionable questions using the Population, Intervention, Control, and Outcomes format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs). RESULTS: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among unselected patients due to the absence of data regarding the benefit and the potential harms of false positive alarms, the risk of alarm fatigue, and cost. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system (GPS). CONCLUSIONS: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU.

Background and objectivesPost-acute COVID-19 syndrome or “long COVID” affects patients even after the recovery from Covid infection in various ways. Persistent headache or New Daily Persistent Headache (NDPH) is one of such symptoms. In this review, we will discuss about the case-reports of post covid-19 headache- NDPH phenotype both after and in the course of COVID-19 infection.MethodsCase reports/studies talked about patients having NDPH around the disease either immediately or late post COVID were included. Data was taken from the source and synthesised on a qualitative basis.ResultsLiterature search showed 3,538 articles, out of which 12 were screened as per the eligibility criteria and finally, 4 case reports on NDPH and Covid-19 were chosen for analysis from the database and by human search. All case reports justify the criteria for acceptability in quality for this systematic review.ConclusionNDPH in and around Covid 19 infection is something that is currently an ingenious debated topic in the scientific community. More case studies should be written and published on the same subject so that a large systematic review could be conducted.Trial Registration InformationThe review is registered in Prospero with no. Identifier (CRD42022354912).Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42022354912).

OBJECTIVES: Refine the administrative data definition of sepsis in hospitalized patients, including less severe cases. Design and Setting: For each of 1928 infection and 108 organ dysfunction codes used in Canadian hospital abstracts, experts reached consensus on the likelihood that it could relate to sepsis. We developed a new algorithm, called AlgorithmL, that requires at least one infection and one organ dysfunction code adjudicated as likely or very likely to be related to sepsis. AlgorithmL was compared with four previously described algorithms, regarding included codes, population-based incidence, and hospital mortality rates-separately for ICU and non-ICU cohorts in a large Canadian city. We also compared sepsis identification from these code-based algorithms with the Centers for Disease Control's Adult Sepsis Event (ASE) definition. SUBJECTS: Among Calgary's adult population of 1.033 million there were 61,632 eligible hospitalizations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AlgorithmL includes 720 infection codes and 50 organ dysfunction codes. Comparison algorithms varied from 42-941 infection codes to 2-36 organ codes. There was substantial nonoverlap of codes in AlgorithmL vs. the comparators. Annual sepsis incidence rates (per 100,000 population) based on AlgorithmL were 91 in the ICU and 291 in the non-ICU cohort. Incidences based on comparators ranged from 28-77 for ICU to 11-266 for non-ICU cohorts. Hospital sepsis mortality rates based on AlgorithmL were 24% in ICU and 17% in non-ICU cohorts; based on comparators, they ranged 27-38% in the ICU cohort and 18-47% for the non-ICU cohort. Of AlgorithmL-identified cases, 41% met the ASE criteria, compared with 42-82% for the comparator algorithms. CONCLUSIONS: Compared with other code-based algorithms, AlgorithmL includes more infection and organ dysfunction codes. AlgorithmL incidence rates are higher; hospital mortality rates are lower. AlgorithmL may more fully encompass the full range of sepsis severity.

Rationale Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. Objective To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. Methods We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC–MS/MS and DI-MS/MS analytical platforms. Results Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. Conclusion Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.

Background We measured the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and re-infections in an adult community-based cohort in southern India. Methods We conducted a 2-year follow-up on 1229 participants enrolled between May and October 2021. Participants provided vaccination histories, weekly saliva samples, and blood samples at 0, 6, 12, and 24 months. Salivary reverse transcription polymerase chain reaction (RT-PCR) and Meso-Scale Discovery panels were used for SARS-CoV-2 detection and anti-spike, anti-nucleocapsid immunoglobulin G quantification. fi cation. Whole genome sequencing was performed on a subset of positive samples. SARS-CoV-2 infection incidence was measured across Pre-Omicron (May-December - December 2021), Omicron-I (December 2021-June - June 2022), and Omicron-II (July 2022-October - October 2023) periods. Findings In total, 1166 (95%) participants with 83% seropositivity at baseline completed the follow-up, providing 2205 person-years of observation. Utilizing both RT-PCR and serology we identified fi ed 1306 infections and yielded an incidence rate of 591.3 per 1000 person-years (95% confidence fi dence interval, 559.6-624.3), - 624.3), which peaked during Omicron-I at 1418.1 per 1000 person-years (95% confidence fi dence interval, 1307.4-1535.6). - 1535.6). During Omicron-I and II, neither prior infection nor vaccination conferred protection against infection. Overall, 74% of infections were asymptomatic. Interpretation Integrated RT-PCR and serology revealed significant fi cant SARS-CoV-2 infection frequency, highlighting the prevalence of asymptomatic cases among previously infected or vaccinated individuals. This underscores the effectiveness of combining surveillance strategies when monitoring pandemic trends and confirms fi rms the role of non-invasive sampling in ensuring participant compliance, reflecting fl ecting national transmission patterns. Health Asia Published https://doi.org/10. 1016/j.lansea.2024. 100470

BACKGROUND:Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain. METHODS:In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days. Antibiotic selection, dosing, and route were at the discretion of the treating team. We excluded patients with severe immunosuppression, foci requiring prolonged treatment, single cultures with possible contaminants, or cultures yielding Staphylococcus aureus. The primary outcome was death from any cause by 90 days after diagnosis of the bloodstream infection, with a noninferiority margin of 4 percentage points. RESULTS:Across 74 hospitals in seven countries, 3608 patients underwent randomization and were included in the intention-to-treat analysis; 1814 patients were assigned to 7 days of antibiotic treatment, and 1794 to 14 days. At enrollment, 55.0% of patients were in the ICU and 45.0% were on hospital wards. Infections were acquired in the community (75.4%), hospital wards (13.4%) and ICUs (11.2%). Bacteremia most commonly originated from the urinary tract (42.2%), abdomen (18.8%), lung (13.0%), vascular catheters (6.3%), and skin or soft tissue (5.2%). By 90 days, 261 patients (14.5%) receiving antibiotics for 7 days had died and 286 patients (16.1%) receiving antibiotics for 14 days had died (difference, -1.6 percentage points [95.7% confidence interval {CI}, -4.0 to 0.8]), which showed the noninferiority of the shorter treatment duration. Patients were treated for longer than the assigned duration in 23.1% of the patients in the 7-day group and in 10.7% of the patients in the 14-day group. A per-protocol analysis also showed noninferiority (difference, -2.0 percentage points [95% CI, -4.5 to 0.6]). These findings were generally consistent across secondary clinical outcomes and across prespecified subgroups defined according to patient, pathogen, and syndrome characteristics. CONCLUSIONS:Among hospitalized patients with bloodstream infection, antibiotic treatment for 7 days was noninferior to treatment for 14 days. (Funded by the Canadian Institutes of Health Research and others; BALANCE ClinicalTrials.gov number, NCT03005145.).

RATIONALE: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care hospitals have implemented systems aimed at detecting and responding to such patients. OBJECTIVES: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients. PANEL DESIGN: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. METHODS: We generated actionable questions using the Population, Intervention, Control, and Outcomes (PICO) format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation Approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs). RESULTS: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among unselected patients. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners’ concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients’ goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system. CONCLUSIONS: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU.

The antimicrobial resistance (AMR) phenomenon in bacteria is in existence well before the discovery of present-day antibiotics, but the rapidity of its development in bacteria is a cause of great concern as it renders the antibiotics ineffective for therapeutic use in human health and animal health. Antimicrobial use (AMU) is one of the main drivers for AMR in bacteria. The global consumption of antimicrobials in the animal sector is phenomenally increasing at great proportions, especially in low- and middle-income countries. The use of antibiotics as growth promoters in animal feeds for improved animal productivity is a cause of great concern. The AMR is transferrable among bacterial species across the human, animal, and environmental sectors. The AMR in animals has not received much-required attention compared to the human counterparts. As global AMR surveillance network for animals is not available, point prevalence surveys are employed to map AMR in animals. Considerable geographic variation in antibiotic resistance levels is observed in foodborne pathogens, viz., Escherichia coli, Campylobacter species, non-typhoidal Salmonella serotypes, and Staphylococcus aureus. Certain classes of antibiotics are listed as critically important in both human medicine and veterinary medicine. Therefore, the rational use of antimicrobials is the need of the hour as antibiotics are indispensable tools in animal health too. In animal sector, the increased AMR is responsible for the financial losses due to higher mortality of animals, reduced productivity, and early culling of breeding and production animals, effecting the livelihoods of livestock and poultry farmers.

Antimicrobial resistance (AMR) has a significant effect on the lives of humans and animals, and it is emerging as a global scrouge. Increased antibiotic resistance in bacterial pathogens of medical and veterinary importance costs dearly to the lives of humans and animals. The AMR affliction must be addressed with appropriate surveillance, prevention, and control strategies. One Health approach involving human health, animal health, and environment sectors (multisectoral action) plays a crucial role in AMR surveillance. The objective behind the One Health surveillance is due to the microbial and genetic movements across human, animal, and environment sectors. As the antimicrobials usage (AMU) in humans and animals is one of the main drivers for AMR, it is quintessential to monitor them with efficient surveillance networks. However, One Health surveillance is a laborious task, requiring harmonization of protocols and collection of bacterial isolates from different sectors (human, veterinary/fishery, and environment). In veterinary and aqua sectors, AMR in foodborne bacteria is more focused as it poses public health threat. Zoonotic and indicator bacteria also assume relevance under One Health approach. AMR data integration and its analysis form the core section of the application and inference aspect of One Health surveillance. Prescription/use of certain antibiotics like doxycycline, azithromycin, etc., during the COVID-19 pandemic also necessitates the AMR surveillance under One Health during/after pandemic. Strong political will with sustained budgetary support is required for the implementation of AMR surveillance under One Health.

Thromboembolic complications after the COVID-19 vaccination have been reported from all over the world. We aimed to identify the thrombotic and thromboembolic complications that can arise after receiving various types of COVID-19 vaccines, their frequency, and distinguishing characteristics. Articles published in Medline/PubMed, Scopus, EMBASE, Google Scholar, EBSCO, Web of Science, the Cochrane Library, the CDC database, the WHO database, ClinicalTrials.gov, and servers like medRxiv.org and bioRxiv.org, as well as the websites of several reporting authorities between December 1, 2019, and July 29, 2021, were searched. Studies were included if they reported any thromboembolic complications post-COVID-19 vaccination and excluded editorials, systematic reviews, meta-analyses, narrative reviews, and commentaries. Two reviewers independently extracted the data and conducted the quality assessment. Thromboembolic events and associated hemorrhagic complications after various types of COVID-19 vaccines, their frequency, and distinguishing characteristics were assessed. The protocol was registered at PROSPERO (ID-CRD42021257862). There were 59 articles, enrolling 202 patients. We also studied data from two nationwide registries and surveillance. The mean age of presentation was 47 ± 15.5 (mean ± SD) years, and 71.1% of the reported cases were females. The majority of events were with the AstraZeneca vaccine and with the first dose. Of these, 74.8% were venous thromboembolic events, 12.7% were arterial thromboembolic events, and the rest were hemorrhagic complications. The most common reported event was cerebral venous sinus thrombosis (65.8%), followed by pulmonary embolism, splanchnic vein thrombosis, deep vein thrombosis, and ischemic and hemorrhagic stroke. The majority had thrombocytopenia, high D-dimer, and anti-PF4 antibodies. The case fatality rate was 26.5%. In our study, 26/59 of the papers were of fair quality. The data from two nationwide registries and surveillance revealed 6347 venous and arterial thromboembolic events post-COVID-19 vaccinations. COVID-19 vaccinations have been linked to thrombotic and thromboembolic complications. However, the benefits far outweigh the risks. Clinicians should be aware of these complications because they may be fatal and because prompt identification and treatment can prevent fatalities.

Although some adults infected with influenza 2009 A(H1N1)pdm09 viruses mounted high hemagglutination inhibition (HAI) antibody response, they still suffered from severe disease, or even death. Here, we analyzed antibody profiles in patients (n = 31, 17–65 years) admitted to intensive care units (ICUs) with lung failure and invasive mechanical ventilation use due to infection with A(H1N1)pdm09 viruses during 2009–2011. We performed a comprehensive analysis of the quality and quantity of antibody responses using HAI, virus neutralization, biolayer interferometry, enzyme-linked-lectin and enzyme-linked immunosorbent assays. At time of the ICU admission, 45% (14/31) of the patients had HAI antibody titers ≥ 80 in the first serum (S1), most (13/14) exhibited narrowly-focused HAI and/or anti-HA-head binding antibodies targeting single epitopes in or around the receptor binding site. In contrast, 42% (13/31) of the patients with HAI titers ≤ 10 in S1 had non-neutralizing anti-HA-stem antibodies against A(H1N1)pdm09 viruses. Only 19% (6/31) of the patients showed HA-specific IgG1-dominant antibody responses. Three of 5 fatal patients possessed highly focused cross-type HAI antibodies targeting the (K130 + Q223)-epitopes with extremely low avidity. Our findings suggest that narrowly-focused low-quality antibody responses targeting specific HA-epitopes may have contributed to severe infection of the lower respiratory tract.

Septic shock is associated with a mortality of 20–40%. The white blood cell count (WBC) at hospital admission correlates with prognosis in septic shock. Here, we explore whether the trajectory of WBC after admission provides further information about outcomes. We aimed to identify groups of patients with different WBC trajectories and the association of WBC trajectory with mortality. We included adult patients with septic shock in two academic intensive care units (ICU) in Winnipeg, MB, Canada between 2006 and 2012. We used group-based trajectory analysis to group patients according to their WBC patterns over the first seven days in the ICU. Our primary analysis was the association of WBC trajectory group on 30-day mortality using multivariable Cox proportional hazards regression. We included 917 patients with septic shock. The final model identified seven distinct WBC trajectories. The rising WBC trajectory was independently associated with increased mortality (hazard ratio, 3.41; 95% confidence interval, 1.86 to 6.26; P < 0.001) compared with the stable WBC trajectory. In patients with septic shock, distinct and clinically relevant groups can be identified by analyzing WBC trajectories. A rising WBC trajectory was associated with higher mortality.