Different Sites Of Infection Research Articles

Biomarker for infection in children with decompensated chronic liver disease: Neutrophilic CD64 or procalcitonin?

ObjectiveBiomarkers with high accuracy for identification of infection in decompensated chronic liver disease (DCLD) are urgently needed. We compared the accuracy of neutrophilic cluster of differentiation 64 (nCD64) with procalcitonin for diagnosis of bacterial infection in children with DCLD. MethodsConsecutive children admitted with DCLD were enrolled prospectively. nCD64 was assessed by flow cytometry and expressed in percentage. nCD64, procalcitonin and hemogram were measured at admission and 7-14 days after treatment in those with infection. Complete work-up for infection was done. Presence, site and severity of infection was classified as per guidelines. Results107 children [64 boys, age 97(18-168) months] were enrolled. 78(72.9%) had infection, 26(24%) had severe sepsis and 60(56%) had systemic inflammatory response syndrome. The commonest site of infection was ascitic fluid (n=37), followed by pneumonia (n=24), urinary tract (n=15), bacteraemia (n=10), cholangitis (n=8) and cellulitis (n=3). nCD64 (cut-off-51%, AUC-0.82) had a higher sensitivity (79.5%) and specificity (82.8%) than procalcitonin (cut-off ≥0.58ng/mL, AUC-0.74, sensitivity-76.9% and specificity-62.1%) for diagnosis of infection. nCD64 and procalcitonin correlated with infection severity, being highest in children with severe sepsis [88(71-97) %and 1.98(0.83-10.36) ng/mL], than in infection alone [72(45-84) % and 1.09(0.45-2.07) ng/mL], and no-infection [36(20.2-48) % and 0.42(0.19-1.08) ng/mL]. There was no difference in diagnostic utility of procalcitonin or nCD64 with different sites of infection. Elevation of all 3 parameters (nCD64, PCT and total leukocyte count) was uncommon but highly specific for presence of infection. ConclusionnCD64 identifies infection better than procalcitonin and correlates well with infection severity in children with DCLD.

Diagnostic and Prognostic Ability of Pancreatic Stone Protein: A Scoping Review.

Pancreatic stone protein (PSP) is an acute-phase reactant mainly produced in response to stress. Its diagnostic and prognostic accuracy for several types of infection has been studied in several clinical settings. The aim of the current review was to assess all studies examining a possible connection of pancreatic stone protein levels with the severity and possible complications of patients diagnosed with infection. We performed a systematic search in PubMed, Scopus, the Cochrane Library and Clinicaltrials.gov to identify original clinical studies assessing the role of pancreatic stone protein in the diagnosis and prognosis of infectious diseases. We identified 22 eligible studies. Ten of them provided diagnostic aspects, ten studies provided prognostic aspects, and another two studies provided both diagnostic and prognostic information. The majority of the studies were performed in an intensive care unit (ICU) setting, five studies were on patients who visited the emergency department (ED), and three studies were on burn-injury patients. According to the literature, pancreatic stone protein has been utilized in patients with different sites of infection, including pneumonia, soft tissue infections, intra-abdominal infections, urinary tract infections, and sepsis. In conclusion, PSP appears to be a useful point-of-care biomarker for the ED and ICU due to its ability to recognize bacterial infections and sepsis early. Further studies are required to examine PSP's kinetics and utility in specific populations and conditions.

Study of some cytokines in patients with brucellosis in Najaf province

Background: To evaluate the levels of pro-inflammatory cytokines for ‘Th1/Th2 brucellosis’ patients serum to determine ‘antimicrobial susceptibilities’ of Brucella strains. Methodology: The study comprised 35 individuals with acute brucellosis, and 21 patients with chronic brucellosis, identified clinically. A group of 20 healthy adult persons was also enrolled in the study. For all of the participants, blood cultures and standard tube agglutination tests for Brucella were performed. ELISA was used to detect cytokine levels in serum samples collected following the treatment period and detect Brucella strains celebrated from different sites of infection, and in order to find-out the susceptibilities against antibiotics including rifampicin (RIF), streptomycin (STR), doxycycline (DOX), and ciprofloxacin (CIP) via the gradient strip (E test). Results: The patients included 22 (39.29 percent) males and 34 (60.71 percent) females based on their gender and age. Fever was the most common clinical feature (92%), sweating came in second place (75%), followed by back pain with 18%. Patients with brucellosis had substantially higher blood levels of interleukin-6 (IL-6), interferon (IFN), and tumor necrosis factor-alpha (TNF-alpha) analogous to the control group (P = 0.05). IL-4 and IL-2 levels between the sick and control groups did not vary significantly. The amounts of these cytokines were found to be identical in acute and chronic individuals. Rendering to "minimum inhibitory concentrations (MIC) 90 levels," CIP was determined to be the most effective antibiotic. Then followed DOX and then STR, correspondingly. All of the samples were CIP and DOX susceptible; 18 (23.2%) strains were discovered to be only mildly sensitive to RIF, with MIC50 and MIC90 maximal values. Conclusions: Our findings point to an important role for IFN and proinflammatory cytokines in brucellosis pathogenesis. However, these changes were shown to be unrelated to the severity or activity of the illness. Furthermore, all strains were identified as Brucella strains. ciprofloxacin, doxycycline, rifampicin and streptomycin were found to be effective for the treatment of brucellosis. Key words: Antimicrobial Susceptibilities; Brucellosis; Cytokines; Interferon; Pro-Inflammatory Cytokines Citation: Abbas KF, Abdul-Hassan LS, Hadi OM, Almulla AF, Kathair ZY. Study of some cytokines in patients with brucellosis in Najaf province. Anaesth. pain intensive care 2024;28(1):39-43; DOI: 10.35975/apic.v28i1.2379 Received: September 15, 2023; Reviewed: November 03, 2023; Accepted: December 23, 2023

Comparing the cost-effectiveness of the MPT64-antigen detection test to Xpert MTB/RIF and ZN-microscopy for the diagnosis of Extrapulmonary Tuberculosis: An economic evaluation modelling study.

Extrapulmonary Tuberculosis (EPTB) poses challenges from patient and health system perspectives. The cost-effectiveness analysis of the Xpert MTB/RIF (Xpert) test to diagnose pulmonary tuberculosis is documented. However, there are no economic evaluations for EPTB. Considering the reported better diagnostic sensitivity of the MPT64 test, this study explored its cost-effectiveness as an alternative diagnostic test. We conducted this economic evaluation to assess the cost-effectiveness of the MPT64 test compared to Xpert and ZN microscopy for EPTB adult patients. We utilised a Markov modelling approach to capture short- and long-term costs and benefits from a health system perspective. For the model inputs, we combined data from our cohort studies in Tanzania and peer-reviewed EPTB literature. We calculated the Incremental Cost Effectiveness Ratio (ICER) by comparing the cost (in USD) of each diagnostic test and Quality Adjusted Life Years (QALYs) as health gain. We found the MPT64 test cost-effective for EPTB diagnosis and absolutely dominated ZN microscopy and Xpert using the baseline model inputs. A scenario analysis showed that the Xpert test might be the most cost-effective at its higher test sensitivity, which corresponds to using it to diagnose lymph node aspirates. The prevalence of HIV among EPTB cases, their probability of treatment, costs of ART, and the probability of the MPT64 test in detecting EPTB patients were the main parameters associated with the highest impact on ICER in one-way deterministic analysis. The most cost-effective option for EPTB at the baseline parameters was the MPT64 diagnostic test. Including the MPT64 test in EPTB diagnostic pathways for previously untreated patients can lead to better resource use. The Xpert test was the most cost-effective diagnostic intervention at a higher diagnostic test sensitivity in scenario analyses based on different sites of infection, such as for the lymph node aspirates.

CLINICOLABORATORY PROFILE OF ABDOMINAL TUBERCULOSIS CASES IN A TERTIARY CARE HOSPITAL IN MANDYA : A CROSS SECTIONAL STUDY

Background- Abdominal tuberculosis (TB)is defined as infection of peritoneum, hollow viscus or solid abdominal organs with mycobacterium tuberculosis. In the present study we aim to describe different sites of infection of abdominal tuberculosis with varied clinical presentations and to describe different investigation methods used to diagnose abdominal tuberculosis cases. Patients & Method- A cross sectional study done from June 2021 to May 2023 in OPD and ward patients in department of General Surgery of tertiary care Hospital , Mandya. During this period 94 patients were studied from June 2021 to May 2023. Patients coming to surgery OPD and diagnosed with Abdominal TB will be included . Presenting complaints of Kochs abdomen like low grade fever , loss of weight, loss of appetite, night sweats ,easy fatiguability ,pallor , abdominal pain , abdominal mass, abdominal distension will be noted down. Follow up done with USG abdomen and pelvis to support diagnosis. Result- 94 patients at our centre between 2022-2023 were studied . 64 patients were managed non operatively and responded to Antitubercular treatment ( ATT ) , 30 patients underwent laparotomy . Conclusion- In our day to day clinical practice medical history , clinical manifestations, laboratory findings, CT findings, histopathological features , and microbiological findings should be comprehensively analysed in order to correctly diagnose abdominal tuberculosis which helps in early initiation of treatment and prevent complications due to abdominal tuberculosis.

Imaging classification and analysis of the diagnosis and treatment of infected pancreatic necrosis:a report of 126 cases

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ2 test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ2=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ2=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.

Hospital-treated infections in early- and mid-life and risk of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis: A nationwide nested case-control study in Sweden.

Experimental observations have suggested a role of infection in the etiology of neurodegenerative disease. In human studies, however, it is difficult to disentangle whether infection is a risk factor or rather a comorbidity or secondary event of neurodegenerative disease. To this end, we examined the risk of 3 most common neurodegenerative diseases in relation to previous inpatient or outpatient episodes of hospital-treated infections. We performed a nested case-control study based on several national registers in Sweden. Cases were individuals newly diagnosed with Alzheimer's disease (AD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) during 1970 to 2016 in Sweden, identified from the National Patient Register. For each case, 5 controls individually matched to the case on sex and year of birth were randomly selected from the general population. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) with adjustment for potential confounders, including sex, year of birth, area of residence, educational attainment, family history of neurodegenerative disease, and Charlson comorbidity index. Infections experienced within 5 years before diagnosis of neurodegenerative disease were excluded to reduce the influence of surveillance bias and reverse causation. The analysis included 291,941 AD cases (median age at diagnosis: 76.2 years; male: 46.6%), 103,919 PD cases (74.3; 55.1%), and 10,161 ALS cases (69.3; 56.8%). A hospital-treated infection 5 or more years earlier was associated with an increased risk of AD (OR = 1.16, 95% CI: 1.15 to 1.18, P < 0.001) and PD (OR = 1.04, 95% CI: 1.02 to 1.06, P < 0.001). Similar results were observed for bacterial, viral, and other infections and among different sites of infection including gastrointestinal and genitourinary infections. Multiple infections before age 40 conveyed the greatest risk of AD (OR = 2.62, 95% CI: 2.52 to 2.72, P < 0.001) and PD (OR = 1.41, 95% CI: 1.29 to 1.53, P < 0.001). The associations were primarily due to AD and PD diagnosed before 60 years (OR = 1.93, 95% CI: 1.89 to 1.98 for AD, P < 0.001; OR = 1.29, 95% CI: 1.22 to 1.36 for PD, P < 0.001), whereas no association was found for those diagnosed at 60 years or older (OR = 1.00, 95% CI: 0.98 to 1.01 for AD, P = 0.508; OR = 1.01, 95% CI: 0.99 to 1.03 for PD, P = 0.382). No association was observed for ALS (OR = 0.97, 95% CI: 0.92 to 1.03, P = 0.384), regardless of age at diagnosis. Excluding infections experienced within 10 years before diagnosis of neurodegenerative disease confirmed these findings. Study limitations include the potential misclassification of hospital-treated infections and neurodegenerative diseases due to incomplete coverage of the National Patient Register, as well as the residual confounding from unmeasured risk or protective factors for neurodegenerative diseases. Hospital-treated infections, especially in early- and mid-life, were associated with an increased risk of AD and PD, primarily among AD and PD cases diagnosed before 60 years. These findings suggest that infectious events may be a trigger or amplifier of a preexisting disease process, leading to clinical onset of neurodegenerative disease at a relatively early age. However, due to the observational nature of the study, these results do not formally prove a causal link.

Post-Operative Infections in Head and Neck Cancer Surgery: Risk Factors for Different Infection Sites.

Background: Post-operative infections in head and neck cancer (HNC) surgery represent a major problem and are associated with an important increase in mortality, morbidity, and burden on the healthcare system. The aim of this retrospective observational study was to evaluate post-operative infections in HNC surgery and to analyze risk factors, with a specific focus on different sites of infection. Methods: Clinical data about 488 HNC patients who underwent surgery were recorded. Univariate and multivariate analyses were performed to identify risk factors for post-operative infections. Results: Post-operative infections were observed in 22.7% of cases. Respiratory and surgical site infections were the most common. Multiple site infections were observed in 3.9% of cases. Considering all infection sites, advanced stage, tracheotomy, and higher duration of surgery were risk factors at multivariate analysis. Median hospital stay was significantly longer in patients who had post-operative infection (38 vs. 9 days). Conclusions: Post-operative infections may negatively affect surgical outcomes. A correct identification of risk factors may help the physicians to prevent post-operative infections in HNC surgery.

Antibiotics susceptibility against Pseudomonas aeruginosa isolated from different infections

In the present study, a total 70 samples were collected from different sites of infection which include 25(35.7%) samples from bronchial wash, 15 (21.4%) samples from urine, 15 (21.4%) samples from ear swabs, and 15 (21.4%) samples wound swabs), these samples have been collected and tested during period from March 2022 to June 2022. The results showed that, out of 70 samples, 62(88.5%) give positive culture, while 8(11.5%) samples were negative culture. Out of 62 positive culture on different types of growth media, and the bacterial was identified according to gram stain, biochemical tests and Vitek compact system, the results showed that, only 18(29.1%) isolates were related to Pseudomonas aeruginosa, while 44 (70.9%) samples were related to other types of microbial agents, these isolates which include 5/18(28%) isolates from bronchial wash, 4/18(22.1%) isolates from urine, 2/18(11.1%) isolates from ear swabs and 7/18(38.8%) isolates from wound swabs. To confirm the isolates of bacteria was used automated Compact Vitek-2 system use GN-ID cards which contained 64 biochemical tests.

Effect Biofilm Formation in Pseudomonas aeruginosa Resistance To Antibiotic

Objective: Due Pseudomonas aeruginosa is the most common type of bacteria that causes hospital-acquired infections because it has multiple resistance mechanisms to antibiotics such as biofilm formation. It is important to understand to investigate biofilm production in multidrug resistant clinical isolates of P. aeruginosa from different sites of infection. Materials and Methods: This work was done on 114 patients were collected from different specimens From hospitals Baghdad. The collected samples were cultured on different media (blood agar, MacConkey agar, nutrient agar, and Cetrimide agar) for isolation of P. aeruginosa bacteria as well as isolates from all patient were tested for antimicrobial susceptibility using disk diffusion method, in vitro formation of biofilm in microtiter plates containing Muller –Hinton broth. Results: Forty specimens (35.1%) were observed to have bacterial growth (positive samples) for P. aeruginos, the results of P. aeruginosa isolates were tested for antibiotic susceptibility showed that among forty positive results, the most isolates were potentially resistant to different antibiotics presented that the isolates resistant to piperacillin (34, 85%), gentamicin (26, 65%), tobramycin (30, 82.5%), amikacin (27, 67.5%), cefepime (25, 62.5%), meropenem (31, 77.5%), carbenicillin (31, 77.5%), ceftriaxone (30, 75%), ciprofloxacin (27, 67.5%), imipenem (22, 55%), ceftazidime 26 (65%), and norfloxacin 24 (60%). The results showed the ability of P. aeruginosa isolates to produce biofilm were 40 (100%) has the ability to produce biofilm, these were the result divided in to strong 19 (47.5%), moderate 12 (30%), and weak 9 (22.5%). Conclusion: There were 40 isolates biofilm producers in divers levels of biofilm strength.

Mortality, sepsis, and organ failure in hospitalized patients with cirrhosis vary by type of infection

Infection is associated with substantial morbidity and mortality in cirrhosis, but presumably, not all infections carry the same risk of mortality. We compared outcomes of different sites of infection in a nationally representative sample of inpatients with cirrhosis. We queried the Nationwide Readmissions Database for patients with cirrhosis from 2011 to 2014. Cirrhosis and infection diagnoses were identified by previously used algorithms of ICD-9 codes. The following infections were compared: urinary tract infection (UTI), pneumonia, cellulitis, spontaneous bacterial peritonitis (SBP), and Clostridium difficile infection (CDI). The primary outcome was inpatient mortality. Secondary outcomes included sepsis, any organ failure, multiple organ failures, and 30-day readmission. Outcomes were analyzed using logistic regression and included a priori covariates. A total of 1798830 weighted index admissions were identified. Infection was present in 29.2% overall-including UTI (13.7%), pneumonia (8.9%), cellulitis (5.2%), CDI (2.8%), and SBP (2.0%). Mortality was significantly higher in pneumonia (19.6%), SBP (18.6%), and CDI (17.4%) compared with cellulitis (7.6%) and UTI (11.8%). Sepsis, any, and multiple organ failures were most commonly seen in pneumonia, SBP, and CDI. Multivariable analysis demonstrated that pneumonia had the highest associated mortality (odds ratio [OR] 2.73, confidence interval [CI] 2.68-2.80) and multiple organ failures (OR 3.59, CI 3.50-3.68). Significantly increased 30-day readmission was seen only with SBP (24.9%). Outcomes of inpatients with cirrhosis vary significantly depending on the type of infection. The severity and epidemiology of infection in cirrhosis appears to be shifting with pneumonia, not SBP, having the highest prevalence of multiple organ failures and inpatient mortality.

Genetic and Biochemical Diversity of Clinical Acinetobacter baumannii and Pseudomonas aeruginosa Isolates in a Public Hospital in Brazil

Life-threatening bacterial infections are a major concern in health care services worldwide. This retrospective study aimed to demonstrate genetic and biochemical diversity in isolates of Acinetobacter baumannii and Pseudomonas aeruginosa from a public hospital in Brazil. A total of 63 isolates collected from different sites of infection and hospital sectors were characterized, and their susceptibility profile to antibiotics was assessed for 18 drugs belonging to 8 antimicrobial categories using the automated BACTEC system. Genetic diversity was assessed using the multiple locus variable number tandem repeat analysis. Among the isolates of A. baumannii, 83% were classified as extensively drug resistant (XDR), and 17 genotypic profiles were identified. About 67% of P. aeruginosa isolates were susceptible to antimicrobials and were distributed into 37 genotypic profiles, revealing genetic heterogeneity. This study has demonstrated the multicolonization of investigated pathogens and the high frequency (95.8%) of multidrug-resistant and XDR, as well as high genetic diversity, among the isolates supporting the continuous need to monitor these species in the hospital environment.

Carbapenem-resistant bacilli in a hospital in southern Brazil: prevalence and therapeutic implications

BackgroundGram-negative bacilli (GNB), notably Acinetobacter spp., Pseudomonas spp., and Klebsiella spp., are becoming increasingly resistant to carbapenems and are associated with high health care costs and mortality, becoming a global concern. ObjectiveTo determine the prevalence rates of carbapenem resistance among Acinetobacter spp., Pseudomonas spp., and Klebsiella spp. in the main sites of nosocomial infection at a tertiary care hospital in southern Brazil and the consequent therapeutic implications. MethodsCultures processed at the institution’s laboratory in 2017 were analyzed, and those positive for Acinetobacter spp., Pseudomonas spp., and Klebsiella spp. were identified. Antibiograms were evaluated for meropenem sensitivity following the Clinical Laboratory Standards Institute guidelines. ResultsAcinetobacter spp. had the lowest prevalence among the three GNB, and resistance of this pathogen to meropenem at different sites of infection ranged from 36% (blood) to 82% (respiratory tract). Pseudomonas spp. was highly prevalent at the respiratory tract (31%) and had a high resistance rate to meropenem in rectal swab samples (71%), but a relatively low frequency at infection sites (skin/soft tissue, 13%; blood, 25%). Klebsiella spp. was identified in 7.5% of the blood cultures and 15% of the urine cultures and was the chief colonizer among all pathogens, representing 54% of all rectal swab samples, of which 53% were meropenem resistant. At sites of infection, rates of Klebsiella spp. resistant to meropenem ranged from 19% (skin) to 55% (vascular catheter). ConclusionsThe prevalence of carbapenem-resistant GNB at our hospital was relatively low compared to national and international data; thus, meropenem remains a good therapeutic option against these bacteria. Other antibiotics effective against GNB, such as ceftazidime, cefepime, and piperacillin-tazobactam, can be used in most cases, while meropenem should be reserved for patients with sepsis. Strict contact precaution measures are still needed, given the high resistance rate observed at the colonizing site.

Clinical Characteristics of Infections Caused by Streptococcus Anginosus Group

This study aimed to investigate the clinical characteristics, distribution of different strains and risk factors of patients infected with Streptococcus anginosus group (SAG). In the population of 463 patients, the male-to-female ratio was 1.95:1, and the patient age ranged from 6 months to 103 years. There were 49 children (10.58%), 311 young and middle-aged adults (67.17%), and 103 elderly adults (22.25%). Approximately 45.4% had underlying conditions, which were mostly malignant tumors and diabetes. Of the 463 specimens, 254 were S. anginosus (54.86%), 173 were S. constellatus (37.37%), and 36 were S. intermedius (7.77%). According to the age distribution, the incidence peaked in the 35–54 year age group. Different sites of infection had statistically significant differences regarding the constituent ratios of these three species. Different age groups also exhibited statistically significant differences in constituent ratios of the pathogenic organisms, as well as organ infections. In our population, 269 were clinically cured, 184 reported satisfactory improvement, and 10 died. SAG, as an opportunistic pathogen, can induce pyogenic infections in patients of all ages and shows no significant gender predilection in any age group. The three pathogenic organisms had differences with respect to patient age and infections of body sites.

Identification of conditionally essential genes for Streptococcus suis infection in pigs

ABSTRACT Streptococcus suis is a Gram-positive bacterium and zoonotic pathogen that causes meningitis and sepsis in pigs and humans. The aim of this study was to identify genes required for S. suis infection. We created Tn-Seq libraries in a virulent S. suis strain 10, which was used to inoculate pigs in an intrathecal experimental infection. Comparative analysis of the relative abundance of mutants recovered from different sites of infection (blood, cerebrospinal fluid, and meninges of the brain) identified 361 conditionally essential genes, i.e. required for infection, which is about 18% of the genome. The conditionally essential genes were primarily involved in metabolic and transport processes, regulation, ribosomal structure and biogenesis, transcription, and cell wall membrane and envelope biogenesis, stress defenses, and immune evasion. Directed mutants were created in a set of 10 genes of different genetic ontologies and their role was determined in ex vivo models. Mutants showed different levels of sensitivity to survival in whole blood, serum, cerebrospinal fluid, thermic shock, and stress conditions, as compared to the wild type. Additionally, the role of three selected mutants was validated in co-infection experiments in which pigs were infected with both wild type and isogenic mutant strains. The genetic determinants of infection identified in this work contribute to novel insights in S. suis pathogenesis and could serve as targets for novel vaccines or antimicrobial drugs.

Phenotypic heterogeneity by site of infection in surgical sepsis: a prospective longitudinal study

BackgroundThe role of site of infection in sepsis has been poorly characterized. Additionally, sepsis epidemiology has evolved. Early mortality has decreased, but many survivors now progress into chronic critical illness (CCI). This study sought to determine if there were significant differences in the host response and current epidemiology of surgical sepsis categorized by site of infection.Study designThis is a longitudinal study of surgical sepsis patients characterized by baseline predisposition, insult characteristics, serial biomarkers, hospital outcomes, and long-term outcomes. Patients were categorized into five anatomic sites of infection.ResultsThe 316 study patients were predominantly Caucasian; half were male, with a mean age of 62 years, high comorbidity burden, and low 30-day mortality (10%). The primary sites were abdominal (44%), pulmonary (19%), skin/soft tissue (S/ST, 17%), genitourinary (GU, 12%), and vascular (7%). Most abdominal infections were present on admission and required source control. Comparatively, they had more prolonged proinflammation, immunosuppression, and persistent organ dysfunction. Their long-term outcome was poor with 37% CCI (defined as > 14 in ICU with organ dysfunction), 49% poor discharge dispositions, and 30% 1-year mortality. Most pulmonary infections were hospital-acquired pneumonia. They had similar protracted proinflammation and organ dysfunction, but immunosuppression normalized. Long-term outcomes are similarly poor (54% CCI, 47% poor disposition, 32% 1-year mortality). S/ST and GU infections occurred in younger patients with fewer comorbidities, less perturbed immune responses, and faster resolution of organ dysfunction. Comparatively, S/ST had better long-term outcomes (23% CCI, 39% poor disposition, 13% 1-year mortality) and GU had the best (10% CCI, 20% poor disposition, 10% 1-year mortality). Vascular sepsis patients were older males, with more comorbidities. Proinflammation was blunted with baseline immunosuppression and organ dysfunction that persisted. They had the worst long-term outcomes (38% CCI, 67% poor disposition, 57% 1-year mortality).ConclusionThere are notable differences in baseline predisposition, host responses, and clinical outcomes by site of infection in surgical sepsis. While previous studies have focused on differences in hospital mortality, this study provides unique insights into the host response and long-term outcomes associated with different sites of infection.

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

BackgroundDecreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics.MethodsWe evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters.ResultsNo differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories (‘early improvers’, ‘delayed or non-improvers’ and ‘decliners’). The probability for adverse outcome (secondary infection or death) was higher in the delayed or non-improvers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0–4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1–7.1], p = 0.03).ConclusionSites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.

Differential gene expression profile of Shigella dysenteriae causing bacteremia in an immunocompromised individual.

Aim:Shigella species has varying levels of virulence gene expression with respect to different sites of infection. In this study, the differential gene expression of S. dysenteriae in response to its site of infection was analyzed by transcriptomics.Methods:This study includes four clinical Shigella isolates. Transcriptomics was done for the stool and blood samples of a single patient. Isolates were screened for the presence of antimicrobial resistance genes.Results:The majority of genes involved in invasion were highly expressed in the strain isolated from the primary site of infection. Additionally, antimicrobial resistance (dhfr1A, sulII, blaOXA. blaCTX-M-1 and qnrS) genes were identified.Conclusion:This study provides a concise view of the transcriptional expression of clinical strains and provides a basis for future functional studies on Shigella spp.

Candida albicans Agar Invasion Assays.

The ability of the human fungal pathogen Candida albicans to disseminate into tissues is promoted by a switch from budding to invasive hyphal growth. This morphological transition is stimulated by multiple environmental factors that can vary at different sites of infection. To identify genes that promote invasive growth, C. albicans mutants can be screened for defects in growing invasively into solid agar medium as a substitute for studying tissue invasion. This in vitro approach has advantages in that it permits the media conditions to be varied to mimic different host environments. In addition, the concentration of agar can be varied to determine the effects of altering the rigidity of the matrix into which the cells invade, as this provides a better indicator of invasive growth than the ability to form hyphae in a liquid culture. Testing under multiple conditions can be used to identify mutant cells with the strongest defects. Therefore, protocols and media for analyzing invasive growth of C. albicans under different conditions will be described that are appropriate for testing a single strain or high-throughput analysis of a collection of mutant C. albicans strains.

Biofilm Measurement, Site Specific Variation in Biofilm Production, Biofilm Typing: An Acinetobacter Trilogy

Acinetobacter baumannii is a member of the ESKAPE pathogens, notorious for causing multidrug resistant nosocomial infections worldwide. Biofilm has an important role in its persistence and spread in hospital environment, as well as its multidrug resistance potential. The present study was aimed at finding out whether the strength of Biofilm formation varies with infection of different organs / system. A total of 136 isolates of Acinetobacter baumannii were taken from a variety of samples. Strength of Biofilm formation, determined by Tissue culture plate method, was graded according to OD value in ELISA reader as nil, moderate and strong. It was seen that association between variations in biofilm forming capacity depending on different sites of infection was statistically significant. We suggest biofilm typing by this method for this pathogen, as a potentially feasible alternative in countries with cost restrained healthcare set ups. Moreover, biofilm typing report would be more meaningful to the clinicians as well.