Bacterial Bloodstream Infections Research Articles

The impact of COVID-19 pandemic on nosocomial multidrug-resistant bacterial bloodstream infections and antibiotic consumption in a tertiary care hospital.

We investigated the change in the epidemiology of nosocomial bloodstream infections (BSIs) caused by multidrug-resistant bacteria during Coronavirus Disease (COVID-19) and antibiotic consumption rates at a pandemic hospital and at the Oncology Hospital which operated as COVID-19-free on the same university campus. Significant increases in the infection density rate (IDRs) of BSIs caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and ampicillin-resistant Enterococcus faecium (ARE) were detected at the pandemic hospital, whereas carbapenem-resistant Klebsiella pneumoniae BSIs were increased at the non-pandemic Oncology Hospital. Pulsed field gel electrophoresis showed a polyclonal outbreak of CRAB in COVID-19 intensive care units. Antibiotic consumption rates were increased for almost all antibiotics, and was most significant for meropenem at both of the hospitals. Increased IDRs of CRAB and ARE BSIs as well as an increased consumption rate of broad-spectrum antibiotics emphasize the importance of a multimodal infection prevention strategy combined with an active antibiotic stewardship program.

Diagnostic Value and Prognostic Significance of Procalcitonin Combined with C-Reactive Protein in Patients with Bacterial Bloodstream Infection.

Objective To study the clinical values and implications for the prognosis of procalcitonin (PCT) combined with C-reactive protein (hs-CRP) in patients with bacterial bloodstream infection. Methods One hundred and twenty patients with infection hospitalized from Mar. 2020 to Jun. 2021 were chosen as subjects. All participants were tested for serum PCT, hs-CRP, and blood culture. According to the types of pathogenic bacteria, they were divided into the gram-negative bacteria bloodstream infection group (n = 53) and the gram-positive bacteria bloodstream infection group (n = 31). Depending on the prognostic outcome of the participants after 28 days, they were categorized into survival and fatality cohorts. The PCT and hs-CRP levels were compared to explore diagnostic value implications for the prognosis of the cases with bacterial bloodstream infection. Results Serum PCT and hs-CRP values in the positive cohort were higher than those in the negative cohort. The levels of serum PCT and hs-CRP in pulmonary infection were higher than those in the group with negative cases, and the difference was statistically significant (P < 0.05). There were 27 gram-positive participants and 9 gram-negative cases in the positive cohort. The serum PCT value of gram-negative bacterial infection was greater than that of gram-positive bacterial infection. The value of serum PCT in the gram-negative bacterial infection group was higher than that in the gram-positive bacterial infection group, and the difference was statistically significant (P < 0.05). The areas under the curve (AUCs) of PCT, combination of hs-CRP and PCT, and hs-CRP were 0.946, 0.783, and 0.991, respectively. The combined examination of PCT and hs-CRP was the largest, PCT was the second, and hs-CRP was the lowest. These results indicated that the accuracy of combined detection of PCT and hs-CRP in the diagnostic bloodstream infection was the highest (0.991), followed by PCT (0.946) and the lowest (0.783). The PCT and hs-CRP levels of the survival cohort were lower than those in the death cohort. AUCs of PCT, hs-CRP and PCT, and hs-CRP were 0.848, 0.826, and 0.934, respectively. The combined examination of PCT and hs-CRP was the largest, followed by PCT and hs-CRP. The accuracy of the combination of PCT and hs-CRP was the highest (0.934), followed by PCT (0.848), and the diagnostic accuracy of hs-CRP was the lowest (0.826). Conclusion There were significant differences in the levels of PCT and CRP between the gram-positive bacteria group and the gram-positive bacteria group. PCT and CRP have high diagnostic values in predicting the short-term prognosis of patients. PCT and CRP assist clinical diagnosis and guide treatment and play a positive role in early treatment and prognosis evaluation of patients.

Clinical and Molecular Analyses of Recurrent Gram-Negative Bloodstream Infections.

The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood. We used a cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk factors associated with recurrent GNB-BSI. Bacterial genotyping (pulsed-field gel electrophoresis [PFGE] and whole-genome sequencing [WGS]) was used to determine whether episodes were due to relapse or reinfection. Multivariable logistic regression was used to identify risk factors for recurrence. Of the 1423 patients with GNB-BSI in this study, 60 (4%) had recurrent GNB-BSI. Non-White race (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.38-4.01; P = .002), admission to a surgical service (OR, 2.18; 95% CI, 1.26-3.75; P = .005), and indwelling cardiac device (OR, 2.73; 95% CI, 1.21-5.58; P = .009) were associated with increased risk for recurrent GNB-BSI. Among the 48 patients with recurrent GNB-BSI whose paired bloodstream isolates underwent genotyping, 63% were due to relapse (30 of 48) and 38% were due to reinfection (18 of 48) based on WGS. Compared with WGS, PFGE correctly differentiated relapse and reinfection in 98% (47 of 48) of cases. Median time to relapse and reinfection was similar (113 days; interquartile range [IQR], 35-222 vs 174 days; IQR, 69-599; P = .13). Presence of a cardiac device was associated with relapse (relapse: 7 of 27, 26%; nonrelapse: 65 of 988, 7%; P = .002). In this study, recurrent GNB-BSI was most commonly due to relapse. PFGE accurately differentiated relapse from reinfection when compared with WGS. Cardiac device was a risk factor for relapse.

Antimicrobial Resistance and Associated Risk Factors of Gram-Negative Bacterial Bloodstream Infections in Tikur Anbessa Specialized Hospital, Addis Ababa.

BackgroundBloodstream infections (BSIs) are significant causes of morbidity and mortality in Ethiopia and worldwide. Alarming is the rapid global spread of antimicrobial resistance (AMR) in bacteria.ObjectiveTo determine the microbial profile, antimicrobial susceptibility pattern, and associated risk factors for bloodstream infections in Tikur Anbessa Specialized Hospital (TASH) Addis Ababa Ethiopia.MethodsA cross-sectional study was conducted between September 2018 and March 2019. Blood collected twice from each septicemia suspected patient were processed following standard bacteriological procedures. AST was performed by using the disk diffusion test according to CLSI 2017 and 2018 guidelines. Data captured in Epidata were cleaned and analyzed by SPSS version 21 software.ResultsThe prevalence of BSI was 28.06% and a higher proportion of pathogene detected were gram-negative bacteria (GNB) (54.5%) and gram-positive bacteria (GPB) (45.43%). The most abundant bacterial species were Klebsiella pneumoniae 17.6%, CoNS 15.2%, and Acinetobacter spp 11.0%. Culture positivity was associated with age below 6 years, neonates AOR p=<0.001, infants AOR p=<0.001, Pre-school P=0.002, ICU admission COR p=<0.001, length of admission >5 days COR P=0.016, temperature greater than 38°C, AOR p=0.013, instrument usage during medical care AOR, p=<0.001, chronic illness AOR p=0.027, and neonatal incubation AOR p=0.013. GNB average drug resistance rate was 57.9% of the commonly used antibiotics and the most efficient and inefficient drugs were amikacin (10.8%) and ampicillin (94.6%). The gram-negative isolates showed a 95.3% rate of multi-drug resistance; and MDR, XDR, and PDR were observed at 55.8%, 32.2%, and 7.3%, of isolates respectively. This finding shows children especially neonates were highly affected by drug resistant BSI.ConclusionPediatric patients and ICU patients are more affected by BSI, and drug-resistant bacteria are a major problem. Therefore, appropriate intervention approaches need to be implemented.

Excess mortality attributable to antimicrobial-resistant bacterial bloodstream infection at a tertiary-care hospital in Indonesia.

The burden of antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs) is largely unknown. Here, we evaluate attributable mortality of AMR infections in Indonesia. We used routine databases of the microbiology laboratory and hospital admission at Dr. Wahidin Sudirohusodo Hospital, a tertiary-care hospital in South Sulawesi from 2015 to 2018. Of 77,752 hospitalized patients, 8,341 (10.7%) had at least one blood culture taken. Among patients with bacteriologically confirmed bloodstream infections (BSI), the proportions of patients with AMR BSI were 78% (81/104) for third-generation cephalosporin-resistant (3GCR) Escherichia coli, 4% (4/104) for 3GCR plus carbapenem-resistant E. coli, 56% (96/171) for 3GCR Klebsiella pneumoniae, 25% (43/171) for 3GCR plus carbapenem-resistant K. pneumoniae, 51% (124/245) for methicillin-resistant Staphylococcus aureus, 48% (82/171) for carbapenem-resistant Acinetobacter spp., and 19% (13/68) for carbapenem-resistant Pseudomonas aeruginosa. Observed in-hospital mortality of patients with AMR BSI was 49.7% (220/443). Compared with patients with antimicrobial-susceptible BSI and adjusted for potential confounders, the excess mortality attributable to AMR BSI was -0.01 (95% CI: -15.4, 15.4) percentage points. Compared with patients without a BSI with a target pathogen and adjusted for potential confounders, the excess mortality attributable to AMR BSI was 29.7 (95%CI: 26.1, 33.2) percentage points. This suggests that if all the AMR BSI were replaced by no infection, 130 (95%CI: 114, 145) deaths among 443 patients with AMR BSI might have been prevented. In conclusion, the burden of AMR infections in Indonesian hospitals is likely high. Similar large-scale evaluations should be performed across LMICs to inform interventions to mitigate AMR-associated mortality.

Burden of bacterial bloodstream infections and recent advances for diagnosis.

Bloodstream infections (BSIs) and subsequent organ dysfunction (sepsis and septic shock) are conditions that rank among the top reasons for human mortality and have a great impact on healthcare systems. Their treatment mainly relies on the administration of broad-spectrum antimicrobials since the standard blood culture-based diagnostic methods remain time-consuming for the pathogen's identification. Consequently, the routine use of these antibiotics may lead to downstream antimicrobial resistance and failure in treatment outcomes. Recently, significant advances have been made in improving several methodologies for the identification of pathogens directly in whole blood especially regarding specificity and time to detection. Nevertheless, for the widespread implementation of these novel methods in healthcare facilities, further improvements are still needed concerning the sensitivity and cost-effectiveness to allow a faster and more appropriate antimicrobial therapy. This review is focused on the problem of BSIs and sepsis addressing several aspects like their origin, challenges, and causative agents. Also, it highlights current and emerging diagnostics technologies, discussing their strengths and weaknesses.

Evaluation of Some Biomarkers in Diagnosis of Bacterial Bloodstream Infection in Children

Evaluation of Some Biomarkers in Diagnosis of Bacterial Bloodstream Infection in Children

Effect of Antibacterial Prophylaxis on Febrile Neutropenic Episodes and Bacterial Bloodstream Infections in Dutch Pediatric Patients with Acute Myeloid Leukemia: A Two-Center Retrospective Study.

Simple SummaryThe intensive chemotherapy that children with acute myeloid leukemia (AML) receive puts them at high risk of infections. Bloodstream infections (BSI) caused by bacteria are common and known for their associated complications but may be prevented by the use of antibacterial agents. Literature on this matter is scarce. We evaluated the effect of different antibacterial prophylaxis regimens on the occurrence of fever and bacterial BSIs in 82 Dutch children with AML. A combination of prophylactic teicoplanin and ciprofloxacin had the best outcomes, resulting in significantly fewer episodes of fever and bacterial BSIs. The combination of teicoplanin and ciprofloxacin was previously suggested by others, but not yet studied. Currently, a randomized trial is ongoing to address and validate the efficacy of teicoplanin prophylaxis in pediatric AML.Bloodstream infections (BSIs), especially those caused by Gram-negative rods (GNR) and viridans group streptococci (VGS), are common and potentially life-threatening complications of pediatric acute myeloid leukemia (AML) treatment. Limited literature is available on prophylactic regimens. We retrospectively evaluated the effect of different antibacterial prophylaxis regimens on the incidence of febrile neutropenic (FN) episodes and bacterial BSIs. Medical records of children (0–18 years) diagnosed with de novo AML and treated at two Dutch centers from May 1998 to March 2021 were studied. Data were analyzed per chemotherapy course and consecutive neutropenic period. A total of 82 patients had 316 evaluable courses: 92 were given with single-agent ciprofloxacin, 138 with penicillin plus ciprofloxacin, and 51 with teicoplanin plus ciprofloxacin. The remaining 35 courses with various other prophylaxis regimens were not statistically compared. During courses with teicoplanin plus ciprofloxacin, significantly fewer FN episodes (43 vs. 90% and 75%; p < 0.0001) and bacterial BSIs (4 vs. 63% and 33%; p < 0.0001) occurred than with single-agent ciprofloxacin and penicillin plus ciprofloxacin, respectively. GNR and VGS BSIs did not occur with teicoplanin plus ciprofloxacin and no bacterial BSI-related pediatric intensive care unit (PICU) admissions were required, whereas, with single-agent ciprofloxacin and penicillin plus ciprofloxacin, GNR BSIs occurred in 8 and 1% (p = 0.004), VGS BSIs in 24 and 14% (p = 0.0005), and BSI-related PICU admissions were required in 8 and 2% of the courses (p = 0.029), respectively. Teicoplanin plus ciprofloxacin as antibacterial prophylaxis is associated with a lower incidence of FN episodes and bacterial BSIs. This may be a good prophylactic regimen for pediatric AML patients during treatment.

Comparison between hospital- and community-acquired septic shock in children: a single-center retrospective cohort study

BackgroundWe explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factors between children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatric intensive care unit (PICU).MethodsThis retrospective study enrolled children with septic shock at the PICU of Beijing Children’s Hospital from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into the HASS and CASS group. Logistic regression analysis was used to identify risk factors for mortality.ResultsA total of 298 children were enrolled. Among them, 65.9% (n = 91) of HASS patients had hematologic/oncologic diseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASS patients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratory or central nervous system. The 28-day mortality was 62.6% and 32.7% in the HASS and CASS groups, respectively (P < 0.001). Platelet [odds ratio (OR) = 0.996, 95% confidence interval (CI) = 0.992–1.000, P = 0.028], positive pathogen detection (OR = 3.557, 95% CI = 1.307–9.684, P = 0.013), and multiple organ dysfunction syndrome (OR = 10.953, 95% CI = 1.974–60.775, P = 0.006) were risk factors for 28-day mortality in HASS patients. Lactate (OR = 1.104, 95% CI = 1.022–1.192, P = 0.012) and mechanical ventilation (OR = 8.114, 95% CI = 1.806–36.465, P = 0.006) were risk factors for 28-day mortality in patients with CASS.ConclusionsThe underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between the HASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patients with septic shock.

#20 Bloodstream Infection is Associated with Prior Gut Microbiome Colonization of the Same Strain in the Neonatal Intensive Care Unit

Abstract Background Infants hospitalized in neonatal intensive care units (NICUs) have high incidence of bacterial bloodstream infections (BSIs) leading to up to 15% mortality and substantial morbidity. Common etiologies of BSI in the NICU are pathogens also capable of colonizing the preterm infant gut. However, differentiating susceptible neonates from those in the same environment remains challenging. We hypothesized that the same strains causing BSI increase in abundance in the gut of affected neonates prior to bacteremia and increased above controls in the same environment. Method We performed shotgun metagenomic sequencing on 462 fecal samples from 19 infants with BSI and 37 controls in the same NICUs paired for gestational age, days of life, antibiotic exposure, delivery mode, and sex. We whole genome sequenced the BSI isolate from 19 cases (6 Staphylococcus aureus, 3 Streptococcus agalactiae, 3 Serratia marcescens, 2 Enterococcus faecalis, 2 Klebsiella pneumoniae, 2 Escherichia coli, and 1 Enterobacter cloacae). We utilized MetaPhLan3 to infer taxonomy and InStrain to track the whole genome sequence of the BSI pathogen within the fecal metagenomes longitudinally. We performed generalized linear mixed effect models with MaAsLin2 to determine significant associations between the microbiome and metadata with subject as a random effect. Results We found no differences in gut microbiome diversity or richness between cases and controls relative to bacteremia day of life. However, infants who experience a BSI possess significantly higher median relative abundances of the causative species in their gut relative to paired controls in the 2 weeks prior to bacteremia (Figure 1A, median 21.4% IQR 0.33-52 vs. 0.4% IQR 0.23-10.5, p&amp;lt;0.05 Wilcoxon). 10/19 infants produced at least 1 stool before bacteremia containing an organism with 0-1 genomic substitutions from the BSI isolate, establishing isogenicity between gut residing and invasive pathogen. The coverage (abundance) of the BSI isolate increased in the stool of affected neonates in the 10 days before infection to an average maximum of 0.48/1.0 (Figure 1B, linear mixed effect model p&amp;lt;0.05). We observed the strongest associations between high gut microbiome abundance of E. faecalis, Klebsiella spp., E. coli, and S. marcescens in the gut microbiome of cases whose BSI was caused by that organism compared to all other samples (p&amp;lt;0.01). Conclusion We show high relative abundance of the same strain in stool prior to bacteremia in hospitalized neonates. The relative abundance of the causative species is higher in cases versus paired controls. These data suggest the potential of gut microbial surveillance and management to identify blooms of gut pathogens to limit the incidence of bacteremia.

α‐hemolysin of Staphylococcus aureus impairs thrombus formation

BackgroundToxins are key virulence determinants of pathogens and can impair the function of host immune cells, including platelets. Insights into pathogen toxin interference with platelets will be pivotal to improve treatment of patients with bacterial bloodstream infections. Materials and MethodsIn this study, we deciphered the effects of Staphylococcus aureus toxins α‐hemolysin, LukAB, LukDE, and LukSF on human platelets and compared the effects with the pore forming toxin pneumolysin of Streptococcus pneumoniae. Activation of platelets and loss of platelet function were investigated by flow cytometry, aggregometry, platelet viability, fluorescence microscopy, and intracellular calcium release. Thrombus formation was assessed in whole blood. Resultsα‐hemolysin (Hla) is known to be a pore‐forming toxin. Hla‐induced calcium influx initially activates platelets as indicated by CD62P and αIIbβ3 integrin activation, but also induces finally alterations in the phenotype of platelets. In contrast to Hla and pneumolysin, S. aureus bicomponent pore‐forming leukocidins LukAB, LukED, and LukSF do not bind to platelets and had no significant effect on platelet activation and viability. The presence of small amounts of Hla (0.2 µg/ml) in whole blood abrogates thrombus formation indicating that in systemic infections with S. aureus the stability of formed thrombi is impaired. Damage of platelets by Hla was not neutralized by intravenous immune globulins. ConclusionOur findings might be of clinical relevance for S. aureus induced endocarditis. Stabilizing the aortic‐valve thrombi by inhibiting Hla‐induced impairment of platelets might reduce the risk for septic (micro‐)embolization.

Combination of C-Reactive Protein and Procalcitonin in Distinguishing Fungal from Bacterial Infections Early in Immunocompromised Children.

Invasive fungal infection (IFI) is life-threatening in children with cancer and hematology disorders, especially when diagnosis and treatment are delayed. Conventional β-D-glucan and galactomannan tests have poor positive predictive values in the diagnosis of IFI in children with cancer. This study aims to access the diagnostic performance of C-reactive protein (CRP) and procalcitonin (PCT) in differentiating IFI from bacterial bloodstream infections in children with malignant and hematology disorders. CRP and PCT levels were measured in samples taken from patients between 12 and 24 h after fever onset, of which 24 and 102 were in the IFI and bacterial groups, respectively. We found that the CRP levels were much higher in the IFI group than the bacterial group (100.57 versus 40.04 mg/L, median, p < 0.001), while the PCT levels remained significantly lower (0.45 versus 1.29 μg/L, median, p = 0.007). Both CRP and PCT showed significant diagnostic utilities with an area under the curve (AUC) of 0.780 (95% CI, 0.664–0.896, p < 0.001) and 0.731 (95% CI, 0.634–0.828, p < 0.001) when using the cut-off values of 94.93 mg/L and 2.00 μg/L, respectively. However, the combined biomarker of CRP and PCT yielded a better diagnostic performance with an AUC of 0.934 (95% confidential interval (CI), 0.881–0.987, p < 0.001), which was significantly higher than that of CRP or PCT (both p < 0.001), with a sensitivity of 87.5% and a specificity of 87.3%. Our study demonstrates high levels of CRP combined with low PCT could differentiate IFI from bacterial bloodstream infections in immunocompromised children.

A prospective observational study of community-acquired bacterial bloodstream infections in Metro Manila, the Philippines.

Community-acquired bacterial bloodstream infections are caused by diverse pathogens with changing antimicrobial-resistance patterns. In low-middle income countries in Southeast Asia, where dengue fever is endemic and a leading cause of fever, limited information is available about bacterial bloodstream infections due to challenges of implementing a blood culture service. This study describes bacterial bloodstream pathogens and antimicrobial-resistance patterns in Metro Manila, the Philippines. We aimed to identify the proportion of patients with a positive blood culture, the bacteria isolated and their antimicrobial resistance patterns, and the clinical characteristics of these patients, in this dengue endemic area. We conducted a prospective observational study in a single hospital enrolling febrile patients clinically suspected of having a community-acquired bacterial bloodstream infection between 1st July 2015 and 30th June 2019. Each patient had a blood culture and additional diagnostic tests according to their clinical presentation. We enrolled 1315 patients and a significant positive blood culture was found in 77 (5.9%) including Staphylococcus aureus (n = 20), Salmonella enterica Typhi (n = 18), Escherichia coli (n = 16), Streptococcus pneumoniae (n = 3) and Burkholderia pseudomallei (n = 2). Thirty-four patients had meningococcal disease diagnosed by culture (n = 8) or blood PCR (n = 26). Additional confirmed diagnoses included leptospirosis (n = 177), dengue virus infection (n = 159) and respiratory diphtheria (n = 50). There were 79 (6.0%, 95%CI 4.8%-7.4%) patients who died within 28 days of enrollment. Patients with a positive blood culture were significantly more likely to die than patients with negative culture (15.2% vs 4.4%, P<0.01). Among S. aureus isolates, 11/20 (55%) were methicillin-resistant (MRSA) and ST30: USA1100 was dominant sequence type (88.9%). Antimicrobial-susceptibility was well preserved in S. enterica Typhi. Among hospitalized patients with clinically suspected community-acquired bacterial bloodstream infection in Metro Manila, the Philippines, 5.9% had a blood culture confirmed infection of whom 15.6% died. S. aureus, including a significant number of MRSA (USA1100 clones), S. enterica Typhi, E.coli and Neisseria meningitidis were frequently identified pathogens.

Microbiologically confirmed infections and antibiotic-resistance in a national surveillance study of hospitalised patients who died with COVID-19, Italy 2020–2021

BackgroundPatients hospitalised for COVID-19 may present with or acquire bacterial or fungal infections that can affect the course of the disease. The aim of this study was to describe the microbiological characteristics of laboratory-confirmed infections in hospitalised patients with severe COVID-19.MethodsWe reviewed the hospital charts of a sample of patients deceased with COVID-19 from the Italian National COVID-19 Surveillance, who had laboratory-confirmed bacterial or fungal bloodstream infections (BSI) or lower respiratory tract infections (LRTI), evaluating the pathogens responsible for the infections and their antimicrobial susceptibility.ResultsAmong 157 patients with infections hospitalised from February 2020 to April 2021, 28 (17.8%) had co-infections (≤ 48 h from admission) and 138 (87.9%) had secondary infections (> 48 h). Most infections were bacterial; LRTI were more frequent than BSI. The most common co-infection was pneumococcal LRTI. In secondary infections, Enterococci were the most frequently recovered pathogens in BSI (21.7% of patients), followed by Enterobacterales, mainly K. pneumoniae, while LRTI were mostly associated with Gram-negative bacteria, firstly Enterobacterales (27.4% of patients, K. pneumoniae 15.3%), followed by A. baumannii (19.1%). Fungal infections, both BSI and LRTI, were mostly due to C. albicans. Antibiotic resistance rates were extremely high in Gram-negative bacteria, with almost all A. baumannii isolates resistant to carbapenems (95.5%), and K. pneumoniae and P. aeruginosa showing carbapenem resistance rates of 59.5% and 34.6%, respectively.ConclusionsIn hospitalised patients with severe COVID-19, secondary infections are considerably more common than co-infections, and are mostly due to Gram-negative bacterial pathogens showing a very high rate of antibiotic resistance.

Clinical Characteristics Associated with Bacterial Bloodstream Coinfection in COVID-19.

IntroductionInappropriate antibiotic use in COVID-19 is often due to treatment of presumed bacterial coinfection. Predictive factors to distinguish COVID-19 from COVID-19 with bacterial coinfection or bloodstream infection are limited.MethodsWe conducted a retrospective cohort study of 595 COVID-19 patients admitted between March 8, 2020, and April 4, 2020, to describe factors associated with a bacterial bloodstream coinfection (BSI). The primary outcome was any characteristic associated with BSI in COVID-19, with secondary outcomes including 30-day mortality and days of antibiotic therapy (DOT) by antibiotic consumption (DOT/1000 patient-days). Variables of interest were compared between true BSI (n = 25) and all other COVID-19 cases (n = 570). A secondary comparison was performed between positive blood cultures with true BSI (n = 25) and contaminants (n = 33) on antibiotic use.ResultsFever (> 38 °C) (as a COVID-19 symptom) was not different between true BSI (n = 25) and all other COVID-19 patients (n = 570) (p = 0.93), although it was different as a reason for emergency department (ED) admission (p = 0.01). Neurological symptoms (ED reason or COVID-19 symptom) were significantly higher in the true BSI group (p < 0.01, p < 0.01) and were independently associated with true BSI (ED reason: OR = 3.27, p < 0.01; COVID-19 symptom: OR = 2.69, p = 0.03) on multivariate logistic regression. High (15–19.9 × 109/L) white blood cell (WBC) count at admission was also higher in the true BSI group (p < 0.01) and was independently associated with true BSI (OR = 2.56, p = 0.06) though was not statistically significant. Thirty-day mortality was higher among true BSI (p < 0.01). Antibiotic consumption (DOT/1000 patient-days) between true BSI and contaminants was not different (p = 0.34). True bloodstream coinfection was 4.2% (25/595) over the 28-day period.ConclusionTrue BSI in COVID-19 was associated with neurological symptoms and nonsignificant higher WBC, and led to overall higher 30-day mortality and worse patient outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00636-6.

Bacterial Bloodstream Infections – Prevalence, Etiology, and their Antibiotic Susceptibility Profile in Mumbai City

Aim: To study bacterial bloodstream infections concerning prevalence, etiology, and antibiotic susceptibility profile of pathogens in Mumbai City&#x0D; Study Design: Retrospective study&#x0D; Place and Duration of Study: Department of Microbiology, InfeXn Laboratories Pvt. Ltd., Thane&#x0D; One-year duration: January 2019- December 2019&#x0D; Methodology: The present retrospective study was performed on around 9397 adult and pediatric blood samples by using a rapid, accurate, and high throughput automated blood culture system for timely diagnosis of BSI.&#x0D; Results and Discussion: Bloodstream infection (BSIs) is considered a medical emergency as it is associated with high morbidity and mortality worldwide. The prevalence of BSI-causing bacteria and their Antibiotic susceptibility (AST) profile vary as per age, season, geographical location, etc. With a large cohort of 9397 samples, the total positivity rate was 17.47 % with gram-negative bacteria (67.69%) being more common than gram-positive (32.30%) in both adult and pediatric populations, with a peak in the Monsoon season. Escherichia coli (26.17%) and Klebsiella pneumoniae (27.31%) were the most isolated pathogens in the adult and pediatric populations, respectively. Carbapenemase production was seen highest in the non-fermentor group of bacteria (42.85%) whereas ESBL production was seen more in the Enterobacterals group (53%). Except for MRSA, gram-positive bacteria showed a very good susceptibility profile to the listed antibiotics. There was no case of VRE observed in the study.&#x0D; Conclusion: The study highlights the need for regular monitoring of BSI-causing bacteria and their antibiogram, which can help better to formulate empirical treatment strategies, controlled use of antibiotics, monitoring trends in drug resistance, and antibiotic stewardship.

Age-Dependent Responses of γδ+ T cells During Bloodstream Infection in Early Life

Abstract Late-onset neonatal sepsis (LOS) is a bloodstream bacterial infection that occurs during the first two months of life. Despite improved clinical care, LOS remains a significant contributor to neonatal mortality. Clinical observations suggest neonates exhibit unique immune responses and excessive inflammation during sepsis compared to adults and older children, however, factors contributing to these differences remain poorly understood. Two common routes of pathogen entry for neonates are direct introduction of a pathogen into the bloodstream, or the translocation of a gut-resident pathobiont. Our lab has developed a mouse model of LOS that disrupts goblet cell homeostasis to increase gut permeability and facilitate the translocation of virulent bacterial species such as E. coli. During both intraperitoneal and oral infection, we observe several key features of clinical LOS including increased pro-inflammatory serum cytokines, organ failure, and death in 5 day-old pups, but not 15 day-old pups. Strikingly, we have found robust activation of γδ+ T cells in 5 day-old pups, following infection, independent of pathogen entry route. This γδ+ T cell activation occurred in an age-dependent manner and was absent in 15 day-old pups. γδ+ T cell activation in 5 day-old pups was also associated with a pro-inflammatory cytokine profile that was absent in older pups. Finally, 5 day-old TCRδ−/− pups were protected from mortality during LOS, suggesting that γδ+ T cells may also contribute to mortality in this model. This study sheds light on the unique responses of γδ+ T cells to bloodstream infection during two distinct periods of early life.

Rapid, label-free antibiotic susceptibility determined directly from positive blood culture.

Bacterial bloodstream infections are a significant cause of global morbidity and mortality. Constrained by low bacterial burdens of 1-100 colony-forming-units per ml blood (CFU/ml), clinical diagnosis relies on lengthy culture amplification and isolation steps prior to identification and antibiotic susceptibility testing (AST). The resulting >60-h time to actionable treatment not only negatively impacts patient outcomes, but also increases the misuse and overuse of broad-spectrum antibiotics that accelerates the rise in multidrug resistant infections. Consequently, the development of novel technologies capable of rapidly recovering bacteria from blood-derived samples is crucial to human health. To address this need, we report a novel bacterial recovery technology from positive blood cultures that couples selective hemolysis with centrifugation through a sucrose cushion to perform rapid, background-free cytometric ASTs without long subculturing steps. Demonstrated on the most common bloodstream infection-causing bacteria: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, near-pure bacteria are rapidly recovered (≤15 min) with minimal user intervention. Susceptibilities of recovered bacteria are readily performed via high throughput flow cytometry with excellent agreement with much slower, standard microbroth dilution assays. Altogether, this novel direct-from-positive blood culture AST technology enables susceptibility determinations within as little as 5h, post blood culture positivity.

A Desirability of Outcome Ranking Analysis of a Randomized Clinical Trial Comparing Seven Versus Fourteen Days of Antibiotics for Uncomplicated Gram-Negative Bloodstream Infection.

BackgroundAlthough a short course (7 days) of antibiotics has been demonstrated to be noninferior to a conventional course (14 days) in terms of mortality and infectious complications for patients with a Gram-negative bacterial bloodstream infection (GNB), it is unknown whether a shorter treatment duration can provide a better overall clinical outcome.MethodsWe applied a bloodstream infection-specific desirability of outcome ranking (DOOR) analysis to the results of a previously completed, randomized controlled trial comparing short versus conventional course antibiotic therapy for hospitalized patients with uncomplicated GNB. We determined the probability that a randomly selected participant in the short course group would have a more desirable overall outcome than a participant in the conventional duration group. We performed (1) partial credit analyses allowing for calculated and variable weighting of DOOR ranks and (2) subgroup analyses to elucidate which patients may benefit the most from short durations of therapy.ResultsFor the 604 patients included in the original study (306 short course, 298 conventional course), the probability of having a more desirable outcome with a short course of antibiotics compared with a conventional course was 51.1% (95% confidence interval, 46.7% to 55.4%), indicating no significant difference. Partial credit analyses indicated that the DOOR results were similar across different patient preferences. Prespecified subgroup analyses using DOOR did not reveal significant differences between short and conventional courses of therapy.ConclusionsBoth short and conventional durations of antibiotic therapy provide comparable clinical outcomes when using DOOR to consider benefits and risks of treatment options for GNB.

The Role of the Oral Immune System in Oropharyngeal Candidiasis-Facilitated Invasion and Dissemination of Staphylococcus aureus.

Candida albicans and Staphylococcus aureus account for most invasive fungal and bacterial bloodstream infections (BSIs), respectively. However, the initial point of invasion responsible for S. aureus BSIs is often unclear. Recently, C. albicans has been proposed to mediate S. aureus invasion of immunocompromised hosts during co-colonization of oral mucosal surfaces. The status of the oral immune system crucially contributes to this process in two distinct ways: firstly, by allowing invasive C. albicans growth during dysfunction of extra-epithelial immunity, and secondly following invasion by some remaining function of intra-epithelial immunity. Immunocompromised individuals at risk of developing invasive oral C. albicans infections could, therefore, also be at risk of contracting concordant S. aureus BSIs. Considering the crucial contribution of both oral immune function and dysfunction, the aim of this review is to provide an overview of relevant aspects of intra and extra-epithelial oral immunity and discuss predominant immune deficiencies expected to facilitate C. albicans induced S. aureus BSIs.