Monomicrobial Bloodstream Infections Research Articles

Low rates of complications and β-lactam resistance in viridans group streptococci bloodstream infection among cancer patients receiving chemotherapy.

Viridans group streptococci (VGS) bloodstream infection (BSI) frequently occurs in cancer patients receiving chemotherapy, and is associated with infective endocarditis (IE) in up to 20% of cases in the general population. In cancer patients receiving chemotherapy with VGS BSI, we aimed to: (i) determine the incidence of infective complications including IE, (ii) assess the utility of echocardiography in this patient population, (iii) determine the duration and type of antimicrobial therapy received for monomicrobial infections, and (iv) determine the evolution of antimicrobial resistance. VGS BSIs (excluding Streptococcus pneumoniae and Streptococcus pseudopneumoniae) in cancer patients receiving chemotherapy were identified from a statewide public pathology database between 2013 and 2022 at our tertiary centre. Medical records were accessed for clinical, microbiological and radiological data. Of 581 patient episodes screened, 183 episodes involving 171 patients met inclusion criteria. Of these, 51% were bone marrow transplantation (BMT) patients, 40% were non-BMT haematology patients, and 8% were solid organ malignancy patients. The median age was 55 years, and 96% were neutropenic at the time of blood culture collection. A transthoracic echocardiogram was performed for 71% of episodes, and one patient met modified Duke's criteria for definite IE, although this diagnosis was not suspected on clinical grounds. Other complications were uncommon. Benzylpenicillin resistance was rare (2.9%) and did not change over time. Most episodes (75%) were treated with piperacillin/tazobactam. For monomicrobial BSIs, the median antibiotic duration was 5 days (IQR 2-7) post-neutropenia resolution. Infective complications and antimicrobial resistance are rare in cancer patients with VGS BSI. This may provide a safe opportunity to limit both investigations (e.g. echocardiogram) and prolonged exposure to broad-spectrum antimicrobials.

Implication of genotypes for prognosis of Candida glabrata bloodstream infections.

Genotyping isolates of a specific pathogen may demonstrate unique patterns of antimicrobial resistance, virulence or outcomes. However, evidence for genotype-outcome association in Candida glabrata is scarce. We aimed to characterize the mycological and clinical relevance of genotypes on C. glabrata bloodstream infections (BSIs). Non-duplicated C. glabrata blood isolates from hospitalized adults were genotyped by MLST, and further clustered by the unweighted pair group method with arithmetic averages (UPGMA). A clonal complex (CC) was defined by UPGMA similarities of >90%. Antifungal susceptibility testing was performed by a colorimetric microdilution method and interpreted following CLSI criteria. Of 48 blood isolates evaluated, 13 STs were identified. CC7 was the leading CC (n = 14; 29.2%), including 13 ST7. The overall fluconazole and echinocandin resistance rates were 6.6% and 0%, respectively. No specific resistance patterns were associated with CC7 or other CCs. Charlson comorbidity index (adjusted OR, 1.49; 95% CI, 1.05-3.11) was the only predictor for CC7. By multivariable Cox regression analyses, CC7 was independently associated with 28 day mortality [adjusted HR (aHR), 3.28; 95% CI, 1.31-8.23], even after considering potential interaction with neutropenia (aHR, 3.41; 95% CI, 1.23-9.42; P for interaction, 0.24) or limited to 34 patients with monomicrobial BSIs (aHR, 2.85; 95% CI, 1.15-7.08). Also, the Kaplan-Meier estimate showed greater mortality with CC7 (P = 0.003). Fluconazole resistance or echinocandin therapy had no significant impact on mortality. Our data suggested comorbid patients were at risk of developing CC7 BSIs. Further, CC7 was independently associated with worse outcomes.

Diagnostic and therapeutic yield of imaging studies in Polymicrobial and Monomicrobial Gram-negative bloodstream infections – a retrospective cohort study

Purpose: Appropriate antimicrobial therapy and surgical drainage, improve survival in patients with Gram negative bloodstream infections (BSI). Data about the yield of imaging studies in polymicrobial BSI is sparse. The aim of the study was to assess the need for imaging studies and surgical drainage among patients with polymicrobial compared to monomicrobial BSI. Results: In a retrospective cohort study of adult patients with Gram negative BSI, 135 patients with monomicrobial BSI were compared to 82 with polymicrobial BSI. Imaging studies were performed in 56.3 % of patients with monomicrobial BSI and in 50 % of polymicrobial BSI (p=0.4), surgical drainage was performed in 20.1 % of patients with monomicrobial BSI and 27.2 % of polymicrobial BSI (p=0.25). Surgical drainage was performed in 26.2 % of patients who survived vs. 11.8 % of patients who died (p=0.035). Conclusions: There is no difference in the diagnostic approach to monomicrobial and polymicrobial Gram-negative BSI. Surgical drainage is associated with decreased mortality.

Efficacy of short- versus prolonged-courses of antimicrobial therapy for carbapenem-resistant Klebsiella pneumoniae bloodstream infections: A propensity score-matched cohort study

BackgroundAs limited antibiotic options are available for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs), the optimal treatment duration for CRKP BSIs is unclear. Our objective was to investigate whether short courses (6–10 days) are as effective as prolonged courses (≥11 days) of active antibiotic therapy for CRKP BSIs. MethodsA retrospective cohort study comprising adults with monomicrobial CRKP BSI receiving a short or prolonged course of in vitro active therapy at a medical center was conducted between 2010 and 2021. Comparisons of two therapeutic strategies were assessed by the logistic regression model and propensity score analysis. The primary endpoint was 30-day crude mortality. Secondary outcomes included recurrent BSIs, the emergence of multidrug-resistant organisms and candidemia during hospitalization after completing antibiotic therapy for CRKP BSIs. ResultsOf 263 eligible adults, 160 (60.8%) were male, and the median (interquartile range) age was 69.0 (53.0–76.0) years. Common comorbidities included diabetes (143 patients, 54.4%), malignancy (75, 28.5%), cerebrovascular accident (58, 22.1%), and hemodialysis (49, 18.6%). The 30-day mortality rate was 8.4% (22 patients). Of 84 propensity score well-balanced matched pairs, the 30-day mortality was similar in the short-course and prolonged-course group (6.0% and 7.1%, respectively; P = 1.00). However, there were less episodes candidemia in the short-course group (1.2% versus 13.1%; odds ratio, 0.08; 95% confidence interval, 0.01–0.63; P = 0.005). ConclusionShort courses of active therapy for CRKP BSIs demonstrate comparable clinical outcomes to prolonged courses and are associated with a lower risk of subsequent candidemia.

Polymicrobial bloodstream infections a risk factor for mortality in neonates at the national hospital, Tanzania: A case-control study.

Polymicrobial bloodstream infections (BSI) are difficult to treat since empiric antibiotics treatment are frequently less effective against multiple pathogens. The study aimed to compare outcomes in patients with polymicrobial and monomicrobial BSIs. The study was a retrospective case-control design conducted at Muhimbili National Hospital for data processed between July 2021 and June 2022. Cases were patients with polymicrobial BSI, and controls had monomicrobial BSI. Each case was matched to three controls by age, admitting ward, and duration of admission. Logistic regression was performed to determine independent risk factors for in-hospital and 30-day mortality. Fifty patients with polymicrobial BSI and 150 with monomicrobial BSI were compared: the two arms had no significant differences in sex and comorbidities. The most frequent bacteria in polymicrobial BSI were Klebsiella pneumoniae 17% (17/100) and Enterobacter species 15% (15/100). In monomicrobial BSI, S. aureus 17.33% (26/150), Klebsiella pneumoniae 16.67% (25/150), and Acinetobacter species 15% (15/150) were more prevalent. Overall, isolates were frequently resistant to multiple antibiotics tested, and 52% (130/250) were multidrug resistance. The 30-day and in-hospital mortality were 33.5% (67/200) and 36% (72/200), respectively. On multivariable analysis, polymicrobial BSIs were independent risk factors for both in-hospital mortality (aOR 2.37, 95%CI 1.20-4.69, p = 0.01) and 30-day mortality (aOR 2.05, 95%CI 1.03-4.08), p = 0.04). In sub-analyses involving only neonates, polymicrobial BSI was an independent risk factor for both 30-day mortality (aOR 3.13, 95%CI 1.07-9.10, p = 0.04) and in-hospital mortality (aOR 5.08, 95%CI 1.60-16.14, p = 0.006). Overall, the median length of hospital stay post-BSIs was numerically longer in patients with polymicrobial BSIs. Overall, polymicrobial BSI was a significant risk for mortality. Patients with polymicrobial BSI stay longer at the hospital than those with monomicrobial BSI. These findings call for clinicians to be more aggressive in managing polymicrobial BSI.

Risk of death in Klebsiella pneumoniae bloodstream infections is associated with specific phylogenetic lineages

Klebsiella pneumoniae species complex (KpSC) bloodstream infections (BSIs) are associated with considerable morbidity and mortality, particularly in elderly and multimorbid patients. Multidrug-resistant (MDR) strains have been associated with poorer outcome. However, the clinical impact of KpSC phylogenetic lineages on BSI outcome is unclear. In an 18-month nationwide Norwegian prospective study of KpSC BSI episodes in adults, we used whole-genome sequencing to describe the molecular epidemiology of KpSC, and multivariable Cox regression analysis including clinical data to determine adjusted hazard ratios (aHR) for death associated with specific genomic lineages. We included 1078 BSI episodes and 1082 bacterial isolates from 1055 patients. The overall 30-day case-fatality rate (CFR) was 12.5%. Median patient age was 73.4, 61.7% of patients were male. Median Charlson comorbidity score was 3. Klebsiella pneumoniae sensu stricto (Kp) (79.3%, n=858/1082) and K. variicola (15.7%, n=170/1082) were the dominating phylogroups. Global MDR-associated Kp clonal groups (CGs) were prevalent (25.0%, n=270/1082) but 78.9% (n=213/270) were not MDR, and 53.7% (n=145/270) were community acquired. The major findings were increased risk for death within 30 days in monomicrobial BSIs caused by K. variicola (CFR 16.9%, n=21; aHR 1.86, CI 1.10-3.17, p=0.02), and global MDR-associated Kp CGs (CFR 17.0%, n=36; aHR 1.52, CI 0.98-2.38, p=0.06) compared to Kp CGs not associated with MDR (CFR 10.1%, n=46). Bacterial traits, beyond antimicrobial resistance, have a major impact on the clinical outcome of KpSC BSIs. The global spread of MDR-associated Kp CGs is driven by other mechanisms than antibiotic selection alone. Further insights into virulence determinants, and their association with phylogenetic lineages are needed to better understand the epidemiology of KpSC infection and clinical outcome.

Polymicrobial bloodstream infections per se do not increase mortality compared to monomicrobial bloodstream infections in sepsis patients: a Korean nationwide sepsis cohort study

BackgroundThere is limited information about the outcomes of polymicrobial bloodstream infections in patients with sepsis. We aimed to investigate outcomes of polymicrobial bloodstream infections compared to monomicrobial bloodstream infections.MethodsThis study used data from the Korean Sepsis Alliance Registry, a nationwide database of prospective observational sepsis cohort. Adult sepsis patients with bloodstream infections from September 2019 to December 2021 at 20 tertiary or university-affiliated hospitals in South Korea were analyzed.ResultsAmong the 3,823 patients with bloodstream infections, 429 of them (11.2%) had polymicrobial bloodstream infections. The crude hospital mortality of patients with sepsis with polymicrobial bloodstream infection and monomicrobial bloodstream infection was 35.7% and 30.1%, respectively (p = 0.021). However, polymicrobial bloodstream infections were not associated with hospital mortality in the proportional hazard analysis (HR 1.15 [0.97–1.36], p = 0.11). The inappropriate use of antibiotics was associated with increased mortality (HR 1.37 [1.19–1.57], p < 0.001), and source control was associated with decreased mortality (HR 0.51 [0.42–0.62], p < 0.001).ConclusionsPolymicrobial bloodstream infections per se were not associated with hospital mortality in patients with sepsis as compared to monomicrobial bloodstream infections. The appropriate use of antibiotics and source control were associated with decreased mortality in bloodstream infections regardless of the number of microbial pathogens.

Time to positivity is a risk factor for death among patients with bloodstream infections: a population-based cohort

ObjectivesStudies examining time to positivity (TTP) of blood cultures as a risk factor for death have shown conflicting results. The study objective was to examine the effect of TTP on all-cause-30-day case-fatality among a population-based cohort of patients with bloodstream infections (BSI). MethodsA retrospective cohort study including all residents of Queensland, Australia with incident monomicrobial BSI managed in the publicly funded healthcare system from 2000 to 2019 was performed. Clinical, TTP and all-cause 30-day case-fatality information was obtained from state-wide sources. ResultsA cohort of 88 314 patients was assembled. The median TTP was 14 hours, with 5th, 25th, 75th, and 95th percentiles of 4, 10, 20, and 53 hours, respectively. The TTP varied significantly by BSI aetiology. The 30-day all-cause case-fatality rate was 2606/17 879 (14.6%), 2834/24 272 (11.7%), 2378/20 359 (11.7%), and 2752/22 431 (12.3%) within the first, second, third, and fourth TTP quartiles, respectively (p < 0.0001). After adjustment for age, sex, onset, comorbidity, and focus of infection, TTP within 10 hours (first quartile) was associated with a significantly increased risk for death (odds ratio 1.43; 95% CI, 1.35–1.50; p < 0.001). After adjustment for confounding variables (odds ratio; 95% CI), TTP within the first quartile for Staphylococcus aureus (1.56; 1.41–1.73), Streptococcus pneumoniae (1.91; 1.49–2.46), β-hemolytic streptococci (1.23; 1.00–1.50), Pseudomonas species (2.23; 1.85–2.69), Escherichia coli (1.37; 1.23–1.53), Enterobacterales (1.38; 1.16–1.63), other Gram-negatives (1.68; 1.36–2.06), and anaerobes (1.58; 1.28–1.94) increased the risk for case-fatality. DiscussionThis population-based analysis provides evidence that TTP is an important determinant of mortality among patients with BSI.

212. Effectiveness of Empirical Piperacillin/tazobactam Compared to Cefepime for Bloodstream Infection Caused by Gram-Negative Bacilli

Abstract Background Piperacillin/tazobactam (PTZ) and cefepime (CFP) are commonly used antibiotics for healthcare-associated infections and immunocompromised patients. However, few studies have compared the clinical effectiveness of these two antibiotics. Thus, we compared the effectiveness of empirical PTZ and CFP in patients with monomicrobial blood-stream infection (BSI) caused by gram-negative bacilli. Methods We conducted a retrospective cohort study of consecutive, non-duplicate monomicrobial BSIs caused by 1 of 4 taxa (Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Acinetobacter species) identified from a nationwide, prospective surveillance (Korean Antimicrobial Resistance Surveillance Network [KARS-Net]). Patients who were treated with PTZ or CFP as the only active empirical antibiotic were included. The primary outcome was all-cause, in-hospital 30-day mortality. Logistic regression with backward selection was used to adjust for imbalance in baseline characteristics. Results A total of 120 cases were included, among which 87 (72.5%) were treated with PTZ and 33 (27.5%) with CFP. Underlying renal disease was more common in the PTZ group whereas malignancy, septic shock, and neutropenia were more common in the CFP group. (Table 1). All-cause 30-day in-hospital mortality was comparable between the two groups (16.1% vs 12.1%, p=0.777; table 2), as well as attributable mortality. However, the early clinical response at 72 hr was significantly more common in the patients treated with CFP (25.3% vs 57.6%, p=0.001) The choice of empirical antibiotics was not significantly associated with mortality in a multivariable logistic regression model (Table 3). Older age (≥65 years; adjusted OR. 16.24; 95% CI, 2.21-119.60), lower ECOG (aOR, 2.91 per 1 point, 95% CI, 1.35-6.25), high PITT score (aOR, 1.68; 95% CI, 1.17-6.25) and chronic liver disease (aOR, 39.70; 95% CI, 2.56-615.13) were significant independent risk factors for 30-day in-hospital mortality. Conclusion In patients with BSI caused by gram-negative bacilli, empirical use of either PTZ or CFP was associated with comparable clinical outcomes. Disclosures All Authors: No reported disclosures

Epidemiology and clinical significance of persistent bacteremia in severely burned patients

BackgroundThe utility of follow-up blood cultures (FUBC) for gram-negative bloodstream infections (BSIs) are controversial due to low rates of positivity. However, recent studies suggest higher rates of positivity in critically ill patients. The utility of FUBC in gram-negative BSI in patients with severe burn injuries is unknown. MethodsPatients ≥ 18 years old admitted to the US Army Institute of Surgical Research Burn Center for combat-related thermal burns from 1/2003–6/2014 with a monomicrobial BSI were included. FUBC were defined as repeat cultures 1–5 days from index BSI. Persistent BSI (pBSI) was defined as isolation of the same organism from initial and FUBC. The primary endpoint was all-cause in-hospital mortality in patients with gram-negative pBSI. ResultsOf 126 patients meeting inclusion criteria with BSI, 53 (42%) had pBSI. Compared to patients without persistence, patients with pBSI had more severe burns with median total body surface area (TBSA) burns of 47% ([IQR 34–63] vs. 35.3% [IQR 23.3–56.6], p = 0.02), increased mortality (38 vs. 11%, p = 0.001) compared to those with non-persistent BSI. On multivariate analysis, pBSI was associated with an odds ratio for mortality of 5.3 [95% CI 1.8–15.8, p = 0.003). Amongst gram-negative pathogens, persistence rates were high and associated with increased mortality (41% vs. 11%, p = 0.001) compared to patients without pBSI. ConclusionIn this cohort of military patients with combat-related severe burns, pBSI was more common than in other hospitalized populations and associated with increased mortality. Given this high frequency of persistence in patients with burn injuries and associated mortality, FUBC are an important diagnostic and prognostic study in this population.

Prediction of methicillin-resistant Staphylococcus aureus and carbapenem-resistant Klebsiella pneumoniae from flagged blood cultures by combining rapid Sepsityper MALDI-TOF mass spectrometry with machine learning

This study investigated combination of the Rapid Sepsityper Kit and a machine learning (ML)-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) approach for rapid prediction of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Klebsiella pneumoniae (CRKP) from positive blood culture bottles. The study involved 461 patients with monomicrobial bloodstream infections. Species identification was performed using the conventional MALDI-TOF MS Biotyper system and the Rapid Sepsityper protocol. The data underwent preprocessing steps, and ML models were trained using preprocessed MALDI-TOF data and corresponding labels. The interpretability of the model was enhanced using SHapely Additive exPlanations values to identify significant features. In total, 44 S. aureus isolates comprising 406 MALDI-TOF MS files and 126 K. pneumoniae isolates comprising 1249 MALDI-TOF MS files were evaluated. This study demonstrated the feasibility of predicting MRSA among S. aureus and CRKP among K. pneumoniae isolates using MALDI-TOF MS and Sepsityper. Accuracy, area under the receiver operating characteristic curve, and F1 score for MRSA/methicillin-susceptible S. aureus were 0.875, 0.898 and 0.904, respectively; for CRKP/carbapenem-susceptible K. pneumoniae, these values were 0.766, 0.828 and 0.795, respectively. In conclusion, the novel ML-based MALDI-TOF MS approach enables rapid identification of MRSA and CRKP from flagged blood cultures within 1 h. This enables earlier initiation of targeted antimicrobial therapy, reducing deaths due to sepsis. The favourable performance and reduced turnaround time of this method suggest its potential as a rapid detection strategy in clinical microbiology laboratories, ultimately improving patient outcomes.

Are enterococcal bloodstream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness?-The Munich multicentric enterococci cohort.

The present study provides a substantial contribution to literature, showing that patients with enterococcal bloodstream infections (BSI) have a lower survival rate than those with Escherichia coli (E. coli) bloodstream infections after adjusting for 17 limiting prognostic factors and excluding patients with a limited life expectancy [metastatic tumor disease, Charlson Comorbidity Index (CCI) (greater than or equal to) 5]. This difference in the 5-year long-term survival was mainly driven by Enterococcus faecium (ECFM) bloodstream infections, with vancomycin resistance not being a significant contributing factor. Our findings imply that E. faecium bloodstream infections seem to be an independent risk factor for poor long-term outcomes. As such, future research should confirm this relationship and prioritize investigating its causality through prospective studies.

Bloodstream Infection Due to Coagulase-Negative Staphylococci: Impact of Species on Prevalence of Infective Endocarditis.

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective study of adults with monomicrobial CoNS BSI who had undergone echocardiography and a risk factor analysis was done to determine the most common CoNS species that cause definite IE; (3) Results: 247 patients with CoNS BSI were included in the investigation; 49 (19.8%) had definite IE, 124 (50.2%) possible IE, and 74 (30.0%) BSI only. The latter two entities were grouped in one category for further analysis. The most common species in CoNS BSI was Staphylococcus epidermidis (79.4%) and most patients (83.2%) had possible IE/BSI only. 59.1% of patients with BSI due to S. lugdunensis had definite IE. The majority of CoNS were healthcare-associated/nosocomial bacteremia. Multivariable analysis demonstrated that valve disease (p = 0.002) and a foreign cardiovascular material (p < 0.001) were risk factors associated with definite IE. Patients with S. lugdunensis BSI had an 8-fold higher risk of definite IE than did those with S. epidermidis BSI and nearly a 13-fold higher risk than did patients with BSI due to other species of CoNS (p = 0.002); (4) Conclusions: The prevalence of definite IE in patients with BSI due to different CoNS species was significant. CoNS bacteremia, particularly with S. lugdunensis, confers a significant risk of IE, particularly in patients with a valve disease or intravascular foreign body material and should not be immediately dismissed as a contaminant.

Impact of vancomycin resistance in Enterococcus faecium bloodstream infection on mortality: A retrospective analysis of nationwide surveillance data

ObjectivesIt is unclear whether the poor outcome of patients with severe vancomycin-resistant enterococci (VRE) infection is attributable to vancomycin resistance or to Enterococcus faecium (Efm), which predominates among VRE. MethodsRetrospective study of a prospectively identified cohort from nationwide surveillance. A cohort of consecutive, nonduplicate episodes of monomicrobial bloodstream infections (BSIs) caused by Efm in 2016 was selected. The primary outcome was all-cause, 30-day, in-hospital mortality. Inverse probability weighting was applied using the propensity score for vancomycin-resistant Efm (VREfm) BSI. ResultsA total of 241 Efm BSI episodes were included, of which 59 (24.5%) were VREfm. Patients with VREfm BSI were younger but had similar comorbidities to those with vancomycin-sensitive Efm (VSEfm) BSI. Multivariable logistic regression revealed that younger age, previous piperacillin-tazobactam use, and steroid use were significant risk factors for VREfm BSI, but 30-day in-hospital mortality did not differ significantly between groups (35.6% and 23.6% for VREfm and VSEfm, respectively; odds ratio, 1.79; 95% confidence interval, 0.95-3.37; P = 0.101). However, Cox regression with inverse probability weighting revealed that vancomycin resistance was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.18; 95% confidence interval, 1.03-4.62; P = 0.041). ConclusionIn patients with Efm BSI, vancomycin resistance was independently associated with mortality.

Mortality Attributable to Bloodstream Infections Caused by Different Carbapenem-Resistant Gram-Negative Bacilli: Results From a Nationwide Study in Italy (ALARICO Network).

Our aim was to analyze mortality attributable to carbapenem-resistant (CR) gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs). Prospective multicentric study including patients with GNB-BSI from 19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales, metallo-β-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aORs) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium. Overall, 1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (P < .001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB. In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.

Impact of direct disk-diffusion testing on time to optimal antibiotic therapy

Abstract We evaluated the impact of preliminary blood-culture antibiotic susceptibility testing on time to optimal antibiotic therapy in a cohort of 503 patients with monomicrobial bloodstream infections. The median time from blood-culture collection to optimal antibiotics was 17 hours earlier in the preliminary antibiotic susceptibility testing group.

Clinical impact of COVID-19 in patients with carbapenem-resistant Acinetobacter baumannii bacteremia.

The aim of this study was to evaluate the impact of coronavirus disease 2019 (COVID-19) on treatment outcomes in critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). This single-centre, retrospective cohort study was conducted in a 1,048-bed university-affiliated tertiary hospital in the Republic of Korea from January 2021 to March 2022. The study participants included consecutive hospitalised adult patients (aged ≥18years) in the intensive care unit with CRAB monomicrobial BSI. During the study period, a total of 70 patients were included in our study, and 24 (34.3%) were diagnosed with COVID-19. The 28-day mortality rate was 64.3%. In the multivariate Cox proportional hazard regression analysis, diagnosis of COVID-19 (hazard ratio (HR), 2.91; 95% confidence interval (CI): 1.45-5.87), neutropenia (HR, 2.76; 95% CI: 1.04-7.29), Pitt bacteraemia score (per point; HR, 1.30; 95% CI: 1.19-1.41), and appropriate definite antibiotic therapy (HR, 0.31; 95% CI: 0.15-0.62) were independent predictors of 28-day mortality in patients with CRAB BSI. In conclusion, our findings suggested that COVID-19 has a negative prognostic impact on patients with CRAB BSI. Further study is needed to investigate the specific mechanisms of how COVID-19 worsens the prognosis of CRAB infection.

Comparative-Effectiveness of Oral Beta-Lactams and Fluoroquinolones for Stepdown Therapy in Patients with Enterobacterales Bloodstream Infections: A Retrospective Cohort Study.

Background: This study compares treatment failure for patients who received oral beta-lactams (BLs) and fluoroquinolones (FQs) for stepdown treatment of Enterobacterales bloodstream infections (BSIs). Methods: We conducted a single-center, retrospective, age- and sex-matched, cohort study, at a Veterans Affairs (VA) hospital in South Texas. Eligible patients were at least 18 years of age with a monomicrobial BSI treated with a single oral BL or FQ antibiotic. Treatment failure was defined as recurrence or all-cause mortality within 90 days of documented BSI. Bivariate (chi-square, Fisher's Exact, and Wilcoxon Rank Sum) and multivariate (logistic regression) statistical tests were used to compare groups. Results: A total of 130 patients were included in this study, with 65 patients per group. Groups were well balanced with respect to exact age, sex assigned at birth, Caucasian race, source control, intensive care unit admission, and Charlson Comorbidity Index. Importantly, 60% of patients in the BL group had cultures that were resistant to FQs and 71% were prescribed cefpodoxime. Patients in the BL group had higher median (interquartile range [IQR]) Pitt bacteremia scores than those in the FQ group: 2 (1-4) vs. 1 (1-2), p=0.04. Patients in the BL group also had a higher median (IQR) duration of intravenous (IV) antibiotics than those in the FQ group: 5 (3-7) vs. 4 (3-5), p=0.02. Treatment failure was statistically comparable for patients in the BL and FQ groups: 15% vs. 12%, p=0.61. This finding was consistent in a multivariate logistic regression model with group (BL vs. FQ) as the independent variable, treatment failure as the dependent variable, and Pitt bacteremia score and duration of IV antibiotics as covariates (OR: 0.76, 95% CI: 0.27-2.18). One patient in the FQ group experienced Clostridioides difficile infection. Conclusion: This study suggests that BLs may be as effective as FQs for oral stepdown treatment of Enterobacterales BSI without the potential associated risks. Furthermore, in the setting of FQ-resistant Enterobacterales BSI secondary to urinary source, third generation oral cephalosporins (i.e., cefpodoxime) may be reasonable alternatives.

Evaluation of the Rapid Sepsityper protocol and specific MBT-Sepsityper module for the identification of bacteremia and fungemia using Bruker Biotyper MALDI-TOF MS.

The rapid identification method, the Rapid Sepsityper protocol with a specific MBT-Sepsityper module (Bruker Daltonics), based on the MALDI Biotyper platform, accurately identified 93.5% (116/124) of microorganisms at the species level in the 124 flagged blood culture samples from patients with monomicrobial bloodstream infections. Gram-negative bacilli (95.6%, 43/45) had a higher identification rate than Gram-positive cocci (93.3%, 70/75) and yeasts (75%, 3/4). The Rapid Sepsityper protocol displayed poor identification performance for polymicrobial samples.

BIOFIRE® Blood Culture IDentification 2 (BCID2) panel for early adaptation of antimicrobial therapy in adult patients with bloodstream infections: a real-life experience

Our objective was to assess the effectiveness of a multiplex PCR panel for blood culture identification (BCID2) on the implementation of appropriate antimicrobial therapy. We conducted a monocentric pre/post study comparing the time to result from direct microscopic examination (DE) to bacterial identification (BI) in positive blood cultures between 2 different periods: P1 without BCID2 and P2 with BCID2. Appropriate treatments prescribed before DE and after DE / BCID2 and after BI / BCID2 were compared using direct proportion comparison and survival analysis. For mono-microbial bloodstream infections, the proportion of appropriate antimicrobial treatment after DE was 50% in P1 vs. 87.5% after BCID2 in P2 (P < 0.001) for Gram-negative bacteria and 33.0% in P1 vs. 64.4% in P2 (P < 0.01) for Gram-positive bacteria. A significant difference (P = 0.04) was recorded with survival curves for Gram positive bacteria. BCID2 seems effective in reducing the time for prescribing appropriate antimicrobials.