Inappropriate Empirical Therapy Research Articles

Comparing the Prognostic Impacts of Delayed Administration of Appropriate Antimicrobials in Older Patients with Afebrile and Febrile Community-Onset Bacteremia

Although prompt administration of an appropriate antimicrobial therapy (AAT) is crucial for reducing mortality in the general population with community-onset bacteremia, the prognostic effects of delayed AAT in older individuals with febrile and afebrile bacteremia remain unclear. A stepwise and backward logistic regression analysis was used to identify independent predictors of 30-day mortality. In a 7-year multicenter cohort study involving 3424 older patients (≥65 years) with community-onset bacteremia, febrile bacteremia accounted for 27.1% (912 patients). A crucial association of afebrile bacteremia and 30-day mortality (adjusted hazard ratio [AHR], 1.69; p < 0.001) was revealed using Cox regression and Kaplan–Meier curves after adjusting for the independent predictors of mortality. Moreover, each hour of delayed AAT was associated with an average increase of 0.3% (adjusted odds ratio [AOR], 1.003; p < 0.001) and 0.2% (AOR, 1.002; p < 0.001) in the 30-day crude mortality rates among patients with afebrile and febrile bacteremia, respectively, after adjusting for the independent predictors of mortality. Similarly, further analysis based on Cox regression and Kaplan–Meier curves revealed that inappropriate empirical therapy (i.e., delayed AAT administration > 24 h) had a significant prognostic impact, with AHRs of 1.83 (p < 0.001) and 1.76 (p < 0.001) in afebrile and febrile patients, respectively, after adjusting for the independent predictors of mortality. In conclusion, among older individuals with community-onset bacteremia, the dissimilarity of the prognostic impacts of delayed AAT between afebrile and febrile presentation was evident.

Pseudomonas aeruginosa bloodstream infections in children and adolescents: risk factors associated with carbapenem resistance and mortality

Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. Retrospective, multicentre study including patients aged <20 years with PA-BSI in 4 tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multivariable logistic regression model. In total, 151 patients with PA-BSI were included, with a median age of 29 months (IQR: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multidrug-resistant and 6.6% extensively drug-resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, p<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, p=0.002) than BSIs caused by carbapenem-susceptible PA. CR was associated with carbapenem treatment in the previous month (adjusted OR [aOR] 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.

An Emergent Change in Epidemiologic and Microbiological Characteristics of Bloodstream Infections in Adults With Febrile Neutropenia Resulting From Chemotherapy for Acute Leukemia and Lymphoma at Reference Centers in Chile, Ecuador, and Peru.

Febrile neutropenia is a life-threatening condition commonly observed in patients with hematologic malignancies. The aim of this article is to provide updated knowledge about bloodstream infections in febrile neutropenia episodes within the Andean region of Latin America. This retrospective study was based in 6 hospitals in Chile, Ecuador, and Peru and included adult patients with acute leukemia or lymphoma and febrile neutropenia between January 2019 and December 2020. Of the 416 febrile neutropenia episodes, 38.7% had a bloodstream infection, 86% of which were caused by gram-negative rods, with Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa being the most frequently identified bacteria. K pneumoniae isolates were more frequently resistant than E coli to cefotaxime (65% vs 39.6%), piperacillin-tazobactam (56.7% vs 27.1%), and imipenem (35% vs 2.1%) and were more frequently multidrug resistant (61.7% vs 12.5%). Among P aeruginosa, 26.7% were resistant to ceftazidime, piperacillin-tazobactam, and imipenem, and 23.3% were multidrug resistant. Overall 30-day mortality was 19.8%, being higher with vs without a bloodstream infection (26.7% vs 15.3%, P = .005). Fever duration was also significantly longer, as well as periods of neutropenia and length of hospital stay for patients with bloodstream infection. Additionally, the 30-day mortality rate was higher for episodes with inappropriate vs appropriate empirical antibiotic therapy (41.2% vs 26.6%, P = .139). Considering the high rates of bacteria-resistant infection and 30-day mortality, it is imperative to establish strategies that reduce the frequency of bloodstream infections, increasing early identification of patients at higher risks of multidrug bacteria resistance, and updating existing empirical antibiotic recommendations.

Antimicrobial resistance patterns and empiric antibiotic selections for patients admitted from post-acute care facilities.

To characterize the susceptibilities of positive bacterial cultures and the appropriateness of empiric antimicrobial regimens for patients admitted from post-acute care facilities (PACFs). This was a retrospective quality improvement study. The study included patients admitted from a PACF to one of 2 tertiary care teaching hospitals within the University of Pennsylvania Health System, located in Philadelphia, PA, from August 2020 to December 2021. Patients were included if they had at least one positive culture within 72 hours of admission. A total of 167 patients and 230 isolates from the study period were evaluated. The majority of positive cultures were from a urinary source (114 of 230, 49.6%). Nineteen patients (11.4%) had a history of multidrug-resistant organisms. The most common empiric antibiotics used were vancomycin (61.7%) and cefepime (59.3%). Sixty-one patients (36.5%) received inappropriate empiric therapy based on the culture results. When comparing our hospitals' general antibiogram to that of only PACF patients, Escherichia coli and Klebsiella pneumoniae had at least a 20% difference in susceptibility to levofloxacin, ceftriaxone, and cefepime. Extended-spectrum β-lactamase resistance was also higher in the PACF cohort (odds ratio, 2.09; 95% confidence interval, 1.4-3.1). Clinically significant differences in antimicrobial susceptibility were found among patients admitted from PACFs compared to our health system's general antibiogram. The increased resistance rates identified in this study support the need for hospitals to evaluate this at-risk patient population, which may drive changes to empiric antibiotic prescribing practices.

Acinetobacter spp. bloodstream infection in hematological patients: a 10-year single-center study

PurposeThis study investigated the clinical and antimicrobial characteristics of Acinetobacter spp. bloodstream infection (BSI) in hematological patients. Risk factors for 30-day mortality and carbapenem-resistant Acinetobacter spp. (CRA) BSI acquisition were also identified.MethodsWe reviewed forty hematological patients with Acinetobacter spp. BSI in a large Chinese blood disease hospital between 2013 and 2022. The remaining CRA isolates were subjected to whole-genome sequencing.ResultsThe 30-day mortality rate was high at 35%. Hematological patients with Acinetobacter spp. BSI often presented with severe conditions and co-infections at multiple sites. All strains were colistin-susceptible and 40.0% were CR. Multivariate analysis identified several risk factors associated with CRA BSI acquisition, including previous exposure to carbapenems within 30 days and CRA colonization. Very severe aplastic anaemia, tetracycline-resistant Acinetobacter spp. BSI, and unresolved neutropenia after infection were closely associated with 30-day mortality. Non-survivors often presented with higher median PCT and CRP levels and severe complications, such as intracranial infection, cardiac dysfunction, respiratory failure, and severe sepsis or septic shock. Our study also identified inappropriate empirical antibiotic therapy as an independent predictor of 30-day mortality (OR: 11.234, 95% CI: 1.261–20.086, P = 0.030). This study was the first to report A. oleivorans as a human pathogen, and to identify its unique oxacillinase, OXA-325.ConclusionAn environment-originated non-pathogenic species can become pathogenic when the body’s immunity is compromised. Our results also highlighted the importance of improving neutropenia after infection, treating severe organ dysfunction, and administering appropriate empirical antibiotic therapy to reduce mortality in this patient population.

Epidemiology and risk factors for recurrence in biliary source bloodstream infection episodes in oncological patients.

We aimed to describe the characteristics and outcomes of biliary source bloodstream infections (BSIs) in oncological patients. Secondarily, we analyzed risk factors for recurrent BSI episodes. All episodes of biliary source BSIs in oncological patients were prospectively collected (2008-2019) and retrospectively analyzed. Logistic regression analyses were performed. A rule to stratify patients into risk groups for recurrent biliary source BSI was conducted. Four hundred biliary source BSIs were documented in 291 oncological patients. The most frequent causative agents were Escherichia coli (42%) and Klebsiella spp. (27%), and 86 (21.5%) episodes were caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). The rates of MDR-GNB increased over time. Overall, 73 patients developed 118 recurrent BSI episodes. Independent risk factors for recurrent BSI episodes were prior antibiotic therapy (OR 3.781, 95% CI 1.906-7.503), biliary prosthesis (OR 2.232, 95% CI 1.157-4.305), prior admission due to suspected biliary source infection (OR 4.409, 95% CI 2.338-8.311), and BSI episode caused by an MDR-GNB (OR 2.857, 95% CI 1.389-5.874). With these variables, a score was generated that predicted recurrent biliary source BSI with an area under the receiver operating characteristic (ROC) curve of 0.819. Inappropriate empirical antibiotic treatment (IEAT) was administered in 23.8% of patients, and 30-d mortality was 19.5%. As a conclusion, biliary source BSI in oncological patients is mainly caused by GNB, with high and increasing MDR rates, frequent IEAT, and high mortality. Recurrent BSI episodes are frequent. A simple score to identify recurrent episodes was developed to potentially establish prophylactic strategies. IMPORTANCE This study shows that biliary source bloodstream infections (BSIs) in oncological patients are mainly caused by Gram-negative bacilli (GNB), with high and increasing rates of multidrug resistance. Importantly, recurrent biliary source BSI episodes were very frequent and associated with delays in chemotherapy, high rates of inappropriate empirical antibiotic therapy, and high 30-d mortality (19.5%). Using the variable independently associated with recurrent BSI episodes, a score was generated that predicted recurrent biliary source BSI with high accuracy. This score could be used to establish prophylactic strategies and lower the risk of relapsing episodes and the associated morbidity and mortality.

Epidemiologic and microbiologic evaluation of catheter-line bloodstream infection in a pediatric hematopoietic stem cell transplant center

Children who underwent hematopoietic stem cell transplant (HSCT) transplants are at high risk of developing central-line-associated bloodstream infections (CLABSIs). The present study aimed to identify possible risk factors for mortality by analyzing the clinical and laboratory characteristics of patients diagnosed with CLABSI in our pediatric hematopoietic stem cell transplant unit. The initial CLABSI episodes of 102 children were analyzed. Medical records of the patients were evaluated by preformed standardized surveys. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors for mortality. Thirty-five patients (34.3%) were female. The median age was 48 months (3-204). The median time to onset of CLABSI was 19 days (4-150). The gram-negative and gram-positive bacteria ratio among the causative agents was 57.8% to 34.3%. The mortality rate was 12.6%. The presence of severe neutropenia, initiation of inappropriate empirical antibiotic therapy, the presence of hypotension, persistent bacteremia, pediatric intensive care unit admission, growth of carbapenemase-positive gram-negative microorganism and multidrug-resistant bacteria were significantly high in the mortality group when compared to survivors. The presence of hypotension, inappropriate empirical antibiotic therapy, and persistent bacteremia were found to be independent risk factors for mortality. Rational use of antibiotics, active surveillance and screening of patients together with improved infection control practices may reduce the incidence and the consequences of CLABSIs.

Clinical Characteristics and Prognosis of Hospital-Acquired Klebsiella pneumoniae Bacteremic Pneumonia versus Escherichia coli Bacteremic Pneumonia: A Retrospective Comparative Study.

This research aimed to investigate the variations in clinical features and prognosis of HABP caused by E. coli and K. pneumoniae. We also aimed to evaluate the risk variables related to 30-day death in the investigated groups. A single-center retrospective cohort research lasting four years was performed. A total of 117 patients with HABP were involved in this research. The primary prognosis was 30-day death. Among 117 patients with HABP, 60 patients were infected with K. pneumoniae (KP-HABP), and 57 patients were infected with E. coli (E. coli-HABP). A higher proportion of males, ICU admission, undergoing tracheotomy and trachea cannulation, carbapenem-resistant strains, inappropriate empirical therapy (IET), immune compromise, diabetes mellitus, and sepsis were observed in the patients with KP-HABP (all P < 0.05). Meanwhile, the median SOFA score and Pitt score were significantly (P < 0.001) higher in the KP-HABP group compared to the E. coli-HABP group. The 30-day death was 48.33% in the KP-HABP group and 24.56% in the E. coli-HABP group (P = 0.008). After adjusting for the main covariates, the hazard ratios for 30-day mortality in KP-HABP were 1.58 (95% CI:0.80-3.12), 3.24 (95% CI:1.48-7.06), 5.67 (95% CI:2.00-16.07), and 5.99 (95% CI:2.10-17.06), respectively. Multivariate logistic regression models revealed that IET, hypoproteinaemia, cerebral vascular disease (CVD), and SOFA score ≥ 5.0 were the independent risk variables for 30-day death in KP-HABP. Simultaneously, SOFA score ≥ 4.0 and Pitt score ≥ 2.0 were independent risk factors for 30-day mortality in E. coli-HABP. The clinical features of HABP vary depending on whether it is caused by Escherichia coli or K. pneumoniae. KP-HABP patients have higher 30-day mortality than E. coli-HABP patients. To ensure greater validity, it is necessary to further verify this conclusion using a larger sample size.

Appropriateness of Empirical Antibiotic Therapy in Hospitalized Patients with Bacterial Infection: A Retrospective Cohort Study.

The incidence of inappropriate and excessive empirical antibiotic therapy is unclear. The aim of this study was to determine the prevalence of different empirical antibiotic therapy prescriptions, related factors, and outcomes in hospitalized patients with bacterial infection. A retrospective cohort study was performed and patients with bacterial infection who were admitted between October 1, 2019, and September 30, 2020, were included. Multivariable analysis was performed by the logistic regression model. A total of 536 (42.6%) of the 1257 included patients received inappropriate empirical antibiotic therapy (IEAT), and 368 (29.3%) patients received appropriate but unnecessarily broad-spectrum empirical antibiotic therapy (AUEAT). MDRO (adjusted OR 2.932 [95% CI 2.201~3.905]; p < 0.001) and fever on admission (adjusted OR 0.592 [95% CI 0.415~0.844]; p = 0.004) were correlates of IEAT; sepsis (adjusted OR 2.342 [95% CI 1.371~3.999]; p = 0.002), age (adjusted OR 1.019 [95% CI 1.008~1.030]; p < 0.001), MDRO (adjusted OR 0.664 [95% CI 0.469~0.941]; p = 0.021), and urinary tract infection (adjusted OR 0.352 [95% CI 0.203~0.611]; p < 0.001) were correlates of AUEAT. Patients who received AUEAT were more likely to have a poor prognosis (63 [17.8%] vs 101 [27.4%]; p = 0.002). Both IEAT (median [IQR], 24,971 [13,135-70,155] vs 31,489 [14,894-101,082] CNY; p = 0.007) and AUEAT (median [IQR], 24,971 [13,135-70,155] vs 30,960 [16,475-90,881] CNY; p = 0.002) increased hospital costs. 45.3% (570/1257) of patients were infected with MDRO and 62.9% of them received IEAT. Inappropriate and excessive empirical antibiotic use was widely prevalent among hospitalized patients. Either inappropriate or excessive use of antibiotics may increase the burden of healthcare costs, the latter of which may be associated with poor prognosis. Clinicians need to be more judicious in choosing antibiotic(s). The MDRO epidemic was severe, especially in patients who received IEAT. It is imperative to take effective measures to improve the current situation of antibiotic abuse and antimicrobial resistance.

Neonatal sepsis: Challenges in data access, harmonisation and analysis to inform empirical antibiotic recommendations in South African neonatal units

&#x0D; &#x0D; &#x0D; Severe bacterial and fungal infections (sepsis) are a leading cause of mortality among neonates in sub-Saharan Africa. In African neonatal units, most sepsis episodes are hospital acquired, and caused by Gram-negative, antimicrobial-resistant pathogens. With rising rates of antimicrobial resistance (AMR) in neonatal sepsis pathogens, there is an increasing probability of inappropriate empirical antibiotic therapy (so called ‘bug-drug’ mismatch or discordant therapy), as confirmation of pathogen identity and antibiotic susceptibility pattern is either not available or delayed. The impact of AMR and discordant empirical treatment on neonatal sepsis outcomes in Africa is largely unknown owing to the lack of the infection surveillance data needed to derive empirical antibiotic treatment recommendations. The Antibiotics for Neonatal Sepsis in Africa (ANSA) study will address this data gap by pooling and harmonising available single-centre research datasets and/or routine laboratory blood culture data to determine which antibiotics should be used for empirical treatment of neonatal sepsis. However, many challenges hamper these datasets, including: variable laboratory methods for pathogen identification and susceptibility testing; difficulty in collating and harmonising data from multiple sites; problems of record linkage in the absence of a single patient identifier; lack of centralised health data capturing systems; and difficulty accessing data due to complex data sharing agreements and custodian permissions. To overcome some of these challenges, minimum guidelines for the collection of neonatal sepsis data need to be defined, to ensure consistency between datasets. Greater collection of, access to and sharing of neonatal sepsis data from institutional, provincial and national laboratories, as well as individual neonatal units, would enable the establishment of a neonatal surveillance network. Development of a sustainably-funded neonatal sepsis surveillance network is a national priority, to ensure effective, evidence-based antimicrobial treatment of hospitalised neonates in South Africa.&#x0D; &#x0D; &#x0D;

Neonatal sepsis: Challenges in data access, harmonisation and analysis to inform empirical antibiotic recommendations in South African neonatal units

&#x0D; &#x0D; &#x0D; Severe bacterial and fungal infections (sepsis) are a leading cause of mortality among neonates in sub-Saharan Africa. In African neonatal units, most sepsis episodes are hospital acquired, and caused by Gram-negative, antimicrobial-resistant pathogens. With rising rates of antimicrobial resistance (AMR) in neonatal sepsis pathogens, there is an increasing probability of inappropriate empirical antibiotic therapy (so called ‘bug-drug’ mismatch or discordant therapy), as confirmation of pathogen identity and antibiotic susceptibility pattern is either not available or delayed. The impact of AMR and discordant empirical treatment on neonatal sepsis outcomes in Africa is largely unknown owing to the lack of the infection surveillance data needed to derive empirical antibiotic treatment recommendations. The Antibiotics for Neonatal Sepsis in Africa (ANSA) study will address this data gap by pooling and harmonising available single-centre research datasets and/or routine laboratory blood culture data to determine which antibiotics should be used for empirical treatment of neonatal sepsis. However, many challenges hamper these datasets, including: variable laboratory methods for pathogen identification and susceptibility testing; difficulty in collating and harmonising data from multiple sites; problems of record linkage in the absence of a single patient identifier; lack of centralised health data capturing systems; and difficulty accessing data due to complex data sharing agreements and custodian permissions. To overcome some of these challenges, minimum guidelines for the collection of neonatal sepsis data need to be defined, to ensure consistency between datasets. Greater collection of, access to and sharing of neonatal sepsis data from institutional, provincial and national laboratories, as well as individual neonatal units, would enable the establishment of a neonatal surveillance network. Development of a sustainably-funded neonatal sepsis surveillance network is a national priority, to ensure effective, evidence-based antimicrobial treatment of hospitalised neonates in South Africa.&#x0D; &#x0D; &#x0D;

Neutropenic Sepsis and Challenges to Combat

Neutropenic sepsis (NS) is a common and predictable complication of bone marrow disorders and cytotoxic chemotherapy. After intensive chemotherapy, the incidence of NS is about 70–100% during the neutropenic phase. Patients with neutropenia are vulnerable to invasive infections, which can be rapidly overwhelming, causing septic shock and death. The epidemiology of sepsis in industrialized countries is mainly influenced by the age of the population and the increasing prevalence of comorbidities, such as chronic organ dysfunctions, non-cancer-related immunosuppressive diseases, or cancer itself. Patients with cancer are at more than 10 times higher risk for sepsis than the general population, with some variability according to the cancer types. There is frequent frustration among physicians caring for patients with neutropenic sepsis. Infections are a frequent complication in leukopenic patients, affecting an estimated 24% of patients after chemotherapy for hematologic diseases or solid organ tumors. Bloodstream infections (BSIs) are the most frequent infection in febrile neutropenic, onco-hematological patients, with incidence rates spanning from 10% to 38%. Septic shock is the most severe clinical presentation form of such infections. This is becoming a cause for growing concern due to several factors. Rates of Gram-negative bacilli (GNB) in oncohematological patients are progressively increasing. It is shown that ~50% of bacteremia in cancer patients was caused by GNB, among which almost 14% were MDR GNB. This could impact a greater percentage of patients presenting with septic shock. The widespread emergence and dissemination of multidrug-resistant Gram-negative bacilli, which are a common cause of infection and sepsis in patients with cancer, is of great concern. Several investigators have reported high rates of bacteremia due to extended-spectrum â-lactamase (ESBL)-producing Enterobacterales, MDR Pseudomonas aeruginosa (MDR-PA), and carbapenem-resistant Enterobacterales. Additionally, empirical antibiotic therapy is challenging in the era of emerging multidrug-resistant (MDR) GNB. Indeed, inappropriate empirical antibiotic therapy (IEAT) has been associated with increased mortality in patients with febrile neutropenia and BSI. Neutropenic sepsis is a medical emergency in which broad-spectrum antibiotics must be given without delay. Delaying treatment in neutropenic sepsis may increase the risk of death. â-Lactam/â-lactamase inhibitors (BL/ BLIs) and carbapenems are often considered for the treatment of sepsis when the main suspected pathogens are Gram-negative bacteria, because of their broad spectrum of coverage. Ceftazidime avibactam is a new molecule available against these bugs. It is a novel combination of ceftazidime (thirdgeneration cephalosporin) and avibactam (novel, nonâ- lactam â-lactamase inhibitor) which covers ESBL isolates like E Coli &amp; K. Pneumoniae, MDR Pseudomonas aeruginosa, and CRE. Ceftazidime and avibactam are now playing a crucial role in combating MDR gram-negative infections in sepsis patients. Many international guidelines recommend using early ceftazidime and avibactam in sepsis patients to achieve better outcomes and reduce volatility. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 197-198

Pseudomonas aeruginosa Bloodstream Infection, Resistance, and Mortality: Do Solid Organ Transplant Recipients Do Better or Worse?

The prevalence of antimicrobial resistance of Pseudomonas aeruginosa (P. aeruginosa) in solid organ transplant (SOT) recipients is higher than that of the general population. However, the literature supporting this statement is scarce. Identifying patients at risk of carbapenem resistance (CR) is of great importance, as CR strains more often receive inappropriate empiric antibiotic therapy, which is independently associated with mortality in bloodstream infections (BSIs). We prospectively recorded data from all consecutive BSIs from January 1991 to July 2019 using a routine purpose-designed surveillance database. The following variables were included: age, sex, type of transplant, use of vascular and urinary catheters, presence of neutropenia, period of diagnosis, treatment with steroids, origin of BSI, source of bacteremia, septic shock, ICU admission, mechanical ventilation, previous antibiotic treatment, treatment of bacteremia, and 30-day all-cause mortality. We identified 2057 episodes of P. aeruginosa BSI. Of these, 265 (13%) episodes corresponded to SOT recipients (130 kidney transplants, 105 liver, 9 hearts, and 21 kidney-pancreas). Hematologic malignancy [OR 2.71 (95% CI 1.33-5.51), p = 0.006] and prior carbapenem therapy [OR 2.37 (95% CI 1.46-3.86), p < 0.001] were associated with a higher risk of having a CR P. aeruginosa BSI. Age [OR 1.03 (95% CI 1.02-1.04) p < 0.001], urinary catheter [OR 2.05 (95% CI 0.37-3.06), p < 0.001], shock at onset [OR 6.57 (95% CI 4.54-9.51) p < 0.001], high-risk source [OR 4.96 (95% CI 3.32-7.43) p < 0.001], and bacteremia caused by CR strains [OR 1.53 (95% CI 1.01-2.29) p = 0.036] were associated with increased mortality. Correct empirical therapy was protective [OR 0.52 (95% CI 0.35-0.75) p = 0.001]. Mortality at 30 days was higher in non-SOT patients (21% vs. 13%, p = 0.002). SOT was not associated with a higher risk of having a CR P. aeruginosa BSI or higher mortality. In our cohort of 2057 patients with P. aeruginosa BSIs, hematologic malignancies and previous carbapenem therapy were independently associated with a risk of presenting CR P. aeruginosa BSI. Age, urinary catheter, high-risk source, bacteremia caused by carbapenem-resistant strains, and severity of the infection were independently associated with mortality, whereas correct empirical therapy was a protective factor. An increasing trend in the resistance of P. aeruginosa was found, with >30% of the isolates being resistant to carbapenems in the last period. SOT was not associated with a higher risk of carbapenem-resistant BSIs or higher mortality.

The Clash of the Titans: COVID-19, Carbapenem-Resistant Enterobacterales, and First mcr-1-Mediated Colistin Resistance in Humans in Romania.

(1) Background: Antibiotic resistance and coronavirus disease-19 (COVID-19) represent a dual challenge in daily clinical practice, inducing a high burden on public health systems. Hence, we aimed to dynamically evaluate the impact of COVID-19 on patients with carbapenem-resistant Enterobacterales (CRE) urinary tract infections (UTIs), as well as the antibiotic resistance trends after the onset of the pandemic. (2) Methods: We conducted a prospective study including patients with CRE UTIs who were enrolled both pre- and during the pandemic from 2019 to 2022. We further performed a standardized and comparative clinical, paraclinical, and microbiological assessment between patients with and without COVID-19. (3) Results: A total of 87 patients with CRE UTIs were included in this study (46 pre-pandemic and 41 during the pandemic, of which 21 had associated Severe Acute Respiratory Syndrome Coronavirus-2 infection). Klebsiella pneumoniae was the main etiological agent of the UTIs, with the majority of strains (82.7%) being carbapenemase producers (mainly OXA-48 producers), while five of the 34 colistin-resistant isolates were harboring the mobile colistin resistance-1 (mcr-1) gene. COVID-19 patients presented a significantly worse outcome with higher rates of intensive care unit (ICU) admissions (66.7% for COVID patients vs. 18.2% for non-COVID patients, p < 0.001), while the fatality rates were also considerably higher among patients with concomitant viral infection (33.3% vs. 12.1%, p < 0.001). Besides COVID-19, additional risk factors associated with increased mortality were urinary catheterization, sepsis with K. pneumoniae, impaired liver and kidney function, and an inappropriate initial empiric antibiotic therapy. (4) Conclusions: COVID-19 showed a pronounced negative impact on patients with CRE UTIs, with significantly longer hospitalizations and higher ICU admissions and mortality rates.

Predicting infection risk from surveillance cultures: frustrating or foretelling?

The global burden of morbidity and mortality due to multidrug-resistant infections is high, and in-vitro inactive empirical antibiotic therapy is a well known risk factor for poor outcomes. 1 Antimicrobial Resistance CollaboratorsGlobal burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399: 629-655 Summary Full Text Full Text PDF PubMed Scopus (1171) Google Scholar , 2 Kadri SS Lai YL Warner S et al. Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: a retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals. Lancet Infect Dis. 2021; 21: 241-251 Summary Full Text Full Text PDF PubMed Scopus (57) Google Scholar Studies have shown that colonisation with resistant pathogens increases the subsequent risk of infection by those same strains. However, when operationalising this principle, deciding how often to use specific broad-spectrum antibiotics if the patient is colonised with a particular pathogen warrants an improved understanding of the relative size of infection risks across different pathogens, host types, and time. 3 Denkel LA Maechler F Schwab F et al. Infections caused by extended-spectrum beta-lactamase-producing Enterobacterales after rectal colonization with ESBL-producing Escherichia coli or Klebsiella pneumoniae. Clin Microbiol Infect. 2020; 26: 1046-1051 Summary Full Text Full Text PDF PubMed Scopus (18) Google Scholar , 4 Tseng W-P Chen Y-C Chen S-Y Chen S-Y Chang S-C Risk for subsequent infection and mortality after hospitalization among patients with multidrug-resistant Gram-negative bacteria colonization or infection. Antimicrob Resist Infect Control. 2018; 7: 93 Crossref PubMed Scopus (33) Google Scholar , 5 Giannella M Bartoletti M Conti M Righi E Carbapenemase-producing Enterobacteriaceae in transplant patients. J Antimicrob Chemother. 2021; 76: i27-i39 Crossref Scopus (6) Google Scholar , 6 Tischendorf J de Avila RA Safdar N Risk of infection following colonization with carbapenem-resistant Enterobactericeae: a systematic review. Am J Infect Control. 2016; 44: 539-543 Summary Full Text Full Text PDF PubMed Scopus (143) Google Scholar Roel P J Willems and colleagues should be congratulated for their systematic review and meta-analysis establishing the cumulative incidence risk and the incidence density of infection in patients with multidrug-resistant Gram-negative bacteria (MDR-GNB) or vancomycin-resistant enterococci (VRE) colonisation of the gastrointestinal or urinary tract. 7 Willems RPJ van Dijk K Vehreschild MJGT et al. Incidence of infection with multidrug-resistant Gram-negative bacteria and vancomycin-resistant enterococci in carriers: a systematic review and meta-regression analysis. Lancet Infect Dis. 2022; (published online Jan 30.)https://doi.org/10.1016/S1473-3099(22)00811-8 Google Scholar Willems and colleagues pool aggregate results from 40 observational studies contributing 5015 VRE carriers and 9034 MDR-GNB carriers with a median study duration of 45 days (IQR 28–140). 7 Willems RPJ van Dijk K Vehreschild MJGT et al. Incidence of infection with multidrug-resistant Gram-negative bacteria and vancomycin-resistant enterococci in carriers: a systematic review and meta-regression analysis. Lancet Infect Dis. 2022; (published online Jan 30.)https://doi.org/10.1016/S1473-3099(22)00811-8 Google Scholar Infection and colonisation were as defined by the authors of each respective study and varied across studies. Incidence of infection with multidrug-resistant Gram-negative bacteria and vancomycin-resistant enterococci in carriers: a systematic review and meta-regression analysisThe risk of infection was substantial, with the highest risk for patients colonised with carbapenem-resistant Gram-negative bacteria and the lowest in patients with VRE. These data might help to guide prophylactic and treatment decisions and form a valuable resource for planning clinical trials on targeted prevention. Full-Text PDF

Association of Appropriate Empirical Antimicrobial Therapy With In-Hospital Mortality in Patients With Bloodstream Infections in the US

Bloodstream infections (BSIs) are a major public health problem associated with high morbidity. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy. To estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality. This retrospective cross-sectional study used data from the Premier Healthcare database from 2016 to 2020. The analysis included 32 100 adult patients (aged ≥18 years) with BSIs from 183 US hospitals who received at least 1 new systemic antimicrobial agent within 2 days after blood samples were collected during the hospitalization. Patients with polymicrobial infections were excluded from the analysis. Appropriate empirical therapy was defined as initiation of at least 1 new empirical antimicrobial agent to which the pathogen isolated from blood culture was susceptible either on the day of or the day after the blood sample was collected. Multilevel logistic regression models were used to estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality for patients infected with gram-negative rods (GNRs), gram-positive cocci (GPC), and Candida species. Among 32 100 patients who had BSIs and received new empirical antimicrobial agents, the mean (SD) age was 64 (16) years; 54.8% were male, 69.9% were non-Hispanic White, and in-hospital mortality was 14.3%. The most common pathogens were Escherichia coli (58.4%) and Staphylococcus aureus (31.8%). Among patients infected with S aureus, methicillin-resistant S aureus was isolated in 43.6%. The crude proportions of appropriate empirical therapy use were 94.4% for GNR, 97.0% for GPC, and 65.1% for Candida species. The proportions of appropriate therapy use for resistant organisms were 55.3% for carbapenem-resistant Enterobacterales species and 60.4% for vancomycin-resistant Enterococcus species. Compared with inappropriate empirical therapy, receipt of appropriate empirical antimicrobial therapy was associated with lower in-hospital risk of death for 3 pathogen groups (GNR: adjusted odds ratio [aOR], 0.52 [95% CI, 0.42-0.64]; GPC: aOR, 0.60 [95% CI, 0.47-0.78]; Candida species: aOR, 0.43 [95% CI, 0.21-0.87]). In this cross-sectional study of patients hospitalized with BSIs, receipt of appropriate initial empirical antimicrobial therapy was associated with lower in-hospital mortality. It is important for clinicians to carefully choose empirical antimicrobial agents to improve outcomes in patients with BSIs.

Bloodstream Infections Caused by Multidrug Resistant Bacteria: Clinical and Microbiological Features and Mortality.

Bloodstream infections (BSI) are associated with high morbidity and mortality. The aim of our study is to determine whether there is a relationship between certain risk factors such as the underlying disease, patient's medical history, or interventional procedures and multidrug resistant (MDR) bacterial infection and to determine the risk factors for mortality. Two hundred and twenty-two outpatients and inpatients who were diagnosed with bacteremia over a 6-month period were included in the study. 232 agents from 222 patients were isolated and tested for antimicrobial susceptibility. The relationship between patients demographic and clinical data and MDR was analyzed. The most common microorganisms were Gram-negative bacteria (59.4%), Gram-positive bacteria (36.9%), Candida species (2.2%), and anaerobic bacteria (1.35%). The most common isolates were Escherichia coli 53 (22.8%), Staphylococcus aureus 35 (%15.1), Klebsiella pneumoniae 26 (11.2%), Pseudomonas spp. (n=17, 7.3%), Acinetobacter spp 17 (7.3%), and Enterococcus spp 14 (6%). Microorganisms with the highest antimicrobial resistance observed were 82.3% in Acinetobacter baumannii, 64.5% in coagulase-negative staphylococci, 60.3% in E. coli, 50% in K. pneumoniae, and 27.2% in Enterobacterales spp. Most patients with BSI caused by MDR bacteria were in the intensive care unit (64%). Sepsis diagnosis, urinary catheter use, history of surgery, and use of broad-spectrum antibiotics as well as risk factors for antibiotic-resistant bacteremia, coronary artery disease, inappropriate empirical therapy, healthcare-associated infections, urinary catheterization, and stay in the ICU were determined as risk factors for mortality. Our study identified the risk factors of BSI caused by MDR bacteria and helped to reveal the relationship between these factors and mortality.

Risk Factors for 7-Day and 21-Day Mortality in Patients with Ventilator-Associated Pneumonia Caused by Gram-Negative Multidrug Resistant Bacteria

Objective: Incidence of ventilator-associated pneumonia, caused by gram-negative multidrug resistant bacteria, is on the increase and early mortality rate is high.&#x0D; We aimed to investigate the effects of aging, comorbidities, high Charlson comobidity index score, high Acute Physiology and Chronic Health Evaluation II score, leukocytosis, high C-reactive protein level, inappropriate empirical antibiotic therapy and antibiotic resistance on mortality in ventilator-associated pneumonia caused by gram-negative multidrug-resistant bacteria.&#x0D; Methods: The study was planned as a retrospective cohort study. Patients aged 18 years and older who were hospitalized between January 01, 2015, and January 01, 2020, diagnosed with ventilator-associated pneumonia, and had Gram-negative multidrug resistant pathogen was detected in blood and/or bronchoalveolar lavage fluid specimen or quantitative endotracheal aspirate cultures were included in the study.&#x0D; Results: A total of 370 patients were included in the study. Median age of the patients was 74 (19-95) years. Most frequent bacteria was Acinetobacter baumannii (52.4%). Resistance to ceftriaxone, meropenem, and colistin was 99%, 68%, and 4%, respectively. 7-day and 21-day mortality rates were 38.3% (n=142) and 85.1% (n=315). In multivariate analysis, 7-day mortality was associated with a Charlson comorbidity index score of ≥4, and risk factors for 7-day mortality were septic shock, amikacin resistance, and white blood cell count ≥15000/mm3. Advanced age was found to be a risk factor for 21-day mortality, and a high Acute Physiology and Chronic Health Evaluation II score and a high Charlson comorbidity index score were associated with 21-day mortality. It was found that the risk of 7-day mortality in patients with tracheostomy was lower than in patients without tracheostomy.&#x0D; Conclusion:Consideration of clinical scoring systems, closer monitoring of elderly patients, following-up with tracheostomy, may provide a decrease in mortality of ventilator-associated pneumonia, caused by multidrug resistant pathogens.

Guidance of empirical antimicrobial therapy by surveillance cultures in high-risk neutropenic patients: a retrospective cohort study

BackgroundIn neutropenic patients, bloodstream infections (BSI) significantly contribute to morbidity and mortality. Appropriate empirical antibiotic therapy (EAT) of BSI is essential, at the same time overconsumption of very broad-spectrum antibiotics should be avoided. We investigated: (1) whether surveillance cultures can predict BSI with third-generation cephalosporin –resistant Enterobacterales and Pseudomonas aeruginosa (3GC-R), (2) the effect of inappropriate empirical antimicrobial therapy (IEAT) on clinical outcome and (3) the potential reduction of carbapenem use when using surveillance cultures to guide therapy.MethodsRetrospective study of adult patients with haematological malignancies with febrile episodes during chemotherapy-induced high-risk neutropenia in whom surveillance cultures were collected weekly. IEAT was defined as the absence of in vitro susceptibility of blood-isolates to the administered EAT. Clinical outcome (ICU admission and death) was evaluated within 30 days.ResultsA total of 673 febrile episodes occurred among 372 high-risk neutropenic patients. BSI was present in 20.1% (135/673), of which 25.9% (35/135) were due to Enterobacterales and P. aeruginosa. Of these, 17/35 were 3GC-R and 70.6% (12/17) were preceded by 3GC-R colonization. Negative predictive value of surveillance cultures for 3GC-R BSI was 99.1%. IEAT due to (3GC-R) BSI was not significantly associated with clinical outcome. Using surveillance cultures to guide EAT could potentially reduce carbapenem use by 82.8%, when compared to standard EAT with carbapenem.ConclusionsThis retrospective analysis shows that in patients with high-risk neutropenia, surveillance cultures can potentially reduce the use of carbapenems with infrequent IEAT for 3GC-R BSI and no negative impact on clinical outcome.

2232. Association between Inappropriate Empiric Therapy (IET) and 30-Day Emergency Department/Inpatient (ED/IP) Visits Among Adult Outpatients (OPs) with Complicated Urinary Tract Infections (cUTIs)

Abstract Background Deleterious outcomes associated with IET are well documented among hospitalized patients with infections. However, scant data exist on the consequences of IET among adult OPs with cUTIs. This study evaluated the association between receipt of IET and 30-day ED/IP visits among adult OPs with cUTIs. Methods Retrospective cohort study among Kaiser Permanente Southern California members from 2017-20. Inclusion criteria were age ≥18 years; cUTI diagnosis during an OP visit; positive urine culture with antibiotic (AB) susceptibility results; receipt of AB ±3 days of index urine culture; and not hospitalized on day of OP visit. For OPs with multiple cUTIs, only the index cUTI was considered. IET was defined as failure to receive an AB with in vitro microbiologic activity against all recovered cUTI pathogens ±3 days of culture collection date. Outcomes included all-cause and cUTI-related ED/IP visits ≥3 days to ≤30 days from index culture date. Logistic regression was used to adjust for baseline differences between appropriateness groups. Results During study period, 25,980 OPs with cUTIs met study criteria. Mean age was 60 years, majority female (57%), and E. coli (66%) was the most common pathogen. IET was noted in 2656 (10%) of patients. Comparison of baseline characteristics between appropriateness groups is shown in Table. Comparison of 30-day all-cause and cUTI-related ED/IP visits between IET and appropriate empiric therapy (AET) is shown in Figure. In the logistic regression, receipt of IET was associated with an increase odds of 30-day all-cause ED/IP visits (adjusted odds ratio (aOR)= 1.3; 95% CI: 1.2-1.4) and 30-day cUTI-related ED/IP visits (aOR=1.5; 95% CI: 1.4-1.7), respectively. Figure Conclusion Thirty-day all-cause and cUTI-related ED/IP visits were significantly higher among adult OPs with cUTI who received IET. As culture and susceptibility results are frequently unknown at the time of empiric therapy selection, the findings highlight the critical need to use institution-specific antibiotic resistance risk stratification tools, in tandem with rapid diagnostic tests, to guide empiric antibiotic decisions among OPs with cUTIs as measures to ensure patients receive AET and maximize chances of a successful clinical outcome. Disclosures Thomas P. Lodise, PharmD, PhD, Spero Therapeutics: Advisor/Consultant Lie Hong H. Chen, DrPH, MSPH, Spero Therapeutics: Grant/Research Support Katia J. Bruxvoort, PhD, MPH, Dynavax: Grant/Research Support|Gilead: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support Rong Wei, MA, Spero Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support Theresa M. Im, MPH, Spero Therapeutics: Grant/Research Support Richard Contreras, MS, Spero Therapeutics: Grant/Research Support Mauricio Rodriguez, PharmD, MS-HEOR, BCPS, BCCCP, BCIDP, Spero Therapeutics: Employee Larry Friedrich, PharmD, Spero Therapeutics: Employee Jennifer Reese, PharmD, Spero Therapeutics: Employee Sara Y. Tartof, PhD MPH, Pfizer: Grant/Research Support|Spero: Grant/Research Support.