Inappropriate Empirical Antibiotic Therapy Research Articles

Bloodstream infections due to multi-drug resistant bacteria in the emergency department: prevalence, risk factors and outcomes-a retrospective observational study.

Multidrug-resistant organisms (MDROs) are prevalent in patients admitted to the Emergency Department (ED) and increase the risk of inappropriate empirical antibiotic therapy. Risk stratification for MDRO infection is essential to early identify patients requiring empirical broad-spectrum antibiotic therapy, but it remains challenging for emergency physicians. This study aimed to evaluate prevalence, risk factors, and outcomes of patients admitted to the ED with a bloodstream infection (BSI) caused by MDROs. A retrospective observational study enrolling all consecutive adult patients admitted with a BSI to the ED of Niguarda Hospital, Italy, from January 2019 to December 2021 was performed. 757 patients were enrolled, 14.1% with septic shock. 156 (20%) patients had a BSI caused by MDRO: extended-spectrum beta-lactamase (ESBL) producing Enterobacterales were the most prevalent followed by methicillin-resistant Staphylococcus aureus (MRSA). Risk factors for BSI due to MDRO and specifically for ESBL were chronic renal failure (OR 2.2; 95%CI 1.4-3.6), nursing home residency (OR 4.4; 95%CI 1.9-10.2) and antibiotic therapy in the last 90-days (OR 2.6; 95%CI 1.7-4), whereas for MRSA were dialysis (OR 12.3; 95%CI 1.8-83), antibiotic therapy and/or hospital admission in the past 90-days (OR 3.6; 95%CI 1.2-10.6) and ureteral stent or nephrostomy (OR 7.8; 95%CI 1.5-40.9). Patients with BSI due to MDRO had a higher rate of inappropriate empirical antibiotic therapy (50%) and longer length of stay, but no higher in-hospital mortality. Among patients admitted to the ED with a BSI, MDROs are frequent and often associated with inappropriate empirical antibiotic therapy. Specific updated risk factors for MDRO may help clinicians to better identify patients requiring a broader antibiotic therapy in the ED, while awaiting microbiological results.

Adult acute leukemia patients with gram-negative bacteria bloodstream infection: Risk factors and outcomes of antibiotic-resistant bacteria.

This study aims to analyze the risk factors for the development of multidrug-resistant (MDR) and carbapenem-resistant (CR) bacteria bloodstream infection (BSI) in a patient with acute leukemia (AL) and the mortality in gram-negative bacteria (GNB) BSI. This is a retrospective study conducted at West China Hospital of Sichuan University, which included patients diagnosed with AL and concomitant GNB BSI from 2016 to 2021. A total of 206 patients with GNB BSI in AL were included. The 30-day mortality rate for all patients was 26.2%, with rates of 25.8% for those with MDR GNB BSI and 59.1% for those with CR GNB BSI. Univariate and multivariate analyses revealed that exposure to quinolones (Odds ratio (OR) = 3.111, 95% confidence interval (95%CI): 1.623-5.964, p = 0.001) within the preceding 30 days was an independent risk factor for MDR GNB BSI, while placement of urinary catheter (OR = 6.311, 95%CI: 2.478-16.073, p< 0.001) and exposure to cephalosporins (OR = 2.340, 95%CI: 1.090-5.025, p = 0.029) and carbapenems (OR = 2.558, 95%CI: 1.190-5.497, p = 0.016) within the preceding 30 days were independently associated with CR GNB BSI. Additionally, CR GNB BSI (OR = 2.960, 95% CI: 1.016-8.624, p = 0.047), relapsed/refractory AL (OR = 3.035, 95% CI: 1.265-7.354, p = 0.013), septic shock (OR = 5.108, 95% CI: 1.794-14.547, p = 0.002), platelets < 30 × 109/L before BSI (OR = 7.785, 95% CI: 2.055-29.492, p = 0.003), and inappropriate empiric antibiotic therapy (OR = 3.140, 95% CI: 1.171-8.417, p = 0.023) were independent risk factors for 30-day mortality in AL patients with GNB BSI. Prior antibiotic exposure was a significant factor in the occurrence of MDR GNB BSI and CR GNB BSI. CR GNB BSI increased the risk of mortality in AL patients with GNB BSI.

Impact of Appropriate Empirical Antibiotic Treatment on the Clinical Response of Septic Patients in Intensive Care Unit: A Single-Center Observational Study.

The appropriate antibiotic treatment of patients with bacterial sepsis in the intensive care unit (ICU) remains a challenge. Considering that current international guidelines recommend 7 days of antibiotic therapy as sufficient for most severe infections, our primary outcome was a comparison of clinical response to initial empirical therapy on day 7 and mortality between two groups of septic patients-with appropriate (AEAT) and inappropriate (IEAT) empirical antibiotic therapy according to the in vitro sensitivity of bacteria detected in a blood culture (BC). Adult patients admitted to the ICU between 2020 and 2023, who were diagnosed with sepsis according to the Sequential Organ Failure Assessment (SOFA) score ≥ 2 in association with a suspected or documented infection, were selected for the study. Of the 418 patients, 149 (35.6%) died within 7 days. Although the AEAT group had a lower mortality rate (30.3% vs. 34.2%) and better clinical improvement (52.8% vs. 47.4%) on day 7 after starting empirical antibiotic therapy, there was no significant difference. A causative organism was isolated from BCs in 30% of septic patients, with gram-negative bacteria (GNB) predominating in 60% of cases, and multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria predominantly detected in the BCs of the IEAT group. Although the AEAT group had slightly worse clinical characteristics at the onset of sepsis than the IEAT group, the AEAT group showed faster improvement on days 7 and 14 of sepsis. In this retrospective cross-sectional study, the AEAT group was associated with better clinical response at day 7 after sepsis onset and lower mortality, but without a significant difference. Comorbidities and the type of bacterial pathogen should also be taken into account as they can also contribute to the prediction of the final outcome. These results demonstrate the importance of daily assessment of clinical factors to more accurately predict the clinical outcome of a septic patient.

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. A retrospective, multi-centre study was carried out, including patients aged <20 years with PA-BSI in four tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multi-variable logistic regression model. In total, 151 patients with PA-BSI were included, with a median age of 29 months (interquartile range: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multi-drug 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 P.aeruginosa. CR was associated with carbapenem treatment in the previous month (adjusted odds ratio (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.

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.

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

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.

413: COST ANALYSIS OF EMPIRIC COVERAGE FOR PATIENTS WITH MDR GRAM-NEGATIVE INFECTIONS

Introduction: Gram-negative resistance to empiric antibiotic therapy has been associated with increased mortality rate, prolonged hospital length of stay and increase cost. The objective of this study is to compare total hospital costs associated with the appropriate and inappropriate empiric antibiotic therapy for critically ill patients with documented Gram-negative infections. Methods: Single-center, retrospective, cohort study conducted at a tertiary academic medical center. Data was collected from the electronic medical record for patients admitted from January 2015 to December 2017. Patients ≥18 years of age with culture-positive Gram-negative infection during the first 2 days of admission and started on antibiotics were included. Appropriate empiric coverage was defined as antibiotics with microbiological activity against the organism subsequently isolated in cultures within 24 hours collection. The primary outcome was the total hospital costs (fixed and variable) for the entire hospital stay. Descriptive statistics were performed and Mann-Whitney U, Fisher’s exact test, and χ-square test were conducted, where appropriate. Results: 832 patients were included in this study with 79 (9.5%) of the patients characterized as receiving inappropriate empiric antibiotics. There were no differences between patients receiving appropriate and inappropriate empiric therapy. Hospital and ICU length of stay were also statistically similar. There were significantly lower pharmacy costs incurred in patents receiving appropriate empiric therapy compared to inappropriate ($1,893 [3,319] vs. $2,252 [5,629], p=0.016). Total hospital costs incurred by patients receiving appropriate empiric therapy were numerically lower ($20,848 [30,377] vs. $23,006 [39,222], p=0.052). Conclusions: Inappropriate empiric antibiotics for patients with culture-positive Gram-negative infections was associated with significant increase in overall pharmacy cost and charges and numerically greater total hospital cost and charges.

Inappropriate empirical antibiotic therapy was an independent risk factor of pediatric persistent S. aureus bloodstream infection.

Inappropriate empirical antibiotic therapy was an independent risk factor of pediatric persistent S. aureus bloodstream infection. Pediatric persistent S. aureus bloodstream infection was associated with metastatic infection and septic shock. • Pathogenic features such as Methicillin-resistant S. aureusand sources of infection such as central venous catheterrelated infection were risk factors of PSBSI in adults. • PSBSI increased the incidence of metastatic infection and mortality in adults. • Inappropriate empirical antibiotic therapy was an independent risk factor of pediatric persistent S. aureus bloodstream infection. • Pediatric persistent S. aureus bloodstream infection was associated with metastatic infection and septic shock.

Clinical Characteristics and Prognosis Analysis of Acinetobacter baumannii Bloodstream Infection Based on Propensity Matching.

In view of the fact that Acinetobacter baumannii bloodstream infection(BSI) is a great threat to human survival, early identification of the risk factors affecting prognosis will be of great benefit to the clinic. A propensity score matching method was used to collect patients identified with Acinetobacter baumannii BSI from 2016 to 2020 from a reputable hospital in China. A total of 398 patients were considered. According to the 28-day prognosis, they were divided into the survival group 150 (37.7%) and the death group 248 (62.3%), and the prognosis was analyzed. Subsequently, Propensity score matching was adjusted for variables with p-values <O.2 in the baseline data, equalized differences in baseline, multivariate paired logistics regression analysis was performed on 63 matched patients and showed that patients with Acinetobacter baumannii BSI who had higher SOFA scores at the time of infection, with septic shock, or mechanical ventilation were more likely to be fatally hit within 28 days and had a poor prognosis. The existence of drug resistance with Acinetobacter baumannii only leads to Inappropriate empirical antibiotic therapy, ultimately, Inappropriate empirical antibiotic therapy was the direct predictor of mortality.

FREQUENCY OF BACTEREMIA CAUSED BY EXTENDED SPECTRUM BETALACTAMASE (ESBL)-PRODUCING ENTEROBACTERIA IN FEBRILE NEUTROPENIC PATIENTS WITH A PREVIOUS EPISODE OF ESBL BACTEREMIA

Bacteremia caused by ESBL-producing enterobacteria may require treatment with a carbapenem. We evaluated the frequency of bacteremia caused ESBL during febrile neutropenia (FN) in patients with a bacteremia by ESBL documented in a previous episode of FN. In this retrospective study we identified all patients with bacteremia by ESBL-producing enterobacteria during an episode of FN and looked at microbiologic documentation infection in subsequent episodes of FN. From 2001 to 2020 we recorded 1624 episodes of FN occurring in 1045 patients, with 64 episodes of FN with ESBL bacteremia occurring in 40 patients. Fourteen patients had at least another episode of FN after the documentation of ESBL bacteremia (median of 1 episode per patient, range 1 – 8). Four of the 14 patients (28.6%) had ESBL bacteremia in a subsequent episode of FN. The agents of bacteremia were Escherichia coli in 2 patients, and Enterobacter cloacae and Klebsiella pneumoniae (1 each). The time from the first to the second bacteremia by ESBL was 2 months, 7 months, 9 months and 10 months, respectively. One patient had an episode of FN without bacteremia between the two episodes with ESBL. Two patients received meropenem as empiric antibiotic therapy in the second episode and survived. Two patients received cefepime. One switched to piperacillin-tazobactam and survived. The other developed ESBL bacteremia on day 6 of cefepime, switched to meropenem but died on day 10 of meropenem. Considering that the initiation of inappropriate empiric antibiotic therapy in FN results in poor outcome, and given the high frequency of recurrence (28.6%) of ESBL (and 1 in 4 deaths), patients who develop a subsequent episode of FN should receive empiric antibiotic therapy with activity against the ESBL identified in the previous episode of FN.