Inappropriate Antibiotic Therapy Research Articles

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.

Viral etiology of severe lower respiratory tract infections in SARS-CoV-2 negative hospitalized patients during the COVID-19 pandemic in Kuwait

BackgroundThe prevalence of respiratory infections is largely underexplored in Kuwait. The aim of our study is to determine the etiology of infections from patients who are SARS-CoV-2 negative hospitalized with severe lower respiratory tract infections (LRTIs) in Kuwait during the coronavirus disease 2019 (COVID-19) pandemic. MethodsWe conducted an observational cross-sectional study among severe LRTI patients between September 2021 and March 2022. Respiratory samples from 545 non-COVID-19 severe LRTIs patients were prospectively evaluated with FTD Respiratory 21 Plus® real-time PCR, targeting 20 different viruses and 1 atypical bacterial pathogen. ResultsAmong all 545 hospitalized cases, 411 (75.4 %) tested positive for at least one respiratory pathogen. The most common were rhinovirus (HRV) (32.7 %), respiratory syncytial virus (RSV) (20.9 %), metapneumovirus (HMPV) (14.1 %), bocavirus (13.2 %), and influenza A (12.7 %). The proportion of pathogens detected was highest in the under-5 age group, while HKU1 (44.4 %) predominated in the elderly (>50 years). ConclusionOur study reveals a high prevalence of respiratory viruses in severe acute lower respiratory tract infections among non-COVID-19 hospitalized patients in Kuwait. HRV remains the main etiology affecting the country, particularly in infants. These results underscore the necessity of employing multiplex PCR for accurate diagnosis and describing the epidemiology of infections among severe lower respiratory tract infections. This will facilitate the use of specific antiviral therapy and help avoid excessive or inappropriate antibiotic therapy.

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.

2794. Assessing the impact of inappropriate antibiotic therapy on mortality among intensive care unit patients

Abstract Background This study evaluates the potential association between inappropriate antibiotic therapy and adverse clinical outcomes in infected patients admitted to ICUs. Methods We analyzed data from infected patients admitted to a medical-surgical Intensive Care Unit (ICU) in Belo Horizonte, a city with a population of three million in Brazil. The data was collected between January 2020 and June 2021, and included patients with healthcare-associated and community-acquired infections. In order to determine the appropriateness of antibiotic therapy, cultures and susceptibility reports were utilized. Empiric antimicrobial therapy was classified as inappropriate if the isolated strain was resistant to all empirically administered antimicrobials, while it was considered adequate if the isolated strain was susceptible to at least one of the antimicrobials used empirically. Results A total of 470 patients who received antimicrobials in the ICU were included in the analysis, all of whom had a positive culture. Among them, 65 patients experienced a FAILURE of the antimicrobial regimen, resulting in an overall failure rate of 14%. The monthly rate of inappropriate antibiotic therapy showed significant heterogeneity during the study period, ranging from 100% success in March 2021 to a failure rate of 33% in June 2021 (Fig 1). The failure rate of antimicrobial regimen was found to be significantly higher in cases where the infection was caused by multidrug-resistant (MR) strains compared to multisensitive (MS) strains, as shown in Table 1. Failure of the antimicrobial regimen was a significant risk factor for patient death, regardless of whether the infection was caused by MS or MR strains (Tables 1 and Fig 2). Patients who died tended to receive more antimicrobials compared to those who were discharged, with an average of three antimicrobials prescribed for patients who progressed to death, while discharged patients received an average of two drugs. Conclusion Inappropriate antibiotic therapy in ICU patients is associated with increased mortality risk, regardless of the type of infection. Timely and appropriate antimicrobial therapy is crucial in the management of ICU infections to improve clinical outcomes. Disclosures All Authors: No reported disclosures

886. Impact of Race on the Early Diagnosis and Treatment of Lyme Disease

Abstract Background Previous studies using single-state and Medicare surveillance data found that Black patients with Lyme Disease (LD) are more likely to present outside of the typical summer months and have higher rates of disseminated disease at diagnosis. We further explored differences in clinical presentation and early treatment of Lyme Disease by self-reported race among a large cohort of patients at an academic research clinic. Methods We abstracted data from all patients with untreated or post-treatment LD seen at the Johns Hopkins Lyme Disease Research Center (LDRC)—either for clinical care or research participation. Patients self-reported their demographics, and clinical information regarding their initial Lyme presentation was either recorded at the time of diagnosis or was abstracted from prior, external medical records. We examined the distribution of race across initial LD clinical presentations—categorized as 1) erythema migrans (EM) rash only, 2) disseminated disease, or 3) non-specific symptoms only—using chi-squared or Fisher’s exact test and fit logistic regression models. We compared racial differences in time to appropriate treatment using a one-sided Mann-Whitney test. Results Of 1363 individuals seen at the LDRC, 93% were white, 3% were Black, 2% were Asian, and 3% self-identified as either ‘other’ or more than one race. Compared to white patients, Black patients were less likely to present with erythema migrans (EM) rash (p &amp;lt; 0.0001) and more likely to present with disseminated disease or non-specific symptoms (p=0.009, p=0.019, respectively). Black patients were more likely to have received a course of inappropriate antibiotic therapy ( 16.7% vs 8.0 %, p= 0.058). Also, Black patients with EM rash experienced longer time to appropriate treatment (16.3 days vs 4.0, p=0.062). Number of asterisks indicates degree of statistical significance. N/S means "non-significant" Conclusion We identified several racial disparities in the early detection and treatment of Lyme Disease, highlighting the need for increased awareness of Lyme and its early manifestations among patients of color and the front-line clinicians who care for them. Because darker skin tones are generally under-represented in medical textbooks and patient education materials, we include several examples of EM rashes from Black patients seen at the LDRC (Figure 2). Disclosures John Aucott, MD, Pfizer, Inc.: Advisor/Consultant

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;

Antimicrobial Stewardship in COVID-19 Patients: Those Who Sow Will Reap Even through Hard Times.

Since the SARS-CoV-2 pandemic emerged, antimicrobial stewardship (AS) activities need to be diverted into COVID-19 management. In order to assess the impact of COVID-19 on AS activities, we analyzed changes in antibiotic consumption in moderate-to-severe COVID-19 patients admitted to four units in a tertiary-care hospital across three COVID-19 waves. The AS program was introduced at the hospital in 2018. During the first wave, COVID-19 forced the complete withdrawal of hospital AS activities. In the second wave, antibiotic guidance calibration for COVID-19 patients was implemented in all units, with enhanced stewardship activities in Units 1, 2, and 3 (intervention units). In a controlled before and after study, antimicrobial usage during the three waves of the COVID-19 pandemic was compared to the 12-month prepandemic unit (Unit 4 acted as the control). Antibiotic consumption data were analyzed as the overall consumption, stratified by the World Health Organization AWaRe classification, and expressed as defined-daily-dose (DDD) and days-of-therapy (DOT) per 1000 patient-day (PD). In the first wave, the overall normalized DOT in units 2-4 significantly exceeded the 2019 level (2019: 587 DOT/1000 PD ± 42.6; Unit 2: 836 ± 77.1; Unit 3: 684 ± 122.3; Unit 4: 872, ± 162.6; p < 0.05). After the introduction of AS activities, consumption decreased in the intervention units to a significantly lower level when compared to 2019 (Unit 1: 498 DOT/1000 PD ± 49; Unit 2: 232 ± 95.7; Unit 3: 382 ± 96.9; p < 0.05). Antimicrobial stewardship activities resulted in a decreased amount of total antibiotic consumption over time and positively affected the watch class and piperacillin-tazobactam use in the involved units. During a pandemic, the implementation of calibrated AS activities represents a sound investment in avoiding inappropriate antibiotic therapy.

Clinical characteristics and outcomes in febrile infants aged 29-90 days with urinary tract infections and cerebrospinal fluid pleocytosis.

Fever without a focus is a common reason for medical evaluations, hospitalizations, and the antimicrobial treatment of infants younger than 90 days. The presence of cerebrospinal fluid (CSF) pleocytosis could be challenge for clinicians who treat febrile young infants with urinary tract infection (UTI). We evaluated the factors associated with sterile CSF pleocytosis and the clinical outcomes of the patients. A retrospective review of patients aged 29-90 days with febrile UTIs who underwent a non-traumatic lumbar puncture (LP) at Pusan National University Hospital from January 2010 to December 2020 was conducted. CSF pleocytosis was defined as white blood cell (WBC) counts ≥9/mm3. A total of 156 patients with UTI were eligible for this study. Four (2.6%) had concomitant bacteremia. However, no patients had culture-proven bacterial meningitis. In correlation analysis, although weak strength, CSF WBC counts were positively correlated with C-reactive protein (CRP) level (Spearman r = 0.234; P = 0.003). Thirty-three patients had CSF pleocytosis [21.2%; 95% confidential interval (CI), 15.5-28.2]. The time from fever onset to the hospital visit, peripheral blood platelet counts, and CRP level at admission were statistically significant in patients with sterile CSF pleocytosis compared to those without CSF pleocytosis. In the multiple logistic regression, only CRP was independently associated with sterile CSF pleocytosis (cutoff, 3.425 mg/dl; adjusted odds ratio, 2.77; 95% CI, 1.19-6.88). The proportion of fever defervescence by hospital day 2 was 87.9% in patients with CSF pleocytosis and 89.4% in those without CSF pleocytosis (P = 0.759). There was no statistical difference in the fever defervescence curves between the two patient groups (P = 0.567). No patients had neurological manifestations or complications. Coexisting sterile CSF pleocytosis among febrile infants with UTIs suggest a systemic inflammatory response. However, the clinical outcomes between the two groups were similar. A selective LP should be considered in young infants with evidence of UTI, and inappropriate antibiotic therapy for sterile CSF pleocytosis should be avoided.

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

Determinants of Mortality for Ventilated Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia.

To determine if vHAP is an independent predictor of mortality among patients with nosocomial pneumonia. Single-center retrospective cohort study conducted at Barnes-Jewish Hospital, St. Louis, MO, between 2016 and 2019. Adult patients with a pneumonia discharge diagnosis were screened and patients diagnosed with vHAP and VAP were included. All patient data was extracted from the electronic health record. The primary outcome was 30-day all-cause mortality (ACM). One thousand one-hundred twenty unique patient admissions were included (410 vHAP, 710 VAP). Thirty-day ACM was greater for patients with vHAP compared with VAP (37.1% vs 28.5%; p = 0.003). Logistic regression analysis identified vHAP (adjusted odds ratio [AOR], 1.77; 95% CI, 1.51-2.07), vasopressor use (AOR, 2.34; 95% CI, 1.94-2.82), Charlson Comorbidity Index (1-point increments) (AOR, 1.21; 95% CI, 1.18-1.24), total antibiotic treatment days (1-d increments) (AOR, 1.13; 95% CI, 1.11-1.14), and Acute Physiology and Chronic Health Evaluation II score (1-point increments) (AOR, 1.04; 95% CI, 1.03-1.06) as independent predictors of 30-day ACM. The most common bacterial pathogens identified as causes of vHAP and VAP were Staphylococcus aureus, Enterobacterales species, and Pseudomonas aeruginosa. In this single-center cohort study with low rates of initial inappropriate antibiotic therapy, vHAP had greater 30-day ACM compared with VAP after adjusting for potential confounding variables including disease severity and comorbidities. This finding suggests that clinical trials enrolling patients with vHAP need to account for this outcome difference in their trial design and data interpretation.

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

A two-year retrospective study of multidrug-resistant Acinetobacter baumannii respiratory infections in critically Ill patients: Clinical and microbiological findings

BackgroundAcinetobacter baumannii infection is a serious public health problem because it is highly resistant to antimicrobial therapy and causes a high fatality rate in critically ill patients. The aim of the study is to examine the demographics, microbiological findings, clinical presentation, and outcomes of multi-drug-resistant Acinetobacter baumannii respiratory infections in adult ICU intubated patients during COVID-19 pandemic. MethodsThis study included 115 mechanically ventilated adult ICU patients who had multi-drug-resistant Acinetobacter baumannii retrieved from respiratory samples during the COVID-19 pandemic in Albaha, Saudi Arabia. The information was obtained from medical and laboratory files. Univariate analysis was used to compare gender, COVID-19 infection, and outcomes. ResultsThe rate of Acinetobacter baumanni respiratory infections among adult ICU patients was 6.2 %. Almost 93 % developed ventilator-associated pneumonia, and five of them developed bacteremia. The isolates had significant antibiotic resistance patterns, of which 3 % were pandrug-resistant bacteria. The death rate was 74 %, with major risk factors including sepsis, septic shock, VAP, liver diseases, and the use of inappropriate antibiotic therapy that lacked both colistin and tigecycline. Patients with COVID-19 coinfection had worse outcomes compared to non-COVID-19 patients. ConclusionsThe identification of MDR-AB as a threat highlights the importance of surveillance studies in this region.

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.