Inappropriate Empirical Treatment 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. 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.

A case-control study of the clinical and economic impact of infections caused by Carbapenemase-producing Enterobacterales (CPE).

The aim was to analyse the clinical and economic impact of carbapenemase-producing Enterobacterales (CPE) infections. Case-control study. Adult patients with CPE infections were considered cases, while those with non-CPE infections were controls. Matching criteria were age (± 5years), sex, source of infection and microorganism (ratio 1:2). Primary outcome was 30-day mortality. Secondary outcomes were 90-day mortality, clinical failure, hospitalisation costs and resource consumption. 246 patients (82 cases and 164 controls) were included. Klebsiella pneumoniae OXA-48 was the most common microorganism causing CPE infections. CPE cases had more prior comorbidities (p = 0.007), septic shock (p = 0.003), and were more likely to receive inappropriate empirical and definitive antibiotic treatment (both p < 0.001). Multivariate analysis identified septic shock and inappropriate empirical treatment as independent predictors for 7-day and end-of-treatment clinical failure, whereas Charlson Index and septic shock were associated with 30- and 90-day mortality. CPE infection was independently associated with early clinical failure (OR 2.18, 95% CI, 1.03-4.59), but not with end-of-treatment clinical failure or 30- or 90-day mortality. In terms of resource consumption, hospitalisation costs for CPE were double those of the non-CPE group. CPE cases had longer hospital stay (p < 0.001), required more long-term care facilities (p < 0.001) and outpatient parenteral antibiotic therapy (p = 0.007). The CPE group was associated with worse clinical outcomes, but this was mainly due to a higher comorbidity burden, more severe illness, and more frequent inappropriate antibiotic treatment rather than resistance patterns as such. However, the CPE group consumed more healthcare resources and incurred higher costs.

144. Impact of Rapid Identification and Resistance Gene Detection using an Algorithm-Based Approach in Gram-Negative Bacteremia

Abstract Background Time to appropriate antimicrobial therapy is the most important predictor of survival among patients with sepsis due to Gram-negative bacteria (GNB). Infections due to multidrug-resistant (MDR) pathogens often result in inappropriate empiric treatment (tx). The GenMark ePlex identifies organisms and resistance markers within 1.5 hours from blood culture positivity compared to 48-72 hours by conventional methods. Methods We are conducting a single-center study to assess outcomes before and after ePlex implementation. The pre-intervention period included patients with GN bacteremia from January to June 2021. Patients were excluded if they received comfort-only care within 48 hours, had polymicrobial GN bacteremia, or were infected by an organism not on the ePlex panel. Primary outcome is time to in-vitro active therapy from blood culture collection. Results 208 patients were identified during the pre-intervention period; 154 met inclusion criteria. Median age was 64 years, 49% were male, and 28% were immunocompromised. Median (IQR) Charlson Comorbidity index and Pitt Bacteremia scores were 6 (4-8) and 2 (1-8), respectively (Table 1). 16% of patients were infected by MDR GNB and 21% received inactive empiric tx. Overall median (IQR) time to in-vitro active tx was 3.9 (1–19) hours, but was 39.5 (13.6-71.9) hours among those who received inactive empiric tx. Median (IQR) time to first antibiotic modification was 2.7 (1.0-3.4) days. 38% of patients were transitioned to oral antibiotics at a median (IQR) of 4.2 (3.1-6.1) days. The median (IQR) duration of tx was 15 (10-17) days; 4.5% of patients were treated with ≤ 7 days. Median (IQR) length of hospitalization was 15.5 (7-36) days. 7.8% were re-admitted within 30 days (Table 2). In-hospital and 30-day mortality rates were numerically higher among patients who received inactive empiric therapy (27% and 21%, respectively) when compared to patients who received active empiric therapy (16.5% and 12%, respectively) (Figure 1). Results Table 1: Patient demographics, underlying conditions and infection and treatment characteristics in the pre-intervention group Results Table 2 Results Figure 1 Conclusion Our pre-intervention data highlight opportunities to improve the management of GN bacteremia. Implementation of ePlex is likely to decrease the proportion of patients treated with inactive therapy, shorten time to optimal tx and reduce lengths of stay. Disclosures Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support

The Holy Grail of endometriosis biomarkers in the diagnostic process – How much would it be worth and what does it look like?

Previously, the gold standard for the diagnosis of endometriosis involved the performance of laparoscopic surgery, which allows the visualization and histological examination of the endometrial tissue. According to the latest guidelines published by the European Society of Human Reproduction and Embryology (ESHRE) in 2022, surgery is recommended only in patients with diagnostic difficulties associated with the use of non-invasive methods or in case of inappropriate or unsuccessful empirical treatment. At the same time, it is not recommended to use the measurement of biomarkers in the endometrial tissue, blood, menstrual or uterine fluids to diagnose endometriosis as the ESHRE guideline development group indicated the need of larger, multi-center prospective studies on this matter. The aim of this narrative review is to present advances in knowledge on non-invasive endometriosis diagnostic opportunities with emphasis on proteomics, the use of endometrial aspiration biopsy, iron metabolism, vitamin D-binding protein, extracellular matrix signaling pathways, epithelial−mesenchymal transformation, and other molecular pathways, together with a critical analysis of studies cited in the recent ESHRE guidelines.

Evaluation of Risk Factors Causing Nosocomial Acinetobacter Bacteremia and Mortality in the Intensive Care Unit

Objective: We aimed to evaluate risk factors for bacteremia and mortality in patients with nosocomial Acinetobacter bacteremia in a university hospital’s Anesthesia and Reanimation Intensive Care Unit (ICU) between 2013-2016. Methods: This study was designed as a retrospective case-control study; the case group consisted of patients older than 18 years, with Acinetobacter species growth in blood cultures taken 48 hours after hospitalization, with clinical bacteremia findings, followed until death or at least 30 days after culture. Patients in the control group consisted of cases without Acinetobacter bacteremia and showed similar characteristics to the case group. Patients were evaluated regarding demographic characteristics, underlying diseases, carbapenem use before blood culture was taken, appropriate empirical treatment, 30-day mortality, nutritional status, Pittsburgh Bacteremia Score (PBS), and interventional procedures. Results: Among case and control groups each consisting of 51 patients, carbapenem use (63.2% and 34.8%, respectively, odds ratio (OR)=3.67; 95% confidence interval (CI)=1.49-9.04, p=0.005) and chest tube placement (23.5% and 7.8%, respectively, OR=7.31; 95% CI=1.43-37.22, p=0.005) were independent risk factors for Acinetobacter bacteremia. Among cases with or without mortality in the case group, there was a significant difference in terms of endotracheal intubation (100%, 76.9%, respectively, p=0.023), PBS (6.6±1.08, 5.0±2.29, respectively, p=0.003), nutritional status (total parenteral nutrition [TPN] or enteral nutrition +TPN) (%28, %0 and %72, %100, respectively, p=0.004) and hypertension (HT) (%52, %19.2, respectively, p=0.03) and also HT [52% and 19.2%, respectively, OR=4.61; 95% CI=1.08-19.57, p=0.038], inappropriate empirical therapy [69.6% and 30.8%, respectively, OR=6.46; 95% CI=1.55-26.94, p=0.01] and albumin level [2.32±0.50 and 2.57±0.44 g/dL, respectively, OR=0.196; 95% CI=0.045-0.847, p=0.029] were independent mortality risk factors. Conclusion: Previous carbapenem use and chest tube insertion are important risk factors for Acinetobacter bacteremia in ICU. Inappropriate empirical treatment, HT, and low albumin levels are important mortality risk factors in Acinetobacter bacteremia in ICU. High PBS scores should be carefully evaluated for mortal Acinetobacter bacteremia.

47 Clinical Approach to Febrile Urinary Tract Infections in Young Children Presenting to the Paediatric Emergency Department: A Retrospective Study of National Guideline Compliance

Abstract Background Antimicrobial resistance is one of the greatest threats to global health. Antibiotic overuse drives antimicrobial resistance. Suspected urinary tract infection (UTI) is a key area of over-prescribing in many clinical settings but has not been investigated in the paediatric emergency department (ED). Objectives Here, we explore compliance with national UTI management guidelines in a paediatric emergency department setting and characterize patient and provider factors associated with guideline non-compliance. Design/Methods We performed retrospective chart review of patients ages 60 days to 36 months, discharged with a diagnosis of UTI from a single, urban, tertiary care paediatric emergency department (PED) with a diagnosis of UTI. Random visits were chosen using a computer algorithm. Primary outcomes were: 1) proportion of patients receiving guideline-compliant investigation and treatment, and 2) the proportion of children whose antibiotic prescriptions were appropriately adjusted upon return of urine culture and antibiotic susceptibilities (C&amp;S). The guideline was the Canadian Paediatric Society statement on management of UTI, as well as the BC Children’s Hospital institutional UTI management guideline. Descriptive statistics and odds ratios between associations were calculated. Results We reviewed 402 charts. The proportion of infants receiving guideline-compliant testing and treatment was 25.9% (95% CI: 21.8-30.4%). Of those who were prescribed antibiotics, 79.6% (95% CI: 74.7-83.8%) received a first-line recommended agent and 58.9% (95% CI: 53.8-63.8%) received fully compliant therapy with respect to agent, dose, duration, and frequency. 19.4% (15.4-24.2%) of patients who were prescribed empiric cephalexin received an inappropriately high total daily dose. The proportion of patients receiving age-appropriate testing method was 52.2% (95% CI: 47.4-57.1). Febrile children were more likely to receive age-appropriate urine sample collection by catheterized sample (OR: 2.77 95% CI: 1.81-4.25) compared with afebrile children. Ultimately, 50.7% (95% CI: 40.4-49.6%) of patients discharged with a diagnosis of UTI and prescription for antibiotic met diagnostic criteria for UTI based on urinalysis and culture results. Of patients whose C&amp;S mandated a change in therapy, 60.8% (95% CI: 55.8-65.7%) had their agent changed or discontinued. Conclusion Paediatric emergency medicine physicians frequently order inappropriate investigation and empiric treatment of UTI in young children. Discontinuation of empiric antibiotics in culture-negative children may be an impactful stewardship intervention in the PED.

Clinical presentation and outcome of hemodialysis tunneled catheter-related bloodstream infection in older persons.

The use of a tunneled catheter as the primary vascular access among old hemodialysis patients is frequent. Catheter-related bloodstream infection (CRBSI) is a common complication, associated with increased mortality. Data regarding the clinical presentation and outcomes of CRBSI among old hemodialysis patients is limited. All chronic hemodialysis patients hospitalized between 2010 and 2022 with CRBSI were included. Patients were classified into two groups: old adults (≥ 75) and younger patients.Clinical, microbiological, and outcome data were collected and analyzed. One hundred and fifty-four patients with CRBSI were identified. Fifty-seven were aged ≥ 75years.Mean age in the older and younger groups was 81.2 ± 5 and 59.7 ± 12.7, respectively. Male gender was predominant (64%). Charlson comorbidity score and Pitt bacteremia score were comparable among both groups. Norton score < 14 was more common among old persons (n = 24, 67% versus n = 21, 31%, p < 0.001), as well as nursing-home residence. Gram-negative pathogens and Staphylococcus aureuswere common in both groups. The frequency of inappropriate empirical antimicrobial treatment was higher among older persons. Overall, in-hospital and 90-day mortality was high (age ≥ 75, 36.8%, age < 75, 24.7%, p = 0.14).Age was not significantly associated with mortality after adjustment for low Norton score, residence, and inappropriate antimicrobial therapy as well as resistance patterns of bloodstream isolates [OR = 1.2 (95% CI 0.4-3.3),p = 0.76]. Clinical characteristics and outcomes of CRBSI were comparable among old and young hemodialysis patients.However, the high mortality rate in this cohort suggests that the use of tunneled catheters as a permanent vascular access should be discouraged in both patient groups.

Clinical impact of the accelerate PhenoTest® BC system on patients with gram-negative bacteremia and high risk of antimicrobial resistance: a prospective before-after implementation study

BackgroundThe Accelerate PhenoTest® BC system (AXDX) is a novel assay for rapid bacterial identification and antimicrobial susceptibility (AST). We report an evaluation of its impact on treatment of patients with Gram-negative bacteremia (GNB) with a high risk of antimicrobial resistance (AMR).MethodsA prospective single-center evaluation before and after implementation of AXDX in addition to standard-of-care (SOC) microbiology and antimicrobial stewardship program (ASP). Patients with GNB reported during laboratory working hours and prespecified risk factors for AMR were included. The primary outcome was an ASP-oriented beneficial antimicrobial change, defined as either an escalation of an inappropriate empiric treatment or de-escalation of a broad-spectrum treatment of a susceptible organism. Main secondary outcomes were time to an appropriate treatment, antimicrobial treatment duration, length of stay (LOS) and mortality.ResultsIncluded were 46 and 57 patients in the pre- and post-intervention periods, respectively. The median time to an AST-oriented beneficial change was 29.2 h vs. 49.6 h, respectively (p < 0.0001). There were no significant differences in the time to appropriate treatment, LOS or mortality. Antimicrobial treatment duration was longer during the intervention period (10 vs. 8 days, p = 0.007). AXDX failed to correctly identify pathogens in all 6 cases of polymicrobial bacteremia. In two cases patient care was potentially compromised due to inappropriate de-escalation.ConclusionsAXDX implementation resulted in a 20.4-hour shorter time to an ASP-oriented beneficial antimicrobial change. This should be weighed against the higher costs, the lack of other proven clinical benefits and the potential harm from mis-identification of polymicrobial bacteremias.

A Retrospective Study of Staphylococcus aureus Bacteremia in a Tertiary Hospital and Factors Associated with Mortality.

Staphylococcus aureus bacteremia (SAB) is a severe infection frequently associated with significant morbidity and mortality. Recent studies have shown that SAB mortality has decreased during the last decades. However, about 25% of patients suffering from the disease will ultimately die. Hence, there is an urgent need for more timely and efficient treatment of patients with SAB. The aim of the present study was to retrospectively evaluate a cohort of SAB patients hospitalized in a tertiary hospital and to identify factors independently associated with mortality. All 256 SAB patients hospitalized from January 2005 to December 2021 in the University Hospital of Heraklion, Greece, were evaluated. Their median age was 72 years, while 101 (39.5%) were female. Most SAB patients were cared for in medical wards (80.5%). The infection was community-acquired in 49.5%. Among all strains 37.9% were methicillin-resistant S. aureus (MRSA), however, definite treatment with an antistaphylococcal penicillin was given only in 22% of patients. Only 14.4% of patients had a repeat blood culture after the initiation of antimicrobial treatment. Infective endocarditis was present in 8%. In-hospital mortality has reached 15.9%. Female gender, older age, higher McCabe score, previous antimicrobial use, presence of a central venous catheter, neutropenia, severe sepsis, septic shock, and MRSA SAB were positively associated with in-hospital mortality, while monomicrobial bacteremia was negatively associated. The multivariate logistic regression model identified only severe sepsis (p = 0.05, odds ratio = 12.294) and septic shock (p = 0.007, odds ratio 57.18) to be independently positively associated with in-hospital mortality. The evaluation revealed high rates of inappropriate empirical antimicrobial treatment and non-adherence to guidelines, as shown, by the lack of repeat blood cultures. These data underline the urgent need for interventions with antimicrobial stewardship, increased involvement of infectious diseases physicians, educational sessions, and creation and implementation of local guidelines for improvement of the necessary steps for timely and efficient SAB treatment. Optimization of diagnostic techniques is needed to overcome challenges such as heteroresistance that may affect treatment. Clinicians should be aware of the factors associated with mortality in patients with SAB to identify those who are at a higher risk and optimize medical management.

Risk Factors and outcomes associated with inappropriate empiric broad-spectrum antibiotic use in hospitalized patients with community-acquired pneumonia

Background: Inappropriate broad-spectrum antibiotic use targeting methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa can result in increased adverse events, antibiotic resistance, and Clostridioides difficile infection. In 2019, revised ATS/IDSA community-acquired pneumonia (CAP) guidelines removed healthcare-associated pneumonia (HCAP) as a clinical entity and modified patient factors warranting empiric broad-spectrum antibiotic (BSA) use. As a result, most patients hospitalized with CAP should receive empiric antibiotics targeting standard CAP pathogens. Based on revised guidelines, we evaluated predictors and outcomes associated with inappropriate BSA use among hospitalized patients with CAP. Methods: Between November 2019 and July 2022, trained abstractors collected data on non-ICU adult medical patients admitted with CAP at 67 Michigan hospitals who received either an inappropriate empiric BSA on hospital day 1 or 2 or a standard CAP regimen. Inappropriate empiric BSA use was defined as use of an anti-MRSA or anti-pseudomonal antibiotic in a patient eligible for standard CAP coverage per IDSA guidelines. Patients with immune compromise, moderate or severe chronic obstructive pulmonary disease (COPD), pulmonary complication, or guideline-concordant treatment with BSA were excluded. Data collected included comorbidities, antibiotic use and hospitalizations in the preceding 90 days, cultures in the preceding year, signs or symptoms of pneumonia, hospital characteristics, and 30-day postdischarge patient outcomes. Data were collected through chart review and patient phone calls. Predictors of inappropriate empiric BSA were evaluated using logistic general estimating equation (GEE) models, accounting for hospital-level clustering. We assessed the effect of inappropriate empiric BSA (vs standard CAP therapy) on 30-day patient outcomes using logistic GEE models controlling for predictors associated with the outcome and probability of treatment. Results: Of 8,286 included patients with CAP, 2,215 (26.7%) were empirically treated with inappropriate BSA. The median BSA treatment was 3 days (IQR, 2.5). After adjustments, factors associated with inappropriate empiric BSA treatment included hospitalization or treatment with high-risk antibiotics in preceding 90 days, transfer from a postacute care facility, hemodialysis, support with ≥3 L supplemental oxygen, severe sepsis, leukocytosis, and higher pneumonia severity index (Fig. 1). After adjustments, patients with inappropriate empiric BSA treatment had higher readmissions 30 days after discharge, more transfers to the intensive care unit, more antibiotic-associated adverse events, and longer hospitalizations (Fig. 2). Conclusions: Patients hospitalized with CAP often received inappropriate BSA as empiric coverage, and this inappropriate antibiotic selection was associated with worse patient outcomes. To improve patient outcomes, stewardship efforts should focus on reducing inappropriate BSA use in patients hospitalized for CAP with historic HCAP risk factors or severe CAP without other guideline-directed indications for BSA.Financial support. H.M.S. initiative is underwritten by Blue Cross and Blue Shield of Michigan.Disclosures: None

Risk factors associated with inappropriate empirical antimicrobial treatment in bloodstream infections. A cohort study.

Introduction: Bloodstream infections (BSI) are a major cause of mortality all over the world. Inappropriate empirical antimicrobial treatment (i-EAT) impact on mortality has been largely reported. However, information on related factors for the election of i-EAT in the treatment of BSI in adults is lacking. The aim of the study was the identification of risk-factors associated with the use of i-EAT in BSI. Methods: A retrospective, observational cohort study, from a prospective database was conducted in a 400-bed acute-care teaching hospital including all BSI episodes in adult patients between January and December 2018. The main outcome variable was EAT appropriation. Multivariate analysis using logistic regression was performed. Results: 599 BSI episodes were included, 146 (24%) received i-EAT. Male gender, nosocomial and healthcare-associated acquisition of infection, a high Charlson Comorbidity Index (CCI) score and the isolation of multidrug resistant (MDR) microorganisms were more frequent in the i-EAT group. Adequation to local guidelines' recommendations on EAT resulted in 91% of appropriate empirical antimicrobial treatment (a-EAT). Patients receiving i-EAT presented higher mortality rates at day 14 and 30 when compared to patients with a-EAT (14% vs. 6%, p = 0.002 and 22% vs. 9%, p < 0.001 respectively). In the multivariate analysis, a CCI score ≥3 (OR 1.90 (95% CI 1.16-3.12) p = 0.01) and the isolation of a multidrug resistant (MDR) microorganism (OR 3.79 (95% CI 2.28-6.30), p < 0.001) were found as independent risk factors for i-EAT. In contrast, female gender (OR 0.59 (95% CI 0.35-0.98), p = 0.04), a correct identification of clinical syndrome prior to antibiotics administration (OR 0.26 (95% CI 0.16-0.44), p < 0.001) and adherence to local guidelines (OR 0.22 (95% CI 0.13-0.38), p < 0.001) were identified as protective factors against i-EAT. Conclusion: One quarter of BSI episodes received i-EAT. Some of the i-EAT related factors were unmodifiable (male gender, CCI score ≥3 and isolation of a MDR microorganism) but others (incorrect identification of clinical syndrome before starting EAT or the use of local guidelines for EAT) could be addressed to optimize the use of antimicrobials.

Intensive care unit-acquired pneumonia caused by Klebsiella pneumoniae in China: Risk factors and prediction model of mortality.

Intensive care unit (ICU)-acquired pneumonia (ICUAP) is a major concern owing to its associated high mortality rate. Few studies have focused on ICUAP caused by Klebsiella pneumoniae (KP). This study aimed to investigate the risk factors for ICUAP-associated death due to KP and to develop a mortality prediction model. Patients with KP-associated ICUAP at Renji Hospital were enrolled from January 2012 to December 2017. The patients were registered from the ICU units of the Surgery, Gynecology and Obstetrics, Neurosurgery, Emergency and Geriatric Departments, and were followed for 30 days. A multivariate analysis was performed to analyze the differences between 30-day survivors and nonsurvivors, and to determine the independent risk factors. Receiver operator characteristic (ROC) curves were also used to determine the predictive power of the model. Among the 285 patients with KP-associated ICUAP, the median age was 70.55 years, and 61.6% were men. Fifty patients died. The nonsurvivors had a lower Glasgow coma score (GCS), platelet count, and albumin concentrations, but higher lactate concentrations, than the survivors. The nonsurvivors were also more likely to be admitted to the ICU for respiratory failure and surgery, and they received less appropriate empirical antimicrobial therapy than the survivors. A lower GCS (odds ratio [OR] = 0.836, 95% confidence interval [CI]: 0.770-0.907), lower albumin concentrations (OR = 0.836, 95% CI: 0.770-0.907), higher lactate concentrations (OR = 1.167, 95% CI: 1.0013-1.344) and inappropriate empirical treatment (OR = 2.559, 95% CI: 1.080-6.065) were independent risk factors for mortality in patients with KP-associated ICUAP. ROC curve analysis showed that the risk of death was higher in patients with 2 or more independent risk factors. The predictive model was effective, with an area under the ROC curve of 0.823 (95% CI: 0.773-0.865). The number of independent risk factors is positively correlated with the risk of death. Our model shows excellent predictive performance.

Phenotypic and genotypic antibiotic susceptibility profiles of Gram-negative bacteria isolated from bloodstream infections at a referral hospital, Lusaka, Zambia.

Bloodstream infections (BSI) caused by antimicrobial-resistant (AMR) Gram-negative bacteria (GNB) are a significant cause of morbidity and mortality. Third-generation cephalosporins (3GCs) have been used as empiric treatment for BSI and other invasive infections for years; however, their overuse could promote the emergence of extended-spectrum beta-lactamases (ESBLs). Thus, this study aimed to determine the epidemiological, clinical and microbiological features and the effects of antimicrobial resistance on the outcomes of BSIs at a referral hospital in Lusaka, Zambia. This was a six-month prospective facility-based study undertaken at a referral hospital in Lusaka, Zambia. As part of the routine diagnosis and patient care, blood samples for bacteriological culture were collected from patients presenting with fever and processed for pathogen identification and antimicrobial susceptibility testing using the VITEK 2 Compact instrument. ESBLs and plasmid-mediated quinolone resistance (PMQR) associated genes were determined using the polymerase chain reaction method. Patient information was collected using a structured data collection sheet and entered in CSpro 7.6. Data were analysed in WHOnet and STATA version 14. A total of 88 GNB were isolated, of which 76% were Enterobacterales, 14% Acinetobacter baumannii and 8% Pseudomonas aeruginosa. Resistance to third and fourth-generation cephalosporins was 75% and 32%, respectively. Noteworthy was the high prevalence (68%) of inappropriate empirical treatment, carbapenem resistance (7%), multi-drug resistance (83%) and ESBL-producers (76%). In comparison to E. coli as a causative agent of BSI, the odds of death were significantly higher among patients infected with Acinetobacter baumannii (OR = 3.8). The odds of death were also higher in patients that received 3GCs as empiric treatment than in those that received 4GCs or other (none cephalosporin) treatment options. Structured surveillance, yearly antibiogram updates, improved infection control and a well functional antimicrobial stewardship (AMS) program, are of utmost importance in improving appropriate antimicrobial treatment selection and favourable patient outcomes.

Economic burden of antimicrobial resistance and inappropriate empiric treatment in Thailand.

To quantify the economic burden of bacterial antimicrobial resistance in Thailand and estimate potential savings from improving the rate of appropriate empiric treatment, where effective coverage is provided within the first days of infection. Cost-of-illness study. A cost-calculator, decision-tree model was developed using published data and records from 3 Thai hospitals for patients hospitalized with antimicrobial-resistant infections between 2015 and 2019. Direct and indirect costs of antimicrobial-resistant infections were assessed over a 5-year time horizon, with outcomes derived separately for cases having received appropriate empiric treatment versus inappropriate empiric treatment. In a real-world scenario, outcomes were estimated using actual rates of inappropriate empiric treatment, and in a hypothetical scenario, outcomes were estimated using decreased rates of inappropriate empiric treatment. Over 5 years, in-hospital antimicrobial-resistant infections produced costs of approximately Thai baht (THB) 66.4 billion (USD 2.1 billion) in the real-world scenario and THB 65.8 billion (USD 2.1 billion) in the hypothetical scenario (0.9% cost savings relative to the real-world scenario). Most costs were attributable to income loss due to in-hospital mortality (real world: THB 53.7 billion [USD 1.7 billion]; 80.9% of costs; hypothetical: THB 53.2 billion [USD 1.7 billion]; 80.8% of costs) and hospitalization (real world: THB 10.3 billion [USD 330.8 million]; 15.5% of costs; hypothetical: THB 10.2 billion [USD 328.9 million]; 15.5% of costs). In-hospital antimicrobial-resistant infections produced a substantial economic toll in Thailand. This public health burden could be reduced with a strategy aimed at decreasing the rate of patients receiving inappropriate empiric treatment.

Survey of healthcare providers' testing practices for vulvovaginal candidiasis and treatment outcomes-United States, 2021.

Vulvovaginal candidiasis (VVC) is a common infection, and high-quality studies report that misdiagnosis is frequent, with diagnostic testing needed to distinguish it from other causes of vaginitis and avoid inappropriate empiric treatment. However, few recent studies have evaluated U.S. healthcare providers' testing practices for VVC in detail. We evaluated healthcare providers' self-reported testing practices for VVC and treatment outcomes as part of a nationwide online survey in order to identify potential opportunities for improving VVC testing and treatment in the United States. Among 1,503 providers surveyed, 21.3% reported "always" (7.4%) or "usually" (13.9%) ordering diagnostic testing for patients with suspected VVC; this proportion was higher among gynecologists (36.0%) compared with family practitioners (17.8%) and internists (15.8%). Most providers (91.2%) reported that patients' VVC "always" (6.4%) or "usually" (84.9%) responds to initial treatment. Whether the symptom resolution reported in this survey was truly related to VVC is unclear given high rates of misdiagnosis and known widespread empiric prescribing. With only about one-in-five providers reporting usually or always performing diagnostic testing for VVC despite guidelines recommending universal use, research is needed to address barriers to proper testing.

Current treatment of nosocomial pneumonia and ventilator-associated pneumonia.

Hospital-acquired pneumonia and ventilator-associated pneumonia are severe nosocomial infections leading to high morbidity and mortality. Broad-spectrum antibiotics with coverage against all likely pathogens are recommended by the international guidelines. Inappropriate empirical treatment is one of the most important prognostic factors. Knowledge of local epidemiology and continuous microbiological surveillance is crucial for improving clinical approaches to empirical antimicrobial treatment. The development of protocols and policies for training healthcare professionals on preventive strategies, such as the "Pneumonia Zero" project, and improved implementation of antimicrobial stewardship practices, will aid early de-escalation of antibiotics and prevent resistance.

The risk of inappropriate empiric treatment and its outcomes based on pathogens in non-ventilated (nvHABP), ventilated (vHABP) hospital-acquired and ventilator-associated (VABP) bacterial pneumonia in the US, 2012–2019

BackgroundInappropriate empiric antimicrobial treatment (IET) contributes to worsened outcomes. While IET’s differential impact across types of nosocomial pneumonia (NP: non-ventilated [nvHABP], ventilated [vHABP] hospital-acquired and ventilator-associated [VABP] bacterial pneumonia) is established, its potential interaction with the bacterial etiology is less clear.MethodsWe conducted a multicenter retrospective cohort study in the Premier Healthcare Database using an administrative algorithm to identify NP. We paired respective pathogens with empiric treatments. Antimicrobial coverage was appropriate if a drug administered within 2 days of infection onset covered the recovered organism(s). All other treatment was IET.ResultsAmong 17,819 patients with NP, 26.5% had nvHABP, 25.6% vHABP, and 47.9% VABP. Gram-negative (GN) organisms accounted for > 50% of all infections. GN pathogens were ~ 2 × as likely (7.4% vHABP to 10.7% nvHABP) to engender IET than Gram-positive (GP, 2.9% vHABP to 4.9% nvHABP) pathogens. Although rare (5.6% nvHABP to 8.3% VABP), GN + GP infections had the highest rates of IET (6.7% vHABP to 12.9% nvHABP). Carbapenem-resistant GNs were highly likely to receive IET (33.8% nvHABP to 40.2% VABP). Hospital mortality trended higher in the IET group, reaching statistical significance in GN + GP vHABP (47.8% IET vs. 29.3% non-IET, p = 0.016). 30-day readmission was more common with IET (16.0%) than non-IET (12.6%, p = 0.024) in GN VABP. Generally post-infection onset hospital length of stay and costs were higher with IET than non-IET.ConclusionsIET is ~ 2 × more common in GN than GP infections. Although the magnitude of its impact varies by NP type, IET contributes to worsened clinical and economic outcomes.

Inappropriate empirical antimicrobial treatment in bloodstream infections patients in the era of multidrug resistance

Background and objectives: Bloodstream infection (BSI) by multidrug-resistant Pseudomonas aeruginosa is a severe infection. This study aimed to evaluate and identify the predictors of mortality in patients who had bloodstream infection by carbapenem-resistant P. aeruginosa. Methods: This is a retrospective cohort study, approved by Committee of Ethics in Research with Human Participants, which included 87 consecutive patients hospitalized in a referral hospital in Brazil. Clinical and demographic information about each patient were obtained from hospital records. The Student’s T-test was used to compare continuous variables and x2 or Fisher’s exact tests to compare categorical variables. To determine independent risk factors for 30-day mortality, a multiple logistic regression model was used. A survival curve was constructed using the Kaplan–Meier method. Results: Among the patients, 87.3% use antibiotics previously, 60.9% received inadequate empirical treatment, and the 30-day mortality rate was 57.5%. Inappropriate antibiotic empirical therapy was independently associated with a 30-days death and mortality rate. Conclusion: These findings can show some insights about the relationship between higher mortality and inappropriate empirical therapy for patients with BSI by P. aeruginosa. There is a need for better diagnostic tests and infection control programs should focus on de-escalation the antibiotic inappropriate therapy, mainly in BSI caused by carbapenem-resistant P. aeruginosa.

Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project.

ABSTRACTBiliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score ≤ 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected.IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score.

Clinical Characteristics, Outcomes, and Risk Factors for Mortality in Patients with Stenotrophomonas maltophilia Bacteremia.

This study aimed to establish the clinical features, outcomes, and factors associated with mortality in patients with Stenotrophomonas maltophilia (S. maltophilia) septicemia. The characteristics and outcome data used in this retrospective study were collected from medical records at Songklanagarind Hospital. Risk factors for survival were analyzed using χ2-tests, Kaplan–Meier curves, and Cox regression. A total of 117 patients with S. maltophilia bacteremia were analyzed. The patients’ median age was 45 years, 77 (70%) were male, 105 (90%) had comorbidities, 112 (96%) had previously undergone carbapenem therapy, and over half of the patients were on invasive medical devices. Trimethoprim-sulfamethoxazole (TMP-SMX) and fluoroquinolone showed high susceptibility rates to S. maltophilia, with 93% and 88% susceptibility, respectively. Patients who received appropriate empirical antibiotic treatment had significantly reduced 14-day, 30-day, and in-hospital mortality rates than those who did not (p < 0.001). The days of hospital stay and costs for those who received appropriate and inappropriate empirical antimicrobial treatment were 21 and 34 days (p < 0.001) and 142,463 and 185,663 baht, respectively (p < 0.002). Our results suggest that an appropriate empirical antibiotic(s) is significantly associated with lower 30-day mortality in hospitalized patients with S. maltophilia septicemia.