Inappropriate Antimicrobial Treatment Research Articles

A One Health perspective on the use of genotypic methods for antimicrobial resistance prediction.

Antimicrobial resistance is a global One Health concern with critical implications for the health of humans, animals, and the environment. Phenotypic methods of bacterial culture and antimicrobial susceptibility testing remain the gold standards for the detection of antimicrobial resistance and appropriate patient care; however, genotypic-based methods, such as PCR, whole genome sequencing, and metagenomic sequencing, for detection of genes conferring antimicrobial resistance are increasingly available without inclusion of appropriate standards for quality or interpretation. Misleading test results may lead to inappropriate antimicrobial treatment and, in turn, poor patient outcomes and the potential for increased incidence of antimicrobial resistance. This article explores the current landscape of clinical and methodological aspects of antimicrobial susceptibility testing and genotypic antimicrobial resistance test methods. Additionally, it describes the limitations associated with employing genotypic-based test methods in the management of veterinary patients from a One Health perspective. The companion Currents in One Health by Maddock et al, AJVR, March 2024, addresses current and future needs for veterinary antimicrobial resistance research.

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.

P18 Treatment patterns and extent of inappropriate antimicrobial treatment among female patients with uncomplicated urinary tract infection in England

P18 Treatment patterns and extent of inappropriate antimicrobial treatment among female patients with uncomplicated urinary tract infection in England

Discernment of Acinetobacter Species in World Scenario

The morphology of Acinetobacter species is Gram-negative, nonmotile, nonfermenting, Strictly aerobic, Oxidase negative, and Catalase positive. It usually results from an infectious agent and is nonpathogenic in healthy people. A. baumannii can survive, for a long time and spread quickly in a hospital setting. Acinetobacter baumannii can cause many infections, the most common of which are bloodstream infections and nosocomial pneumonia in severe patients. These infections have a high mortality rate &amp; the global emergence of antibiotic-resistant strains from multiple classes has- reduced the number of drugs that still have activity against this pathogen. The lack of A. baumannii isolates that produce carbapenemase in addition to having a minimal inhibitory concentration of imipenem greater than carbapenem resistance. The overview of the prevalence of Acinetobacter in the Indian scenario and world scenario. Comparision between carbapenem resistance and multidrug resistance. According to the studies, carbapenem resistance is rapidly increasing. Infection with Acinetobacter is linked to high mortality and morbidity. According to our review, patients who have an infection with A. baumannii may be at an increased risk of dying. However, due to the confounding factors of illness severity, inappropriate impractical antimicrobial treatment, and small sample size, cautious interpretations are necessary. We covered the main factor that make A. baumannii such a prevalent nosocomial pathogen in this review, including such as its virulence components, desiccation resistance, and carbapenem resistance mechanisms. With the emergence of extended resistance to even more recent antibiotics, Acinetobacter species are rapidly proliferating. They can develop resistance much more quickly than other gram-negative organisms.

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID–IRI study

Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management. The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n=117, 27.1%), Klebsiellae (n=95, 22% %), Pseudomonadaceae (n=63, 14.6%), Coagulase-negative Staphylococci (n=57, 13.2%), Staphylococcus aureus (n=30, 7%), and Enterococci (n=21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.

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.

Bacteremia caused by Aeromonas species in patients with cancer: Clinical manifestations and outcomes.

Oncologic patients can have severe infections due to Aeromonas. This study aims to investigate the clinical characteristics and outcomes of cancer patients with bloodstream infections (BSI) caused by Aeromonas. We included patients with bacteremia caused by Aeromonas species from 2011 to 2018. Seventy-five BSI events in the same number of patients were identified. Forty patients were men (53.3%); the mean age was 49 years (IQR 28-61). A. caviae was the most frequent isolate (n = 29, 38.6%), followed by A. hydrophila (n = 23, 30.6%), A. sobria (n = 15, 20%), and A. veronii (n = 8, 10.6%). The most frequent underlying diagnosis was hematologic malignancy (n = 33, 44%), followed by breast cancer (n = 12, 16%) and gastrointestinal tract cancer (n = 8, 10.6%). The most frequent type of bacteremia was CRBSI in 32 cases (42.6%), followed by mucosal barrier injury-laboratory confirmed BSI (n = 20, 26.7%). Sixteen (26.2%) were hospital-acquired BSI. Attributable mortality occurred in 11 patients (14.6%). In univariate analysis A. hydrophila bacteremia, liver failure, skin/soft tissue infection, septic shock, inappropriate antimicrobial treatment, and relapse or cancer progression were associated with 30-day mortality. In multivariate analysis, only septic shock, inappropriate antimicrobial treatment, and relapse or cancer progression were associated with 30-day mortality. Aeromonas species should be considered one of the causative pathogens of healthcare-associated bacteremia, especially in immunocompromised patients. In addition, it can be associated with high fatality, particularly in patients with severe clinical infections.

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.

Utility of the BioFire® FilmArray® Pneumonia Panel plus assay for syndromic testing of lower respiratory tract infections in a low/middle-income setting.

Determining lower respiratory tract infection (LRTI) aetiology is complex. Culture-based methods are laborious with poor sensitivity. Molecular assays improve detection of potential pathogens, but incorrect interpretation of results may lead to inappropriate antimicrobial therapy. The utility of the BioFire® FilmArray® Pneumonia Panel plus (FA-PP) to detect LRTI pathogens, and the potential impact on antimicrobial stewardship in a low-resource setting, were assessed. Routine LRT samples were included from adult patients with clinically suspected LRTI or with a concomitant blood culture at Groote Schuur Hospital and referring facilities. Culture and FA-PP results were compared, and pharmacy data analysed to determine appropriateness of antibiotic therapy. There was an 80% correlation between cultured LRTI pathogens and the FA-PP bin ≥107 results. Compared with culture, the FA-PP detected substantially more pathogens (86.6% versus 17.9%) and produced a combined 100% positive percent agreement, and 88% negative percent agreement. The FA-PP detected bacterial/viral coinfections in 27% of samples. Correlation of FA-PP results with pharmacy data (n = 69) indicated a potential antibiotic change in 75% of cases, but this is difficult to accurately characterize without a 'gold standard' for treatment or complete clinical data. The FA-PP increased the number of positive samples with typical bacteria, but the semi-quantitative reporting algorithm does not describe the correlation between the different bin values and colonization versus infection. This complicates result interpretation and may lead to inappropriate antimicrobial treatment. This study highlights the potential positive impact of rapid molecular assays for routine care in lower-income settings, but also underscores the interpretive challenges associated with these tests.

1832. Epidemiology, risk factors for mortality and resistance associated with Stenotrophomonas maltophilia bacteremia at a tertiary care hospital in Korea over 7 years

Abstract Background Stenotrophomonas maltophilia (SM) is an important emerging nosocomial pathogen. This study aimed to describe the epidemiological, clinical, and microbiological charateristics of SM bacteremia at a tertiary care hospital in Korea over 7 years. Methods A retrospective study was conducted at a 1150-bed tertiary care hospital in Busan, South Korea. Data were collected between January, 2013 and November, 2019. Results A total of 79 bacteremia patients (median age: 61 years; 62% males) were reviewed; 38 (48.1%) were in 2013-2016 and 41 (51.9%) were in 2017-2019. The overall SM bacteremia-related 30-days mortality was 31.6%. Susceptibility to levofloxacin, sulfamethoxazole-trimethoprim (SMX/TMP) and minocycline were 87.3%, 92.4% and 100%, respectively. The most common clinical syndrome was central line-associated bloodstream infection (n=37, 46.8%). The others were intra-abdominal infection (n=18, 22.8%), skin and soft tissue infection (n=5, 6.3%) and pneumonia (n=5, 6.3%). In 50.6%, SM was the only pathogen of bacteremia, whereas in 49.4%, more than one causative organisms were isolated. Acinetobacter baumanii (in 8 cases) was the most frequent co-isolated pathogen, followed by Enterococcus faecium (in 6 cases), Pseudomonas aeruginosa (in 5 cases), Staphylococcus epidermidis (in 5 cases), Enterococcus gallinarum (in 3 cases) and Klebsiella pneumoniae (in 3 cases). Age (OR, 6.60; 95% Cl, 1.59-27.41; P = 0.009), inappropriate antimicrobial treatment (OR, 3.47; 95% Cl, 1.14-10.56; P = 0.029), and levofloxacin-resistant strains (OR, 7.86; 95% Cl, 1.20-51.41; P = 0.031) were independent risk factors for SM bacteremia-related 30-days mortality in multivariate analysis. Conclusion SM bacteremia has a high early mortality rate. In our study, old age, inappropriate antimicrobial treatment and levofloxacin-resistant strains were significant independent risk factors for early mortality in SM bacteremia patients. Early diagnosis and immediate use of appropriate antibiotics are recommended to improve mortality of SM bacteremia. Disclosures All Authors: No reported disclosures.

Why Are We Frequently Ordering Urinalyses in Patients without Symptoms of Urinary Tract Infections in the Emergency Department?

(1) Background: In the emergency department (ED), ordering urine tests in patients without symptoms of a urinary tract infection can lead to inappropriate antimicrobial treatment. We aimed to identify factors contributing to the unnecessary ordering of urinalyses in the ED. (2) Methods: An online survey study among nurses and physicians working in the EDs of five hospitals in the Netherlands was conducted. (3) Results: The overall response rate was 26% (221/850; 85 nurses and 136 physicians). The vast majority of the respondents reported knowing when to order urine tests (197/221; 90%). Almost two-thirds of the respondents (145/221; 66%) agreed that they ordered urinalyses because it is rapid and non-invasive to patients. Most nurses (66/86; 78%) said they informed the doctor if they thought the urine test would not contribute to the patient’s diagnosis, but only one-third of the physicians agreed with this statement (44/136; 32%). Most respondents (160/221; 72%) thought guidelines or protocols about urinalyses in the ED would be functional. (4) Conclusions: These results suggest urinalyses were frequently ordered in the ED to achieve a fast work process. Nurses and physicians could improve their communication about the indications for urine tests. Developing diagnostic guidelines for urine testing may be convenient.

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.

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.

In Vitro Selective Antibacterial and Antiproliferative Effects of Ethanolic Extracts from Cambodian and Philippine Plants Used in Folk Medicine for Diarrhea Treatment.

Bacterial diarrhea remains a global health problem, especially in developing tropical countries. Moreover, dysbiosis caused by diarrheagenic bacteria and inappropriate antimicrobial treatment has been associated with intestinal carcinogenesis. Despite the rich tradition of the use of herbs for the treatment of gastrointestinal disorders in Cambodian and Philippine folk medicine, many of them have not yet been systematically studied for their in vitro selective inhibitory effects on intestinal bacteria and cells. In the present study, in vitro inhibitory activities of 35 ethanolic extracts derived from 32 Cambodian and Philippine medicinal plants were determined by broth microdilution method against 12 pathogenic bacteria. Furthermore, cytotoxicity against intestinal cancer cells (Caco-2 and HT-29) using thiazolyl blue tetrazolium bromide cytotoxicity assay and safety to six beneficial intestinal bacteria (bifidobacteria and lactobacilli) and intestinal normal cells (FHs 74 Int) were determined for the antimicrobially active extracts. Selectivity indices (SIs) were calculated among the averages of minimum inhibitory concentrations (MICs), half-maximal inhibitory concentrations (IC50), and 80% inhibitory concentrations of proliferation (IC80) for each type of the tested agents. The extracts of Artocarpus blancoi (Elmer) Merr. (Moraceae), Ancistrocladus tectorius (Lour.) Merr. (Ancistrocladaceae), and Pentacme siamensis (Miq.) Kurz (Dipterocarpaceae) produced significant growth-inhibitory effects (MICs = 32–512 μg/ml) against intestinal pathogenic bacteria at the concentrations nontoxic to normal intestinal cells (IC80 values >512 μg/ml; SIs = 0.11–0.2). Moreover, the extract of P. siamensis (Miq.) Kurz was relatively safe to beneficial bacteria (MICs ≥512 μg/ml; SI = 0.1), and together with A. blancoi (Elmer) Merr., they selectively inhibited intestinal cancer cells (IC50 values ≥51.98 ± 19.79 μg/ml; SIs = 0.3 and 0.6). Finally, a strong selective antiproliferative effect on cancer cells (IC50 values 37.89 ± 2.68 to 130.89 ± 13.99 μg/ml; SIs = 0.5) was exerted by Ehretia microphylla Lam. (Boraginaceae), Lagerstroemia cochinchinensis Pierre ex Gagnep. (Lythraceae), and Melastoma saigonense (Kuntze) Merr. (Melastomataceae) (leaves with flower buds). The results suggest that the above-mentioned species are promising materials for the development of new selective antibacterial and antiproliferative agents for the treatment of infectious diarrhea and associated intestinal cancer diseases. However, further research is needed regarding the isolation and identification of their active constituents.

Risk of Hemolytic Uremic Syndrome Related to Treatment of Escherichia coli O157 Infection with Different Antimicrobial Classes.

Treatment of Shiga toxin-producing Escherichia coli O157 (O157) diarrhea with antimicrobials might alter the risk of hemolytic uremic syndrome (HUS). However, full characterization of which antimicrobials might affect risk is lacking, particularly among adults. To inform clinical management, we conducted a case-control study of residents of the FoodNet surveillance areas with O157 diarrhea during a 4-year period to assess antimicrobial class-specific associations with HUS among persons with O157 diarrhea. We collected data from medical records and patient interviews. We measured associations between treatment with agents in specific antimicrobial classes during the first week of diarrhea and development of HUS, adjusting for age and illness severity. We enrolled 1308 patients; 102 (7.8%) developed confirmed HUS. Antimicrobial treatment varied by age: <5 years (12.6%), 5–14 (11.5%), 15–39 (45.4%), ≥40 (53.4%). Persons treated with a β-lactam had higher odds of developing HUS (OR 2.80, CI 1.14–6.89). None of the few persons treated with a macrolide developed HUS, but the protective association was not statistically significant. Exposure to “any antimicrobial” was not associated with increased odds of HUS. Our findings confirm the risk of β-lactams among children with O157 diarrhea and extends it to adults. We observed a high frequency of inappropriate antimicrobial treatment among adults. Our data suggest that antimicrobial classes differ in the magnitude of risk for persons with O157 diarrhea.

Secondary Infections After Diagnosis of Severe Radiation Pneumonitis (SRP) Among Patients With Non-Small Cell Lung Cancer: Pathogen Distributions, Choice of Empirical Antibiotics, and the Value of Empirical Antifungal Treatment

This study aimed to assess pathogen distributions and antimicrobial sensitivity characteristics in patients with non-small cell lung cancer (NSCLC) with severe radiation pneumonitis (SRP) and secondary infections. Data from 1746 patients with NSCLC and SRP after thoracic radiation therapy from January 2009 to December 2020 were retrospectively analyzed. Pneumonia incidence, causative pathogens, and antibiotic resistance characteristics in patients with secondary lung infections were analyzed. Risk factors associated with mortality were identified through univariate and multivariate analyses. Antifungal drug efficacy and duration-related effects were assessed with Forest plots and receiver operating characteristic curves. Overall, 44.5% of patients with NSCLC and SRP (777 of 1746 patients) were diagnosed with secondary lung infections. In total, 899 bacterial strains were isolated from these patients, with Acinetobacter baumannii (n=206; 27%), Klebsiella pneumonia (n=200; 26.2%), and Pseudomonas aeruginosa (n=104; 13.6%) being the most common. Carbapenem and cefoperazone-sulbactam resistance rates of 52.7% and 32.2%, 28.8% and 26.4%, and 23.7% and 20.2% were observed for these isolates, respectively. Infection-related deaths occurred in 22.4% of patients with SRP. Independent risk factors for infection-related death included poor performance status scores, inappropriate empirical antimicrobial treatment, bacteria/fungal coinfection, and lack of empirical antifungal treatment. Receiver operating characteristic curves showed that the cutoff value of empirical antifungal treatment duration was 9 (area under the curve: 0.819). For patients with SRP and secondary lung infections, appropriate empirical antimicrobial treatment could decrease infection-related mortality, and cefoperazone-sulbactam may be an appropriate antibacterial drug. Empirical antifungal treatment for a minimum of 9 days might contribute to better outcomes. Although this represents a promising treatment approach for patients with SRP and secondary lung infections before antibacterial susceptibility testing, further prospective validation is essential.

HB&L system for rapid phenotypic detection of clinical carbapenem-resistant Enterobacterales isolates

The prevalence of carbapenem-resistant Enterobacterales (CRE) has increased rapidly worldwide in the last two decades. CRE infection poses a huge challenge for today's clinical therapy. Rapid and accurate detection of clinical CRE isolates can avoid inappropriate antimicrobial treatment and reduce mortality. However, existing detection methods are either time consuming, expensive or inaccurate, making them unable to fully meet clinical demands. In this study, the HB&L system was designed to distinguish CRE from carbapenem-susceptible Enterobacterales (CSE), as it can accelerate the growth of bacteria, detect both carbapenemase-producing CRE (CP-CRE) and non-CP-CRE isolates in real time, and provide time-kill curves. The broth microdilution method and PCR and sequencing were used as the reference methods to identify CRE and carbapenemase-producing Enterobacterales (CPE) isolates, respectively. Three methods for detecting CRE isolates, including the Carba NP test, modified carbapenem inactivation method (mCIM) and HB&L system, were evaluated. The accuracy of the HB&L system was extremely high with 100% sensitivity and 96.0% specificity at only 6 h of culture time for detecting CRE. Time-kill curves may provide information on effective treatment options for clinicians. This system is superior to the mCIM (20-24 h detection time; 90.6% sensitivity and 96.6% specificity) and Carba NP test (2 h detection time; 85.2% sensitivity and 98.4% specificity), which are only designed to detect CP-CRE. The HB&L system is promising for wide application for detection of clinical CRE in hospitals.

Predictors of mortality in patients with carbapenem-resistant Klebsiella pneumoniae infection: a meta-analysis and a systematic review.

Cases of carbapenem-resistant Klebsiella pneumoniae infection have been increasing. Patients with carbapenem-resistant Klebsiella pneumoniae infection have a poor prognosis and a high mortality rate. Identification of potential risk factors associated with carbapenem-resistant Klebsiella pneumoniae infection-related mortality may help improve patient outcomes. Embase, PubMed, and the Cochrane Library databases were searched to identify articles describing predictors of mortality in patients with carbapenem-resistant Klebsiella pneumoniae infection. The quality of articles was assessed with the Newcastle-Ottawa Scale score (NOS). Review Manager was used for statistical analyses. Twenty-seven observational studies were included in the analysis. Factors associated with higher mortality were septic shock [odds ratio (OR): 4.41, 95% CI: 3.17-6.15], congestive heart failure (OR: 2.65, 95% CI: 1.71-4.13), chronic obstructive pulmonary disease (COPD; OR: 2.43, 95% CI: 1.87-3.15), chronic kidney disease (CKD; OR: 1.78, 95% CI: 1.43-2.22), diabetes mellitus (OR: 1.41, 95% CI: 1.16-1.72), mechanical ventilation (OR: 1.65, 95% CI: 1.25-2.18), and inappropriate empirical antimicrobial treatment (OR: 1.25, 95% CI: 1.03-1.52). The average Acute Physiology and Chronic Health Evaluation (APACHE) II score at the time of diagnosis of carbapenem-resistant Klebsiella pneumoniae infection was considerably higher in patients who did not survive than in those who survived (weighted mean difference: 5.86, 95% CI: 2.46-9.26). Patient condition, timing appropriate antimicrobial treatment, and disease severity according to the APACHE II score are the most important risk factors for death in patients with carbapenem-resistant Klebsiella pneumoniae infection. Our finding may help predict patients' outcomes and improve management for them. 20210417EuEGX/INPLASY2020100037.

Sepsis and septic shock – an observational study of the incidence, management, and mortality predictors in a medical intensive care unit

AimTo prospectively determine the number of patients with sepsis and septic shock in a medical intensive care unit (ICU) using the Sepsis-3 definition; to analyze patients' characteristics, clinical signs, diagnostic test results, treatment and outcomes; and to define independent risk factors for ICU mortality.MethodsThis prospective observational study enrolled all patients with the diagnosis of sepsis treated in the medical ICU of “Sestre Milosrdnice” University Hospital Center, Zagreb, between April 2017 and May 2018.ResultsOut of 116 patients with sepsis, 54.3% were female. The median age was 73.5 years (IQR 63-82). The leading source of infection was the genitourinary tract (56.9%), followed by the lower respiratory tract (22.4%). A total of 35.3% of the patients experienced septic shock. Total ICU mortality for sepsis was 37.9%: 63.4% in patients with septic shock and 24.0% in patients without shock. Independent risk factors for ICU mortality were reduced mobility level (odds ratio [OR] 11.16, 95% confidence interval [CI] 2.45-50.91), failure to early recognize sepsis in the emergency department (OR 6.59, 95% CI 1.09-39.75), higher Sequential Organ Failure Assessment score at admission (OR 2.37, 95% CI 1.59-3.52), and inappropriate antimicrobial treatment (OR 9.99, 95% CI 2.57-38.87).ConclusionWhile reduced mobility level and SOFA score are predetermined characteristics, early recognition of sepsis and the choice of appropriate antimicrobial treatment could be subject to change. Raising awareness of sepsis among emergency department physicians could improve its early recognition and increase the number of timely obtained specimens for microbial cultures.

Blood culture contamination in the emergency department: An integrative review of strategies to prevent blood culture contamination

BackgroundBlood culture collection remains the gold standard to diagnose bacteraemia. Current evidence suggests that the emergency department (ED) often has blood culture contamination (BCC) rates above the recommended 3%, contributing to increased hospital length of stay, unnecessary or inappropriate antimicrobial treatment, and increased economic burden. The aim of this review is to identify effective strategies to improve blood culture collection in EDs to decrease contamination rates and improve patient safety. MethodsAn integrative literature review methodology was utilised to conduct a structured search of contemporary literature using CINAHL, Embase, Medline, Pubmed and Scopus databases. All eligible literature was screened with those included in the final review collated and appraised using a quality assessment tool. ResultsEleven reports were included in the final review, which identified bundled approaches, education and feedback, equipment and technique, and stakeholder engagement as strategies that improve BCC rates in the ED. ConclusionsAll studies reported a reduction in BCC rates regardless of the strategies implemented. A bundled approach yielded the most significant results and was identified to be practical, inexpensive, and adaptable. Further research focusing on specific aspects of a bundled approach may be beneficial to understand which strategies are most effective.