Community-onset Infections Research Articles

Damage-associated molecular patterns in bacteraemic infection, including a comparative analysis with bacterial DNA, a pathogen-associated molecular pattern

Damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) are key triggers of inflammation in sepsis. However, they have rarely been studied simultaneously. Thus, in the present study of patients with bacteraemic infection, we aimed to study how DAMP dynamics are linked to disease severity and outcome and to compare diagnostic and prognostic properties of a DAMP and a previously analysed PAMP (16S rDNA). In a prospective study of adult patients hospitalized with culture-proven community-onset bacteraemic infection, caused by Streptococcus pneumonia (n = 30), Staphylococcus aureus (n = 27), or Escherichia coli (n = 26), dynamics of a PAMP, i.e. 16S rDNA, have previously been presented. For the present study, blood samples obtained on hospital days 1–2 (when blood culture was positive), 3–4, 7 ± 1, 14 ± 2, and 28 ± 4 were analysed for four different DAMPs, i.e., nuclear DNA (nDNA), mitochondrial DNA (mtDNA), heat shock protein 90 alpha (HSP90α), and extracellular high mobility group box 1 (HMGB1). Sepsis was defined according to the Sepsis-3 criteria. The study outcomes were sepsis at admission and negative outcome, defined as intensive care unit (ICU) admission and/or death within 60 days. Of 83 study patients, sepsis was noted in 41 patients (49%) and a negative outcome was noted in 17 patients (20%). nDNA had areas under the receiver operating characteristic (ROC) curves of 0.78 for sepsis and 0.76 for negative outcome, which were higher than those of the other DAMPs and additional biomarkers (CRP, IL-6, IL-8, and IL-10). The nDNA and positive 16S rDNA results on day 1–2 were correlated with each other (r = 0.68, p < 0.001). Multivariate analyses showed that high day 1–2 concentrations of both nDNA and 16S rDNA were independently associated with sepsis. In addition, high day 1–2 concentration of nDNA was independently associated with negative outcomes. While 16S rDNA dissipated from the circulation within days, nDNA concentrations remained elevated throughout the follow-up period in patients with negative outcome. In conclusion, nDNA outperformed the other DAMPs regarding sepsis detection and outcome prediction. Both nDNA (a DAMP) and 16S rDNA (a PAMP) were independently linked to sepsis; nDNA was also associated with negative outcomes and persisted elevated in such cases. This highlights nDNA as an interesting marker within sepsis pathogenesis and as a promising clinical biomarker, warranting further studies.

Risk factors and drug resistance of adult community-onset urinary tract infections caused by Escherichia coli-producing extended-spectrum β-lactamase in the Chongqing region, China: a retrospective case-control study.

To evaluate the prevalence, resistance and risk factors of community-onset urinary tract infections (COUTIs) caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) for providing a basis for the selection of clinical therapeutic agents. A retrospective case-control study. The Affiliated Dazu Hospital of Chongqing Medical University (also known as The People's Hospital of Dazu Chongqing), a 1000-bed tertiary hospital in China. This study encompassed adult patients diagnosed with community-acquired urinary tract infections (UTIs) caused by E. coli between May 2017 and December 2022 with exclusion criteria including incomplete clinical data, disagreement to participate in the study, hospitalisation duration exceeding 48 hours prior to confirmation of diagnosis and prior history of urinary tract infection caused by E. coli. The risk factors for COUTIs caused by ESBL-EC were evaluated using a case-control design, defining patients who were diagnosed with UTIs and had an ESBL-positive urine culture as the case group and patients who were diagnosed with UTIs and had an ESBL-negative urine culture as the control group. Perform drug susceptibility testing and resistance analysis on isolated ESBL-EC. In total, 394 cases of COUTIs caused by E. coli were included; 192 cases were ESBL-positive with a detection rate of 48.7% (192/394). Parenchymal tumour, history of urolithiasis stone fragmentation, history of urological surgery, hospitalisation within 6 months, indwelling catheter outside the hospital and antibiotic use (mainly third-generation cephalosporins) were the factors significantly associated with COUTIs caused by ESBL-EC (p<0.05) through logistic regression for univariate analysis. Multivariate analysis revealed that a history of urolithiasis stone fragmentation (OR=2.450; 95% CI: 1.342 to 4.473; p=0.004), urological surgery (OR=3.102; 95% CI: 1.534 to 6.270; p=0.002), indwelling catheter outside hospital (OR=2.059; 95% CI: 1.025 to 4.133; p=0.042), hospitalisation within 6 months (OR=2.127; 95% CI: 1.207 to 3.748; p=0.009) and use of third-generation cephalosporins (OR=1.903; 95% CI: 1.069 to 3.389; p=0.029) were the independent risk factors for COUTIs caused by ESBL-EC. The results of the drug susceptibility testing revealed that ESBL-EC exhibited the highest resistance rates to ampicillin, ceftriaxone and cefixime, all at 100%. Mezlocillin followed with a resistance rate of 98.7%. On the other hand, ESBL-EC strains displayed the highest sensitivity to carbapenem antibiotics (imipenem, meropenem, ertapenem) and amikacin, all at 100%. Sensitivity rates were also high for cefotetan at 96.6%, piperacillin/tazobactam at 95.3% and nitrofurantoin at 87.9%. Our results revealed high ESBL-EC detection rates. COUTIs caused by ESBL-EC are more likely to occur in patients with parenchymal tumour, a history of urolithiasis stone fragmentation, a history of urological surgery, hospitalisation within 6 months, indwelling catheter outside the hospital and use of third-generation cephalosporins. These patients were highly resistant to penicillins, cephalosporins and quinolones.

Effect of Universal Masking on Non-Severe Acute Respiratory Syndrome Coronavirus 2 Healthcare-Associated Respiratory Viral Infections.

Respiratory viral infections are common and are a major cause of morbidity and mortality. We evaluated the impact of universal masking implemented during the coronavirus disease 2019 (COVID-19) pandemic on other healthcare-associated respiratory viral infections (HA-RIs) in an academic medical center. A retrospective cohort study was performed among all inpatients aged ≥18 years admitted between 1 May 2019 and 30 June 2022. Universal masking was implemented in May 2020 at our hospital and state-level mask mandates had been lifted by May 2021. We evaluated and compared the HA-RI rates, adjusted for monthly community-onset viral infections, during the premasking period, universal masking period, and post-community mandate period. We identified 3015 patients (median age, 58 years; 48.0% males) with a positive respiratory viral test within 14 days prior to, or during, their hospitalization; 441 (14.6%) patients had an HA-RI. Rhinovirus/enterovirus (51.0%), parainfluenza virus (14.3%), coronaviruses (229E, OC43, HKU1, and NL63; 13.2%) and influenza (10.0%) were the predominant HA-RI viruses detected. The monthly HA-RI rate decreased 34.9% (95% confidence interval, 8.8%-51.8%) after the implementation of universal masking (0.71 premasking period vs 0.19 universal masking period vs 0.35 infections per 1000 patient-days in the post-community mandate period) while accounting for a drop in the community-onset respiratory viral infections using a structural time-series model analysis (P < .001), with no significant change in HA-RI rates with the relaxation of community masking mandate. Implementation of universal masking at our hospital was associated with a significantly reduced incidence of HA-RIs.

A simple scoring algorithm predicting paravertebral and/or iliopsoas abscess among adults with community-onset bloodstream infections: matters of PVL-producing Staphylococcus aureus

A simple scoring algorithm predicting paravertebral and/or iliopsoas abscess among adults with community-onset bloodstream infections: matters of PVL-producing Staphylococcus aureus

Analysis of bacteraemia caused by group C and G Streptococcus (Streptococcus dysgalactiae subsp. equisimilis) in Western Sydney over a 6-year period (2015-2020).

Streptococcus dysgalactiae subsp. equisimilis (SDSE) has increasingly been recognised as a significant pathogen that causes a myriad of infections, ranging from cellulitis to invasive infections, including bacteraemia and even toxic shock syndrome. The aim of this study was to examine the epidemiology and disease manifestations of bacteraemia caused by SDSE. We retrospectively reviewed cases of SDSE bacteraemia in adults aged ≥ 18 years admitted to four public hospitals in Western Sydney, Australia, between January 2015 and December 2020. We reviewed demographics, comorbidities, disease manifestations, management, and outcomes. There were 108 patients with SDSE bacteraemia over a six-year period. The median age of individuals with SDSE bacteraemia was 70 years (interquartile range, IQR, 58-85 years). Cardiovascular disease (46%), chronic skin conditions (44%) and diabetes (37%) were the most common comorbidities. Ten patients (9%) with SDSE bacteraemia had healthcare-acquired infections. Skin and skin structure infections (SSTIs) were the most common presentations (59%), while bone and joint infections (BJIs) represented 13% of the cases. Twenty patients (19%) had septic shock on presentation. Fifteen patients (14%) were prescribed clindamycin, while one patient received intravenous immunoglobulin (IVIg). Infective endocarditis (IE) was present in 3% of patients; however, only 44% of the total patients had an echocardiogram. The 30-day mortality rate was 13%, but it was greater in those aged > 75 years (21%). The average length of hospital stay for patients who survived was 15 days, and the average duration of intravenous therapy was 12 days. SDSE bacteraemia is typically a community-onset infection with a fifth of patients in our cohort presenting with septic shock. Though complications such as BJI (13%) and IE (3%) are infrequent, 30-day mortality is high at 21% in those aged > 75 years.

Clinical characteristics of community-onset Clostridioides difficile infections at a tertiary hospital in mainland China: A fourteen-year (2010–2023) retrospective study

BackgroundClostridioides difficile infection (CDI) is an increasingly common disease in healthcare facilities and community settings. However, there are limited reports of community-onset CDI (CO-CDI) in China. MethodsWe collected diarrheal stool samples from 3885 patients who went to outpatient department or emergency department in a tertiary hospital in China during 2010–2023, analyzed the correlation between patients’ basic information and the detection rate of CDI. Besides, all stool samples from 3885 outpatients included were tested by culturing. Moreover, we randomly selected 89 patients’ stools during the 14 years and isolated 126 C. difficile strains from them. The presence of toxin genes (tcdA, tcdB, cdtA, and cdtB) were confirmed by PCR. Toxigenic strains were typed using multilocus sequence typing (MLST). Susceptibility to 9 antimicrobials was evaluated using the E-test. Results528 of 3885 patients (13.6 %) with diarrhea were finally diagnosed as CDI. The median age of patients included was 51 years (6 months-95 years), while the median of patients with CDI was older than patients with negative results [55.5 years (6 months-93 years) vs. 50 years (9 months −95 years), p < 0.001]. In winter, patients with diarrhea might be more likely to have CDI. The detection rate of CDI of patients in emergency department was much higher than those in other outpatients (20.7 % vs. 12.4 %, p < 0.001), and did differ from each outpatient departments (p < 0.05). There were 95 isolated strains detected as toxigenic C. difficile. Among these strains, 82 (86.3 %) had the tcdA and tcdB genes (A+B+) and 5 of these 82 strains were positive for the binary toxin genes (cdtA and cdtB) (A+B+CDT+). There were 15 different sequence types (STs) by multilocus sequence typing (MLST), while the most ST was ST-54 (23.2 %). ST types composition was relatively stable over the time span of this study. Some strains had high resistance to ciprofloxacin, clindamycin, and erythromycin. Twenty-three isolates (24.2 %) were multidrug-resistant. ConclusionsOutpatients with CDI were common among patients having diarrhea during this period in our hospital. Elderly patients and patients went to emergency department may be susceptible to CDI. Based on MLST, the result revealed that the C. difficile isolates had high genetic diversity and maintained stability in this period. All isolates were susceptible to metronidazole and vancomycin, and nearly one quarter of all isolates had multidrug resistance.

Predictive biomarker of mortality in children with infectious diseases: a nationwide data analysis.

Biomarkers play a crucial role in the early identification of high-risk children with infectious diseases. Despite their importance, few studies evaluated biomarkers' capabilities in predicting mortality. The aim of this study was to evaluate the biomarkers' predictive capabilities for mortality in children with infectious diseases. From an inpatient database covering ≥200 acute-care hospitals in Japan, we included children who underwent blood culture, and received antimicrobial treatment between 2012 and 2021. Biomarkers' results from the day of the initial blood culture were used. Biomarker discriminative capabilities were assessed using the area under receiver operating characteristic curves (AUCs). Of 11,365 eligible children with presumed infection, 1,378 (12.1%) required mechanical ventilation or vasoactive agents within 2 days of blood culture, and 100 (0.9%) died during admission. Of all children, 10,348 (91.1%) had community-onset infections and 1,017 (8.9%) had hospital-onset infections. C-reactive protein and white blood cell demonstrated limited discriminatory capabilities with AUCs of 0.44 [95% confidence interval (CI): 0.38-0.51] and 0.45 (95% CI: 0.39-0.52). In contrast, pH, prothrombin time-international normalized ratio, and procalcitonin exhibited strong discriminatory capabilities with AUCs of 0.77 (95% CI: 0.65-0.90), 0.77 (95% CI: 0.70-0.84) and 0.76 (95% CI: 0.29-1.00). In conclusions, our real-world data analysis suggested that C-reactive protein and white blood cell may not be reliable indicators for predicting mortality in children with presumed infection. These findings could warrant future studies exploring promising biomarkers, including those from blood gas analyses, coagulation studies and procalcitonin.

Association between hospital-onset SARS-CoV-2 and ending universal admission testing and masking at five US hospitals

Background: Many US hospitals have stopped universal masking and testing all patients on admission for SARS-CoV-2. We assessed the association of ending universal masking and admission testing with the incidence of hospital-onset SARS-CoV-2 infections in five Massachusetts hospitals. Method: We conducted a retrospective study of all patients admitted between March 6, 2020 and December 14, 2023 and identified hospital-onset SARS-CoV-2 infections (newly positive SARS-CoV-2 PCR tests &gt;4d after arrival) and community-onset infections (newly positive ≤4d after arrival). We excluded cases if local infection control teams discontinued precautions within 4d (suggesting a false positive or remote/resolved infection). We calculated weekly ratios between hospital-onset and community-onset SARS-CoV-2 cases to account for changes in community SARS-CoV-2 incidence over time. We then performed interrupted time series analysis, looking for changes in the ratio of hospital-onset to community-onset cases across three periods: pre-Omicron period with universal testing and masking in place (March 6, 2020–Dec 16, 2021); Omicron period with universal testing and masking in place (Dec 17, 2021–May 11, 2023); and Omicron period without universal testing and masking (May 12, 2023–Dec 14, 2023). We performed medical record reviews on 100 randomly selected hospital-onset cases after May 12, 2023 to examine if community-onset cases were being misclassified as hospital-onset cases. Result: During the study period, there were 626,908 patient admissions, including 24,980 with community-onset and 1,510 with hospital-onset SARS-CoV-2 infections. The mean weekly ratio of new hospital-onset to community-onset SARS-CoV-2 infections rose from 2.6% before Omicron, to 8.5% (95% CI, 7.0–9.9%) during Omicron, to 17% (95% CI, 15–19%) after universal admission testing and masking ended (Figure 1). There was a significant immediate level change after the pre-Omicron-to-Omicron transition (140% relative increase; 95% CI, 40–240%) and after universal admission testing and masking ended (110% relative increase; 95% CI, 73–150%). On medical record review of 100 randomly selected hospital-onset SARS-CoV-2 cases after universal admission testing had ended, 89% had new symptoms at the time of testing, 80% had PCR cycle thresholds ≤30, 27% had a known COVID-19 exposure, and 97% met at least one of these criteria. In-hospital mortality occurred in 8% of the 100 reviewed cases. Conclusion: Stopping universal masking and admission testing of all hospitalized patients at five Massachusetts hospitals was associated with a significant increase in hospital-onset COVID-19. Nosocomial COVID-19 remains a common complication of hospital care. Preventing nosocomial infections in this vulnerable population remains an important safety goal.Disclosure: Theodore Pak: Founder/CEO - The East Harlem Software Company, Inc.

Urinary Tract Infections among Febrile Infants in Qatar: Extended-Spectrum-Beta-Lactamase (ESBL)-Producing Versus Non-ESBL Organisms.

The escalating prevalence of ESBL-producing Enterobacteriaceae in Qatar's pediatric population, especially in community-onset febrile urinary tract infections (FUTIs), necessitates a comprehensive investigation into this concerning trend. Over the course of one year, a total of 459 infants were diagnosed and subsequently treated for UTIs. Cases primarily occurred in infants aged over 60 days, predominantly non-Qatari females born from term pregnancies. Notably, E. coli and K. pneumoniae were the most frequently identified organisms, accounting for 79.7% and 9.8% in the ESBL group and 57.2% and 18.7% in the non-ESBL group, respectively. Interestingly, hydronephrosis emerged as the most prevalent urological anomaly detected in both ESBL (n = 10) and other organism (n = 19) groups. In this retrospective cohort study conducted in Qatar, we meticulously evaluated the prevalence of pediatric FUTIs. Our study focused on febrile infants aged less than 1 year, excluding those with urine samples not obtained through a catheter. E. coli and K. pneumoniae prevailed as the predominant causative agents in febrile children in Qatar, with hydronephrosis being identified as the most common urological anomaly. Moreover, our findings suggested that gentamicin served as a viable non-carbapenem option for hospitalized ESBL cases, while oral nitrofurantoin showed considerable promise for uncomplicated ESBL UTIs.

Relapsing bronchopneumonia due to community-associated methicillin-resistant Staphylococcus aureus: a case report

BackgroundThe emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has increased the incidence of community-onset MRSA infection. Respiratory tract infections caused by MRSA has been noted for their severity; however, repeated relapses that require extended antibiotic therapy are rare.Case presentationWe report a case of relapsing bronchopneumonia caused by CA-MRSA in a 56-year-old man. The patient responded to antibiotics, but repeatedly relapsed after stopping treatment. MRSA was consistently isolated from airway specimens during each relapse. Extended oral antibiotic treatment with trimethoprim/sulfamethoxazole (TMP/SMX) for 6 months achieved infection control. Whole-genome sequencing of the isolated strain revealed that the causative agent was sequence type (ST)1/staphylococcal cassette chromosome mec (SCCmec) type IVa, a clone that is rapidly increasing in Japan.Discussion and conclusionsThis patient had an unusual course of MRSA bronchopneumonia with repeated relapses. Although the choice of antibiotics for long-term use in MRSA respiratory tract infections has not been well established, TMP/SMX was effective and well tolerated for long-term therapy in this case. The clinical course of infections related to the rapid emerging clone, ST1/SCCmec type IVa warrants further attention.

Surveillance and Resistance of Community-Onset Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumonia in Oral and Maxillofacial Surgery Site Infections.

Background: The prevalence of community-onset infections of extended spectrum β-lactamase (ESBL)-producing strains has increased globally, yet surveillance and resistance in patients with oral and maxillofacial surgery site infections is less investigated. Patients and Methods: A retrospective cohort study was performed to investigate risk factors and resistance of ESBL-producing Escherichia coli (ESBL-EC) and ESBL-producing Klebsiella pneumonia (ESBL-KP) among community-onset patients with oral and maxillofacial surgery during January 2010 to December 2016. Demographic features, predisposing factors, clinical outcomes, and antibiotic agent costs were analyzed. Antimicrobial susceptibility testing of nine antimicrobial agents against ESBL-KP and ESBL-EC were measured. Results: Among 2,183 cultures from infection sites in patients with oral and maxillofacial surgery site (45 cases [2.06%]) were confirmed with community-onset ESBL-KP (24; 1.10%) or ESBL-EC (21; 0.96%) infection. Multivariable analysis showed the independent risk factors for ESBL-producing bacterial infection were prior history of hospitalization (adjusted odds ratio [aOR], 10.984; 95% confidence interval [CI], 5.965-59.879; p = 0.025) and malignant condition (aOR, 3.373; 95% CI 2.947-7.634; p = 0.024). Based on antimicrobial susceptibility testing, 57.8% ESBL-KP and ESBL-EC were found receiving inappropriate antimicrobial therapy, and antibiotic agent costs were higher than non-ESBL-producing bacterial infections ($493.8 ± $367.3 vs. $304.1 ± $334.7; p = 0.031). Conclusions: Infections caused by ESBL-KP and ESBL-EC among patients in sites with oral and maxillofacial surgery are associated with prior history of hospitalization and malignant conditions. Prompt detection and appropriate antibiotic administration for community-onset infections of ESBLs are necessary for such populations.

An emergency department intervention to improve earlier detection of community-onset bloodstream infection among hospitalized patients

Blood cultures (BCs) are essential microbiologic tests, but blood culturing diagnostic stewardship is frequently poor. We aimed to study the process-related failures and to evaluate the effect of an emergency department (ED) intervention on BCs collection practices and yield. We implemented an ED-quality improvement intervention including educational sessions, phlebotomists addition, promoting single-site strategy for BC-collection and preanalytical data feedback. BC-bottles collected, positive BCs, blood volumes and documentation of collection times were measured, before (December 2021-August 2022) and after (September 2022-July 2023) intervention. Results were corrected to hospitalizations admissions or days. We used interrupted-time series analyses for comparisons. A total of 64,295 BC bottles were evaluated, 26,261 before and 38,034 postintervention. The median ED-BCs collected per week increased from 88 to 105 BCs (P<.0001), resulting from increased early sampling (P=.0001). Solitary BCs decreased (95%-28%), documented times increased (2.8%-25%), and average blood volume increased (3mL to 4.5mL) postintervention. Community-onset Bloodstream infections (BSIs) increased (39.6-52 bottles/1,000 admissions, P=.0001), while Health care-associated BSIs decreased (39-27 bottles/10,000 days, P=.0042). Contamination rates did not change. An ED-focused intervention based on the education sessions and single-site strategy improved culturing stewardship and facilitated the early identification of BSI without an increase in contamination.

From Epidemiology of Community-Onset Bloodstream Infections to the Development of Empirical Antimicrobial Treatment-Decision Algorithm in a Region with High Burden of Antimicrobial Resistance.

Antimicrobial-resistant (AMR) infections have increased in community settings. Our objectives were to study the epidemiology of community-onset bloodstream infections (BSIs), identify risk factors for AMR-BSI and mortality-related factors, and develop the empirical antimicrobial treatment-decision algorithm. All adult, positive blood cultures at the emergency room and outpatient clinics were evaluated from 08/2021 to 04/2022. AMR was defined as the resistance of organisms to an antimicrobial to which they were previously sensitive. A total of 1151 positive blood cultures were identified. There were 450 initial episodes of bacterial BSI, and 114 BSIs (25%) were AMR-BSI. Non-susceptibility to ceftriaxone was detected in 40.9% of 195 E. coli isolates and 16.4% among 67 K. pneumoniae isolates. A treatment-decision algorithm was developed using the independent risk factors for AMR-BSI: presence of multidrug-resistant organisms (MDROs) within 90 days (aOR 3.63), prior antimicrobial exposure within 90 days (aOR 1.94), and urinary source (aOR 1.79). The positive and negative predictive values were 53.3% and 83.2%, respectively. The C-statistic was 0.73. Factors significantly associated with 30-day all-cause mortality were Pitt bacteremia score (aHR 1.39), solid malignancy (aHR 2.61), and urinary source (aHR 0.30). In conclusion, one-fourth of community-onset BSI were antimicrobial-resistant, and one-third of Enterobacteriaceae were non-susceptible to ceftriaxone. Treatment-decision algorithms may reduce overly broad antimicrobial treatment.

2848. Risk factors for recurrence of community-onset urinary tract infections caused by extended spectrum cephalosporin-resistant Enterobacterales

Abstract Background Extended spectrum cephalosporin-resistant Enterobacterales (ESCR-E) are increasingly implicated in community-onset urinary tract infections (UTIs). In this study, we assessed risk factors for recurrence among patients with community-onset UTI caused by ESCR-E. Methods This retrospective cohort study included adult patients evaluated April 2018 – December 2021 in the Duke University Health System with community-onset ESCR-E UTI, defined as (1) ESCR-E in a urine culture obtained in an outpatient clinic, emergency department, or within 48 hours of hospital admission; (2) ≥10 leukocytes per high-power field on urine microscopy or urine dipstick positive for leukocyte esterase; and (3) new antibiotic administration or prescription. ESCR-E UTI recurrence was assessed 14 to 180 days after completion of antibiotic treatment for the index UTI. Patients were right censored at end of follow up period or upon death. Univariate Cox proportional hazards regression was performed to evaluate the relationships between candidate risk factors and time to recurrence. Results 1428 patients were included; 207 (14.5%) experienced recurrence. In unadjusted analyses, risk factors for recurrent ESCR-E UTI included diabetes mellitus (hazard ratio [HR] = 1.4, 95% confidence interval [CI]: 1.1 to 1.9, p = 0.01), chronic renal insufficiency (HR = 1.6, 95% CI: 1.2 to 2.1, p &amp;lt; 0.001), neurogenic bladder (HR = 2.1, 95% CI: 1.4 to 2.9, p &amp;lt; 0.001), previous UTI diagnosis within one year (HR = 2.6, 95% CI: 1.9 to 3.5, p &amp;lt; 0.001), fluoroquinolone non-susceptibility (HR = 1.6, 95% CI: 1.2 to 2.2, p = 0.004), and trimethoprim-sulfamethoxazole non-susceptibility (HR = 1.3, 95% CI: 1.0 to 1.8, p = 0.045). Patients with ESCR Klebsiella pneumoniae UTI had a 53% greater hazard of recurrence compared to patients with ESCR E. coli UTI (HR = 1.5, 95% CI: 1.1 to 2.1, p = 0.008). Conclusion ESCR-E UTI recurrence was common, and several clinical and microbiologic characteristics were associated with recurrence. Patients with these characteristics should receive particular consideration for aggressive UTI risk factor modification and other non-antibiotic prevention strategies. Future studies should evaluate strategies to reduce the risk of recurrence among patients with ESCR-E UTI. Disclosures All Authors: No reported disclosures

2455. National Trends in the Rates of Drug-resistant Bacteria Commonly Associated with Healthcare in U.S. Acute Care Hospitals, 2019-2021

Abstract Background The 2022 Special Report: COVID-19 U.S. Impact on Antimicrobial Resistance identified significant increases in the rate of hospital-onset (HO) infections during the year 2020 for bacteria commonly associated with healthcare. Using the same data sources and methodology, we provide updated estimates for the year 2021. Methods We identified a cohort of patients from the PINC AI PHD and BD Research Insights databases with a clinical culture yielding an isolate of an organism of interest with accompanying susceptibility testing. Isolates from patients with no culture yielding the same resistance phenotype of interest in the previous 14 days were counted as an incident case. Community-onset (CO) cultures were obtained ≤ day 3 of hospitalization; HO cultures were obtained ≥ day 4. We used a raking-procedure to determine weights for extrapolating the number of discharges included in our sample to match the distribution of discharges, stratified by bed size, U.S. census division, urban/rural designation, and teaching status, for U.S. hospitals included in the American Hospital Association survey. We examined temporal trends using a multivariable logistic model incorporating a survey design with the corresponding weights and hospital designation as the specific cluster controlling for hospital characteristics, month of discharge, proportion of patients in specific age group, proportion of male patients, and database. Results were stratified by HO and CO. Results From 2019-2021, the overall number of hospitals contributing data was 640. HO rates were significantly higher in 2020 and 2021 compared with 2019. The HO rates of VRE, MDRPseu, and CRE were significantly higher in 2021 when compared to 2020 (Table 1). For CO infections, we found that MRSA rates decreased significantly during the study period, while VRE and CRAB were significantly higher in 2021 compared to 2019 (Table 1). Conclusion Hospital onset antibiotic resistant infection rates in 2021 remain higher than pre-pandemic rates with increasing rates for several pathogens in 2021 compared to 2020, while CO MRSA declined. As infections caused by resistant pathogens represent a serious threat to patient safety, further study of factors contributing to the continued increases and decreases may inform prevention strategies. Disclosures All Authors: No reported disclosures

179. From Epidemiology of Community-onset Bloodstream Infections to the Development of Empirical Antimicrobial Treatment-decision Algorithm in a Region with High Burden of Antimicrobial Resistance

Abstract Background More antimicrobial-resistant (AMR) infections have emerged in community settings. Our objectives were to study the epidemiology of community-onset bloodstream infections (BSIs), identify risk factors for AMR-BSI and factors associated with mortality, and develop the empirical antimicrobial treatment-decision algorithm. Methods A retrospective cohort study was conducted at a tertiary-care hospital. All positive blood cultures from adult patients at the emergency room and outpatient clinics were identified from 1 Aug 2021-15 Apr 2022. AMR was defined as the resistance of organisms to an antimicrobial to which they were at first sensitive. Risk factors associated with AMR-BSI and factors associated with 30-day mortality were determined. The independent risk factors for AMR-BSI were placed into steps to create an empirical treatment-decision algorithm. C-statistics were calculated. The internal validation cohort was evaluated. Results A total of 1,151 positive blood cultures were identified. There were 450 initial episodes of bacterial BSI, and 114 BSIs (25%) were AMR-BSI. Nonsusceptibility to ceftriaxone was detected in 40.9% of 195 E. coli isolates and 16.4% among 67 K. pneumoniae isolates. A treatment-decision algorithm was developed based on the independent risk factors for AMR-BSI: the presence of multidrug-resistant organisms (MDROs) within 90 days (aOR 3.63; 95% CI 1.95-6.75; P&amp;lt; 0.001), prior antimicrobial exposure within 90 days (aOR 1.94; 95% CI 1.08-3.50; P=0.03), and urinary source (aOR 1.79; 95% CI 1.06-3.01; P=0.03). The positive and negative predictive values were 53.3% (95% CI 45.4-61.1%) and 83.2% (95% CI 80.4-85.6%), respectively. The C-statistic was 0.73. Factors significantly associated with 30-day all-cause mortality were Pitt bacteremia score (aHR 1.39; 95% CI 1.20–1.62; P&amp;lt; 0.001), solid malignancy (aHR 2.61; 95% CI 1.30–5.24; P=0.01), and urinary source (aHR 0.30; 95% CI 0.11–0.79; P=0.02). Univariable analysis and multivariable analysis of risk factors for antimicrobial resistance Proposed empirical antimicrobial treatment algorithm for patients with suspected community-onset bloodstream infections Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and C-statistics of the algorithm in predicting antimicrobial resistant infection Conclusion One-fourth of community-onset BSI were antimicrobial-resistant, and almost one-third of Enterobacteriaceae were nonsusceptible to ceftriaxone. Treatment-decision algorithm based on the presence of MDROs within 90 days, prior antimicrobial use within 90 days, and the urinary source may reduce overly broad antimicrobial treatment. Disclosures All Authors: No reported disclosures

Different evolution of S. aureus methicillin-resistant and methicillin-susceptible infections, Argentina

Staphylococcus aureus-(SA) is widespread among healthcare-associated-(HA) and the community-associated-(CA) infections. However, the contributions of MRSA and MSSA to the SA overall burden remain unclear.In a nationally-representative-survey conducted in Argentina, 668 SA clinical isolates from 61 hospitals were examined in a prospective, cross-sectional, multicenter study in April 2015. The study aimed to analyze MRSA molecular epidemiology, estimate overall SA infection incidence (MSSA, MRSA, and genotypes) in community-onset (CO: HACO, Healthcare-Associated-CO and CACO, Community-Associated-CO) and healthcare-onset (HO: HAHO, Healthcare-associated-HO) infections, stratified by age groups. Additionally temporal evolution was estimated by comparing this study's (2015) incidence values with a previous study (2009) in the same region. Erythromycin-resistant-MSSA and all MRSA strains were genetically typed.The SA total-infections (TI) overall-incidence was 49.1/100,000 monthly-visits, 25.1 and 24.0 for MRSA and MSSA respectively (P = 0.5889), in April 2015. In adults with invasive-infections (INVI), MSSA was 15.7 and MRSA was 11.8 (P = 0.0288), 1.3-fold higher. HA SA infections, both MSSA and MRSA, surpassed CA infections by over threefold.During 2009–2015, there was a significant 23.4 % increase in the SA infections overall-incidence, mainly driven by MSSA, notably a 54.2 % increase in INVI among adults, while MRSA infection rates remained stable. The MSSA rise was accompanied by increased antimicrobial resistance, particularly to erythromycin, linked to MSSA-CC398-t1451-ermT + -IEC+-pvl- emergence. The SA-infections rise was primarily attributed to community-onset-infections (37.3 % and 62.4 % increase for TI and INVI, respectively), particularly HACO-MSSA and HACO-MRSA in adults, as well as CACO-MSSA. The main CA-MRSA-PFGE-typeN-ST30-SCCmecIVc-PVL+/− clone along with other clones (USA300-ST8-IV-LV-PVL+/−, PFGE-typeDD-ST97-IV- PVL−) added to rather than replaced CA-MRSA-PFGE-typeI-ST5-SCCmecIVa-PVL+/− clone in HA invasive-infections. They also displaced clone HA-MRSA-PFGE-typeA-ST5-SCCmecI, mainly in HAHO infections.The overall-burden of SA infections is rising in Argentina, driven primarily by community-onset MSSA, particularly in adults, linked to increased erythromycin-resistance and MSSA-CC398-t1451-ermT + -IEC+-pvl- emergence. Novel knowledge and transmission-control strategies are required for MSSA.

Assessing the impact of discordant antibiotic treatment on adverse outcomes in community-onset UTI: a retrospective cohort study.

To investigate the risk of adverse outcomes following discordant antibiotic treatment (urinary organism resistant) for culture-confirmed community-onset lower urinary tract infection (UTI). Cohort study using routinely collected linked primary care, secondary care and microbiology data from patients with culture-confirmed community-onset lower UTI (COLUTI). Antibiotic treatment within ±3 days was considered concordant if the urinary organism was sensitive and discordant if resistant.The primary outcome was the proportion of patients experiencing urinary infection-related hospital admission (UHA) within 30 days. Secondary outcomes were the proportion of patients experiencing reconsultation within 30 days, and the odds of UHA and reconsultation following discordant treatment, adjusting for sex, age, risk factors for complicated UTI, previous antibiotic treatment, recurrent UTI and comorbidities. A total of 11 963 UTI episodes in 8324 patients were included, and 1686 episodes (14.1%, 95% CI 13.5%-14.7%) were discordant. UHA occurred in 212/10 277 concordant episodes (2.1%, 95% CI 1.8%-2.4%) and 88/1686 discordant episodes (5.2%, 95% CI 4.2%-6.4%). Reconsultation occurred in 3961 concordant (38.5%, 95% CI 37.6%-39.5%) and 1472 discordant episodes (87.3%, 95% CI 85.6%-88.8%). Discordant treatment compared with concordant was associated with increased odds of UHA (adjusted OR 2.31, 95% CI 1.77-3.0, P < 0.001) and reconsultation (adjusted OR 11.25, 95% CI 9.66-13.11, P < 0.001) on multivariable analysis. Chronic kidney disease and diabetes mellitus were also independently associated with increased odds of UHA. One in seven COLUTI episodes in primary care were treated with discordant antibiotics. In higher risk patients requiring urine culture, empirical antibiotic choice optimization could meaningfully reduce adverse outcomes.

Mortality, hospital length of stay, and recurrent bloodstream infections associated with extended-spectrum beta-lactamase-producing Escherichia coli in a low prevalence region: A 20-year population-based large cohort study

ObjectivesThis population-based study aimed to investigate the risk factors and effect of extended-spectrum beta-lactamase (ESBL) production on clinical outcomes in Escherichia coli bloodstream infection (BSI) patients. MethodsThe study population was defined as patients aged ≥15 years with E. coli BSI in Queensland, Australia, from 2000 to 2019. Outcomes were defined as 30-day case fatality, hospital length of stay (LOS), and recurrent E. coli BSI. ResultsA total of 27,796 E. coli BSIs were identified, of which 1112 (4.0%) were ESBL-producers. Patients with ESBL-Ec BSI were more frequently older, male, with comorbidity, recurrent E. coli BSI, and less likely with community-associated community-onset infections as compared to non-ESBL-Ec BSI patients. The standardized mortality rate of ESBL-Ec BSI increased 8-fold from 2000 to 2019 (1 to 8 per million residents) and case fatality was 12.8% (n = 142) at 30 days from positive blood culture. Patients with ESBL-Ec BSI were not at higher risk of 30-day case fatality (adjusted hazard ratio [HR] = 0.98, 95% CI: 0.83-1.17), but had higher risk of recurring episodes (adjusted subdistribution HR = 1.58, 95% CI: 1.29-1.92) and observed 14% longer LOS (adjusted incidence rate ratio = 1.14, 95% CI: 1.10-1.18) than non-ESBL-Ec BSI patients. ConclusionIn this large patient cohort, ESBL-Ec BSI did not increase case fatality risk but observed higher hospital LOS and recurrent E. coli BSI than non-ESBL-Ec BSI. Clinical resources are warranted to account for the higher morbidity risk associated with ESBL production and incidence.

Risk Factors for Recurrence of Community-Onset Urinary Tract Infections Caused by Extended-Spectrum Cephalosporin-Resistant Enterobacterales.

Extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) are an increasingly important cause of community-onset urinary tract infections (UTIs), including recurrent infections. We evaluated risk factors for recurrence among patients with community-onset ESCrE UTI. This retrospective cohort study included adults with community-onset ESCrE UTI in the Duke University Health System from April 2018 through December 2021. ESCrE UTI recurrence by the same species was assessed 14-180 days (ie, 6 months) after completion of antibiotic treatment. We evaluated the relationships between candidate risk factors and time to recurrence using Cox proportional hazards regression models. Among 1347 patients with community-onset ESCrE UTI, 202 (15.0%) experienced recurrent infection during the 6-month follow-up period. Independent risk factors for recurrence included neurogenic bladder (adjusted hazard ratio [aHR], 1.8 [95% confidence interval {CI}, 1.2-2.6]; P = .005), prior history of UTI (aHR, 2.4 [95% CI, 1.7-3.3]; P < .001), and fluoroquinolone nonsusceptibility of the index UTI (aHR, 1.5 [95% CI, 1.1-2.1]; P = .02). Klebsiella pneumoniae infection was associated with recurrence in univariate analysis (HR, 1.6 [95% CI, 1.1-2.1]; P = .007) but not multivariate analysis (aHR, 1.4 [95% CI, 1.0-1.9]; P = .06). Inappropriate initial or definitive antibiotic therapy was not predictive of ESCrE UTI recurrence. Recurrence of community-onset ESCrE UTI was common and associated with several patient and pathogen-level risk factors. Future studies should evaluate microbial risk factors for recurrence and improve the management of ESCrE UTI.