Community-onset Infections Research Articles

1686. Microbiology of Community-Onset Urinary Tract Infections in the United States, 2012-2017

BackgroundCommunity-onset urinary tract infections (coUTIs) are one of the most common indications for antibiotic prescribing. It is important to understand patient demographic factors associated with microorganisms causing coUTI and their antibiotic resistance profiles, to tailor antibiotic prescribing practices. We analyzed microbiology data to understand factors associated with coUTI in the United States (US).MethodsCoUTIs were identified in the Premier Healthcare Database and Cerner Health Facts among patients treated at participating healthcare facilities in the US between 2012-2017. Cases were defined by urine cultures yielding a bacterial organism and were collected in outpatient settings or within three days of hospitalization. Only the first specimen for each encounter was included in the analysis. Data on the organisms isolated, patient’s age, sex, and US census regions of the submitting facilities were described and compared using chi-square tests for associations. Encounters were classified as inpatient (INPT), observation (OBS), emergency department (ED), and outpatient (OTPT) based on the setting in which the culture was submitted.ResultsUsing data from 637 acute care hospitals, urine samples from 3,291,561 encounters were included, with 776,653 (25.7%) INPT, 1,063,219 (34.8%) ED, 107,760 (3.5%) OBS, and 1,092,658 (35.8%) OTPT. The pathogens most frequently associated with coUTIs were Escherichia coli (57.3%), Klebsiella pneumoniae (9.7%), Enterococcus faecalis (5.1%), Proteus mirabilis (4.9%), and Pseudomonas aeruginosa (2.9%). Female sex, age < 65y and OTPT and ED settings were associated with higher relative frequency of E. coli (all p < 0.0001). Male sex, INPT setting and age >65 y were associated with higher relative frequency of P. aeruginosa, P. mirabilis and E. faecalis (all p < 0.0001, Figure). K. pneumoniae was found at higher relative frequency in those >45y, and in INPT and OBS settings (all p < 0.0001).Figure. Distribution of pathogens most frequently associated with community onset urinary tract infections ConclusionUnderstanding patient factors associated with the microbiology of coUTIs is an important step in developing treatment recommendations and antibiotic stewardship efforts. Further analyses will include assessing the impact of major antibiotic resistance phenotypes, geographic and healthcare settings.Disclosures All Authors: No reported disclosures

845. Trends and Regional Differences in Community-Onset Fluoroquinolone-Resistant E. coli in Hospitalized Adults in the United States

Background Escherichia coli is a common cause of community-onset (CO) infections, including urinary tract and abdominal infections, and CO sepsis. Fluoroquinolones (FQ) are used in the empiric treatment of E. coli infections, but FQ-resistance may limit their effectiveness. We examined trends and regional differences in FQ-resistant E. coli clinical cultures among hospitalized adult patients in the U.S.MethodsWe measured the incidence of E. coli clinical cultures among hospitalized adults in a cohort of hospitals in the Premier Healthcare Database and Cerner Health Facts from 2012 through 2017. FQ resistance was defined as resistance to ciprofloxacin, levofloxacin, or moxifloxacin. Only cultures collected prior to day 4 of hospitalization, defined as CO, were considered. We extrapolated national estimates using a raking procedure to generate weighted adjustments matching the American Hospital Association distribution for U.S. acute care hospitals. Weights were based on U.S. census division, bed size category, teaching status, and urban/rural designation. We used a weighted means survey procedure to calculate national estimates and weighted multivariable logistic regression to examine trends and regional differences.ResultsIn 2017, we estimated 949,393 CO E. coli infections with FQ susceptibility testing; 312,304 (33%) were due to E. coli resistant to FQ. Of FQ-resistant E. coli isolates, 76% were isolated from urine. We did not observe a significant trend in FQ-resistant E. coli from 2012 to 2017 (p = 0.85). Percent FQ-resistant varied significantly by region (p < 0.0001) with an estimated range of 19% (Mountain) to 42% (Southeast Central) in 2017. We also found variability by hospital (2017 Q1: 26% and Q3: 39%). FQ-resistance rates were higher in urine (36%: 95% CI 34-38%) than blood isolates (27%: 95% CI 26-29%) and higher for males (40%: 95% CI 38-42%) than females (33%: 95% CI 31-35%).ConclusionFQ-resistance is common in CO E. coli infections with significant variability by region and hospital. Empiric FQ treatment for infectious syndromes commonly caused by E. coli may need to be reconsidered. Clinicians should consult with local antibiograms and antibiotic stewardship programs to determine the most appropriate empiric treatment of E. coli infections in hospitalized adults.Disclosures All Authors: No reported disclosures

Virulence genotypes and phylogenetic distribution of the community-onset Escherichia coli

Background: The concept that not all E. coli are equally able to cause UTI, and that the uropathogenic E. coli (UPEC) strains possess distinctive traits that confer enhanced virulence potential compared to other source E. coli, is supported by abundant epidemiologic and experimental evidence. Virulence factors (VFs) are the specific genes encoding a diverse array of specialized properties that are postulated to contribute to virulence. The aim of this study was to find the prevalence difference of virulence genes and phylogenetic lineages between E. coli from community-onset urinary tract infection (CO-UPEC) and hepatobiliary infection (CO-HBEC) compared to rectal commensal E. coli (RCEC) in a healthy population. Methods and materials: We conducted a case-control study of patients with positive UPEC & HBEC between 2006 and 2008 at a teaching hospital in South Korea. Community-onset (CO) was the isolated from the patients from whom the specimen was obtained within 2 calendar days of hospitalization or at outpatient department. We also collected the rectal commensal E. coli (RCEC) of healthy people. All isolates underwent PCR-based microarray for phylotyping and detection of 11 VFs, including adhesins (prf, sfa, drb, prsGj96, papGad), toxins (hly, cnf1), siderophores (iroN, aer), capsule (kpsMT), and other (ompT). The virulence score was defined as the number of virulence genes identified. Results: A total of 548 CO-UPEC and 140 HBEC with 486 CREC isolates were collected. Compared with CREC, CO-UPEC showed higher VFs (3.92 ± 2.22 vs. 2.28 ± 1.90, p < 0.001) and CO-HBEC averaged fewer VFs (1.56 ± 1.64 vs. 2.28 ± 1.90, p < 0.001). Overall distribution of phylogenic group were B2(52.5%) and D(33%) in CO-UPEC, A(37.9%) and D(31.4%) in CO-HBEC and A(38.3%) and B2(29%) in RCEC. Conclusion: In conclusion, we observed the differences of VFs between clones from community- onset UPECs and HBECs compared to RCEC, and this result explain that UPECs would be more virulent than HBECs which could be less virulent than RCECs considering only VFs distribution. In phylogenetic analysis, each group of E. coli showed different phylogenic distribution, which imply group B E. coli might be more specifically associated with uropathogenecity.

Antibiotic Resistance Crisis in Urinary Tract Infections Utis in Egypt

Abstract Introduction/Objective Bacterial adaptation to antibiotics has been very successful. Over the past decade, the increase in antibiotic resistance has generated considerable medical problems. UTIs are one of the most common community-onset infections. The emergence of resistance to all classes of antibiotics in previously susceptible bacterial pathogens is a major challenge to infectious disease medicine. Thus, it is important that we forcefully implement strategies to reduce the rate of appearance and spread of resistant bacteria to allow new drug discovery to catch up with bacterial resistance development. Objectives: Methods The aim of this study is to predict the percentage of urine cultures antibiotic resistance in patients with UTIs in Egypt. Subjects and methods: A total of 200 subjects were enrolled in this study from The Delta region in Egypt; 38% males and 62% females with a median age of 39 years and 35 years respectively. Identification of the isolated organisms was identified by the cultural characters (Morphological characters of the purified bacterial isolates were carried out according to the colony characters, Gram stain reaction and biochemical tests for each organism using a standard semi-automated technique Results 98 cultures (49%) were observed to have resistance to 3- 5 classes of antibiotics including, 98% Cephalosporins, 85% β-lactam inhibitors and 71% fluoroquinolones; 66 females (57 gram -ve stain and 9 gram +ve stain) and 33 males (27gm -ve stain, 6gm +ve stain). 82 cultures (41%) were not resistant to any classes.; 32 males (28 gram -ve stain and 3 gram +ve stain) and 50 females (45 gram -ve stain and 5 gram +ve stain). 19 cultures (9.5%) were observed to be resistant to all antibiotics.; 12 males (11 gram -ve stain and 1 gram +ve stain) and 7 females (2 gram -ve stain and 5 gram +ve stain). Conclusion This study highlights the highest antibiotic resistance associated with urinary tract infection in Egypt as well as the classification of the organisms. The high resistance percentage is due to the overuse of antibiotics by public and inappropriate antibiotic prescribing. Antibiotics are unregulated and available over the counter without a prescription in Egypt which makes it easily accessible. We recommend regulating the use of antibiotics and lunch antimicrobial stewardship programs in Egypt.

Trends in Hospital Onset Clostridioides difficile Infection Incidence, National Healthcare Safety Network, 2010–2018

Background:Clostridioides difficile infection (CDI) is one of the most common laboratory-identified (LabID) healthcare-associated events reported to the National Healthcare Safety Network (NHSN). CDI prevention remains a national priority, and efforts to reduce infection burden and improve antibiotic stewardship continue to expand across the healthcare spectrum. Beginning in 2013, the Centers for Medicare and Medicaid Services (CMS) required acute-care hospitals participating in CMS’ Inpatient Quality Reporting program to report CDI LabID data to NHSN and, in 2015, extended this reporting requirement to emergency departments (ED) and 24-hour observation units. To assess national progress, we evaluated changes in hospital onset CDI (HO-CDI) incidence during 2010–2018. Methods: Cases of HO-CDI were reported to NHSN by hospitals using the NHSN’s LabID criteria. Generalized linear mixed-effects modeling was used to assess trends of HO-CDI by treating the hospital as a random intercept to account for the correlation of the repeated responses over time. The data were summarized at the quarterly level, the main effect was time, and the covariates of interest were the following: CDI test type, inpatient community-onset (CO) infection rate, hospital type, average length of stay, medical school affiliation, number of beds, number of ICU beds, number of infection control professionals, presence of an ED or observation unit , and an indicator for 2015 to account for CDI protocol changes that required hospitals to conduct surveillance in both inpatient and ED or observation unit setting. Results: During 2010–2013, the number of hospitals reporting CDI increased and then stabilized after 2013 (Table 1). Crude HO-CDI rates decreased over time, except for an increase in 2015 and steeper reduction thereafter. (Table 2). During 2010–2014, the adjusted quarterly rate of change was −0.45% (95% CI, −0.57% to −0.33%; P &lt; .0001). The rate of reduction was smaller in 2010–2014 compared to those of 2015–2018 (−2.82%; 95% CI, −3.10% to −2.54%; P &lt; .0001). Compared to 2014, the adjusted rate in 2015 increased by 79.14% (95% CI, 72.42%–86.11%; P &lt; .0001). Conclusions: The number of hospitals reporting CDI LabID data grew substantially in 2013 as a result of the CMS requirement for reporting. Adjusted HO-CDI rates decreased over time, with a rate hike in the year of 2015 and a rapid decrease thereafter. The increase in 2015 may be explained by changes in the NHSN CDI surveillance protocol and better test type classification in later years. Overall decreases in HO-CDI rates may be influenced by prevention strategies.Funding: NoneDisclosures: None

Burden and Trends of Hospital-Associated Community-Onset (HACO) Infections From Antibiotic Resistant and Nonresistant Bacteria

Background: Studies on the effectiveness of hospital-based interventions often measure hospital-onset infections as the outcome of interest. However, hospital-associated infections may manifest after patient discharge (classified as hospital-associated community-onset, HACO), and the epidemiology may vary by antibiotic resistance (AR) profile. We examined the epidemiology and trends of HACO infections of AR and non–antibiotic-resistant (non-AR) bacteria. Methods: We included clinical community-onset (CO) cultures (obtained sooner than or on day 3 of hospitalization) yielding the bacterial species of interest among hospitalized patients in 260 hospitals in the Premier Healthcare Database from 2012 to 2017. HACO infections were defined as CO cultures in a patient who had a previous hospitalization in the same hospital within 30 days. We examined methicillin resistance among Staphylococcus aureus (MRSA), vancomycin resistance among Enterococcus spp (VRE), carbapenem resistance among Enterobacteriaceae (E. coli, Klebsiella spp, and Enterobacter spp) (CRE), extended-spectrum cephalosporin resistance suggestive of extended-spectrum β-lactamase (ESBL) production in Enterobacteriaceae, carbapenem resistance among Acinetobacter spp (CRAsp), and carbapenem resistance among Pseudomonas aeruginosa (CRPA). We described the proportion of CO infections that were HACO, the proportion of HACO infections from sterile sites, overall HACO rates, and annual trends for sensitive and resistant phenotypes. Generalized estimating equation regression models that accounted for hospital-level clustering were used to estimate annual trends controlling for hospital characteristics and month of discharge. Results: The rate of HACO infections by pathogen ranged from 0.78 to 38.76 per 10,000 hospitalizations; 7%–34% were sterile site infections (Table 1). For each bacterial pathogen, a significantly higher proportion of AR CO infections had a previous hospitalization compared to non-AR CO infections (all χ2, P &lt; .05). The annual trends for AR and non-AR HACO infections between 2012 and 2017 were significantly decreasing for most pathogens, except ESBL HACO infections. Conclusions: Even when using a definition limited to readmission to the same hospital, HACO infections occur commonly with differing rates by pathogen and antibiotic resistance profile. Although these rates are decreasing for most of the pathogens studied, improving surveillance and identifying prevention strategies for these infections are necessary to further reduce the burden of hospital-associated infections.Funding: NoneDisclosures: None

Molecular Epidemiology of Community-Onset (CO), Community-Onset Healthcare-Associated (CO-HA) and Hospital-Onset (HO) Methicillin-Resistant Staphylococcus aureus (MRSA)

Background: Previous work suggests an intermingling of community and hospital transmission networks driving the MRSA epidemic, but how those with CO-HA infections fit into the network remains unclear. We integrated epidemiologic data and whole-genome sequencing (WGS) from existing MRSA clinical isolates to determine whether there were distinguishable features of CO-HA MRSA infections that could guide interventions. Methods: We examined 955 existing clinical MRSA isolates from 2011 to 2013 from patients at Cook County Health, the major public healthcare network in Chicago, Illinois. We performed electronic and manual chart review to ascertain community (eg, illicit drug use, incarceration history) and healthcare exposures and comorbidities. WGS was performed on all sequences, and sequences were typed with multilocus sequence typing (MLST). We assessed the distribution of epidemiological factors and sequence type (ST) across onset type. Results: Infections were more frequent in males (70%); 61% of individuals with infection were African American and 21% were Hispanic. Overall, wound infections were the most common (81%) followed by blood (7%) and respiratory (6%). 82% of infections were ST8 (most USA300), 8% were ST5 (USA100) and 10% were other STs (Fig. 1a). Using standard epidemiologic definitions, we identified 523 CO, 295 CO-HA, and 137 HO infections. USA300 infections were common across CO, CO-HA, and HO categories, whereas USA100 was more frequently observed among CO-HA and HO. Current illicit drug use and history of incarceration—factors typically associated with CO-MRSA—were observed among both CO-HA and HO infections. 38% of CO-HA and 36% of HO had a history of MRSA infection or nasal colonization in the prior 6 months. As expected, 73% of CO-HA had a history of recent hospitalization, but this was also true for 44% of HO cases; points for intervention for both groups, especially CO-HA patients, include outpatient, inpatient, and ER care. Diabetes was common across categories, and HIV was more commonly observed among CO-HA cases (Fig. 1b). Conclusions: We characterized the genomic and epidemiologic features of CO-HA MRSA infections relative to CO and HO. By MLST and epidemiological analysis, CO-HA infections share similarities to both CO and HO. Although USA300 infections were the most common strain type, our findings highlight the need for WGS to discern relationships between individuals to understand the intermixing of healthcare and community networks for CO-HA infections. Higher resolution genomic analysis may help guide whether interventions need to be at hospital discharge or in the community to have the most impact on decreasing CO-HA MRSA infections.Funding: Funding: from CDC Broad Agency Announcement: Genomic Epidemiology of Community-Onset Invasive USA300 MRSA Infections; Contract ID: 75D30118C02923Disclosures: None

Risk Factors Associated With Hospital-Onset MRSA Proportion—National Healthcare Safety Network, 2017–2018

Background:Staphylococcus aureus is frequently implicated in healthcare-associated infections in the United States, and a substantial proportion of these infections are attributed to methicillin-resistant Staphylococcus aureus (MRSA). Although MRSA infections have decreased in health care settings, accurate estimates of the rate of decline call for risk-adjusted methods for calculating the resistant proportion (%R), that is, the proportion of S. aureus resistant to cefoxitin or oxacillin. Risk-adjusted %R also enables more accurate interhospital comparisons and can serve as a quantitative guide and evaluation metric for prevention efforts. Methods: To develop a risk-adjusted %R for S. aureus, we analyzed the antimicrobial susceptibility test (AST) results for S. aureus isolates reported to the CDC NHSN Antimicrobial Resistance Option during 2017–2018. Isolates were reported for cerebrospinal fluid (CSF), blood, lower respiratory tract (LRT), and urine. Isolates without cefoxitin and oxacillin test results, or from the facilities that had &gt;10% missing test results were excluded. Test results were differentiated between those associated with community-onset and hospital-onset (HO) infections by defining the latter group as test results for isolates obtained 3 days or more after hospital admission. Logistic regression was used to evaluate the factors associated with oxacillin/cefoxitin resistance. Hospital, patient and isolate-level variables from NHSN annual survey and AR option were assessed as covariates. Variable entry into the models is based on significance level P &lt; .05. Results: Among 9,992 hospital-onset SA isolates from 9,019 patients in 315 facilities, 5,488 (54.9%) were MRSA. Logistic regression showed that a higher proportion of HO-MRSA was significantly associated with older age, female, particular sources of specimen (urine and LRT), and selected hospital characteristics: hospitals not serving as major teaching hospitals, hospitals with a higher proportion of MRSA among community-onset SA isolates, hospitals with lower percentage of beds in intensive care units, and hospitals outsourcing AST service (Table 1). Conclusions: HO-MRSA is independently associated with community burden of MRSA, older and female patient populations, and hospital teaching status and AST practices, which highlights the importance of public health engagement and regional collaborations to prevent MRSA. To provide a standardized MRSA proportion for public health surveillance, taking some of these factors into account in MRSA proportion standardization should be considered.Funding: NoneDisclosures: None

Modified Veterans Health Administration Clostridioides difficile Infection (CDI) Prevention Bundle: Progress Over 8 Years Decreasing CDI Laboratory-Identified (LabID) Events at a Large Veterans Affairs Medical Center

Background: In March 2012, the Veterans’ Health Administration (VHA) published the Guideline for the Prevention of Clostridium difficile infection (CDI) in VHA Inpatient Acute-Care Facilities, with a goal of 30% reduction of cases within 2 years. In March 2011, this facility, along with 31 others, served as a pilot site to develop the guidelines. Methods: The CDI prevention bundle was implemented to prevent new onset CDI cases in the facility with 4 core measures: (1) environmental cleaning (EMS), (2) hand hygiene, (3) contact precautions, and (4) cultural transformation. Education was provided to EMS staff, nursing, and care providers on the CDI case definition, criteria for testing, empiric isolation for patients with diarrhea, hand hygiene, and PPE to control spread. In 2014, antimicrobial stewardship was added, and within 5 years an algorithm for isolation and testing was published. Cases were reviewed weekly using TheraDoc software and were reported monthly to the national VHA Inpatient Evaluation Center (IPEC). Isolation was communicated using a ward roster/isolation list in TheraDoc for all unit champions to consult daily. CDI cases were classified using NHSN definitions for a laboratory-identified (LabID) event, recurrent cases, and community-onset cases. Real-time case review and weekly multidisciplinary case discussions identified opportunities for improved compliance with the core measures. Results: Over an 8-year period, CDI healthcare-onset LabID events decreased by 73%. The cases decreased from 149 to 40 over the 8-year period. The infection rate decreased 70% from 16.19 per 10,000 bed days of care in FY2011 (October 2010) to 4.88 in FY2019. The incidence of community onset infections increased from 75 in FY2011 to a high of 146 in FY2018 for a rate of 8.15 to 18.17. In FY2019, there was a decrease in both LabID events and community-onset cases to lows of 40 and 102, respectively. Inappropriate testing decreased by 84% from 50 in FY2011 to 8 in FY2019. Conclusions: A multidisciplinary team approach that included support from leadership and clinical providers as well as front line staff involvement, daily rounding, and case review by infection preventionists has reduced all CDI cases over an 8-year period using the modified VHA CDI bundle. TheraDoc enabled case review, correct isolation, changes to cleaning practices, and more appropriate lab testing. The antimicrobial stewardship program that includes clinical pharmacists working daily with providers was a strong driver for change.Funding: NoneDisclosures: None

Appropriateness of Anti-MRSA Therapy in Hospitalized Patients With Suspected Community-Onset Infections

Background: Inappropriate use of MRSA-spectrum antibiotics is an important antimicrobial stewardship target. Contributors to inappropriate use include empiric treatment of patients who are determined to not be infected or who are infected but lack MRSA risk factors, and by excessive treatment duration when suspected MRSA infection is disproven. To characterize opportunities for improvement, we conducted a medical use evaluation (MUE) in 27 VA medical centers. The primary objectives were to assess the following proportions: (1) courses of unjustified empiric vancomycin therapy (patients in whom all antibacterials were halted within 2 days or without a principal or secondary discharge infection diagnosis); (2) courses of unjustified continuation of anti-MRSA therapy beyond day 4 (no MRSA risk factors or proven MRSA infection); and (3) excess anti-MRSA days of therapy (DOT), that is, DOT in unjustified empiric courses plus DOT after day 4 in unjustified continued courses. Methods: Clinical pharmacists performed retrospective, structured, manual record reviews of patients started on intravenous vancomycin on day 1 or 2 of hospitalization from June 2017 to May 2018. Exclusion criteria included surgical prophylaxis, recent MRSA infection, β-lactam allergy, renal insufficiency, severe immunosuppression, or infection that warranted anti-MRSA therapy other than vancomycin. Results: Of 2,493 evaluated patients, 1,320 met the inclusion criteria. Among them, 44% of courses were initiated in the emergency department, 37% of patients had ≥1 risk factor for healthcare-associated infections, and 50% of patients had ≥2 SIRS criteria or required vasopressor support. The most common admission diagnoses were skin and soft-tissue infection (SSTI, 40%; 68% nonpurulent) and pneumonia (27%; 46% without healthcare risk factors). Clinical cultures recovered MRSA from 8% of patients. Empiric therapy was not justified in 342 patients (26%; 57% were clinically stable). Continued therapy was unjustified in 46% of the 320 patients who received &gt;4 days of anti-MRSA therapy. Of all days of anti-MRSA therapy, 23% were unjustified; 65% of these were due to unjustified empiric therapy. Site-specific variations in unjustified empiric therapy better correlated with the proportion of unjustified DOT than did unjustified continuation of therapy (Pearson correlation coefficients [PCC], 0.75 and 0.54, respectively) (Fig. 1). Facility-specific proportions of unjustified DOT modestly correlated with anti-MRSA DOT (PCC, 0.45; n = 27) (Fig. 2) but not the anti-MRSA standardized antimicrobial administration ratio (PCC, 0.15; n = 21). Conclusions: In this multicenter MUE, 26% of all days of anti-MRSA therapy lacked justification; this rate correlated with total facility-specific anti-MRSA DOT. Unnecessary empiric therapy, largely in the ED and for nonpurulent SSTIs and pneumonia without risk factors, was the principal contributor to unjustified DOT.Funding: NoneDisclosures: None

Antimicrobial Resistance, an Update from the Ward: Increased Incidence of New Potential Pathogens and Site of Infection-Specific Antibacterial Resistances.

In order to monitor the spread of antimicrobial resistance, the European Union requires hospitals to be equipped with infection control centers. With this aim, we analyzed 1583 bacterial strains isolated from samples of different origin from patients with community-onset and nosocomial infections in a public tertiary University Hospital on the outskirts of Turin, Italy. Statistical analyses of the isolates (source, type) and their antimicrobial resistance (AMR) were performed. The survey revealed infections associated with bacterial species considered as not-commensal and not-pathogenic, hence potentially emerging as new threats for human health. Conversely to the general observation of nosocomial strains being more resistant to antibiotics compared to community-acquired strains, nosocomial strains isolated in this study were more resistant only to 1/42 tested antibiotics (tetracycline). By adopting an ecological approach, we observed that blood infections are associated with the broadest range of species compared to infections affecting other areas and we obtained clear indications on the antibiotics that should be preferred in the treatment of infections at specific body sites. Future investigations carried out on a larger geographical scale will clarify whether these indications are limited to the geographical region investigated over this study, or whether the same trends are visible at national or international level.

Outcome of community-onset ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and urinary tract infection: a population-based cohort study in Denmark.

To assess the impact of ESBL production on mortality and length of hospital stay (LOS) of community-onset infections due to Escherichia coli or Klebsiella pneumoniae. A population-based cohort study including all adult patients hospitalized with a first-time community-onset E. coli or K. pneumoniae bacteraemia or urinary tract infection in the North Denmark Region between 2007 and 2017. For each bacterial agent, we computed 1 year Kaplan-Meier survival curves and cumulative incidence functions of LOS, and by use of Cox proportional hazard regression we computed HRs as estimates of 30 day and 1 year mortality rate ratios (MRRs) and LOS among patients with and without ESBL-producing infections. We included 24 518 cases (among 22350 unique patients), of whom 1018 (4.2%) were infected by an ESBL-producing bacterium. The 30 day cumulative mortality and adjusted MRR (aMRR) in patients with and without ESBL-producing isolates was as follows: E. coli bacteraemia (n = 3831), 15.8% versus 14.0%, aMRR = 1.01 (95% CI = 0.70-1.45); E. coli urinary tract infection (n = 17151), 9.5% versus 8.7%, aMRR = 0.97 (95% CI = 0.75-1.26); K. pneumoniae bacteraemia (n = 734), 0% versus 17.2%, aMRR = not applicable; and K. pneumoniae urinary tract infection (n = 2802), 13.8% versus 10.7%, aMRR = 1.13 (95% CI = 0.73-1.75). The 1 year aMRR remained roughly unchanged. ESBL-producing E. coli bacteraemia was associated with an increased LOS compared with non-ESBL production. ESBL production was not associated with an increased short- or long-term mortality in community-onset infections due to E. coli or K. pneumoniae, yet ESBL-producing E. coli bacteraemia was associated with an increased LOS.

Empiric Antibacterial Therapy and Community-onset Bacterial Coinfection in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19): A Multi-hospital Cohort Study.

BackgroundAntibacterials may be initiated out of concern for bacterial coinfection in coronavirus disease 2019 (COVID-19). We determined prevalence and predictors of empiric antibacterial therapy and community-onset bacterial coinfections in hospitalized patients with COVID-19.MethodsA randomly sampled cohort of 1705 patients hospitalized with COVID-19 in 38 Michigan hospitals between 3/13/2020 and 6/18/2020. Data were collected on early (within 2 days of hospitalization) empiric antibacterial therapy and community-onset bacterial coinfections (positive microbiologic test ≤3 days). Poisson generalized estimating equation models were used to assess predictors.ResultsOf 1705 patients with COVID-19, 56.6% were prescribed early empiric antibacterial therapy; 3.5% (59/1705) had a confirmed community-onset bacterial infection. Across hospitals, early empiric antibacterial use varied from 27% to 84%. Patients were more likely to receive early empiric antibacterial therapy if they were older (adjusted rate ratio [ARR]: 1.04 [1.00–1.08] per 10 years); had a lower body mass index (ARR: 0.99 [0.99–1.00] per kg/m2), more severe illness (eg, severe sepsis; ARR: 1.16 [1.07–1.27]), a lobar infiltrate (ARR: 1.21 [1.04–1.42]); or were admitted to a for-profit hospital (ARR: 1.30 [1.15–1.47]). Over time, COVID-19 test turnaround time (returned ≤1 day in March [54.2%, 461/850] vs April [85.2%, 628/737], P < .001) and empiric antibacterial use (ARR: 0.71 [0.63–0.81] April vs March) decreased.ConclusionsThe prevalence of confirmed community-onset bacterial coinfections was low. Despite this, half of patients received early empiric antibacterial therapy. Antibacterial use varied widely by hospital. Reducing COVID-19 test turnaround time and supporting stewardship could improve antibacterial use.

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bacteremia

ObjectivesThe aims of this study were to identify whether the site of acquisition or the underlying carbapenem-resistant Enterobacteriaceae (CRE) resistance mechanism was associated with clinical outcomes, and to evaluate risk factors for 14-day mortality in patients with CRE bacteremia. Materials and methodsA retrospective cohort study was conducted at a 2700-bed tertiary center. All adult patients with monomicrobial carbapenem-resistant Escherichia coli or Klebsiella pneumoniae bacteremia from 2011 to 2018 were included. All blood isolates collected were tested with a modified carbapenem inactivation method for phenotypic detection of carbapenemase. ResultsOf 133 patients with monomicrobial CRE bacteremia, 63 (47.4%) were infected with carbapenemase-producing CRE (CP-CRE), and 70 (52.6%) with non-CP-CRE. Patients with community-onset infection (COI) were more likely to present with biliary or urinary tract infections, less likely to have ineradicable or non-eradicated foci and to receive appropriate empirical therapy, and marginally more likely to have CP-CRE compared with those with hospital-acquired infection (HAI). However, 14-day mortality was significantly lower in COI than HAI (7% vs 29%, P = 0.01). Patients who died were more likely to have had a higher APACHE II score, ineradicable or non-eradicated foci, and a lower chance of having received appropriate antibiotic treatment. Multivariate analysis revealed that HAI, high APACHE II score, and inappropriate antibiotic treatment were independent risk factors for mortality. Carbapenemase production did not affect mortality. ConclusionsThe results of this study indicate that timely, appropriate treatment is essential for managing CRE bacteremia, regardless of carbapenemase production, particularly in critically ill patients with hospital-acquired bacteremia.

Genomic features of a carbapenem-resistant OXA-219-positive Acinetobacter baumannii of international ST15 (CC15) from a patient with community-onset urinary tract infection in Chilean Patagonia

ObjectiveCarbapenemase-producing Acinetobacter baumannii has been recognized as a critical priority pathogen by the World Health Organization. We hereby report the identification and the draft genome sequence of a carbapenem-resistant A. baumannii isolated from a patient with community-onset urinary tract infection, in a Chilean Patagonian city. MethodsThe whole genome was sequenced on an Illumina NextSeq platform and de novo assembled using Unicycler v.0.4. Resistome analysis and epidemiological investigation (based on MLST data and Pasteur scheme) were performed using bioinformatics tools available from the Center for Genomic Epidemiology. ResultsThe genome size was calculated at 3890824 bp, with a GC content of 39.1%, comprising 3864 total genes, 30 tRNAs, 3 rRNAs, 4 ncRNAs, and 109 pseudogenes. Carbapenem-resistant A. baumannii Ab3_Ch strain belonged to the international sequence type ST15 (clonal complex, CC15), and harboured the ISAba-1-blaOXA-219 gene array, along to blaTEM-1B and blaADC-6 β-lactamase genes, and aac(3)-IIa and aph(3′)-VIa aminoglycoside resistance genes. Additionally, efflux pump encoding genes (abaF, abaQ, abeS, adeI, adeK, adeL, adeN, adeR, adeS, and amvA) were identified, and mutations in the quinolone resistance-determining region of gyrA (Ser81Leu) and parC (Ser84Leu) were considered responsible for fluoroquinolone resistance. ConclusionThis genome sequence data could be used for comparative genomic studies of critical priority A. baumannii strains, as well as to understand the specific features of hospital-associated A. baumannii lineages of international clonal complexes emerging in community settings.

An International Prospective Cohort Study To Validate 2 Prediction Rules for Infections Caused by Third-generation Cephalosporin-resistant Enterobacterales.

BackgroundThe possibility of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacterales (3GC-R-BSI) leads to a trade-off between empiric inappropriate treatment (IAT) and unnecessary carbapenem use (UCU). Accurately predicting 3GC-R-BSI could reduce IAT and UCU. We externally validate 2 previously derived prediction rules for community-onset (CO) and hospital-onset (HO) suspected bloodstream infections.MethodsIn 33 hospitals in 13 countries we prospectively enrolled 200 patients per hospital in whom blood cultures were obtained and intravenous antibiotics with coverage for Enterobacterales were empirically started. Cases were defined as 3GC-R-BSI or 3GC-R gram-negative infection (3GC-R-GNI) (analysis 2); all other outcomes served as a comparator. Model discrimination and calibration were assessed. Impact on carbapenem use was assessed at several cutoff points.Results4650 CO infection episodes were included and the prevalence of 3GC-R-BSI was 2.1% (n = 97). IAT occurred in 69 of 97 (71.1%) 3GC-R-BSI and UCU in 398 of 4553 non–3GC-R-BSI patients (8.7%). Model calibration was good, and the AUC was .79 (95% CI, .75–.83) for 3GC-R-BSI. The prediction rule potentially reduced IAT to 62% (60/97) while keeping UCU comparable at 8.4% or could reduce UCU to 6.3% (287/4553) while keeping IAT equal. IAT and UCU in all 3GC-R-GNIs (analysis 2) improved at similar percentages. 1683 HO infection episodes were included and the prevalence of 3GC-R-BSI was 4.9% (n = 83). Here model calibration was insufficient.ConclusionsA prediction rule for CO 3GC-R infection was validated in an international cohort and could improve empirical antibiotic use. Validation of the HO rule yielded suboptimal performance.

Integration of FDG-PET/CT in the Diagnostic Workup for Staphylococcus aureus Bacteremia: A Prospective Interventional Matched-cohort Study

Staphylococcus aureus bacteremia (SAB) is uniquely characterized by focal pyogenic complications that might not be apparent clinically. We investigated the benefit of adding fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in the workup of patients with SAB. In a matched-cohort study patients with SAB (intervention group) were prospectively recruited to undergo FDG-PET/CT 7-14 days after diagnosis. Treatment was directed by FDG-PET/CT findings. Clinical outcomes were compared with a control group of patients with SAB who had not undergone FDG-PET/CT, matched by age, Charlson score, methicillin susceptibility, and survival duration to FDG-PET/CT. The primary outcome was 90-day mortality. Residual confounding was controlled through regression analyses. During the study period 149 patients with 151 separate episodes of SAB underwent FDG-PET/CT and were compared with 150 matched patients with 151 SAB episodes. Patients in the intervention group acquired infections more frequently in the community and had less frequently solid malignancies and more frequently high-risk SAB. Ninety-day mortality in the intervention group was significantly lower than in the control group (21/151 [13.9%] vs 43/151 [28.5%], P = .002). The difference remained significant in a subgroup analysis of patients with community-onset infections without malignancy and among patients with low-risk SAB. Controlling for other risk factors for mortality, FDG-PET/CT performance among all patients was independently associated with lower mortality (OR, .39; 95% CI, .18-.84). Patients in the intervention group had longer duration of treatment and more focus control procedures performed compared with the control group. FDG-PET/CT in patients with SAB seems to improve survival through guidance of treatment duration and co-interventions.

COVID-19: a retrospective cohort study with focus on the over-80s and hospital-onset disease

BackgroundData from the UK COVID-19 outbreak are emerging, and there are ongoing concerns about a disproportionate effect on ethnic minorities. There is very limited information on COVID-19 in the over-80s, and the rates of hospital-onset infections are unknown.MethodsThis was a retrospective cohort study from electronic case records of the first 450 patients admitted to our hospital with PCR-confirmed COVID-19, 77% of the total inpatient caseload to date. Demographic, clinical and biochemical data were extracted. The primary endpoint was death during the index hospital admission. The characteristics of all patients, those over 80 years of age and those with hospital-onset COVID-19 were examined.ResultsThe median (IQR) age was 72 (56, 83), with 150 (33%) over 80 years old and 60% male. Presenting clinical and biochemical features were consistent with those reported elsewhere. The ethnic breakdown of patients admitted was similar to that of our underlying local population. Inpatient mortality was high at 38%.Patients over 80 presented earlier in their disease course and were significantly less likely to present with the typical features of cough, breathlessness and fever. Cardiac co-morbidity and markers of cardiac dysfunction were more common, but not those of bacterial infection. Mortality was significantly higher in this group (60% vs 28%, p < 0.001). Thirty-one (7%) patients acquired COVID-19 having continuously been in hospital for a median of 20 (14, 36) days. The peak of hospital-onset infections occurred at the same time as the overall peak of admitted infections. Despite being older and more frail than those with community-onset infection, their outcomes were no worse.ConclusionsInpatient mortality was high, especially among the over-80s, who are more likely to present atypically. The ethnic composition of our caseload was similar to the underlying population. While a significant number of patients acquired COVID-19 while already in hospital, their outcomes were no worse.

Impact of a Multiplex Polymerase Chain Reaction Assay on the Clinical Management of Adults Undergoing a Lumbar Puncture for Suspected Community-Onset Central Nervous System Infections.

Patients admitted from the community with a suspected central nervous system (CNS) infection require prompt diagnostic evaluation and correct antimicrobial treatment. A retrospective, multicenter, pre/post intervention study was performed to evaluate the impact that the BioFire® FilmArray® meningitis/encephalitis (ME) panel run in-house had on the clinical management of adult patients admitted from the community with a lumbar puncture (LP) performed for a suspected CNS infection. The primary outcome was the effect that this intervention had on herpes simplex virus (HSV) polymerase chain reaction (PCR) turnaround time (TAT). Secondary outcomes included the effect that this intervention had on antiviral days of therapy (DOT), total antimicrobial DOT, and hospital length of stay (LOS). A total of 81 and 79 patients were included in the pre-intervention and post-intervention cohorts, respectively. The median HSV PCR TAT was significantly longer in the pre-intervention group (85 vs. 4.1 h, p < 0.001). Total antiviral DOT was significantly greater in the pre-intervention group (3 vs. 1, p < 0.001), as was total antimicrobial DOT (7 vs. 5, p < 0.001). Pre-intervention hospital LOS was also significantly longer (6.6 vs. 4.4 days, p = 0.02). Implementing the ME panel in-house for adults undergoing an LP for a suspected community-onset CNS infection significantly reduced the HSV PCR TAT, antiviral DOT, total antimicrobial DOT, and hospital LOS.

Incidence of community-onset extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae infections: an 11-year population-based study in Denmark

Background: Data elucidating trends of community-onset extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae infections remain sparse in low prevalence areas. We conducted a population-based study to determine the incidence, temporal trends and co-resistance of community-onset ESBL infections.Methods: We identified all recorded episodes of E. coli and K. pneumoniae bacteraemia and urinary tract infections in adult patients (>15 years) in the North Denmark Region between 2007–2017. Using population-based registries, we obtained information on demographics and place of acquisition, and investigated the standardized incidence rates and temporal trends of community-onset ESBL infections and the associated patterns of co-resistance.Results: A total of 3741 episodes of community-onset ESBL E. coli or K. pneumoniae infections were observed during the study period, with the annual standardized incidence rate increasing from 7.5 to 105 per 100,000 person-years between 2007–2017. The increase was conveyed primarily by a rise in E. coli urinary tract infections shifting from being mainly healthcare-associated to community-acquired. ESBL-producing isolates increased from 0.5 to 4.0% with considerable co-resistance.Conclusion: The proportion of E. coli and K. pneumoniae isolates producing ESBL have increased considerably in the North Denmark Region. The increasing incidence and frequent co-resistance should raise awareness among physicians responsible for empirical antibiotic treatment.