Associations of Antimicrobial-Resistant Gram-Negative Bloodstream Infections with Outcomes among Hospitalized Pediatric Patients in the United States

Author(s):  
Alicen Burns Spaulding ◽  
David Watson ◽  
Jill Dreyfus ◽  
Phillip Heaton ◽  
Christina Koutsari ◽  
...  

Abstract Objective The aim of this study was to assess the impact of pediatric antimicrobial-resistant gram-negative bloodstream infections (GNBSIs). Methods A retrospective cohort study (2009–2016) was conducted using the Premier Healthcare Database among pediatric admissions with GNBSIs at hospitals reporting microbiology data. Infections for neonates and nonneonates were classified as multidrug resistance (MDR), resistant to one or two antibiotic drug classes (1–2DR), or susceptible. Results Among 1,276 GNBSIs, 266 (20.8%) infections were 1–2DR and 23 (1.8%) MDR. Compared with susceptible GNBSIs, MDR nonneonates had higher mortality and higher costs, whereas 1–2DR neonates had longer stays and higher costs. Conclusions Antimicrobial-resistant GNBSIs were associated with worse outcomes among pediatric hospitalized patients.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S73-S73
Author(s):  
Alicen B Spaulding ◽  
David Watson ◽  
Jill Dreyfus ◽  
Phillip Heaton ◽  
Anupam Kharbanda

Abstract Background Antimicrobial-resistant (AMR) Gram-negative bloodstream infections (GNBSIs) are more challenging to treat and may be associated with higher rates of morbidity and mortality. However, no recent studies have assessed the impact of pediatric AMR GNBSIs on outcomes. This study’s objective was to analyze the impact of AMR GNBSIs on mortality, length of stay (LOS), and costs among pediatric hospital admissions in the United States. Methods We conducted a retrospective cohort study of patients ages < 19 from the Premier Healthcare Database (2009–2016) limited to hospitals reporting ≥4 years of blood culture data and to encounters with susceptibility testing among the five most common laboratory-confirmed GNBSIs. AMR was defined per pathogen according to Centers for Disease Control and Prevention criteria. Outcomes mortality, LOS, and total patient encounter costs were compared between AMR and susceptible GNBSIs using Bayesian hierarchical regression modeling, which allowed us to analyze outcomes at the pathogen-level and to incorporate adjustment for confounding factors in order to produce risk-adjusted average differences or risk ratios (RR), and corresponding 95% credible intervals (CrI). Results Among 1,279 GNBSI encounters with susceptibility testing from 104 hospitals, 153 (12%) were AMR, but varied by pathogen. AMR GNBSI occurred more often among non-neonates (62% vs. 51%); non-neonates more often had hospital-acquired infections (27% vs. 13%) or were transferred from a healthcare facility (16% vs. 10%) vs. susceptible GNBSIs. The adjusted RR for mortality was 1.31 (95% CrI 0.62, 3.07) and adjusted average differences for LOS were 6.8 days (95% CrI: −0.3, 16.3) and for cost $23800 (95% CrI $400, $53900) comparing AMR to susceptible GNBSIs. Conclusion This study analyzed the impact of AMR GNBSIs, which were rare, on pediatric patient outcomes using laboratory-confirmed GNBSIs with susceptibility results and advanced statistical methods, finding the greatest impact of pediatric AMR on costs. Knowing the impact of AMR GNBSIs can help improve management of these serious infections, increase clinician and patient awareness of the issue, and further strengthen evidence for justifying pediatric antimicrobial stewardship. Disclosures All Authors: No reported Disclosures.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S725-S725
Author(s):  
Sibylle Lob ◽  
Meredith Hackel ◽  
C Andrew DeRyke ◽  
Kelly Harris ◽  
Katherine Young ◽  
...  

Abstract Background Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for complicated urinary tract (cUTI) and complicated intraabdominal infections (cIAI), as well as hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in patients ≥18 years. Clinical trials studying the use of C/T for pediatric patients with cUTI and cIAI are completed, and HABP/VABP pediatric studies are underway. We evaluated the antimicrobial activity of C/T against gram-negative isolates collected from patients ≤17 years in the United States (US) as part of the global SMART surveillance program. Methods In 2017-2019, 27 US clinical labs each collected up to 250 consecutive gram-negative pathogens per year. A total of 1336 isolates were collected from pediatric patients. MICs were determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible Enterobacterales (Ebact) and P. aeruginosa were screened for genes encoding β-lactamases. Results Among the 944 collected Ebact and 220 P. aeruginosa isolates, 40.7% and 76.4%, respectively, were collected from patients with respiratory tract infections, 37.0% and 10.0% from UTI, 13.7% and 8.2% from IAI, and 8.3% and 5.0% from bloodstream infections. The table shows antimicrobial susceptibility of Ebact, P. aeruginosa, and select phenotypes. C/T was active against 98% of Ebact, including 50 of 51 and 12 of 13 ESBL-non-CRE phenotype E. coli and K. pneumoniae, respectively. Among P. aeruginosa, C/T was active against 95% of isolates, 9-21 percentage points higher than the comparator β-lactams, and it maintained activity against 71-75% of P. aeruginosa isolates nonsusceptible to commonly used β-lactams. Among the 21 C/T-nonsusceptible Ebact, 2 isolates carried KPC and ESBL and 3 isolates carried only ESBL; in 16 isolates no β-lactamases were detected, of which 15 were species with intrinsic AmpC. Among 12 C/T-nonsusceptible P. aeruginosa, no acquired β-lactamases were detected, likely indicating chromosomally-mediated resistance mechanisms. Results Table Conclusion C/T could be a potential new treatment option for US pediatric patients with infections caused by Ebact and P. aeruginosa, including resistant phenotypes. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kelly Harris, PharmD, BCPS, Merck & Co. Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)


2004 ◽  
Vol 48 (9) ◽  
pp. 3491-3497 ◽  
Author(s):  
Mathias W. R. Pletz ◽  
Lesley McGee ◽  
James Jorgensen ◽  
Bernard Beall ◽  
Richard R. Facklam ◽  
...  

ABSTRACT The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, ≥8 mg/liter) S. pneumoniae isolates (n = 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002. Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (P = 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes. Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups. Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain23F-1 clone being most frequent (16% of all isolates). Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones. Fifty percent of the isolates were resistant to any three drug classes. Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes. In 16% of the isolates, there was evidence of an active efflux mechanism. An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter). Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread.


Author(s):  
Christina M Ackerman ◽  
Jennifer L Nguyen ◽  
Swapna Ambati ◽  
Maya Reimbaeva ◽  
Birol Emir ◽  
...  

Abstract Background Pregnant women with coronavirus disease 19 (COVID-19) may be at greater risk of poor maternal and pregnancy outcomes. This retrospective analysis reports clinical and pregnancy outcomes among hospitalized pregnant women with COVID-19 in the United States. Methods The Premier Healthcare Database – Special Release was used to examine the impact of COVID-19 among pregnant women aged 15–44 years who were hospitalized and who delivered compared with pregnant women without COVID-19. Outcomes evaluated were COVID-19 clinical progression, including the use of supplemental oxygen therapy, intensive care unit admission, critical illness, receipt of invasive mechanical ventilation/extracorporeal membrane oxygenation, and maternal death, and pregnancy outcomes, including preterm delivery and stillbirth. Results Overall, 473,902 hospitalized pregnant women were included, of whom 8584 (1.8%) had a COVID-19 diagnosis (mean [SD] age 28.4 [6.1] years; 40% Hispanic). The risk of poor clinical and pregnancy outcomes was greater among pregnant women with COVID-19 compared with pregnant women without a COVID-19 diagnosis in 2020; the risk of poor clinical and pregnancy outcomes increased with increasing age. Hispanic and Black non-Hispanic women were consistently observed to have the highest relative risk of experiencing poor clinical or pregnancy outcomes across all age groups. Conclusions Overall, COVID-19 had a significant negative impact on maternal health and pregnancy outcomes. These data help inform clinical practice and counselling to pregnant women regarding the risks of COVID-19. Clinical studies evaluating the safety and efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 in pregnant women are urgently needed.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S360-S360 ◽  
Author(s):  
Thomas P Lodise ◽  
Roger Echols ◽  
Weiying Wang ◽  
Frank Corvino ◽  
Bin Cai

Abstract Background Carbapenem resistance (CR) is a growing threat in hospitals in the United States and worldwide. We evaluated the prevalence and geographic distribution of CR among six most common Gram-negative (GN) bloodstream infection (BSI) pathogens in US hospitals. Methods We analyzed microbiology data in a cohort of adults (≥18 years) hospitalized in 181 US hospitals contributing microbiology data to the Premier Healthcare Database (October 2010–September 2015) with blood cultures positive for six most common GN pathogens (S. maltophilia assumed 100% CR). We report CR prevalence by pathogen, hospital ward (ICU vs. floor), and census region. Results Of the 43,095 GN BSIs included, 1,513 (3.5%) were caused by the six most common CR pathogens (Figure 1). CR was more frequently isolated from patients with an ICU stay (4.7%) vs. those without (2.7%). Nearly 75% (n = 1,100) of CR occurred in nonfermenters (S. maltophilia, P. aeruginosa, and A. baumannii). Among individual organisms, the prevalence of CR—outside of S. maltophilia—was highest among A. baumannii, 35.1%, and lowest among E. coli, 0.2% (Figure 2). Geographically, CR prevalence ranged from highest in the Mountain region (7.1%) to lowest in the West North Central (2.3%) (Figure 3). The maximum CR prevalence occurred in A. baumannii from the East North Central (55.7%), and the minimum in E. coli from the West North Central (0.05%) regions. Conclusion Among six most frequently isolated pathogens in BSI, the overall CR prevalence is 3.5%. The wide variations in prevalence based on organism, location in the hospital, and geography emphasize the clinical importance of knowing local pathogen and resistance patterns in order to optimize empiric treatment. Disclosures A. F. Shorr, Astellas: Consultant and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. Cidara: Consultant, Consulting fee. Merck & Co.: Consultant and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. T. P. Lodise Jr., Motif BioSciences: Board Member, Consulting fee.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S852-S853
Author(s):  
Natalie McCarthy ◽  
James Baggs ◽  
Kelly M Hatfield ◽  
Hannah Wolford ◽  
Snigdha Vallabhaneni ◽  
...  

Abstract Background Opioid misuse is epidemic in the United States (US), and persons who inject drugs are at increased risk for serious bacterial and fungal infections, including Candida bloodstream infections. Historically, candidemia has occurred almost exclusively among patients with severe underlying illness and extensive healthcare exposure. We examined whether the opioid crisis may be having an impact on the epidemiology of candidemia in the United States. Methods Using data from 200 US hospitals reporting to the Premier Healthcare Database (PHD) between 2012–2017, we conducted a retrospective study among hospitalized persons ≥ 18 years. Candidemia was defined by any blood culture yielding Candida species. Drug use-associated (DUA)-candidemia hospitalizations were defined as hospitalizations having both candidemia and at least one ICD-9-CM or ICD-10-CM diagnostic code for recreational drug use; drugs were classified as opioids, cocaine, amphetamines, or other drugs (excluding cannabis, alcohol, and nicotine). We described the characteristics and annual trends of candidemia hospitalizations, stratified by drug use. Results Of 7,590 candidemia hospitalizations during 2012–2017, 679 (9%) were DUA-candidemia. During this time, the rate of DUA-candidemia increased from 3.6 to 9.1 per 100,000 hospitalizations, while the rate of non-DUA-candidemia decreased from 64.7 to 55.6 per 100,000 hospitalizations. Patients with DUA-candidemia were younger (median 40 vs. 64 years), had a longer lengths of stay (median 14 vs. 13 days), and had lower in-hospital mortality (12% vs. 26%). Among DUA-candidemia hospitalizations, opioids accounted for 78% of substances identified. Among patients aged 18–44 years, the proportion of candidemia hospitalizations associated with drug use more than tripled from 13% in 2012 to 44% in 2017 (Figure 1). Conclusion DUA-candidemia hospitalizations increased almost 3-fold during 2012–2017, with drug use identified in nearly half of candidemia patients ages 18–44 years in 2017. These data suggest that the opioid crisis is having an impact on the epidemiology of candidemia in the United States, especially among young adults, underscoring an additional negative consequence of the ongoing crisis. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Bin Cai ◽  
Glenn Tillotson ◽  
Darrin Benjumea ◽  
Patrick Callahan ◽  
Roger Echols

Abstract Background Stenotrophomonas maltophilia is an opportunistic pathogen observed in both nosocomial and community-onset infections. S. maltophilia is intrinsically resistant to many currently available broad-spectrum antibiotics and is often not included in antimicrobial resistance surveillance studies or stewardship programs’ guidelines. Methods A retrospective cohort study of patients with S. maltophilia bloodstream infection (BSI) in the United States was conducted using the 2010–2015 US Premier Healthcare Database. This study described patient characteristics, infection characteristics, antibiotic treatment, and discharge status. Results S. maltophilia was the most common carbapenem-resistant, gram-negative pathogen causing BSIs in this database. Of 486 unique patients with S. maltophilia BSI, 44.6% were assessed as community-onset, 95% of cultures were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and 84% were susceptible to fluoroquinolones; 39.1% of patients received a potentially effective antibiotic (fluoroquinolone, doxycycline, ceftazidime, minocycline, or TMP-SMX) during the empiric treatment period (≤3 days post–index culture date), whereas 85.8% received a potential effective antibiotics during the definitive treatment period. The most common antibiotic received as definitive treatment was levofloxacin (48.9%). TMP-SMX was used infrequently empirically (10.5%) and in 38.3% during the definitive period. Compared with BSIs caused by other carbapenem-resistant gram-negative pathogens, S. maltophilia BSIs were more likely to be community-onset, and were more likely to be discharged to home and to have a lower mortality rate. Conclusions This study demonstrated that patients at risk for S. maltophilia BSI are highly variable and that standard of care is not clearly defined, leading to questions regarding the appropriateness of antibiotic treatment among patients. Further efforts are needed to better recognize and treat S. maltophilia BSI.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S737-S737
Author(s):  
Alicen B Spaulding ◽  
David Watson ◽  
Jill Dreyfus ◽  
Phillip Heaton ◽  
Anupam Kharbanda

Abstract Background Distinguishing blood culture (BC) results between common contaminants (CC) and truly pathogenic organisms can be challenging, especially among pediatric patients, but is important for effective clinical care. However, no recent studies have analyzed the true positivity of common BC contaminants in pediatric patients using linked laboratory data from a large national sample of United States hospitals. Methods We conducted a retrospective cohort study among patients ages < 19 using the Premier Healthcare Database (2009–2016), limiting to hospitals reporting ≥ 4 years of BC data and encounters with one of the five most frequent CC among laboratory-confirmed BC. True positivity was defined for each CC as a second positive BC within 48 hours among all BCs. A multivariable logistic regression model including all variables significant in univariate analyses was created comparing encounters: (1) with and without a second BC; and (2) second BC positive vs. negative, with corresponding adjusted odds ratios (aOR) and 95% confidence intervals (CI) reported. Results A total of 5056 isolates corresponding to 4915 encounters with a CC were included in this analysis; 3075 (61%) isolates had a second BC within 48 hours. Adjusted odds of a second BC were higher for encounters from urban (aOR: 1.73, 95% CI: 1.31, 2.29) and ≥ 500 bed hospitals (aOR 1.40, 95% CI: 1.20,1.63). True positivity was 20.2% for coagulase-negative staphylococci (CoNS), 5.9% for Bacillus spp., 5.2% for Viridans group streptococci, 5.0% for Diphtheroids spp., and 3.1% for Micrococcus spp. True positivity for CoNS was higher among neonates but all other organisms were higher for non-neonates (figure). Adjusted odds of true positivity were higher for encounters with chronic conditions (OR 1.44, 95% CI: 1.13, 1.82), a central line in place (OR: 1.65, 95% CI: 1.30, 2.10), per length of stay day (OR: 1.01 (1.01, 1.01), and with an intensive care unit admission (OR: 1.39, 95% CI: 1.08, 1.77). Conclusion True positivity varied substantially by organism, and in most cases was higher among non-neonates. Regional variations for conducting a second BC within 48 hours were found, and more seriously ill patient encounters were more likely to have a common contaminant be pathogenic. Disclosures All authors: No reported disclosures.


Sign in / Sign up

Export Citation Format

Share Document