bluuebunny/crossref_metadata_2025 huggingface dataset:
482. Time Series Analysis of Antimicrobial Consumption and Pseudomonas aeruginosa Resistance in an Academic Medical Center in the United States (2013–2018)
Authors: Dewart Courtney M , Hebert Courtney , Pancholi Preeti , Stevenson Kurt
Published: October 2019

Background

Monitoring antimicrobial use and resistance are key components of initiatives to promote antimicrobial stewardship and prevent antimicrobial-resistant infections. In this surveillance study, we evaluated trends in resistance among healthcare-associated P. aeruginosa isolates and potential associations with antimicrobial consumption.

Methods

We established a retrospective cohort of P. aeruginosa isolates collected ≥48 hours after inpatient admission at a 1,300-bed academic medical center from July 1, 2013 to July 31, 2018. We included isolates from all clinical cultures and retained the first isolate for a patient encounter. We defined the multidrug-resistant (MDR) status in accordance with the phenotype definitions established by the Centers for Disease Control and Prevention. We calculated the monthly percentage of class-specific resistance and MDR status among isolates. We measured monthly antimicrobial consumption as days of therapy per 1,000 patient-days. To evaluate potential associations between identified trends in resistance and antimicrobial use, we constructed autoregressive integrated moving average models (ARIMA) with transfer functions.

Results

Of 1,897 isolates included in the analysis, 303 (16.0%) were classified as MDR P. aeruginosa. The rate of healthcare-associated P. aeruginosa infections and percent of MDR isolates remained stable over the five-year study period. However, we identified trends in resistance to specific antimicrobial classes: there was a significant increase in resistance to antipseudomonal carbapenems, while resistance to aminoglycosides and extended-spectrum cephalosporins decreased. Using the ARIMA modeling strategy, bivariable analyses of resistance and antimicrobial use revealed that carbapenem-resistant P. aeruginosa was positively correlated with the use of antipseudomonal carbapenems at a 1-month lag and ertapenem at a 5-month lag.

Conclusion

Risk assessments that only measure rates of MDR organisms may miss underlying trends in class resistance. Increasing carbapenem resistance despite a stable proportion of MDR isolates highlights a critical area for continued monitoring and antimicrobial stewardship initiatives targeted at carbapenem use in our hospital.

Disclosures

All authors: No reported disclosures.
497. Changing Molecular Epidemiology of CRE from 2016–2018, Increase in the Unknown
Authors: Le Mi , Bhaurla Sandeep , OYong Kelsey , McKinnell James , Yang Yang , Manalo Audrey , Ramirez Julio , Hemarajata Peera , Green Nicole , Terashita Dawn
Published: October 2019

Background

Historically, endemic Klebsiella pneumoniae carbapenemase (KPC) has accounted for the majority of carbapenem-resistant Enterobacteriaceae (CRE) in Los Angeles County (LAC). The LAC Department of Public Health (DPH) initiated enhanced CRE surveillance in 2016 to determine CRE prevalence and track emerging non-KPC resistance mechanisms (IMP, NDM, OXA, and VIM) among CRE to describe characteristics and identify local epidemiology for novel multi-drug-resistant organism (N-MDRO) infection and colonization.

Methods

CRE isolates were voluntarily submitted by local clinical laboratories for mechanism detection by LAC Public Health Laboratory via MALDI-TOF and Nanosphere BC-GN. Baseline isolates were collected in 2016. Results are then presented by year through 2018. For N-MDRO cases, LACDPH interviewed healthcare facility (HCF) staff and cases to obtain case characteristics. Data were analyzed via Microsoft Access and SAS.

Results

CRE surveillance isolates were voluntarily submitted by 31 labs representing 34% (34/96) LAC hospitals and 1 large regional lab serving 60% of skilled nursing facilities from January 2016 to December 2018. LACDPH tested 1438 CRE isolates during the study period, 1168 (81%) were carbapenemase producing (CP). The proportion of CP CRE and KPC CRE declined over the study period (Table 1). NDM was the most common non-KPC (n = 30) followed by OXA (n = 28). The proportion of CRE with no genotypic marker increased over the course of the study. Case characteristics were obtained from 41 non-KPC CP CRE cases; median age was 66 years (range: 6–94 years); 12 (29%) expired. Among the 41 cases, 20 (49%) had a central line; 11 (27%) had surgery; 14 (34%) had antibiotics in the 6 months prior to culture date. Of the 41 cases, 11 (27%) had international healthcare exposure within 12 months with an invasive procedure and/or antibiotics.

Conclusion

Surveillance in a large urban setting suggests the molecular epidemiology of CRE is changing, with declining prevalence of KPC, increasing metallo-β-lactamase CP, and large proportion of isolates without resistance markers detected. Given the worrisome trends in non-KPC CRE, more systematic surveillance is warranted, potentially using more robust molecular epidemiology.

Disclosures

All authors: No reported disclosures.
499. Carbapenem-resistant Enterobacteriaceae (CRE)-associated Infections and Prolonged Colonization among Hospitalized Patients Colonized by CRE
Authors: Khawcharoenporn Thana , Laichuthai Wipada
Published: October 2019

Background

This study aims to determine rates of subsequent carbapenem-resistance Enterobacteriaceae (CRE)-associated infections and prolonged colonization among patients colonized by CRE and to identify risk factors of such conditions.

Methods

This study was conducted among a cohort of hospitalized adult patients colonized by CRE at any sites from June 1, 2015 to December 31, 2018. The patients had been prospectively identified by the Infection Control (IC) Division of a Thai tertiary-care hospital. According to the hospital’s IC protocol, patients with CRE colonization/infections were isolated and underwent CRE cultured at the colonized/infected sites every week until the cultures have turned negative for 2 consecutive times. Prolonged colonization was defined as having CRE colonization more than 30 days.

Results

Of the 125 patients identified, 25 were excluded due to death, being transferred, or discharged within 48 hours of CRE colonization detected. The final cohort included 100 patients, the median age was 74 years, 48% were male, the most common colonized site was rectum (37%) and 20 patients (20%) developed subsequent CRE-associated infections. The median time from colonization to infection was 13 days and the most common site of infection was bloodstream (45%). Independent factors associated with subsequent CRE-associated infections were the number of colonization sites [adjusted odds ratio (aOR) 7.98, P < 0.001)], central line insertion during admission (aOR 7.97, P = 0.009) and receipt of vancomycin during admission (aOR 24.77, P = 0.02). Prolonged colonization was observed in 13 of 77 evaluable patients (17%). There were trends toward significance that the length of hospital stay and duration of antibiotic prior to colonization were associated with prolonged colonization (P < 0.10).

Conclusion

The findings suggest high rates of subsequent CRE-associated infections and prolonged colonization among the study population. Patients with risk factors for subsequent infections should be closely monitored and empirically-treated with antibiotics active against CRE while those with risk factors for prolonged colonization should receive continued surveillance and isolation to prevent CRE transmission.

Disclosures

All authors: No reported disclosures.
503. Comparison of IMP Carbapenemase-Producing Enterobacteriaceae (CPE) and Non-Carbapenemase-Producing Enterobacteriaceae: A Multicenter Prospective Study of Clinical and Molecular Epidemiology in Japan
Authors: Hayakawa Kayoko , Nakano Ryuichi , Hase Ryota , Shimatani Michitsugu , Kato Hideaki , Hasumi Jumpei , Doi Asako , Sekiya Noritaka , Nei Takahito , Okinaka Keiji , Kasahara Kei , Kurai Hanako , Nagashima Maki , Miyoshi-Akiyama Tohru , Kakuta Risako , Yano Hisakazu , Ohmagari Norio
Published: October 2019

Background

IMP CPE are the dominant CPE type in Japan. We aimed to compare its epidemiology to that of non-CPE (NCPE).

Methods

Patients with isolation of carbapenem-resistant Enterobacteriaceae (CRE) with meropenem MIC ≥2 mg/L or imipenem MIC ≥2 mg/L and cefmetazole MIC ≥64 mg/L were included from August 2016 to March 2018. Adjusted outcome analyses were conducted using a generalized estimating equation model with weighting based on the inverse probability of propensity scores (PS).

Results

Ninety isolates (27 CPE and 63 NCPE) were collected from 88 patients (53 male) in 7 hospitals. CPE included 10 E. cloacae (ENC), 6 K. pneumoniae (KP), 4 E. coli (EC), 3 C. freundii (CF), 2 K. oxytoca, and 1 each of E. aerogenes (EA) and S. marcescens (SM). NCPE included 34 EA, 15 ENC, 4 each of KP, SM, and 2 CF. All CPE were positive for IMP carbapenemase (11 IMP-11, 6 IMP-42, 4 IMP-6, and 3 each of IMP-10 and IMP-1). Most of CPE/NCPE were isolated from sputum (39%), intra-abdomen (21%), and urine (20%). Levofloxacin, gentamicin, and amikacin resistance were found in 6 (22%), 4 (15%), and 1 (4%) CPE, respectively, and 6 (10%), 6 (10%), and 0 NCPE, respectively. Eighteen (67%) blaIMP were transferable by conjugation. Cases of CPE involved older patients with more frequent use of devices and carbapenem exposure than those in cases of NCPE (table). The mortality was similar in the 2 groups. Length of hospital stay (LOS) after CPE/NCPE isolation was significantly higher in the CPE group after PS adjustment (P = 0.02).

Conclusion

CPE had distinct epidemiological characteristics, and CPE isolation was associated with a prolonged hospital stay. Defining the underlying resistance mechanism of CRE is important for appropriate management.

Disclosures

All authors: No reported disclosures.
522. In Vitro Antimicrobial Activity of Ceftazidime/Avibactam Compared with Ceftolozane/Tazobactam Against Real-world Clinical Isolates of Pseudomonas aeruginosa at a Large Academic Tertiary Care Hospital
Authors: Patel Twisha S , Kaye Keith S , Marshall Vince , Krishnan Jay , Mills John , Albin Owen , Smith Aaron , Young Carol , Lephart Paul , Pogue Jason M
Published: October 2019

Background

Ceftazidime/avibactam (CZA) and ceftolozane-tazobactam (CT) are new additions to the antibiotic armamentarium with activity against gram-negative pathogens, most notably drug-resistant Pseudomonas aeruginosa (PSA). The purpose of this study was to compare the in vitro activity of CZA and CT against a large real-world sample of clinical isolates of PSA displaying different phenotypes of resistance to conventional β-lactams at an institution where both CZA and CT are routinely tested on all isolates.

Methods

All cultures from patient infections with PSA from May 2018 to February 2019 at Michigan Medicine were included. Minimum inhibitory concentrations (MICs) for all β-lactams were determined using TREK broth microdilution panels and isolates were considered susceptible to CZA if the MIC was ≤8 mg/L and CT if the MIC was ≤4 mg/L.

Results

A total of 2,972 isolates of PSA from clinical specimens were included. Table 1 compares CZA and CT susceptibility, MIC50, MIC90, and MIC range for all isolates including those displaying resistance to various β-lactams. Among all isolates of PSA, CZA (96.2% susceptible) was slightly more active than CT (94.2%) and both agents were ~10% more active than the closest comparator (ceftazidime, 86.6%). In vitro activity of cefepime, piperacillin/tazobactam, and meropenem were 84.8%, 78%, and 80.3%, respectively. The activity of both CZA and CT dropped significantly among isolates with pan-β-lactam resistance (i.e., resistance to all conventional anti-pseudomonal β lactams, PBR) but CZA remained more active than CT (59.4% vs. 41.5%, P < 0.001). Of isolates displaying resistance to CT, 84 (48.6%) were susceptible to CZA. However, of those with resistance to CZA, only 24 (21.2%) were susceptible to CT (Table 2).

Conclusion

CZA was the most active β-lactam against PSA isolates at Michigan Medicine. Among PSA with PBR, CZA demonstrated superior activity compared with CT. Additionally, a significant number of isolates with resistance to CT were susceptible to CZA. Our findings are unique compared with other published reports where CT has consistently demonstrated greater activity than CZA against resistant P. aeruginosa and suggest routine testing of both CT and CZA should occur.

Disclosures

All authors: No reported disclosures.
524. Understanding the Treatment of Carbapenem-Resistant Enterobacteriaceae (CRE) Infections in the United States (US): Insights from a Survey of Hospital-Based Pharmacists
Authors: Potoski Brian , Buehrle Deanna , Nguyen Minh-Hong , Clancy Cornelius J
Published: October 2019

Background

New anti-CRE antibiotics (ceftazidime–avibactam, C-A; meropenem-vaborbactam, M-V; plazomicin, PLZ) are associated with improved outcomes and lower toxicity than polymixins (PMs; colistin; polymyxin B) in treating CRE infections. We previously demonstrated that ~40% (range: 28–71%) and ~23% (16–41%) of CRE infections in the United States were treated with PMs or new agents, respectively, as of 1/19.

Methods

To understand formulary status, availability and positioning of new anti-CRE agents and PMs, we surveyed hospital-based Society of ID Pharmacists (SIDP) members (11–12/18; Qualtrics).

Results

There were 218 respondents from 41 states. Mean CRE infections encountered were 2.7/mo (0–36). C-A, M-V, PLZ were formulary restricted or non-formulary but available at 84%, 68% and 31% of hospitals, respectively; agents were stocked at 80%, 37% and 4%. In 33% of instances, C-A was presented to P&T a second time prior to approval. In rank order, reasons for adding a new agent to formulary were improved outcomes/efficacy, safety/toxicity, and local stewardship (ASP) opinion. Ranked reasons for not adding a new agent were infrequency of CRE, cost, concern for misuse, and limited data. A new agent was positioned as first-line against CRE pneumonia (PNA), bacteremia (BSI), abdominal (IAI) and urinary infections by 87%, 90%, 83% and 56% of respondents [Table]. Smaller hospitals (stratified as ≤200, 201–400, >400 beds) were more likely to have not made a formulary decision or have new agents as no buy (P = 0.0005), and less likely to have a new agent stocked (P = 7e-8) or to position a new agent as first line against CRE PNA, BSI and IAI (P = 0.009). Similar associations were not evident by hospital type (academic, community teaching, or non-teaching).

Conclusion

New agents are positioned as the first line against CRE PNA, BSI and IAI at most US hospitals with an SIDP member pharmacist, but they are still prescribed less against CRE infections than PMs nationally. Smaller hospitals are less likely to have mechanisms for using new agents or to position them as the first line. Discrepancies between positioning and use of new agents may reflect a bias in SIDP membership toward larger hospitals with ASP, lags between endorsing a first-line agent and incorporating it into care, and/or conservative ASP approval of agents in individual cases.

Disclosures

All authors: No reported disclosures.
527. Project “Isolation Zero”: Discontinuing Contact Precautions for Patients Colonized/Infected with Multidrug-Resistant Organisms through Community-Level Follow-Up in Spain
Authors: Pérez Martínez Olaia , Rapela Freire Alba , José Pereira Rodríguez Mª
Published: October 2019

Background

In an effort to prevent and control the spread of multidrug-resistant organisms (MDROs), hospitals implement contact precautions (CP) for patients colonized/infected with MDROs. All agencies related to the prevention and control of infections recommend this practice, but they also recognize that is not exempt from unintended consequences. In 2017, SHEA published an expert guideline where they provide recommendations for discontinuation of CP. Currently, the most accepted recommendation is to perform at least one microbiological culture prior to discontinuing CP. The main objective of this project is to implement and evaluate a novel community -level approach to safely discontinue CP in patients with a history of colonization/infection with an MDRO.

Methods

The “Isolation Zero” project (IZ) was rolled out in November 2018 in the healthcare area of A Coruña, Spain. All clinical records of patients included in the MDROs alert system between 2005–2012 in A Coruña were reviewed. Patients included in the study were those who reside in the healthcare area of A Coruña and did not have any positive microbiological culture for MDROs in the last 2 years (Figure 1). Those who met the inclusion criteria were sent a letter suggesting that they obtain a nurse consultation in the next 2 months and that they provide specific MDRO cultures (Figure 2). Finally, the Department of Preventive Medicine (PM) reviewed all the results and identified patients for which CP could be safely discontinued in future hospitalizations.

Results

A total of 792 clinical records were reviewed (Table 1). 184 patients met the inclusion criteria. The response rate was 60.3% (111 patients). The most frequent MDRO tested was MRSA (84.8%), followed by MDR Acinetobacter (7.6%). CP were withdrawn for a total of 83 patients, while 15 patients continued to test positive (Table 2).

Conclusion

These results suggest that even after more than 2 years without a positive result, 13,5% of patients remain positive for MDROs. Therefore, in order to safely minimize the use of CP, we conclude that an approach similar to that used in IZ is a good option for PM Departments. Follow-up at the community -level can help reduce the number of hospital isolations required and can help improve the overall quality of care.

Disclosures

All authors: No reported disclosures.
528. Longitudinal Evaluation of Chlorhexidine Resistance Among Multidrug-Resistant Organisms in Relation to Intervention of Daily Chlorhexidine Bathing in Adult Intensive Care Units
Authors: Ja Kim Min , Seung Chung You , Lee Hojin , Woong Suh Jin , Cheong Yoojung , Kyu Lee Chang
Published: October 2019

Background

Chlorhexidine digluconate (CHG), the most widely used antiseptic, has recently been applied to patient washing to decolonize the multidrug-resistant organisms (MDROs), but there are little data on susceptibilities of MDROs to CHG. The purpose of this study was to evaluate CHG resistance among MDROs before and after the intervention of daily CHG bathing in adult intensive care units (ICUs).

Methods

The intervention of daily body washing with 2% CHG cloths were taken in adult patients the medical or surgical ICU of 23-bed by a crossover manner for 6 months (MICU, July to December 2017; SICU, January to June 2018) in a 1,050-bed, university hospital in the Republic of Korea. Available MDRO isolates were randomly selected from clinical cultures of ICU patients within 6 months before, during and after the intervention, including MRSA, MR-CoNS, VRE, Carbapenem-resistant Pseudomonas aeruginosa (CR-PA), CR-Acinetobacter baumannii (CR-AB). Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method set by the Clinical Laboratory Standards Institute. Determination of the minimum bactericidal concentrations (MBCs) was performed by subculturing 10 µL from each well without visible microbial growth. Cumulative amounts of CHG used in both ICUs was estimated across the study period from January 2008 to June 2018.

Results

The cumulative CHG consumption from both ICUs increased sharply from 27,503 g to 29,556 g after one-year intervention. The ranges of MICs and MBCs of CHG among MDRO clinical isolates selected by a 6-month phase are summarized in Table 1. Particularly, CR-PA and CR-AB isolates revealed four to eight times higher MICs and MBCs compared with the majority of Gram-positives excepting some VRE isolates. On the other hand, neither MICs and MBCs ranges of CHG from the MDRO isolates nor the monthly incidence of the MDROs from both ICUs were significantly increased before and after the intervention of daily CHG bathing.

Conclusion

This study indicates that some Gram-negative MDRO isolates with higher MICs and MBCs of CHG might be from longstanding exposure to CHG or efflux pumps. Although 2% daily CHG bathing uses over 1,000 times higher concentrations than the lethal concentration, it might be needed to monitor CHG resistance among MDROs.

Disclosures

All authors: No reported disclosures.
535. Multicenter Study of the Prevalence of Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae in Patients Admitted to the Intensive Care Units of 7 Major Hospitals in Kuwait
Authors: Al Fadhli Amani , Jamal Wafaa Y , Rotimi Vincent O
Published: October 2019

Background

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has become an important epidemiological change in infectious diseases in the last 10 years. The gut is an important reservoir for these isolates thereby creating an opportunity for dissemination in a hospital setting especially the intensive care units (ICUs). The objective of this study was to investigate the colonization rates of patients, by CRE, admitted to the ICUs of 7 teaching hospitals.

Methods

Rectal swabs were collected during July 2017 to November 2018 from all patients on the day of ICU admission and 1 week after in each hospital. The samples were screened by direct plating on MacConkey agar containing 10-μg meropenem. Bacterial species identification was performed using the VITEK-2 system. The minimum inhibitory concentrations (MICs) of 14 antibiotics were determined by using Etest. Genes encoding carbapenem resistance was detected by PCR and sequencing. Their clonal relationship was determined by pulsed-field gel electrophoresis (PFGE).

Results

A total of 2580 Enterobacteriaceae were isolated from all patients. Seventy-four (2.9%) were confirmed as CRE most of which were from patients in Adan (AH: 36.5%) and Mubarak (MH: 46%) hospitals. Sixty (81.1%) harbored one or more of the tested carbapenemases genes. Forty-six (62.2%) carried blaOXA-181, 9 (12.2%) blaOXA-48, one blaKPC-2, while 14 (18.9%) carried 2 genes. Combinations of blaKPC-2 and blaOXA-181 genes were found in 5 (6.8%), blaVIM-1 and blaOXA-181 in 4 (5.4%), blaNDM-5 and blaOXA-181 in 3 (4.1%) and blaNDM-1 and blaOXA-181 in 2 (3.3%). The XbaI PFGE profile-based Dendrogram, at 85% similarity criterion, resolved 7 pulsotypes among isolates carrying blaOXA-181 in AH and MH designated A, B, C, D, E, F, and G. Further analysis revealed that 7 subpulsotypes A1, A2, A5, A6, C1, C2, and E1 were from unit D in the medical ICU of MH and A3, A4, B1, B3, D1, D2, D3, D4, F1, F2, F3, G1, and G2 were from surgical/medical ICUs in AH. 100% similarity was demonstrated among 8 isolates from AH and 2 from MH.

Conclusion

The prevalence of rectal colonization by CRE in the ICU patients was lower than expected. Detection of blaOXA-181 variety and blaNDM-5 is new to the milieu of genes so far described in isolates from Kuwait.

Disclosures

All authors: No reported disclosures.
539. Canaries in a Coal Mine?: Early Identification of Regional Spread of Novel Multidrug-resistant Organisms (MDROs) Using Sentinel Surveillance in Skilled Nursing Facilities Caring For Ventilated Patients (vSNFs)
Authors: Paul Prabasaj , Slayton Rachel , Walters Maroya S , Jernigan John A
Published: October 2019

Background

Regional containment of novel or targeted MDROs depends on detecting their presence as soon as possible following their introduction. Prior modeling studies suggest that after importation to a region, novel MDROs appear relatively quickly in certain high-risk post-acute long-term care facilities via patient movement. Sentinel surveillance in such facilities might facilitate early detection of emergent MDROs, thereby enhancing the effectiveness of containment efforts.

Methods

We simulated the introduction and spread of carbapenem-resistant Enterobacteriaceae (CRE) in a region using an adaptation of a previously described susceptible-infectious-susceptible model (Clin Infect Dis. 2019 March 28 doi: 10.1093/cid/ciz248). The model includes the patient sharing network among healthcare facilities in an exemplar US state, using claims data and the Minimum Data Set from the Centers for Medicare & Medicaid Services for 2015. Disease progression, transmission and testing rates were estimated for CRE using data from the literature. Each simulated outbreak was initiated with a single importation to a Dartmouth Atlas of Health Care hospital referral region. The predicted timing of first CRE detection using two different data sources was compared: (1) real-time monitoring of clinical microbiology test results, or (2) results from quarterly point prevalence colonization surveys (PPSs). For each data source, the timing of earliest detection was compared according to availability of data from: (a) all healthcare facilities statewide, (b) only long-term acute care hospitals, (c) only vSNFs, or (d) only the largest acute care hospitals in the state (n = 23).

Results

Compared with real-time monitoring of clinical microbiology testing results from all facilities statewide, quarterly PPSs at all facilities detected CRE 446 days (median; range 312–608 days) earlier, while PPSs at only vSNFs (representing 4.4% of inpatient beds statewide) detected CRE 385 days (range 194–553 days) earlier (figures).

Conclusion

Regular point prevalence surveys in vSNFs may detect new MDROs in a region approximately one year sooner than real-time monitoring of clinical microbiology results, and may be an efficient strategy for early regional detection and subsequent containment.

Disclosures

All authors: No reported disclosures.
543. Biocide Resistance Genes in Klebsiella spp. Infections from Trauma Patients in Iraq and Afghanistan
Authors: Kiley John L , Blyth Dana M , Blyth Dana M , Beckius Miriam , Kaiser Susan , Carson M Leigh , Lu Dan , Whitman Timothy , Petfield Joseph , Tribble David , Mende Katrin
Published: October 2019

Background

Biocides play an integral role in infection control. Paralleling concern about rising incidence of multidrug-resistant (MDR) organisms is a concern for resistance to biocides. In small studies, several genes involved in the production of efflux pump proteins have been identified as markers of biocide resistance in Klebsiella spp., namely cepA, qacA, qacE, qac∆E, and acrA. This study aimed to analyze the Klebsiella spp. isolates of a previously defined military trauma group with a high incidence of MDR organisms for the presence of these genes and their correlation with other resistance.

Methods

All infecting K. pneumoniae, K. variicola, and K. quasipneumoniae isolates archived by the Trauma Infectious Disease Outcomes Study (June 2009–December 2014) were selected. Additionally, all colonizing isolates linked with infecting isolates were included; the remainder to total 50 MDR and 46 non-MDR colonizing isolates were chosen randomly. Antimicrobial identification and susceptibilities were determined by CLSI criteria using the BD Phoenix Automated Microbiology System. PCR according to published methods for cepA, qacA, qacE, qac∆E, and acrA was accomplished in duplicate. MDR was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems and/or fluoroquinolones or production of an ESBL or KPC.

Results

A total of 237 isolates (221 K. pneumoniae, 10 K. variicola, 6 K. quasipneumoniae) met inclusion criteria, of which 149 (63%) were MDR. All isolates had been exposed to antimicrobials prior to isolation. Of all isolates, 234 (98%) carried cepA: 218 (98%) K. pneumoniae carried cepA, 10 (100%) K. variicola carried cepA, and 6 (100%) of K. quasipneumoniae carried cepA. In addition, 148 (62%) isolates with cepA were MDR. One (10%) K. variicola isolate carried qacE along with cepA. This isolate was the only MDR K. variicola. None of the isolates carried qacA, qac∆E, or acrA.

Conclusion

We confirmed the near universal presence of the cepA biocide resistance gene in Klebsiella spp. isolated from trauma patients in Iraq and Afghanistan. In the largest evaluation of biocide resistance genes in Klebsiella spp. to our knowledge, the presence of qacA, qacE, qac∆E, and acrA was less common than has been reported elsewhere.

Disclosures

All authors: No reported disclosures.
552. Within-Host Evaluation of Colonization During Active Methicillin-Resistant S. aureus Bacteremia
Authors: Berbel Caban Ana B , Dupper Amy , Van de Guchte Adriana , Obla Ajay , Chung Marilyn , Gottlieb Lindsey B , Mills Alexandra , Fox Lindsey , Oussenko Irina , Samaroo Flora , Smith Melissa L , Polanco Jose , Patel Gopi , Gitman Melissa R , Sullivan Mitchell , Van Bakel Harm , Altman Deena R
Published: October 2019

Background

Staphylococcus aureus is a common commensal pathogen and a frequent cause of bacteremia, with nasal and blood isolates from single patients matching >80% of the time. Based on our prior work on paired single-patient isolates,1 our aim was to collect a contemporary set of colonizing isolates from those with methicillin-resistant S. aureus (MRSA) bloodstream infections (BSIs), evaluate the within-host diversity by whole-genome sequencing (WGS), and detail the clinical features linked to colonization.

Methods

Adult patients with MRSA BSIs were screened for MRSA in the anterior nares from July 2018 to March 2019. Blood isolates underwent WGS, and spa and agr function screens were performed on three unique nasal isolates per patient. Clinical data from the electronic medical records underwent uni- and multivariate analyses on clinical features and outcomes.

Results

Of 55 unique patients with MRSA BSIs, screening of 45 subjects revealed that 67% were colonized with MRSA. The majority (64%) were males, 32% had prior colonization, and the most common infection sources were vascular access (27%), skin (24%), and unknown (24%). For those with nasal colonization, blood isolates were composed of 57% clonal complex (CC)5/t002, 33% CC8/t008, and 10% other. 81% of nasal isolates matched the blood, with 20% of nasal isolates harboring diverse spa types and 23% carried agr mutants. During this time frame, WGS found one transmission event involving a colonized subject. Colonization was associated with male gender (OR=4.52 95% CI [1.05–19.49]; P = 0.04) and prior hospital admission within the last 3 months (OR=6.12 95% CI [1.44–26.09]; P = 0.01) in multivariate analysis, with no differences in outcomes.

Conclusion

Colonization is an important component of invasive MRSA disease, and we found high rates of colonization with a predominance of the CC5. We also noted significant diversity and high proportion of agr mutants. At-risk groups included males and those with prior hospitalization. Combined molecular and clinical analyses can define the intrahost and interhost transmission dynamics of MRSA, and enables the development of targeted approaches in order to curtail disease.

1. Altman, D. R. et al. Genome Plasticity of agr-defective Staphylococcus aureus during clinical infection. Infect. Immun.(2018).

Disclosures

All authors: No reported disclosures.
555. The Burden of Invasive Staphylococcus Aureus Disease Among Native Americans on the Navajo Nation
Authors: Sutcliffe Catherine , Grant Lindsay , Reid Angelina , Douglass Grace K , Weatherholtz Robert , Hubler Robin , Quintana Alvaro , Reid Raymond , Yazzie Del , Santosham Mathuram , O’Brien Katherine , Hammitt Laura
Published: October 2019

Background

Native Americans in the southwestern United States (US) may be at higher risk for invasive infections due to Staphylococcus aureus. The objective of this study was to determine the burden of invasive S. aureus among Native Americans on the Navajo Nation.

Methods

Prospective population and laboratory-based surveillance for invasive S. aureus infections was conducted from May 2016 through April 2018. A case was defined as a Native American individual living on or around the Navajo Nation with S. aureus isolated from a normally sterile body site. Incidence rates were calculated using the Indian Health Service User Population from 2016 and 2017 as the denominators for Years 1 and 2, respectively. Age-standardized incidence rates were calculated using US Census data from 2015 as the reference group.

Results

363 cases were identified (Year 1: 159; Year 2: 204). Most cases were adults (96.9%; median age: 56.0 years) and had ≥1 underlying medical condition (94.5%), of which the most common were diabetes (63.2%), hypertension (39.1%), and obesity (37.2%). 38.0% of cases were categorized as community acquired and 28.7% of infections were methicillin-resistant (MRSA). 83.2% of cases were hospitalized, 10.7% required amputation, and 6.5% died within 30 days of the initial culture. The overall incidence of invasive S. aureus was 74.4 per 100,000 persons (95% confidence interval [CI]: 67.1, 82.4) with a significantly higher incidence in the second year (Year 1: 64.9; Year 2: 84.0; incidence rate ratio: 1.29; 95% CI: 1.05, 1.59). The overall incidence of invasive MRSA was 21.3 per 100,000 persons (95% CI: 17.6, 25.8) with no significant difference by year (Year 1: 21.2; Year 2: 21.4; incidence rate ratio: 1.01; 95% CI: 0.69, 1.48). The incidence of invasive S. aureus and MRSA increased with age and was highest among individuals ≥65 years of age. The overall age-standardized incidence of invasive MRSA was 25.9 per 100,000 persons (Year 1: 26.0; Year 2: 25.7; for comparison US 2015 general population: 18.8 per 100,000 persons).

Conclusion

The Navajo Nation has a higher burden of invasive MRSA than the general US population. Further research is needed to evaluate trends over time and identify prevention strategies and opportunities for intervention.

Disclosures

All authors: No reported disclosures.
558. Evaluating Length of Stay Data for Use in Targeting Prevention of Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections
Authors: Gouin Katryna , Hatfield Kelly M , Yi Sarah H , Reddy Sujan , Wolford Hannah , Li Qunna , Edwards Jonathan R , Slayton Rachel , Baggs James , O’Hagan Justin
Published: October 2019

Background

Evidence suggests that interventions such as MRSA decolonization are useful in the prevention of MRSA bloodstream infections (BSI) both during hospitalization and post-discharge. However, decolonization may be costly and have diminishing effectiveness when used on all inpatients. Hospital length of stay (LOS) is a known risk factor for MRSA BSI. To determine whether LOS could be useful in prioritizing patients for intervention, we aimed to evaluate (i) distribution of time from admission to hospital-onset (HO) MRSA BSI, and (ii) frequency and LOS of hospitalizations that preceded community-onset (CO) MRSA BSI.

Methods

MRSA-positive blood cultures among adults admitted to New York hospitals from 2013 to 20s16 were identified in the Centers for Disease Control and Prevention’s (CDC’s) National Healthcare Safety Network (NHSN). We linked these data to admissions in New York’s hospital discharge dataset, the Statewide Planning and Research Cooperative System (SPARCS), where the NHSN blood culture collection date was between a patient’s SPARCS admission and discharge dates and there was an exact match for birth date, gender and facility. Time to MRSA BSI was defined as the number of days from admission (day 1) to collection of a blood culture positive for MRSA. We defined positive blood cultures collected on days 1–3 as CO, and those collected ≥day 4 as HO.

Results

We linked 10,425 (79%) MRSA BSIs from NHSN to SPARCS. 78% (8,147) of MRSA BSIs were CO and 22% (2,278) were HO. The median time to HO MRSA BSI was 10 days (IQR 6–21) (Figure 1), in contrast to the median LOS for all hospitalizations of 4 days (IQR 3–7). By definition, 35% of all hospitalizations were never at risk of HO MRSA BSI because their LOS was < 4 days. Among CO MRSA BSI, 48% were discharged from a hospital in the 90 days preceding their BSI (Figure 2). The median LOS of these prior hospitalizations was 8 days (IQR 5–14), and 87% were at least 4 days in length.

Conclusion

Over half of HO MRSA BSI occur on or after day 10 of hospitalization and a large fraction of CO MRSA BSI had a lengthy hospitalization shortly before their BSI diagnosis. Our results suggest that patients likely to have a long LOS could be evaluated as potential targets for prevention strategies (e.g., decolonization) to reduce both HO and CO MRSA BSI.

Disclosures

All authors: No reported disclosures.
561. Genomic Epidemiology of Methicillin-Resistant Staphylococcus aureus in Two Cohorts of High-Risk Military Trainees
Authors: Lee Robyn S , Millar Eugene V , Callendrello Alanna , English Caroline E , Krasniewski Alexander E , Bennett Jason W , Hanage William P
Published: October 2019

Background

Methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections (SSTIs) are common among military recruits. Identifying which strains are responsible for SSTI and understanding the underlying transmission dynamics is critical to developing appropriate interventions for this high-risk population.

Methods

A cohort study of US Army Infantry trainees at Fort Benning, GA (June and September 2015). Participants from two training Companies were screened for colonization on multiple anatomic sites throughout the 14-week cycle as well as the time of clinical infection. MRSA+ samples were sequenced with Illumina HiSeq. Multi-locus sequence type (MLST) and virulence genes were identified in silico. Single nucleotide polymorphism (SNP) distances between soldiers’ bacteria were compared with assessing for potential transmission.

Results

Of 383 soldiers enrolled, 84 (22%) were colonized with MRSA during the study. Forty-two of 84 had a single positive colonization sample, of which 76% were from anatomical sites other than the nares (36% oropharyngeal, 26% perianal, 14% inguinal). Twelve trainees had MRSA SSTI during training (50% had colonization detected prior to or at infection). All were PFGE-type US300 (ST8) and were lukS/lukF-positive. SNP-based phylogenetic analyses and epidemiologic data indicate that most MRSA positives at baseline were due to unique importations from various community origins, suggesting that the ongoing MRSA epidemic is not due to a single endemic strain circulating on base. Following importation, extensive transmission then occurred, with multiple STs implicated. Transmission appeared restricted to within Companies, and predominantly within platoons.

Conclusion

Frequent colonization at baseline suggests a need for extensive MRSA screening and decolonization upon arrival to base, followed by ongoing infection control measures throughout training to prevent recolonization/infection. As multiple anatomical sites appear to play a role in transmission of MRSA, this may have important implications for screening protocols and control both in community and hospital-based settings.

Disclosures

All authors: No reported disclosures.
564. A Five-Year Evolutionary Study of the Minimum Inhibitory Concentrations of Methicillin-resistant Staphylococcus aureus to Mupirocin, Chlorhexidine, and Octenidine in a Singaporean Tertiary Institution
Authors: Zheng Shuwei , Jasmine Chung Shimin , Chiak James Sim Heng , Zhu Xiaoyi , Xuan Tan Si , Chlebicka Tara M , Huak Chan Yiong , Peng Lim Tze , Hoon Andrea Kwa Lay , Piotr Chlebicki Maciej
Published: October 2019

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of healthcare-associated infection. Eradication of MRSA carriage reduces clinical infection and prevents transmission. In Singapore General Hospital, a series of hospital-wide measures were instituted over three years (Figure 1) to reduce mupirocin (MUP) resistance, and to decrease the bioburden of MRSA colonization amongst inpatients using octenidine (OCT)-based products.

Methods

A prevalence study was conducted at three time points (TPs) on consecutive MRSA screening isolates to evaluate for their minimum inhibitory concentrations (MICs) to CHG, OCT and MUP using broth microdilution sensitive plates and the presence of the ileS-2 gene, in 2013 (pre-intervention TP, TP1; n = 160), 2016 (early post-intervention TP, TP2; n = 99) and 2017 (late post-intervention TP, TP3; n = 76). Statistical analyses were performed using the Chi-square test with reference from TP1.

Results

A significant improvement in MUP susceptibility by MIC (256 µg/mL) and ileS-2 testing reduced from 25.0% (TP1) to 12.1% (TP2; P = 0.014) to 5.3% (TP3; P = 0.001) and 30.0% (TP1) to 18.2% (TP2; P = 0.036) to 9.2% (TP3; P = 0.001), respectively. OCT MIC range remained stable at 0.5 to 1 across all three TPs. The number of isolates with reduced CHG susceptibility (MIC ≥4 mg/L) increased over the three TPs from 23.1% to 27.2% (P = 0.45) to 42.1% (P = 0.003), despite decreasing CHG prescription.

Conclusion

A restrictive MUP usage policy can improve MUP susceptibility amongst MRSA isolates over time. Widespread OCT use did not appear to result in a rise of OCT MIC over the intervention period. Although the clinical significance of reduced susceptibility to CHG remains uncertain, this worrying trend in our institution deserves further studies to better understand mechanisms of CHG resistance.

Disclosures

All authors: No reported disclosures.
566. Reduction of Hospital-Onset Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia in an Acute Care Hospital: Impact of Bundles and Universal Decolonization
Authors: Jimenez Adriana , Sposato Kathleen , de Leon-Sanchez Alicia , Williams Regina , Francois Reynande , Wilson Juliana , Lisondra Benjamin , Abbo Lilian
Published: October 2019

Background

MRSA is a major concern for hospitalized patients in the United States. Hospital-Onset (HO) MRSA bacteremia is used as a proxy measurement of MRSA healthcare acquisition, exposure, and infection burden. HO MRSA bacteremia standardized infection ratio (SIR) is used by several national agencies as a quality report metric. Our institution had more than expected HO MRSA bacteremia cases despite several interventions. We describe the impact of a bundle of interventions aimed to decrease HO MRSA bacteremia in an acute care facility.

Methods

This quality improvement project was implemented in a 380-bed community hospital in Miami, FL from January 2015 to March 2019. HO MRSA bacteremia was defined as non-duplicate MRSA isolated from a blood culture collected >3 days after admission. SIR was calculated dividing the number of observed events by the number of predicted events; predicted events were obtained from the NHSN report. During baseline period (Figure1 Phase 1 January 2015–August 2016) all adult patients in the intensive care unit (ICU) were screened for MRSA nasal colonization on admission and weekly thereafter, ICU patients received daily Chlorhexidine (CHG) bathing, and colonized/infected patients with MRSA were placed in contact precautions. In Phase 2 (September 2016–June 2017)daily CHG bathing was switched from 2% wipes to 4% soap foam and expanded to all adult patients; ICU patients also received nasal decolonization with mupirocin. Nasal mupirocin in ICU was replaced with alcohol-based nasal sanitizer for all adult units in July 2017 (Phase 3). In April 2017 we discontinued using contact precautions for MRSA patients; nasal surveillance cultures were discontinued in October 2017. In May 2018 (Phase 4) we introduced alcohol-based wipes for patient hand hygiene at the bedside. SIR were compared by exact binomial test.

Results

We observed 48 HO MRSA bacteremia cases during the study period. The SIR decreased from 3.66 to 0.97 from baseline to postintervention periods (P = 0.003). The largest decrease in cases and SIR was attained using combined hospital-wide daily CHG bathing, alcohol-based nasal sanitizer, and alcohol wipes for patient hand hygiene during Phase 4 (Table 1).

Conclusion

Our bundle of interventions for universal decolonization was successful in decreasing HO MRSA bacteremia.

Disclosures

All authors: No reported disclosures.
569. Evaluation of a Povidone-Iodine Preparation for Nasal Decolonization of Methicillin-Resistant Staphylococcus aureus
Authors: Abou Ghaddara Hussein , Cadnum Jennifer , Ng Wong Y Karen , Donskey Curtis
Published: October 2019

Background

Mupirocin is commonly used for nasal decolonization of Staphylococcus aureus, but it has limitations including frequent emergence of resistance and non-adherence due to the need for repeated applications. Povidone-iodine is increasingly used as an alternative for nasal decolonization because it has a low propensity for emergence of resistance and rapid in vitro antibacterial activity. However, limited data are available on the microbiological efficacy of povidone-iodine for suppression of nasal S. aureus.

Methods

We compared the effectiveness of a single application or 5 days of twice daily application of a commercial 10% povidone-iodine preparation vs. phosphate-buffered saline for a reduction in nasal MRSA in methicillin-resistant S. aureus (MRSA)-colonized patients (9–11 per treatment group). Nasal swabs were collected for quantitative culture of MRSA before and at 1, 6, 12 and 24 hours after the single application or before each dose for the 5-day regimen. Analysis of variance was used to compare MRSA colony counts in povidone iodine vs. control patients.

Results

The concentrations of MRSA in the nares were similar for povidone-iodine and control group patients prior to treatment. As shown in the figure, the single application of povidone-iodine resulted in a statically significant reduction in nasal MRSA in comparison to controls at 2 and 6 hours after treatment (P10 colonies per swab).

Conclusion

Our findings suggest that single preoperative applications povidone-iodine could be useful for short-term suppression of S. aureus during the perioperative period. Additional studies are needed to evaluate the efficacy of the povidone-iodine preparation for MRSA decolonization when used at more frequent dosing intervals or in combination with chlorhexidine bathing.

Disclosures

All authors: No reported disclosures.