bluuebunny/crossref_metadata_2025_split huggingface dataset:
2786. Characterizing Ertapenem Neurotoxicity: A Systematic Review
Authors: Mitaka Hayato , Jain Rupali , Rakita Robert M , Pottinger Paul S 
Published: November 2023

Abstract

Background
Ertapenem is frequently used to treat ESBL-producing Enterobacterales infections. Although ertapenem has the highest incidence of delirium reported among antibiotics evaluated in a pharmacovigilance study of the FDA adverse event reporting system, little is known about clinical characteristics of its neurotoxicity. In this systematic review, we synthesize the existing literature on ertapenem neurotoxicity, focusing on comorbidities, clinical manifestations, and outcomes.

Methods
We searched PubMed and EMBASE for all peer-reviewed articles from inception through April 2023 using the following search terms: "ertapenem" AND ("Neurotoxicity" OR "Encephalopathy" OR "Seizures" OR “status epilepticus” OR "Convulsions" OR "Delirium" OR "Psychosis" OR "Hallucinations" OR “altered mental status” OR coma OR stupor OR obtundation). Studies were included if they described ertapenem specifically and reported clinical data related to neurologic adverse events.

Results
A total of 651 articles were identified through the initial database search and subsequent manual search. After removing duplicated items and screening based on title and abstract, 43 articles were assessed for eligibility. Finally, 30 studies with 114 patients were included in our data analysis. Of the 114 cases found, the mean age was 73, and 67% were male. The most common clinical signs and symptoms were seizures (69%), altered mental status/delirium/cognitive impairment (27%), and hallucinations (18%). The most common electroencephalogram (EEG) finding was slow waves, observed in 59%. Median time to onset was 4 days (IQR, 3–7 days) after starting ertapenem. Complete resolution of the symptoms was observed in 84% after discontinuation of ertapenem. Median time to recovery was 6.5 days (IQR, 3–8 days). Urinary tract infection was the most common indication for ertapenem use (49%). Renal dysfunction and predisposing central nervous system condition were noted in 70% and 32% of the patients, respectively.

Conclusion
This systematic review summarizes the current evidence and clinical characteristics of ertapenem neurotoxicity. Our study underscores the need for raising awareness among clinicians and a large observational study to accurately assess the true incidence, risk factors, and outcomes.

Disclosures
All Authors: No reported disclosures
167. Duration of Methicillin-Resistant Staphylococcus aureus (MRSA) Nares PCR Positivity while Receiving Highly Active Anti-Staphylococcal Drugs
Authors: Wu Maximillian S , Kufel Wesley D , Riddell Scott W , Steele Jeff , Asiago-Reddy Elizabeth 
Published: November 2023

Abstract

Background
A growing body of evidence has demonstrated a close association between nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) and its invasive presence systemically. Thus, several hospitals have implemented MRSA nares PCR screening for all patients initiating treatment active against MRSA for various infections to help de-escalate an anti-MRSA antibiotic in the event of a negative result. However, little is known about the effects of anti-MRSA systemic agents on MRSA nasal colonization, potentially affecting the use of MRSA PCR as an effective screening tool if not conducted immediately upon hospital admission.

Methods
Adult Upstate University Hospital patients ≥ 18 years of age with an initial positive MRSA nares PCR result were considered for inclusion, starting from September 2022. Eligible patients were individuals who had a positive MRSA nares PCR performed within 36 hours of their initial dose of a systemic anti-MRSA antibiotic. Positive MRSA nares cultures were also considered if PCRs were initially indeterminate. Anti-MRSA antibiotics included vancomycin, daptomycin, linezolid, ceftaroline, and clindamycin. Patients who were received these agents for a duration of 48-96 hours were consented for their participation. If consented, a follow-up MRSA nares swab and PCR were collected at a goal timepoint of 72 hours post initiation of anti-MRSA antibiotics (sample collection ranged from 48-96 hours post initiation). MRSA colonization was reassessed with a repeat nares PCR and reflex to culture for indeterminate results if applicable.

Results
As of April 21st, 2023, 61 follow-up MRSA nares samples were collected from eligible participants. Follow-up samples were collected an average of 66.51 hours after their first dose of anti-MRSA drugs (IQR = 11.47). Of these follow-up samples, 56/61 (91.80%) resulted as a positive MRSA nares PCR or culture result.

Conclusion
Our interim results demonstrated that MRSA colonization in the nares via PCR generally persists even after 48-96 hours of continuous systemic administration of anti-MRSA antibiotics. These findings suggest that MRSA nares swabs can still be used after anti-MRSA antibiotic administration, increasing its utility as a screening tool.

Disclosures
Wesley D. Kufel, Pharm.D., BCPS, BCIDP, AAHIVP, Merck & Co.: Grant/Research Support Elizabeth Asiago-Reddy, MD, Glaxo-Smith-Kline: Grant/Research Support|Pfizer: Grant/Research Support
2792. Determining the activity of imipenem/relebactam (I/R) plus aztreonam (ATM) against constitutive Pseudomonas derived cephalosporinase (PDC)- and metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa in a hollow fiber infection model (HFIM)
Authors: O’Donnell J Nicholas , Moolick Kelly E , Nahorniak Avery I , Gifford Maxwell J , Young Katherine , Lodise Thomas 
Published: November 2023

Abstract

Background
Few treatment options exist for serious infections caused by MBL-PSA. While ATM retains activity against some MBL-PSA, isolates often constitutively produce PDCs, resulting in resistance. I/R is a new β-lactam/β-lactamase inhibitor with expanded activity against constitutive PDC-producing PSA, but has no standalone activity against MBL-PSA. This study aimed to evaluate the effect of I/R plus ATM against PDC- and MBL-producing PSA in the HFIM.

Methods
Two isogenic, constitutive PDC-and MBL-producing PSA isolates (MB10480: IMP-1; MB10620: VIM-1) were studied at a starting inoculum of 8 log10 colony forming units (CFU)/mL in the HFIM over 96 hrs. Humanized exposures of I/R (500/250mg q6h as a 0.5 hr infusion) were evaluated alone and in combination with 3 ATM regimens (1.5g q6h; 2g q8h; 2g q6h as 2 hr infusions). Combination regimens were tested in triplicate with inoculum (log10 cfu/mL) averaged across runs. MIC testing with ATM and relebactam (set at 4 mg/L) was conducted on isolates recovered from the model at 96 hrs.

Results
Monotherapy arms mirrored the growth control for MB10620 (ATM/relebactam MIC: 4/4 mg/L); combination arms resulted in bacteriostasis through 96 hrs. Maximal killing of each regimen (∼2 log10 CFU/mL; all units log10 cfu/mL change vs. baseline) was achieved through 32 hrs, followed by regrowth across all regimens (Figure 1). Bacterial counts at 96 hrs were similar to the starting inoculum for all combinations, but lowest for I/R plus ATM 2g q6h (I/R plus ATM 1.5g q6h: +1.75 CFU/mL; 2g q8h: +1.74 CFU/mL; 2g q6h: -0.20 CFU/mL;). Similar results were observed with MB10480 (ATM/relebactam MIC: 8/4 mg/L) (Figure 2). Maximal killing was achieved through 56 hrs (∼2 log10 CFU/mL), followed by regrowth across all combination regimens (I/R plus ATM 1.5g q6h: +0.19 CFU/mL; 2g q8h: -0.34 CFU/mL; 2g q6h: -0.35 cfu/mL). Across combination regimens for both isolates, 2 morphologies of PSA were recovered. Retested isolate MICs were occasionally, but not consistently, elevated by &gt;2 dilutions (MB10620: 10/18; MB10480: 4/18).

Conclusion
I/R plus ATM resulted in initial killing followed by regrowth over 96 hrs for constitutive PDC- and MBL-producing PSA isolates. Further study is needed to evaluate optimal dosing and suppression of regrowth in the HFIM.

Disclosures
J Nicholas O'Donnell, Pharm.D., Merck and Co, Inc.: Grant/Research Support Thomas Lodise, Jr., Pharm.D., PhD, merck: Grant/Research Support|merck: Honoraria
2795. Cefepime Versus Meropenem for Infections Due to HECCcK-YeS-MAm Organisms with Cefepime MICs of 4-8 mCg/mL (S-DD)
Authors: Purdy Andrew Scott , Howe Zach , Desai Armisha 
Published: November 2023

Abstract

Background
Recent guidance from IDSA recommends meropenem for treatment of organisms at moderate-high risk for inducible chromosomal AmpC β-lactamase hyperproduction (AmpC organisms) with a cefepime minimum inhibitory concentration (MIC) of 4-8 mCg/mL (susceptible dose-dependent or S-DD).1 This runs contrary to pharmacokinetic/pharmacodynamic data and Clinical and Laboratory Standards Institute (CLSI) M100 guidance, which considers organisms ≥ 16 mCg/mL resistant.2 The purpose of this study is to evaluate the clinical efficacy of cefepime versus meropenem for the treatment of infections caused by AmpC organisms with a S-DD cefepime MIC.

Methods
This was a retrospective study evaluating patients treated within Indiana University Health from 2015-2022. All cefepime S-DD AmpC isolates were included. Exclusion criteria were &lt; 48 hours of treatment, multiple days of therapy with another active agent, inadequate dosing, extended spectrum β-lactamase (ESBL) co-production, and carbapenem resistance. The primary endpoint of this study was a composite of in-hospital all-cause mortality and antibiotic escalation due to clinical worsening. Secondary endpoints include positive repeat blood cultures within 7 days of treatment initiation, and ESBL or carbapenem resistant organism isolation during or following treatment.

Results
355 isolates were screened. 71 patients were included in the final analysis, 43 in the cefepime group and 28 in the meropenem group. Baseline characteristics were not significantly different. Enterobacter cloacae made up 79% of cases. The primary endpoint occurred in 13/43 (30%) of patients on cefepime and 7/28 (25%) of patients on meropenem (P=0.63). Treatment escalation and escalation due to clinical worsening was higher in the cefepime group with 7 (16%) and 6 (14%) incidents respectively compared to none in the meropenem group (P=0.03; P=0.04). No other endpoints, including all-cause mortality, were significantly different between groups.

Conclusion
Cefepime remains a viable treatment option for ESBL-negative, AmpC organisms with MICs in the S-DD range.

Disclosures
All Authors: No reported disclosures
168. Promising Changes In Antibiotic Utilization Associated With Implementation Of Rapid Multiplex Polymerase Chain Reaction Testing For Bloodstream Infection
Authors: Yau Tat , Blyth Michelle , Figueroa Julio E 
Published: November 2023

Abstract

Background
BioFire® Blood Culture Identification 2 (BCID2) panel is a rapid multiplex polymerase chain reaction (rm-PCR) testing for 43 organisms associated with bloodstream infections and 10 antimicrobial resistance genes. Previous literature suggested combination of rm-PCR and antibiotic stewardship program (ASP) would improve time to organism identification, optimal therapy, and de-escalation of antibiotics.

Methods
This study was a retrospective study at Touro Infirmary in New Orleans, Louisiana. All adult patients with positive blood cultures before and after BCID2 implementation in January 2022 (April to September 2021 and April to September 2022 respectively) were included. The outcomes of interest included time to organism identification, time to change of antibiotics (either appropriate escalation or de-escalation), hospital length of stay, 30-day re-admission, and 30-day mortality.

Results
A total of 117 patients met the study criteria (refer to Figure 1 and Table 1 for the flowchart of participants and characteristics of participants respectively). Patients with blood cultures that grew one of the organisms of interest were analyzed: methicillin sensitive Staphylococcus aureus (MSSA), coagulase negative Staphylococcus species, extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), AmpC beta-lactamase-producing Enterobacterales, and Pseudomonas aeruginosa. There was a significant difference in the time to organism identification between pre- and post-BCID groups (45 hours vs. 25.1 hours, p &lt; 0.0001) and there was no discordance between the BCID and blood culture results. In addition, there was a significant decrease in time to antibiotics change between pre- and post-BCID groups (p &lt; 0.01). Notably for patients with MSSA bacteremia, post-BCID group had significantly shorter duration to de-escalate antibiotics than pre-BCID group (43 hours vs. 66.7 hours, p &lt; 0.038). However, there is no statistical difference between pre- and post-BCID groups regarding hospital length of stay, 30-day readmission, and 30-day mortality.
Flowchart of Participants
Organisms of interest include: methicillin sensitive Staphylococcus aureus, coagulase negative Staphylococcus species, extended-spectrum beta-lactamase producing Enterobacterales, AmpC beta-lactamase producing Enterobacterales, and Pseudomonas aeruginosa. Abbreviations: BCID, blood culture identification panel, BCx, blood cultures.
Characteristics of Participants

Conclusion
BCID2 significantly reduced the time to organism identification and improved time to effective therapy for MSSA bacteremia. However, significance was limited in other measures due to small sample size.

Disclosures
All Authors: No reported disclosures
2803. The Medical Trends and Economic Burden of XDR Typhoid Compared to Non-XDR Typhoid: A Single Center Retrospective Study from Karachi, Pakistan
Authors: Sayeed Muneeba Ahsan 
Published: November 2023

Abstract

Background
In 2016, Pakistan reported the first outbreak of an Extensively Drug Resistant (XDR) typhoid showing susceptibility only to Meropenem and Azithromycin which created a treatment dilemma and raised concerns not only in developing countries but also globally. In this study, we compared the medical trends and economic burden of XDR typhoid with non-XDR typhoid at a tertiary care hospital of Karachi, Pakistan.

Methods
A retrospective study was conducted at the Sindh Infectious Diseases Hospital & Research Centre Karachi, Pakistan from June 2022 to April 2023. All hospitalized patients 14 years and above with confirmed Salmonella typhi on blood culture were included. Medical records were reviewed for clinical data and antibiotic cost. Statistical analysis was done using SPSS.

Results
Thirty-five patients were included of which 23 (65.7%) had XDR typhoid while 12 (34.3%) patients had non-XDR typhoid. Of the 12 non-XDR typhoid cases, nine were MDR (Multi Drug Resistant) while three had ampicillin sensitive strain. The mean age was 21.14 years with 27 (77.1%) males. Compared to non-XDR, majority of the XDR typhoid patients had diarrhea (60.9% vs. 16.7%, p-value= 0.02, OR 7.7, 95% CI: 1.3-44.0). XDR typhoid was treated with either Meropenem alone or Meropenem and Azithromycin combination while MDR typhoid was treated with Ceftriaxone. The time to defervescence was prolonged in XDR typhoid compared to non-XDR typhoid (7.95 days vs. 4.67 days, p-value= 0.007, OR 1.6, 95% CI: 1.14-2.3), with higher per day cost of antibiotics and total inpatient-antibiotic cost (US$20.3 vs. US$11, p-value= 0.006, OR 1.4, 95%CI 1.1-1.9) and (US$193 vs. US$139, p-value= 0.048] respectively. Within XDR group, the mean defervescence time was more in patients who received combined Meropenem and Azithromycin compared to Meropenem alone group (10.1 days vs 6.4 days, p-value=&lt; 0.001) with a consequent higher per day in-patient antibiotic cost (USD$22 vs USD$ 18.8, p-value= &lt; 0.001) and total in-patient cost (USD$ 235 vs. USD$ 158K, p-value= 0.009).

Conclusion
XDR typhoid has emerged not only as a heath care but also as an economic challenge owing to its prolonged defervescence time and increased per day/ total in-patient antibiotic cost.

Disclosures
All Authors: No reported disclosures
2805. Extended-Infusion versus Intermittent-Infusion Piperacillin/tazobactam for High Minimum Inhibitory Concentration Pseudomonas aeruginosa Infections
Authors: Shifko Carlee R , Carr Dustin R , Walsh Thomas L , Moffa Matthew A , Shively Nathan R , Bremmer Derek N 
Published: November 2023

Abstract

Background
Extended-infusion (EI) piperacillin/tazobactam, compared to intermittent-infusion (II) piperacillin/tazobactam, has been associated with improved clinical outcomes for both critically ill and febrile neutropenic patients. However, there is a paucity of data on whether these clinical benefits apply to broader populations. Infections involving high minimum inhibitory concentration (MIC) Pseudomonas aeruginosa represent an additional group where optimization of pharmacokinetic parameters may impact treatment success.

Methods
Medical records of adults who received II or EI piperacillin/tazobactam for pneumonia and/or bacteremia caused by Pseudomonas aeruginosa with MIC 8 or 16 mcg/mL were reviewed. The primary outcome was 30-day all-cause mortality. Hospital and/or intensive care unit (ICU) length of stay (LOS) and recurrence of infection were also recorded. Additionally, an escalation of care composite was assessed by need for new ICU transfer, new vasopressor start, new mechanical ventilation, or rescue antibiotic therapy change. Finally, a safety outcome of acute kidney injury (AKI) was recorded.

Results
A total of 69 patients were included, 31 in the II group and 38 in the EI group. Bacteremia was detected in 19.4% and 23.7% of the II and EI groups, respectively (p = 0.66). Baseline demographics and characteristics of treatment were similar between groups. The most common dosing regimens were 3.375 g IV every 6 hours over 30 minutes and 3.375 g IV every 8 hours over 4 hours. 30-day mortality was 32.3% in the II group and 39.5% in the EI group (p = 0.54). Similarly, hospital LOS (19 versus 15 days, p = 0.27) and ICU LOS (23 versus 15 days, p = 0.15), as well as recurrence (29.4% versus 23.5%, p = 1) and therapy escalation (38.7% versus 47.4%, p = 0.47), were not significantly different between groups. 43.5% of patients in the II group and 40.6% of patients in the EI group developed AKI (p = 0.83).

Conclusion
The present study found no significant difference in outcomes between piperacillin/tazobactam infusion strategies. However, the small sample size and complex patient factors may have limited the comparison.

Disclosures
Dustin R. Carr, PharmD, BCPS, BCIDP, Merck: Advisor/Consultant Thomas L. Walsh, MD, Accelerate Diagnostics: Advisor/Consultant Derek N. Bremmer, PharmD, BCIDP, Thermo Fisher Scientific: Advisor/Consultant
2809. In Vitro Synergy of Antibiotic Combinations Against Enterococcus gallinarum
Authors: Landman David , Cherniak Meir , Strahilevitz Jacob 
Published: November 2023

Abstract

Background
Enterococci are an important cause of endocarditis, particularly involving prosthetic valves. The prevalence of E. gallinarum has been increasing in recent years. Unlike E. faecalis, no information is available regarding the bactericidal activity of ampicillin alone or combined with gentamicin or ceftriaxone against E. gallinarum.

Methods
Ten blood culture isolates of E. gallinarum were studied. The isolates came from unique patients at a single hospital. MICs of ampicillin, ceftriaxone and gentamicin were done by the CLSI microdilution method. ATCC strains E. faecalis 29212 and P. aeruginosa 27853 were used as controls. Time-kill studies were performed in CA-MHB for ampicillin 10 mg/L, ceftriaxone 10 mg/L, gentamicin at 0.25 x MIC up to a maximum of 4 mg/L, ampicillin + ceftriaxone, and ampicillin + gentamicin. Bactericidal activity was defined as a 1,000-fold decrease in the log10 cfu/mL at 24 h. Synergy was defined as a 100-fold decrease in the log10 cfu/ml at 24 h in a combination compared to each single agent.

Results
The MICs of ampicillin ranged from 1 to 8 mg/L, gentamicin from 2 to 16 mg/L, and ceftriaxone were all ≥ 32 mg/L. Results of the time-kill studies are summarized in the Table. Ampicillin alone was bactericidal against a single isolate. For that isolate, testing of ampicillin at 0.25 x MIC with gentamicin demonstrated synergy. The combination of ampicillin + ceftriaxone was synergistic against a single isolate, but was otherwise similar to ampicillin alone. Ampicillin + gentamicin was bactericidal against all isolates and was synergistic against all but one isolate.

Conclusion
Ampicillin alone was generally not bactericidal against E. gallinarum but had synergistic bactericidal activity when combined with gentamicin, similar to the findings with E. faecalis. However, unlike E. faecalis, ampicillin + ceftriaxone was not bactericidal against most isolates of E. gallinarum. These findings support the suggestion that ampicillin + gentamicin might be the optimal treatment for endovascular infections caused by E. gallinarum.

Disclosures
All Authors: No reported disclosures
2811. Real-World Experience Utilizing Cefiderocol for Serious Multidrug Resistant Gram-Negative Infections
Authors: Teran Nicholas S , Zidaru Andrei , Phe Kady 
Published: November 2023

Abstract

Background
Cefiderocol is a novel siderophore cephalosporin that demonstrated in vitro activity against carbapenem-resistant Enterobacterales, Acinetobacter baumannii (AB), Pseudomonas aeruginosa (PA), and Stenotrophomonas maltophilia. Cefiderocol demonstrated promising efficacy in randomized, clinical trials; however, real-world utilization of cefiderocol is not well characterized.

Methods
This was a retrospective study of adults who received cefiderocol for ≥72h for serious meropenem-resistant Gram negative infections at our institution between 11/2021 and 12/2022. Patients with all sources of infection were considered for inclusion. Clinical failure was defined as all-cause 90d or in-hospital mortality, or the lack of resolution of signs or symptoms of infection. Microbiological failure was defined as positive cultures growing the index pathogen after ≥7d of initiating therapy or ≤60d of completing therapy. Descriptive statistics were used to compare outcomes by the index pathogen.

Results
Of 55 patients who received cefiderocol, 35 patients were included. The remaining 20 patients were excluded for receiving &lt; 72h of therapy. The most common infections were pneumonia (n = 17, 48.6%), skin and skin structure infections (n = 6, 17.1%), and osteomyelitis (n = 5, 14.3%) wherein PA (n = 17, 48.6%) and AB (n = 14, 40%) were isolated most frequently. The overall 90d and in-hospital mortality rates were 9 (25.7%) and 11 (31.4%) patients, respectively. Clinical failure, assessed in 34 patients, occurred in 10 (29.4%) patients and was similar between pathogens (p = 0.71). Microbiological failure, assessed in 26 patients, occurred more commonly in infections caused by PA (n = 11/12, 91.7%) compared to all other pathogens (n = 3/14, 21.4%; p &lt; 0.01). Notably, most microbiological failures due to PA were in the setting of pneumonia (n = 6/11, 54.5%).

Conclusion
Real-world experience demonstrated that most patients receiving cefiderocol for serious Gram-negative infections did well; however, microbiological failure among patients with PA infections may be attributed to the difficulty in differentiating true pathogens and colonizers in respiratory infections.

Disclosures
All Authors: No reported disclosures