bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 >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

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 < 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

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 < 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 < 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 < 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

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=< 0.001) with a consequent higher per day in-patient antibiotic cost (USD$22 vs USD$ 18.8, p-value= < 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

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

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

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 < 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 < 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
2812. Clinical Impact of the Ceftolozane-Tazobactam Shortage on Difficult-To-Treat Resistant Pseudomonas aeruginosa Infections at an Academic Medical Center
Authors: Vance Mary K , Cimino Christo , Ereshefsky Benjamin , Humphries Romney , Nelson George E
Published: November 2023

Background

Difficult-to-treat resistant Pseudomonas aeruginosa (DTR PA) infections are a serious threat, requiring treatment with ceftolozane-tazobactam (C/T), ceftazidime-avibactam, or imipenem-cilastatin-relebactam due to extensive resistance. C/T was unavailable January to December 2021 so alternative agents were used. This study compared clinical outcomes in patients with documented DTR PA infections during periods of availability and shortage.

Methods

This retrospective cohort study included adult patients admitted to Vanderbilt University Medical Center January 2019 to December 2022 who were treated for DTR PA. Patients admitted January to December 2021 were included in the C/T shortage group and all others were included in the C/T available group. DTR PA was defined as nonsusceptibility to fluoroquinolones and traditional antipseudomonal β-lactams. Patients who received antibiotics < 48 hours or were transferred to an outside facility or hospice prior to completing therapy were excluded. The primary outcome was a composite of 90-day survival and clinical success, defined as improvement or resolution of signs of infection such that no further treatment was needed. Secondary outcomes included infection-related mortality, emergence of resistance, and adverse events.

Results

A total of 29 patients were included, 22 in the C/T available group and 7 in the C/T shortage group. DTR PA was most commonly isolated from respiratory (31%) and wound cultures (31%). Significantly more patients in the C/T shortage group received combination therapy (57% vs. 9%, p=0.018). The primary outcome occurred in 50% of those in the C/T available group versus 71% of those in the C/T shortage group, which was not a significant difference (p=0.41). There were also no significant between group differences in any of the secondary outcomes, including infection-related mortality (14% vs. 14%, p=1), resistance development (5% vs. 0%, p=1), and adverse events (18% vs. 14%, p=1).

Conclusion

No significant differences were seen in clinical outcomes between patients with DTR PA treated during C/T shortage and available periods. This analysis was limited by a small sample size. Further studies are needed to assess the efficacy of C/T compared to alternative therapy and the role of combination therapy for DTR PA.

Disclosures

Romney Humphries, PhD, D(ABMM), M(ASCP), Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Ventorx: Advisor/Consultant
2821. A Comparison of Empirical Therapy with Cefazolin Versus Ceftriaxone for the Treatment of Complicated Urinary Tract Infections in a Tertiary Care VA Medical Center
Authors: Carcamo Paola , Hopkins Teri L , Yang Linda , Frei Christopher R , Cadena-Zuluaga Jose , Walter Elizabeth
Published: November 2023

Background

Limited data exist regarding the utilization of a narrow-spectrum agent such as cefazolin for the treatment of complicated urinary tract infections (cUTIs). The objective of this study was to evaluate cefazolin compared with ceftriaxone for the empirical treatment of cUTIs in an inpatient setting.

Methods

We conducted a single center, retrospective cohort study of Veteran patients who received ≥24 hours of cefazolin or ceftriaxone for the empirical treatment of cUTIs between November 1, 2019 and September, 30 2022. The primary outcome was clinical success, defined as resolution of signs and symptoms of infection without re-initiation of antibiotics during hospitalization or relapse, at 30 days after cUTI diagnosis. Secondary outcomes included hospital length of stay and Clostridioides difficile infection (CDI) within 30 days of the end of antibiotic therapy. A multivariate logistic regression analysis was also conducted to identify independent factors associated with 30-day clinical success.

Results

We identified 118 patients (median age, 72 years; 97% men) with cUTI treated with cefazolin (n = 57) or ceftriaxone (n = 61) who met study criteria. Both study groups had similar demographics, although patients treated with ceftriaxone more frequently had subjective fever on admission or nephrolithiasis while cefazolin-treated patients had more urinary catheters or receipt of another antibiotic prior to study drug. Clinical success was achieved in 51 (90%) and 53 (87%) in the cefazolin and ceftriaxone groups, respectively (P = 0.66). Multivariate analysis identified patients with urinary catheters as an independent predictor of decreased clinical success, with an odds ratio at 30 days of 0.21 (95% CI, 0.06-0.75). Patients treated with cefazolin had a significantly longer length of hospital stay (median 0.4 days longer) compared with ceftriaxone-treated patients (P = 0.02). There were no patients in the cefazolin arm and 4 (7%) patients in the ceftriaxone arm who had CDI within 30 days (P = 0.12).

Conclusion

Cefazolin was similar to ceftriaxone for the treatment of cUTI based on the outcome of clinical success. Local susceptibility patterns to urinary pathogens should guide empiric treatment.

Disclosures

Christopher R. Frei, PharmD, FCCP, BCPS, AstraZeneca: Grant/Research Support
2830. Clinical Characteristics, Outcomes and Antimicrobial Resistance of Non-aeruginosa Pseudomonas Infection in Adult Cancer Patients
Authors: Gu Hyundam , Aslam Sadaf , Horn Cody , Greene John
Published: November 2023

Background

Pseudomonas aeruginosa a gram-negative bacteria that is known to cause severe nosocomial infections. Other species of Pseudomonas are considered to be part of the human indigenous microbiota, commonly found in sites such as the gastrointestinal tract and skin. Although believed to be non-pathogenic for many years, these species can cause diseases in immunocompromised patients, albeit less virulent than P. aeruginosa. In this report, we will discuss the characteristics of non-aeruginosa Pseudomonas infections in cancer patients.

Methods

We conducted a retrospective study investigating culture results of adult inpatients with Pseudomonas spp. infections, excluding P. aeruginosa, at a Florida cancer center from 2012-2022. Data collected included infection source, antibiotics used, resistance against fluoroquinolones, surgical procedures or chemotherapy in the past month, polymicrobial infection, and 30-day mortality.

Results

Of 104 cases, P. putida was the most common species, followed by P. fluorescens, P. stutzeri, and P. mendocina. P. putida infections were often associated with urine (44%), respiratory and skin wounds (16% each). Respiratory tract was the most common source for P. fluorescens infections (38%). Solid tumors accounted for 71% of malignancies in the P. putida group, while hematologic malignancies accounted for 29%. For P. fluorescens, solid tumors and hematologic malignancies accounted for 62% and 38%, respectively. P. stutzeri and P. mendocina were mostly associated with solid malignancies. All groups were susceptible to quinolones (86-100%), and polymicrobial infections were frequently observed (68%, 73%, 63%, and 50%, respectively). P. putida and P. fluorescens had 7% and 19% 30-day mortality rates, respectively. P. stutzeri and P. mendocina had no observed mortality.

Conclusion

Our study highlights non-aeruginosa Pseudomonas infections are rare but notable in cancer patients. In the majority of cases, the disease course is less severe, and treatment with appropriate antibiotics, such as fluoroquinolones, leads to complete recovery.

Disclosures

All Authors: No reported disclosures
2832. Gepotidacin Efficacy in E. coli Drug-Resistant Phenotypes: A Pooled Analysis of the EAGLE-2 and EAGLE-3 Randomized Controlled Trials in Uncomplicated Urinary Tract Infection
Authors: Hooton Thomas M , Perry Caroline R , Janmohamed Salim , Sheets Amanda , Dennison Jeremy , Millns Helen , Jarvis Emily , Scangarella-Oman Nicole E , Huang Chun
Published: November 2023

Background

Uncomplicated urinary tract infections (uUTI) are among the most common community-acquired infections in women worldwide. Recommended treatment is largely empiric. Rates of antimicrobial resistance among Escherichia coli (E. coli) isolates, specifically extended-spectrum beta-lactamase positive (ESBL+) and multidrug-resistant (MDR) strains, are increasing worldwide. Gepotidacin is a first-in-class, triazaacenaphthylene, bactericidal antibiotic that inhibits bacterial DNA replication by inhibiting two enzymes, where a target-specific single mutation does not significantly impact susceptibility. We report gepotidacin efficacy against E. coli drug-resistant phenotypes in a pooled analysis of the EAGLE-2 and EAGLE-3 trials in uUTI.

Methods

EAGLE-2 and EAGLE-3 were near-identical global, Phase 3, randomized, double-blind, double-dummy, active-controlled noninferiority trials comparing gepotidacin with nitrofurantoin. Females aged ≥ 12 years with ≥ 2 UTI symptoms were eligible and were randomized 1:1 to oral gepotidacin (1500mg) or nitrofurantoin (100mg), twice daily for 5 days. Therapeutic success at test-of-cure visit (Day 10–13) was defined as combined clinical success (complete symptom resolution) and microbiological success (from ≥ 105 to < 103 CFU/mL) without the need for other systemic antimicrobials. Analysis of the pooled microbiological intent-to-treat (micro-ITT) population was performed.

Results

The pooled micro-ITT population comprised 1421 patients (732 gepotidacin, 689 nitrofurantoin). Table 1 shows E. coli drug-resistant phenotypes at baseline. Therapeutic, clinical and microbiological success rates at test-of-cure numerically favored gepotidacin over nitrofurantoin for clinically important E. coli drug-resistant phenotypes: ESBL+, fluroquinolone-resistant (FQ-R), trimethoprim/sulfamethoxazole-resistant (SXT-R), and MDR (Figure 1). Adverse events were reported in 35% (gepotidacin) and 23% (nitrofurantoin) of patients.

Conclusion

Gepotidacin showed consistent efficacy (therapeutic, clinical and microbiological success) versus nitrofurantoin in patients with E. coli drug-resistant phenotypes (ESBL+, FQ-R, SXT-R, MDR). Gepotidacin has potential as a novel oral treatment for uUTI in key patient subgroups.

Disclosures

Thomas M. Hooton, MD, GSK: Advisor/Consultant Caroline R. Perry, PhD, GSK: Employee and shareholder Salim Janmohamed, MD, GSK: Employee and shareholder Amanda Sheets, PhD, GSK: Employee and shareholder Jeremy Dennison, MD, GSK: Employee and shareholder Helen Millns, PhD, GSK: Employee and shareholder Emily Jarvis, MSc, GSK: Employee and shareholder Nicole E. Scangarella-Oman, MS, GSK: Employee and shareholder Chun Huang, PhD, GSK: Employee and shareholder
2841. Skipping the Urine Culture before Genitourinary Surgeries May Not be Associated with Increased Risk of Postoperative UTI
Authors: Plasencia Juan Teran , O’Brien William , Lerner Lori , Schweizer Marin , Strymish Judith , Gupta Kalpana
Published: November 2023

Background

Detection of bacteriuria prior to most genitourinary (GU) procedures is a guideline-supported standard of care for prevention of postoperative UTI. Little is known about the frequency of concordance with guidelines and impact on outcomes. We hypothesized that GU surgeries in which a preoperative urine culture was indicated but not performed would be associated with an increased rate of postoperative UTI.

Methods

We obtained national data on all elective GU surgeries performed in VHA operating rooms during 2015-2022. CPT codes were flagged as indicated for preoperative urine culture based on risk of mucosal injury and AUA guidelines. Surgeries not indicated for urine culture were excluded. We identified urine cultures performed within 45 days before surgery. UTI outcome was defined as occurrence of ICD-10 code N39.0 within 30 days after surgery.

Multiple logistic regression estimated the independent association of preoperative culture performance with the outcome of UTI. Other independent variables included age, sex, ASA Class, antibiotics, and the 29 Elixhauser comorbidities.

Results

The study population included 221,018 surgeries at 123 VA Medical Centers. Mean (SD) age was 69.4 (11.0), 96.0% were men, and 76.1% were ASA Class 3-5. The most common surgeries were cystoscopy (62.8%), lithotripsy (9.9%), and TURP (8.7%). The comorbidity burden was typical for VA population studies (Table 1).

Preoperative urine cultures were performed in 65.5% of surgeries. In regression analysis controlling for comorbidities and antibiotics, the risk for postoperative UTI in those who did not have a urine culture performed despite being indicated, compared with those who did, was OR 0.56 [95%CI 0.53-0.58] (Table 2).

Multivariate Logistic Regression to Predict 30-day Postoperative UTI in GU Surgery Patients

Conclusion

In this large national cohort covering 8 years of GU surgeries, we found that non-performance of an indicated urine culture was common but was not independently associated with increased risk of postoperative UTI. The finding of significantly reduced risk was surprising and suggests that confounding patient factors, rather than procedure type, are driving the risk of postoperative UTI. Further work is warranted to identify these factors and explore the potential for de-implementation of standardized preoperative urine cultures for lower risk GU surgery patients.

Disclosures

Lori Lerner, MD, Janssen Pharmaceutical: Grant/Research Support Kalpana Gupta, MD, MPH, GSK: Advisor/Consultant|IDSA UTI Guidelines: Advisor/Consultant|qiagen: Advisor/Consultant|UpToDate: Advisor/Consultant
2842. Characteristics and Outcomes of Urinary Tract Infections (UTIs) Caused by Enterococci at a Tertiary Academic Medical Center in Saudi Arabia
Authors: Thabit Abrar K , Alharthi Khalid F , Baotab Salem M , Bankhar Abdullah M , Mahrous Ahmad J
Published: November 2023

Background

Enterococci are Gram-positive coccus bacteria that are normally present in the gastrointestinal tract and ordinarily function commensally with humans. They are generally considered opportunistic and often associated with healthcare-associated infections. We aimed to characterize patients with UTIs due to Enterococci and their outcomes.

Methods

This was a retrospective cohort study between June 2012 and November 2022 of patients who had clinically and microbiologically confirmed Enterococcal UTI. Inclusion criteria included a urine culture positive for E. faecalis or E. faecium with a count of ≥ 105 CFU/mL and having urinary tract symptoms.

Results

Of 4,094 patients screened, 125 were eligible and included. Patients had a median age of 63.3 years and were mostly females (60%). The most common characteristics were having a catheter, hospitalization in a non-ICU ward, and recent use of antibiotics within 90 days. Infection with E. faecalis was more common than E. faecium (78.4% vs. 21.6%). However, the latter exhibited higher rates of antibiotic resistance (P < 0.001) and was associated with significantly higher median temperature (38 vs. 37.1°C; P < 0.001), mortality rates (24% vs. 6.9%; P = 0.020), and median length of stay (32 vs. 13 days; P < 0.001).

Conclusion

Most patients with enterococcal UTIs had a history of catheter and recent antibiotic use and were mostly females and hospitalized in non-ICU wards. Patients infected with E. faecium had more severe episodes compared with patients infected with E. faecalis. Therefore, patients infected with E. faecium should be followed more closely and have their antibiotics evaluated by infectious diseases experts of physicians and clinical pharmacists to potentially improve their outcomes.

Disclosures

All Authors: No reported disclosures
2843. Risk Factors for Unplanned Healthcare Encounters in Patients Discharged from the Emergency Department with Extended-spectrum β-lactamase Urinary Tract Infections
Authors: Brochu Jessica M , Kenney Rachel M , Herbin Shelbye , Gunaga Satheesh , Veve Michael
Published: November 2023

Background

The management of extended spectrum β-lactamase (ESBL) urinary tract infections (UTIs) in the emergency department (ED) has not been well documented in literature. The purpose of this study was to describe treatment and outcomes of patients with ESBL UTIs in the ED, which can inform best practices for antimicrobial stewardship.

Methods

This IRB approved, retrospective cohort analysis included patients who were discharged from the ED with an ESBL UTI between January 2020 and November 2022. The primary outcome of interest was any unplanned healthcare encounter related to the UTI within 30 days of the index ED visit, which included phone/virtual visits, clinic visits, ED visits, and hospitalizations. Patients ≥18 years of age treated for symptomatic UTI with a monomicrobial urine culture were included, while those with altered mental status, history of renal transplant, abnormal urinary tract, or were on active antibiotic therapy prior to the ED visit were excluded. Patient characteristics, initial and definitive antibiotic therapy, culture results including pathogen and susceptibilities were described. Logistic regression analysis was used to identify any exposures that were independently associated with unplanned healthcare encounters related to the UTI.

Results

162 patients were included; 103 (64%) had an unplanned healthcare encounter. Patient characteristics are depicted in Table 1. Complicated lower UTI was most frequent occuring in 71 patients (44%). Susceptibility data revealed that nitrofurantoin was effective in 121 (75%) patients, aminoglycosides in 117 (72%) patients, TMP/SMX in 66 (41%) patients, and quinolones in 62 (38%) patients. 76 (74%) patients with unplanned encounters received an inactive empiric prescription: β-lactams being prescribed to 52 (51%) patients with cephalexin used for 49/52 (94%). Of the 81 patients with lower UTI, 20 (25%) initially received a prescription for nitrofurantoin. Factors associated with an unplanned healthcare encounter are described in Table 2.Table 2.Factors Associated with Unplanned Healthcare Encounters. Abbreviations: Un-Adj OR = unadjusted odds ratio; Adj OD = adjusted odds ratio

Conclusion

Patients discharged from the ED with an ESBL UTI were at higher risk for unplanned healthcare encounters if they had CKD or were initially prescribed an oral β-lactam. Prescribing first line therapy with nitrofurantoin for lower UTI is a potential area for improvement.

Disclosures

Michael Veve, PharmD, MPH, National Institutes of Health: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support
2844. Impact of Altered Mental Status on Antibiotic Prescribing in Patients with Pyuria
Authors: Boerckel Haley , Dumkow Lisa E , Worden Lacy , Salvati Lisa , Jameson Andrew
Published: November 2023

Background

The Infectious Diseases Society of America’s guidelines for the management of asymptomatic bacteriuria state that altered mental status (AMS) is non-specific and alone should not be classified as a symptom of urinary tract infection (UTI). Careful observation, rather than treatment, is recommended to avoid adverse medication events and antibiotic resistance. The purpose of this study was to evaluate the burden of antibiotic overtreatment, patient outcomes, and risk factors for treatment of AMS patients with asymptomatic pyuria within a community teaching hospital.

Methods

This retrospective cohort study evaluated adult inpatients admitted with AMS and pyuria (10 WBC/hpf) between February 1, 2020 and October 1, 2021. The primary objective was to compare outcomes between patients with AMS treated for asymptomatic pyuria (AMS+Tx) vs. those without treatment (AMS-NoTx) using a composite endpoint of readmission for AMS or development of

Clostridiodes difficile within 30-days, or development of new antibiotic resistance within 90 days. Secondary outcomes included characterizing the burden of overtreatment and identifying risk factors for treatment of pyuria in patients with AMS. Multi variate logistic regression identified risk factors independently associated with treatment of asymptomatic pyuria in patients with AMS. Patients were excluded who had noted urinary symptoms, admission to critical care, history of renal transplant, urological surgery, co-infection, pregnancy, or neutropenia.

Results

A total of 200 patients were included (AMS+Tx, n= 160; AMS-NoTx, n=40). No difference was observed between groups in the composite primary outcome (AMS+Tx 23.5% vs AMS-NoTx 18.1%, p=0.465). The burden of overtreatment was 80%. An alternative diagnosis of AMS occurred more frequently when antibiotics were withheld (AMS+Tx 65.6% vs.AMS-NoTx 87.5%, p=0.007). Urinalyses showing bacteria (OR 2.63; 95% CI 1.15-6.03) and positive urine culture (OR3.76; 95% CI 1.67-8.48) were associated with the use of antibiotics.

Conclusion

Patient-related outcomes were similar between groups highlighting the burden of antibiotic overtreatment and need for stewardship interventions in inpatients with AMS and pyuria presenting without other urinary symptoms.

Disclosures

All Authors: No reported disclosures
173. Staphylococcus Aureus Bacteremia at a Community Hospital in the Southeastern United States June 2021-June 2022
Authors: Arnoczy Gretchen S , Gibson Heather , Starr Kimberly
Published: November 2023

Background

Staphylococcus aureus bacteremia is a common condition with high risk for mortality. Recent COVID-19 infection may influence the incidence and outcome of S. aureus bacteremia.

Methods

We performed a retrospective chart review of individuals with Staphylococcus aureus bacteremia from June 2021-June 2022 in a rural community health care system in the Southeastern United States. Primary outcome was mortality—variables included methicillin resistance, persistent bacteremia, ID consult, history of injection drug use, cardiac imaging, and COVID-19 infection within the previous 90 days.

Results

172 individuals experienced 188 episodes of Staphylococcus aureus bacteremia. 79 were MRSA, 99 were MSSA. 57 individuals were deceased within 6 months of the positive blood culture (33% mortality). 31 individuals had known injection drug use complicating their illness, endocarditis was confirmed in 18 (58%) of these individuals compared to 33 (19%) of the entire population. 116 individuals (67%) had an ID consult. This study occurred during the delta and omicron COVID-19 surges in the region – 18 episodes of S. aureus bacteremia occurred within 90 days of a positive COVID-19 test, and 10 (56%) of those individuals were deceased within 6 months of the positive blood culture.

Conclusion

S. aureus bacteremia carries a high risk for mortality. Endocarditis was confirmed more frequently in individuals with known injection drug use. Six month mortality in S. aureus bacteremia was higher when bacteremia occurred in the 90 days post COVID-19 infection.

Disclosures

All Authors: No reported disclosures
968. Universal Newborn Testing for Congenital Cytomegalovirus (cCMV) Infection Comes of Age: Clinical Sensitivity of Screening Tests and Infant Outcomes in a cCMV Screening Study in Minnesota
Authors: Schleiss Mark R , Osterholm Erin , Hernandez-Alvarado Nelmary , Kruc Rebecca , Herd Hannah , Sidebottom Abbey , Licensed Genetic Sondra Rosendahl , Dollard Sheila , Lanzieri Tatiana
Published: November 2023

Background

Universal congenital cytomegalovirus (cCMV) screening is controversial. In 2023, we completed a study evaluating analytical and clinical sensitivity of dried blood spots (DBS) for detection of cCMV infection and disease. Analytical sensitivity is the ability of an assay to detect infection, while clinical sensitivity is an assay's ability to identify individuals with disease. The completion of this study coincided with implementation of new legislation making Minnesota the first state in the USA to mandate universal cCMV testing.

Methods

In six newborn nurseries in Minnesota, consented newborns were screened for cCMV, comparing PCR of saliva with PCR of the DBS obtained for routine newborn screening. Screen-positive infants had a confirmatory urine PCR, and a diagnostic clinical evaluation. Using international consensus criteria, we categorized cCMV cases as: moderate-to-severe; mildly symptomatic; asymptomatic with isolated sensorineural hearing loss (SNHL); or asymptomatic.

Results

From February 2016 - January 2023, among 23,644 newborns screened, 87 (3.7 per 1,000) were identified with cCMV. Analytical sensitivity of saliva was 93.1% (81); for DBS, it was 73.6% (64) by the UMN lab, and 77.0% (67) by the CDC lab. At birth, 67 (77%) infants were asymptomatic; 6 moderately-to-severely symptomatic (2 with SNHL); 10 mildly symptomatic; and 4 asymptomatic with isolated SNHL. 4 infants had delayed-onset SNHL (2 asymptomatic, 2 symptomatic). Among 20 infants with symptomatic cCMV at birth and/or SNHL, clinical sensitivity of saliva was 95% (19), and for DBS was 75% (15) in the UMN lab, and 85% (17) in the CDC lab.

Conclusion

This unselected screening study demonstrated a prevalence of 3.7/1000 of cCMV in Minnesota newborns. The enhancement in clinical sensitivity of DBS (over analytical sensitivity) to identify children with symptoms or sequelae suggests their usefulness for cCMV screening, though most identified infants will be asymptomatic. In parallel with this work, in the spring of 2023, Minnesota became the first state to screen all newborns for cCMV, using the newborn DBS. Continued evaluation of CMV DBS testing methods for reproducibility, efficiency, high-throughput capability and clinical correlation will be important as other states consider universal cCMV screening.

Disclosures

All Authors: No reported disclosures
970. Assessing the burden of Acinetobacter baumannii and Candida auris among ventilated patients in Maryland: A statewide period prevalence survey of two urgent threats
Authors: Harris Anthony , Pineles Lisa , Kristie Johnson J , O’Hara Lyndsay M , Smith Lauren Leigh , French Indira , Rubin Jamie , Perlmutter Rebecca , Heller Ashley , Klein Liore , Blythe David , Vaeth Elisabeth
Published: November 2023

Background

To date, only one statewide prevalence survey has been performed for Acinetobacter baumannii (2009) in the United States, and no statewide prevalence survey has been performed for Candida auris. We aimed to determine the prevalence of A. baumannii and C. auris among mechanically ventilated patients in Maryland.

Methods

The Maryland MDRO Prevention Collaborative performed a statewide point prevalence survey of mechanically ventilated patients admitted to acute care hospitals (ACH) and long-term care (LTC) facilities between March 7, 2023, and June 8, 2023. Surveillance cultures were obtained from all mechanically ventilated patients. Sputum, peri-anal, and arm/leg cultures were cultured for A. baumannii and antibiotic susceptibility testing was performed. Axilla/groin cultures were tested by PCR for C. auris.

Results

One hundred percent of all eligible healthcare facilities participated. 482 ventilated patients were included in the analysis. A. baumannii was cultured from at least one body site in 148/482 (31%) patients, CRAB was identified in 88/482 (18%) patients and C. auris in 31/470 (7%) patients. LTC patients were more likely to be colonized with A. baumannii (RR 7.7, 95% CI 5.1-11.5, p< .0001), with CRAB (RR 5.5, 95% CI 3.4-8.9, p< .0001) and C. auris (RR 2.0, CI 0.99-3.9, p=.05) compared to acute care hospital patients (Figure 1). Nine (29%) C. auris-positive patients were previously unknown to the Maryland Department of Health. Susceptibilities for A. baumannii are in Table 1.

Figure 1: Prevalence of A. baumannii, carbapenem-resistant A. baumannii, and C. auris stratified by type of facility. Figure 2. Resistance Mechanisms in Carbapenem-Resistant Isolates (N=88) Table 1: Antimicrobial Data: All patient A. baumannii isolates demonstrating antimicrobial susceptibility, N (% susceptible)

Conclusion

A. baumannii, CRAB and C. auris colonization are common among mechanically ventilated patients in both ACH and LTC facilities. Both pathogens were significantly more common in long-term care facilities than acute care facilities. Ventilated long-term care patients are an extremely high-risk population for emerging pathogens and surveillance and infection prevention efforts should be targeted to these facilities.

Disclosures

Anthony Harris, MD, MPH, Merck: Grant/Research Support|UpToDate: Infection Control Editor