Descriptive Epidemiology and Outcomes of Hospitalizations With Complicated Urinary Tract Infections in the United States, 2018

Background Hospitalizations with complicated urinary tract infection (cUTI) in the United States have increased. Though most often studied as a subset of cUTI, catheter-associated UTI (CAUTI) afflicts a different population of patients and carries outcomes distinct from non-CA cUTI (nCAcUTI). We examined the epidemiology and outcomes of hospitalizations in these groups. Methods We conducted a cross-sectional multicenter study within the 2018 National Inpatient Sample (NIS) database, a 20% stratified sample of discharges from US community hospitals, to explore characteristics and outcomes of patients discharged with a UTI diagnosis. We divided cUTI into mutually exclusive categories of nCAcUTI and CAUTI. We applied survey methods to develop national estimates. Results Among 2 837 385 discharges with a UTI code, 500 400 (17.6%, 19.8% principal diagnosis [PD]) were nCAcUTI and 126 120 (4.4%, 63.8% PD) were CAUTI. Though similar in age (CAUTI, 70.1 years; and nCAcUTI, 69.7 years), patients with nCAcUTI had lower comorbidity (mean Charlson, 4.3) than those with CAUTI (mean Charlson, 4.6). Median (interquartile range [IQR]) length of stay (LOS) was 5 (3–8) days in nCAcUTI and 5 (3–9) days in CAUTI. Overall median (IQR) hospital costs were similar in nCAcUTI ($9713 [$5923–$17 423]) and CAUTI ($9711 [$5969–$17 420]). Though low in both groups, hospital mortality was lower in nCAcUTI (2.8%) than in CAUTI (3.4%). Routine discharges home were higher in nCAcUTI (41.5%) than CAUTI (22.1%). Conclusions There are >626 000 hospital admissions with a cUTI, comprising ~1.8% of all annual admissions in the United States; 4/5 are nCAcUTI. Because CAUTI is frequently the reason for admission, preventive efforts are needed beyond the acute care setting.

Cefiderocol- A New Antimicrobial for Complicated Urinary Tract Infection (CUTI) Caused by Carbapenem Resistant Enterobacteriaceae (CRE)

: The incidence of Carbapenem resistant gram negative (CRGNB) bacterial infections has increased globally. The wide diversity of strains, multiplicity of infections and rapid development and spread of resistance are a matter of great concern both in community and hospital settings. Cefiderocol is a novel injectable siderophore containing cephalosporin with potent microbicidal activity against most Carbapenem Resistant Enterobacteriaceae (CRE). It has recently been approved by USFDA for the treatment of complicated urinary tract infections (cUTI) caused by susceptible gram-negative microorganisms. This review focuses on the salientpharmacological profile of the drug and the clinical studies that were undertaken.

Complicated urinary tract infection in a patient with severe COVID-19

Introduction. At the end of 2019, the world faced a pandemic of infection caused by the SARS-CoV-2 coronavirus. The disease caused by this virus is referred to as COVID-19, and is characterized by multiorgan lesion. The leading syndrome is the syndrome of immune response disregulation or the «cytokine storm». According to the studies, which were used as the basis of patient management clinical protocols, antiinterleukin-6 agents, and glucocorticosteroids, are the most effective in stopping the «cytokine storm». At the same time, the use of immunosuppressive drugs increases the risk of secondary infectious complications not associated with the COVID-19 viral infection.The aim of the study was to present a successful case of treating a secondary bacterial infection in a patient with a severe new coronavirus infection in the context of a limited choice of antimicrobial therapy.Materials and methods. The report presents a clinical case of a complicated urinary tract infection associated with an extremely resistant Kl.pneumoniae strain in a 58-year-old patient hospitalized with severe COVID-19. Due to comorbidity, combined with long-term hospitalization, the need in immunosuppressive therapy, and long-term catheterization of the urinary tract, the patient got affected by Kl.pneumoniae. This pathogen demonstrated microbiological and clinical resistance to all studied classes of antibiotics, including carbapenems, aminoglycosides and polymyxins. The patient developed an abscess of the prostate, and orchiepididymitis, which required repeated surgical interventions.Results and Discussion. The multidisciplinary approach to patient treatment, as well as the use of local and regional epidemiological data made it possible to choose the most effective drug therapy. The combination of adequate surgical debridement and combined antibiotic therapy (ceftazidime/avibactam and aztreonam) led to regression of the complicated urinary tract infection manifestations and clinical recovery.Conclusions. The use of ceftazidime/avibactam and aztreonam combination is a promising therapeutic option for the treatment of infections caused by extremely resistant strains of Enterobacterales, in which the combined production of serine proteases and metallobetalactamases is expected.

Rare case of Proteus mirabilis native mitral valve endocarditis in an immunocompromised patient

Background Bacterial infective endocarditis caused by Proteus mirabilis is rare and there are few cases in the literature. The natural history and treatment of this disease is not as clear but presumed to be associated with complicated urinary tract infection (cUTI). Case presentation A 65-year-old female with a history of rheumatoid arthritis, factor V Leiden hypercoagulability, and prior saddle pulmonary embolism presented to the emergency department following a mechanical fall. Computed Tomography showed evidence of acute/subacute splenic emboli. Complicated UTI was likely secondary to a ureteral stone. Blood and urine cultures also grew out P. mirabilis. Transthoracic echocardiography revealed a mobile echogenic density on the anterior mitral valve (MV) leaflet consistent with a vegetation. The patient underwent MV replacement, and P. mirabilis was isolated from the surgically removed valve. Conclusions We hypothesize that the patient’s immunocompromised status following steroid and Janus Kinase inhibitor usage for rheumatoid arthritis contributed to Gram-negative bacteremia following P. mirabilis UTI, ultimately seeding the native MV. Additional studies with larger numbers of Proteus endocarditis cases are needed to investigate an association between immunosuppression and Proteus species endocarditis.

POCUS Evaluation in Acute Kidney Injury

Acute kidney injury is a common clinical problem encountered in general internal medicine. The evaluation of acute kidney injury is mainly driven by the patient’s clinical history, physical exam and basic urinary/laboratory investigation. Point of care ultrasound (POCUS) may be a useful tool to help clinicians to narrow and/or prioritize differential diagnosis in patients presenting with acute kidney injury. Here we present a case of a 67-year old male presenting with dysuria, fevers, and flank pain along with elevation in serum creatinine who was admitted for acute kidney injury secondary to complicated urinary tract infection. Subsequent renal POCUS showed bilateral anechoic fluid collection within the renal sinus with dilated calyces suggestive of bilateral hydronephrosis most likely due to a new diagnosis of benign prostatic hyperplasia. This case demonstrates the use of POCUS added valuable diagnostic information and therapeutic management for this patient presenting with acute kidney injury.

Clinical management of cUTI, cIAI, and HABP/VABP attributable to carbapenem-resistant Gram-negative infections in Spain

Introduction. Carbapenem-resistant Gram-negative (CRGN) infections are a major public health problem in Spain, often implicated in complicated, healthcare-associated infections that require the use of potentially toxic antibacterial agents of last resort. The objective of this study was to assess the clinical management of complicated infections caused by CRGN bacteria in Spanish hospitals. Methods. The study included: 1) a survey assessing the GN infection and antibacterial susceptibility profile in five participating Spanish hospitals and 2) a non-interventional, retrospective single cohort chart review of 100 patients with complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) attributable to CRGN pathogens. Results. In the participating hospitals CRGN prevalence was 9.3% amongst complicated infections. In the retrospective cohort, 92% of infections were healthcare-associated, and Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common pathogens. OXA was the most frequently detected carbapenemase type (71.4%). We found that carbapenems were frequently used to treat cUTI, cIAI, HABP/VABP caused by CRGN pathogens. Carbapenem use, particularly in combination with other agents, persisted after confirmation of carbapenem resistance. Clinical cure was 66.0%, mortality during hospitalization 35.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. Conclusion. Our results reflect the high burden and unmet needs associated with the management of complicated infections attributable to CRGN pathogens in Spain and highlight the urgent need for enhanced clinical management of these difficult-to-treat infections.

1159. Pharmacokinetics, Safety, and Tolerability of Imipenem/Cilastatin/Relebactam in Pediatric Participants With Confirmed or Suspected Gram-negative Bacterial Infections: A Phase 1b, Open-label, Single-Dose Clinical Trial

Background Imipenem/cilastatin/relebactam (IMI/REL) is approved for treating hospital-acquired/ventilator-associated bacterial pneumonia, complicated urinary tract infection, and complicated intra-abdominal infection in adults. This study assessed single-dose pharmacokinetics (PK), safety, and tolerability of IMI/REL in neonatal and pediatric participants with confirmed or suspected gram-negative bacterial infections. Methods This was a phase 1, open-label, non-comparative study (NCT03230916). Age- and weight-adjusted dosing is summarized in Table 1. The primary objective was to characterize the PK profiles for imipenem and relebactam after a single intravenous dose of IMI/REL. PK parameters were analyzed using population modeling. The PK target for imipenem was the percent time of the dosing interval that the unbound plasma concentration exceeded the minimum inhibitory concentration (%fT >MIC) of ≥30% (MIC used, 2 µg/mL). The PK target for relebactam was an area under the curve (AUC)/MIC ratio >8 (MIC used, 2 µg/mL), corresponding to AUC0-24h >58.88 μM∙h. Safety and tolerability were assessed for up to 14 days after drug infusion. Results Of the 46 participants who received IMI/REL, 42 were included in the PK analysis. The mean plasma concentration-time profiles for imipenem and relebactam were generally comparable across age cohorts (Figure). For imipenem, the geometric mean %ƒT >MIC ranged from 50% to 94% and the mean maximum concentration (Cmax) ranged from 65 μM to 126 μM (Table 2). For relebactam, the geometric Cmax ranged from 33 μM to 87 μM and mean AUC0-6h ranged from 51 μM·h to 159 μM·h across the age cohorts (Table 2). IMI/REL was well tolerated with 8 (17.4%) participants experiencing ≥1 adverse events (AE) and 2 (4.3%) participants experiencing AE that were deemed drug related by the investigator. Drug-related AE were increased alanine aminotransferase, increased aspartate aminotransferase, anemia, and diarrhea, which were non-serious, mild in severity, and resolved within the follow-up period of 14 days. Figure 1 Conclusion Imipenem and relebactam exceeded the pediatric plasma PK targets across pediatric age cohorts in the study; the single doses of IMI/REL were well tolerated. These results will inform IMI/REL dose selection for further pediatric clinical evaluation. Disclosures Camilla Tøndel, MD, PhD, Merck & Co., Inc., (Grant/Research Support) Emmanuel Roilides, MD, PhD, FIDSA, FAAM, FESCMID, FECMM, FISAC, Merck Sharp & Dohme Corp. (Consultant, Grant/Research Support) Matthew S. Kelly, MD, MPH, Merck Sharp & Dohme Corp. (Consultant, Grant/Research Support) Munjal Patel, PhD, Merck Sharp & Dohme Corp. (Employee, Shareholder) Pavan Vaddady, PhD, Merck Sharp & Dohme Corp. (Employee) Alok Maniar, MD, MPH, Merck Sharp & Dohme Corp. (Employee, Shareholder) Ying Zhang, PhD, Merck & Co., Inc. (Employee, Shareholder) Amanda Paschke, MD MSCE, Merck Sharp & Dohme Corp. (Employee, Shareholder) Joan R. Butterton, MD, Merck Sharp & Dohme Corp. (Employee, Shareholder) Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck (Employee)

598. A 3-Year Evaluation of Antibiotic Resistance Patterns in Gram-Negative Genitourinary Tract Infections Treated in Outpatient Infusion Centers (POICs)

Background Resistant Gram-negative pathogens (GNP) are common causes of genitourinary tract infections (GUI) often requiring outpatient parenteral antibiotic therapy (OPAT). Data are sparse regarding antibiotic resistance of GNP in patients (pts) treated with OPAT. We analyzed GNP of GUI pts treated in Infectious Disease OICs over a 3-year period stratified by location prior to OPAT. Methods Records from 18 POICs were queried for GUI pts with ≥1 GNP receiving OPAT from 2018 to 2020. Demographics, pt location prior to OPAT, infection type, year of therapy, and GNP were recorded. Antibiotic resistance patterns were defined as extended-spectrum beta-lactamase (ESBL) or multi-drug resistant (MDR). Chi Square and Fisher’s exact test were used to determine if ESBL status was associated with GNP or location prior to OPAT (hospital vs. community). The Cochran-Armitage test was used to analyze temporal trend in ESBL expression. Statistical significance was defined as P< 0.05 for all tests. Results A total of 634 GNP were identified in 601 pts (mean age: 64±16, 58% female). Infections were 75% complicated urinary tract infection, 20% pyelonephritis, and 5% prostatitis/other. Overall, 56% (n=339) were treated directly from the community and 44% (n=262) following hospital discharge. GNP isolated were 56% E. coli, 19% Pseudomonas spp., 16% Klebsiella spp. and 9% others. Of the 611 GNP with potential to express ESBL, 43% (n=265) were ESBL producers (Table 1). Significantly more ESBL-producing GNP occurred in pts discharged from a hospital prior to OPAT compared to the community (53% vs. 36%, P< 0.001). Overall, the incidence of MDR constituted 36% (n=231) of GNP, which did not differ by location prior to OPAT. Evaluation of ESBL incidence by year showed a significant increase from 2018 to 2020 (P=0.03). Although a slight increase in MDR was noted from 2018 to 2020, this was not significant (Figure 1). Table 1. Frequency of ESBL and MDR by Location prior to OPAT Figure 2. Prevalence of ESBL producers and MDR Pathogens by Year Conclusion Resistant GNP were observed in the OPAT setting for GUI with both ESBL and MDR pathogens. We saw a significantly higher rate of ESBL with GNP from hospital discharged pts compared to community-acquired infections and an increase in the overall incidence of ESBL over time. Management of Gram-negative genitourinary infections in the OPAT setting requires close monitoring of emerging resistance patterns. Disclosures Kimberly A. Couch, PharmD, MA, FIDSA, FASHP, AbbVie (Speaker's Bureau) Lucinda J. Van Anglen, PharmD, Merck & Co. (Research Grant or Support)

1415. Allergies to Antimicrobial Agents Among US Females with Uncomplicated Urinary Tract Infection

Background Uncomplicated urinary tract infections (uUTI) are generally treated empirically with antibiotics. However, antibiotic (AB) allergies limit the available oral treatment options for some patients. We assessed the proportion of self-reported AB allergies among US females with uUTI. Methods We performed a cross-sectional survey of US females ≥ 18 years of age with a self-reported urinary tract infection (UTI) in the 60 days prior to participation and a prescription of oral AB. Participants were further screened for evidence of a complicated urinary tract infection and, after exclusions, participants with a uUTI completed an online questionnaire about their most recent episode. Participants were from the Northeast (20%), Midwest (44%), South (20%), and West (16%) US. Descriptive self-reported allergy data were stratified into subgroups by whether the participant had recurrent UTI (defined as ≥ 2 uUTIs in the past 6 months or ≥ 3 uUTIs in past 12 months including index UTI), the number of different ABs given for the index episode (1, 2, ≥ 3), and whether the treatment was clinically appropriate according to Infectious Diseases Society of America uUTI guidelines. Results Overall, 375 female participants completed the questionnaire. The most commonly prescribed ABs for participants’ most recent uUTI were trimethoprim-sulfamethoxazole (TMP-SMX; 38.7%), ciprofloxacin (22.7%), and nitrofurantoin (18.9%) (Table 1). Most participants received only 1 AB for their uUTI (62.7%) and the majority were classified as having a non-recurrent uUTI (56.5%). No AB allergies were reported for most participants (69.3%); overall, 24.0% reported 1 AB allergy and 6.7% reported ≥ 2. A higher proportion of participants reported ≥ 2 allergies in the recurrent uUTI, ≥ 3 AB, and multiple AB subgroups (Table 2). The most common allergy was to TMP-SMX (15.7%), followed by amoxicillin-clavulanate (8.3%) and ciprofloxacin (5.3%) (Table 2). Similar allergy trends were seen across subgroups, except higher rates of ciprofloxacin allergy were seen in participants given multiple ABs (Table 2). Table 1. Antibiotics used to treat most recent uUTI Table 2 . Frequency of antibiotic allergies across cohort subgroups Conclusion AB allergies were relatively frequent in this uUTI cohort and the most common allergy was to TMP-SMX, which was the most prescribed AB. Allergies to ABs reduce the available treatment options for uUTI in some patients. Disclosures Jeffrey Thompson, PhD, Kantar Health (Employee, Employee of Kantar Health, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Jonathon Wright, BSc, Kantar Health (Employee, Employee of Kantar Health, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)