Invasive Urinary Tract Infection Research Articles

Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli.

Cefmetazole is active against extended-spectrum β-lactamase-producing Escherichia coli (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcomes included clinical and microbiological effectiveness, recurrence within 28 d, and all-cause mortality (14 d, 30 d, in-hospital). Outcomes were adjusted for the inverse probability of propensity scores for receiving cefmetazole or meropenem. Eighty-one and forty-six patients were included in the cefmetazole and meropenem groups, respectively. Bacteremia accounted for 43% of the cefmetazole group, and 59% of the meropenem group. The crude clinical effectiveness, 14 d, 30 d, and in-hospital mortality for patients in the cefmetazole and meropenem groups were 96.1% vs 90.9%, 0% vs 2.3%, 0% vs 12.5%, and 2.6% vs 13.3%, respectively. After propensity score adjustment, clinical effectiveness, the risk of in-hospital mortality, and the risk of recurrence were similar between the two groups (P = 0.54, P = 0.10, and P = 0.79, respectively). In all cases with available data (cefmetazole : n = 61, meropenem : n = 22), both drugs were microbiologically effective. In all isolates, bla CTX-M was detected as the extended-spectrum β-lactamase gene. The predominant CTX-M subtype was CTX-M-27 (47.6%). Cefmetazole showed clinical and bacteriological effectiveness comparable to meropenem against invasive urinary tract infection due to ESBLECs.

658. Evaluation of Effectiveness of Cefmetazole vs Meropenem for Invasive Urinary Tract Infections Caused by ESBL-Producing Escherichia coli: A Prospective Multicenter Observational Study

Abstract Background ESBL-producing E. coli (ESBLEC) continues to increase worldwide. For the infection due to ESBLEC, no antimicrobial agent has clearly demonstrated therapeutic effectiveness comparable to that of carbapenem. Overuse of carbapenems may lead to an increase in carbapenem-resistant bacteria. Cefmetazole (CMZ) is active against ESBLEC, however, there are limited multicenter studies on the effectiveness of CMZ, an important carbapenem-sparing therapy for the treatment of ESBLEC. Methods This prospective, observational study included patients hospitalized for invasive urinary tract infection (iUTI) due to ESBLEC between March 2020 and November 2021 at 10 centers in Japan, with either CMZ or meropenem (MEM) initiated within 96 hours of culture submission as definitive therapy, and used for at least 4 days. The diagnosis of iUTI was made in patients with a fever of ≥37.5°C, symptom of pyelonephritis such as back pain, pyuria, and ESBLEC detected in urine (≥10^4 CFU/mL). Outcomes included clinical effectiveness (resolution of all clinical symptoms or improvement to pre-infection status) between day 4 to 6 of treatment (early) and between the final day of treatment and 2 days later (late), microbiological effectiveness (reduction to ≤10^3 CFU/ml) between day 4 to 6, and mortality. Outcomes were adjusted for the inverse probability of propensity scores (PS) for receiving CMZ or MEM treatment. Results Seventy-seven patients in the CMZ group and 46 in the MEM group were included. In univariate analysis, the CMZ group was older than the MEM group, although the MEM group had higher qSOFA, CRP, more frequent medical device use and concurrent bacteremia at the start of study drugs than the CMZ group (Table). Univariate analysis showed no difference in clinical effectiveness, and 30-day mortality was higher in the MEM group. In all cases with available data (CMZ: n=57, MEM: n=22), both drugs were microbiologically effective. After PS adjustment, clinical effectiveness did not differ between the two groups. The risk of 30-day mortality was lower in CMZ group, whereas the risk of recurrence was similar in both groups. Conclusion CMZ is as effective as MEM for the treatment of iUTI, suggesting that it is a promising carbapenem-sparing therapy. Disclosures Sho Saito, MD, PhD, DAIICHI SANKYO: Grant/Research Support|EVEC: Grant/Research Support|EVEC: Patents obtained through collaborative research|SHIONOGI: Grant/Research Support|Takeda: Advisor/Consultant.

97 Decreasing invasive urinary tract infection screening in a paediatric emergency department: A quality improvement initiative

Abstract Primary Subject area Emergency Medicine - Paediatric Background Fever is a common presentation among children coming to the Emergency Department (ED) and a urinary tract infection (UTI) often needs to be excluded. Sterile techniques, like catheterization, are invasive, can be traumatizing to children, and are time consuming to complete. A two-step approach has been shown to reduce the catheterization rate in febrile, young children without unintended consequences. Objectives Our aim was to implement a two-step approach for UTI screening in febrile children 6-24 months in order to decrease unnecessary urine catheterizations by 50% without impacting ED length of stay (LOS) or return visits (RVs). Design/Methods After engaging key stakeholders and a nursing champion, we created a process map to understand the current urine collection process in our ED, and areas for targeted improvement. Using the model for improvement, we adopted a 2-step pathway for a suspected UTI in children 6-24 months as our change idea. The pathway involved identifying children who met inclusion criteria for UTI screening, followed by urine bag application and urinalysis (UA) if clinically indicated. Only if the UA was positive, a second urine sample was collected via catheterization, for repeat UA and culture. Through multiple PDSA cycles, our pathway was implemented in the ED along with concurrent staff education. The outcome measure was the rate of ED urine catheterizations. Process measures included the total number of urine cultures sent to microbiology and percent positivity. The balancing measures included ED LOS and RVs. Results Since project initiation in July 2019, the ED catheterization rate decreased from 73% to 53% (Figure 1) and the number of urine cultures sent to Microbiology decreased by 23%. The number of urine cultures sent to Microbiology decreased by 23% with a mild improvement in the positivity rate by 2% (Figure 2). There was no significant change in RVs. There was a slight 10-min increase in ED LOS, most likely confounded by the COVID pandemic. Conclusion Using improvement methodology, we successfully decreased the number of unnecessary catheterizations in children and the number of urine cultures sent to microbiology. Further refinements to our intervention are ongoing and include optimizing urine screening equipment in patient rooms, poster reminders, re-education for providers, and introducing a parent resource explaining the 2-step pathway. This improvement work is also being spread to the paediatric wards and can easily be adopted by other paediatric centres. It has also been adapted by the Choosing Wisely hospital campaign.

Retrospective evaluation of appropriate dosing of cefmetazole for invasive urinary tract infection due to extended-spectrum β-lactamase-producing Escherichia coli

IntroductionThe frequency of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales is steadily increasing worldwide. Therefore, we aimed to evaluate the efficacy and appropriate dosing of cefmetazole (CMZ) in invasive urinary tract infection (iUTI) caused by ESBL-producing Escherichia coli (ESBLEC). MethodsPatients who developed ESBLEC iUTI and received CMZ between January 2007 and December 2018 were identified, and their medical records were reviewed. The time above minimum inhibitory concentration (MIC) (TAM) was calculated using the MIC value obtained from each patient and its simulated CMZ concentration. ResultsThirty-nine patients were included in the study. The median TAM was 92.6% (interquartile range [IQR], 67.6–100). CMZ was clinically efficacious in 38 (97.4%) patients overall and in 11 out of 12 (91.7%) patients with normal renal function who received CMZ at 1 g every 8 h. ConclusionsIn normal renal function, 1 g CMZ infused for over 1 h every 8 h is an efficacious treatment for iUTI caused by ESBLEC with MIC =< 4 mg/L.

Vitamin D-deficient mice have more invasive urinary tract infection

Vitamin D deficiency is a common health problem with consequences not limited to bone and calcium hemostasis. Low levels have also been linked to tuberculosis and other respiratory infections as well as autoimmune diseases. We have previously shown that supplementation with vitamin D can induce the antimicrobial peptide cathelicidin during ex vivo infection of human urinary bladder. In rodents, however, cathelicidin expression is not linked to vitamin D and therefore this vitamin D-related effect fighting bacterial invasion is not relevant. To determine if vitamin D had further protective mechanisms during urinary tract infections, we therefore used a mouse model. In vitamin D-deficient mice, we detected more intracellular bacterial communities in the urinary bladder, higher degree of bacterial spread to the upper urinary tract and a skewed cytokine response. Furthermore, we show that the vitamin D receptor was upregulated in the urinary bladder and translocated into the cell nucleus after E. coli infection. This study supports a more general role for vitamin D as a local immune response mediator in the urinary tract.

Clinical Use of a Prediction Rule to Guide Admission Policy in Community-Acquired Invasive Urinary Tract Infection: A Randomized Clinical Trial

A total of 370 patients were included, 237 in the control period and 133 in the intervention period. Use of PRACTICE significantly reduced the primary hospitalization rate (from 92%, in the control group to 72%, in the intervention group, p <0.01). The secondary hospital admission rate after initial outpatient treatment was 6% in control patients and 27% in intervention patients (1/17 and 10/37; p<0.001). In none of these secondary admissions intensive care treatment was required, and no complications were noted. Introduction

Metabolism and Fitness of Urinary Tract Pathogens.

Among common infections, urinary tract infections (UTI) are the most frequently diagnosed urologic disease. The majority of UTIs are caused by uropathogenic Escherichia coli. The primary niche occupied by E. coli is the lower intestinal tract of mammals, where it resides as a beneficial component of the commensal microbiota. Although it is well-known that E. coli resides in the human intestine as a harmless commensal, specific strains or pathotypes have the potential to cause a wide spectrum of intestinal and diarrheal diseases. In contrast, extraintestinal E. coli pathotypes reside harmlessly in the human intestinal microenvironment but, upon access to sites outside of the intestine, become a major cause of human morbidity and mortality as a consequence of invasive UTI (pyelonephritis, bacteremia, or septicemia). Thus, extraintestinal pathotypes like uropathogenic E. coli (UPEC) possess an enhanced ability to cause infection outside of the intestinal tract and colonize the urinary tract, the bloodstream, or cerebrospinal fluid of human hosts. Due to the requirement for these E. coli to replicate in and colonize both the intestine and extraintestinal environments, we posit that physiology and metabolism of UPEC strains is paramount. Here we discuss that the ability to survive in the urinary tract depends as much on bacterial physiology and metabolism as it does on the well-considered virulence determinants.

Febrile urinary tract infection in the emergency room.

To review the recent advances in the diagnostic and therapeutic approach to adults presenting with febrile urinary tract infection (UTI) in the emergency department (ED). Recent research suggests overdiagnosis and therefore overtreatment of UTI in the ED, especially in the elderly. Antimicrobial pretreatment, an indwelling catheter, and malignancy are independent risk factors for bacteremia with uropathogens that cannot be cultured from urine. A simple clinical prediction rule can predict clinically relevant radiologic findings in patients with invasive UTI. Procalcitonin is a marker for bacteremia; pro-adrenomedullin predicts a complicated course and 30-day mortality in complicated UTI. Several reports have identified the risk factors for resistant uropathogens in community-acquired febrile UTI. Adherence to the guidelines and early culture-guided intravenous-to-oral switch reduces the length of hospitalization. An effective strategy is needed to improve the diagnosis of UTIs in acute care. Further research regarding biomarker-guided triage might improve the management of patients with febrile UTI. Future efforts should be directed toward the improvement of adherence to UTI treatment guidelines.

Diagnostic criteria for urinary tract infection in hospitalized elderly patients over 75 years of age: A multicenter cross-sectional study

Abstract Introduction Urinary tract infection (UTI) is one of the most frequent infections in geriatric patients. Nevertheless, the diagnosis remains difficult because of the high prevalence of asymptomatic bacteriuria (AB). We studied the diagnosis criteria used by physicians in geriatric patients 75 years of age or more. Method A multicenter study was carried out in October 2009 in acute care wards (geriatrics, infectious diseases, internal medicine). During 1 week, the local investigator collected all positive urine microscopy and culture in geriatric patients 75 years of age or more and filled out a questionnaire on the final diagnosis (AB, cystitis, pyelonephritis, prostatitis), symptoms, clinical signs, and other infectious diagnosis. Results Two hundred and forty-one questionnaires were filled out in 48 wards. Physicians diagnosed AB in 91 patients (37.8%), cystitis in 72 (29.9%), pyelonephritis in 48 (19.9%), prostatitis in 20 (8.3%). 28.2% of patients were asymptomatic; 35% presented with clinical signs. General signs were significantly associated with invasive infection and the absence of functional signs with AB. Among the patients presenting with an invasive UTI, 27.9% also presented with another infection. This other infection was not statistically associated with AB, cystitis, or invasive UTI. Conclusion Too many urine microscopy and culture procedures are not justified, and too many patients are diagnosed with several infections. Usual functional and clinical signs are important for the diagnosis but are infrequent. It seems necessary to review the range of clinical presentations and diagnostic criteria for UTI in geriatric patients.

Recurrent urinary tract infections in men. A role for aberrant bacterial forms

We studied 45 infected a symptomatic men who had experienced recurrent urinary tract infections classified as bacterial relapse. These patients did not have ilial loop bladder, urethral catheters, suprupubic catheters or condom drainage. We had to process more than 1000 urines from patients attending the neurosurgery clinic at Hamad Shihab Hospital from March 2000 to July 2000 to identify the 45 study patients. A positive antibody coated bacteria influences test was detected on the urinary sediment of each of these patients.This selected study group was subjected to excretory urography and a 2–weeks course of antibiotic in accordance with the results of in vitro susceptibility tests. Eight patients experienced a cure.Recurrences developed in 32 patients (24 relapses, 8 reinfections). And in 4 patients a super infection emerged. No pathogenic role could be attributed to aberrant bacterial forms in this patient's population of symptomatic patients with recurrent invasive urinary tract infection.

Decreased invasive capacity of quinolone-resistant Escherichia coli in patients with urinary tract infections.

Quinolone-resistant (QR) Escherichia coli may have lower invasive capacity than does quinolone-susceptible E. coli. To evaluate this, we prospectively collected data regarding all cases of E. coli invasive urinary tract infections (IUTI) in 669 adults admitted to the Infectious Diseases Unit of our hospital during a 3-year period, as well as 10,950 patients with cystitis or asymptomatic bacteriuria who presented to the outpatient clinic during a 1-year period. QR E. coli was isolated in 20% of patients with cystitis, compared with 8% of those with IUTI (P<.05). The proportion of E. coli isolates that were quinolone resistant was similar in patients with bacteremic and nonbacteremic IUTI. The factors of urinary manipulation and structural abnormalities were independently associated with the presence of quinolone resistance. Old age was the only variable independently associated with blood invasion. QR E. coli is less likely to produce invasive disease (pyelonephritis and prostatitis) than is quinolone-susceptible E. coli. However, once pyelonephritis or prostatitis have developed, there is no difference in the incidence of bacteremia.

Invasive disease caused by ciprofloxacin-resistant uropathogenic Escherichia coli.

To evaluate the invasiveness of ciprofloxacin-resistant Escherichia coli isolated from the urinary tract, the susceptibility to ciprofloxacin of Escherichia coli strains from patients with invasive urinary tract infection was compared with that of isolates from patients with noninvasive disease. In a 14-month period, 2054 different isolates of Escherichia coli were analyzed, of which 554 (27%) were resistant to ciprofloxacin. One hundred twelve (5.4%) strains were isolated from patients with invasive disease. Resistance was significantly less frequent in isolates from patients with invasive disease (4.5%) than in isolates from patients with noninvasive disease (28.3%) (OR, 0.12; CI 95%, 0.05-0.29; P<0.001). Most ciprofloxacin-resistant strains associated with invasive disease were isolated from bacteremic patients who had recently undergone an invasive procedure involving the urinary tract. Invasive disease is caused more frequently by ciprofloxacin-susceptible strains of Escherichia coli, suggesting that resistance to ciprofloxacin may decrease the invasiveness of uropathogenic Escherichia coli.

Phagocytosis of urinary pathogens in persons with spinal cord injury

Urinary tract infections (UTI) are a major source of morbidity in persons with spinal cord injury (SCI), often prolonging hospitalization, interfering with rehabilitation, and leading to secondary urologic complications. Greater understanding of host and bacterial factors that may predispose to invasive UTI and identification of persons at greatest risk for renal deterioration could facilitate development of measures to improve the quality of life for these individuals. A prospective investigation of host phagocyte-bacterial interactions was undertaken as a means to assess whether persons with SCI who develop renal deterioration may be deficient in this important means by which invasive bacteria are eliminated from tissues. Neutrophil phagocytic and serum opsonic activities against uropathogenic Escherichia coli and Enterococcus fecalis were studied in 17 persons with SCI who had diminished renal function and 25 persons with SCI who had normal renal function. Phagocytic and opsonic activities of neurologically intact persons were also comparatively studied as an additional control group. No differences in efficiency of opsonization or phagocytosis were detected when persons with SCI and impaired renal function were compared with persons with SCI who had normal renal function or neurologically intact controls. Whether biochemical characteristics of urine or other undefined local aspects of the urinary tract influence host-bacterial relationships and urologic outcome following SCI are topics worthy of future investigation.

Epidemiology of Bacteremic Urinary Tract Infections in Chronically Hospitalized Elderly Men

We sought to determine the contribution of. pathogen-specific factors to the pathogenesis of invasive urinary tract infections in chronically institutionalized elderly men with symptomatic bacteriuria. We found that Escherichia coli was the most invasive pathogen, being found in 46% of the bacteremic as opposed to 25% of the nonbacteremic, rigorously defined urinary tract infections (p <0.01). The predominance of E. coli in bacteremic urinary tract infections was observed regardless of whether indwelling urinary drainage devices were used. The finding that E. coli accounted for a greater proportion of bacteremic than nonbacteremic urinary tract infections indicates that bacteremia arising from the geriatric urinary tract is not simply a consequence of mechanical factors, such as urinary tract obstruction. Thus, further investigations are warranted to assess the specific contribution of previously defined E. coli virulence factors to the pathogenesis of urinary tract infections in such patients.

Recurrent urinary tract infections in men: an assessment of contemporary treatment

A prospective study was performed on 30 men with asymptomatic, recurrent urinary tract infections in order to assess contemporary treatment of this disease. Patients had to have significant bacteriuria with a pure culture of Pseudomonas aeruginosa or a member of the Enterobacteriaceae family that was susceptible in vitro to the antimicrobial agent prescribed, and a urinary sediment that demonstrated a positive antibody-coated bacteria immunofluorescence test of at least 2+ intensity. All patients were subjected to excretory urograms. Therapeutic response was appraised in accordance with previously issued FDA protocol guidelines. Colonial morphology, biochemical tests, antimicrobial susceptibility testing and serotyping of the E coli isolates and pyocin typing of Pseudomonas aeruginosa were the methods used to differentiate bacterial relapse, a measure of drug ineptitude, from reinfection, a measure of inadequate host defenses. Sterility of the urine for a minimum of six weeks after therapy developed in only 29% of the patients who could complete the two-week course of therapy. Bacterial relapse, the prevalent form of recurrence, could not be explained by the isolation of cell wall-defective bacteria, rapid emergence of resistant mutants or inadequately treated chronic bacterial prostatitis. The customary practice of prescribing a two-week course of therapy to men with recurrent, invasive urinary tract infections falls far short of the desired treatment goal.