scholarly journals Oral beta-lactam step down in bacteremic E. coli urinary tract infections

2020 ◽  
Author(s):  
Stephan Saad ◽  
Neil Mina ◽  
Colin Lee ◽  
Kevin Afra

Abstract Background: Literature is scarce regarding oral step down to beta-lactams in bacteremic urinary tract infections. Oral fluoroquinolones are an accepted and common step down for bacteremic urinary tract infections; however, their use is associated with mounting safety concerns. We compared clinical cure in patients with E. coli bacteremic urinary tract infections who were stepped down to oral beta-lactams compared to oral fluoroquinolones.Methods: This multicentre retrospective cohort study included patients with first positive concurrent urine and blood cultures from January 2016 to December 2016. Patients were included if they received empiric intravenous beta-lactam therapy with step down to either oral beta-lactam or fluoroquinolone for treatment completion. The primary outcome was clinical cure. Secondary outcomes were length of hospitalization, all-cause mortality and C. difficile infection. Multivariate analysis and propensity score were used to control for confounding.Results: A total of 207 patients were identified with bacteremic E.coli urinary tract infections. Clinical cure was achieved in 72/77 (94%) in the oral beta-lactam group versus 127/130 (98%) in the oral fluoroquinolone group (absolute difference − 4.2%, 95% confidence interval [CI] -10.3–1.9%, p = 0.13). The adjusted odds ratio (OR) for clinical cure with oral beta-lactams was 0.31 (95% CI 0.05–1.90, p = 0.21); propensity score adjusted analysis showed a similar result. There was no statistically significant difference in secondary outcomes.Conclusions: Oral beta-lactams appear to be a safe and effective step down option in bacteremic E. coli urinary tract infections compared to oral fluoroquinolones.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Stephan Saad ◽  
Neil Mina ◽  
Colin Lee ◽  
Kevin Afra

Abstract Background Literature is scarce regarding oral step down to beta-lactams in bacteremic urinary tract infections. Oral fluoroquinolones are an accepted and common step down for bacteremic urinary tract infections; however, their use is associated with mounting safety concerns. We compared clinical cure in patients with E. coli bacteremic urinary tract infections who were stepped down to oral beta-lactams compared to oral fluoroquinolones. Methods This multicentre retrospective cohort study included patients with first positive concurrent urine and blood cultures from January 2016 to December 2016. Patients were included if they received empiric intravenous beta-lactam therapy with step down to either oral beta-lactam or fluoroquinolone for treatment completion. The primary outcome was clinical cure. Secondary outcomes were length of hospitalization, all-cause mortality and C. difficile infection. Multivariate analysis and propensity score were used to control for confounding. Results A total of 207 patients were identified with bacteremic E.coli urinary tract infections. Clinical cure was achieved in 72/77 (94%) in the oral beta-lactam group versus 127/130 (98%) in the oral fluoroquinolone group (absolute difference − 4.2, 95% confidence interval [CI] -10.3 to 1.9%, p = 0.13). The adjusted odds ratio (OR) for clinical cure with oral beta-lactams was 0.31 (95% CI 0.05–1.90, p = 0.21); propensity score adjusted analysis showed a similar result. There was no statistically significant difference in secondary outcomes. Conclusions Oral beta-lactams appear to be a safe and effective step down option in bacteremic E. coli urinary tract infections compared to oral fluoroquinolones.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S828-S829
Author(s):  
Stephan Saad ◽  
Neil Mina ◽  
Colin Lee ◽  
Kevin Afra

Abstract Background Literature is scarce regarding oral step down to beta-lactams in bacteremic urinary tract infections. Oral fluoroquinolones are an accepted and common step down for bacteremic urinary tract infections; however, their use is associated with mounting safety concerns. We compared clinical cure in patients with E. coli bacteremic urinary tract infections who were stepped down to oral beta-lactams compared to oral fluoroquinolones. Methods This multicentre retrospective cohort study included patients with first positive concurrent urine and blood cultures from January 2016 to December 2016. Patients were included if they received empiric intravenous beta-lactam therapy with step down to either oral beta-lactam or fluoroquinolone for treatment completion. The primary outcome was clinical cure. Secondary outcomes were length of hospitalization, all-cause mortality and C. difficile infection. Multivariate analysis and propensity score were used to control for confounding. Results A total of 207 patients were identified with bacteremic E.coli urinary tract infections. Clinical cure was achieved in 72/77 (94%) in the oral beta-lactam group versus 127/130 (98%) in the oral fluoroquinolone group (absolute difference -4.2%, 95% confidence interval [CI] -10.3% to 1.9%, p=0.13). The adjusted odds ratio (OR) for clinical cure with oral beta-lactams was 0.31 (95% CI 0.05 – 1.90, p=0.21); propensity score adjusted analysis showed a similar result. There was no statistically significant difference in secondary outcomes. Table 2 Table 3 Table 4 Conclusion Oral beta-lactams appear to be a safe and effective step down option in bacteremic E. coli urinary tract infections compared to oral fluoroquinolones. Disclosures All Authors: No reported disclosures


2020 ◽  
Author(s):  
Stephan Saad ◽  
Neil Mina ◽  
Colin Lee ◽  
Kevin Afra

Abstract Background. Literature is scarce regarding oral step down to beta-lactams in bacteremic urinary tract infections. Oral fluoroquinolones are an accepted and common step down for bacteremic urinary tract infections; however, their use is associated with mounting safety concerns. We compared clinical cure in patients with E. coli bacteremic urinary tract infections who were stepped down to oral beta-lactams compared to oral fluoroquinolones.Methods. This multicentre retrospective cohort study included patients with first positive concurrent urine and blood cultures from January 2016 to December 2016. Patients were included if they received empiric intravenous beta-lactam therapy with step down to either oral beta-lactam or fluoroquinolone for treatment completion. The primary outcome was clinical cure. Secondary outcomes were length of hospitalization, all-cause mortality and C. difficile infection. Multivariate analysis and propensity score were used to control for confounding.Results. A total of 207 patients were identified with bacteremic E.coli urinary tract infections. Clinical cure was achieved in 72/77 (94%) in the oral beta-lactam group versus 127/130 (98%) in the oral fluoroquinolone group (absolute difference -4.2%, 95% confidence interval [CI] -10.3% to 1.9%, p=0.13). The adjusted odds ratio (OR) for clinical cure with oral beta-lactams was 0.31 (95% CI 0.05 – 1.90, p=0.21); propensity score adjusted analysis showed a similar result. There was no statistically significant difference in secondary outcomes.Conclusions. Oral beta-lactams appear to be a safe and effective step down option in bacteremic E. coli urinary tract infections compared to oral fluoroquinolones.


2007 ◽  
Vol 1 (03) ◽  
pp. 257-262 ◽  
Author(s):  
Samuel Kariuki ◽  
Gunturu Revathi ◽  
John Corkill ◽  
John Kiiru ◽  
Joyce Mwituria ◽  
...  

Background: Uropathogenic Escherichia coli are increasingly becoming resistant to flouroquinolones and to other commonly available antimicrobials. We sought to investigate the genetic basis for fluoroquinolone and extended spectrum beta-lactam (ESBL) resistance in 17 fluoroquinolone-resistant (MIC of levofloxacin and ciprofloxacin >32 μg/ml) E. coli isolated from patients with urinary tract infections (UTIs). Methods: We applied PCR and Pulsed Field Gel Electrophoresis (PFGE) to characterize resistance genes and to determine clonal relatedness of strains, respectively. Results: Twelve of the 17 E. coli were resistant to multiple drugs, including ampicillin, co-amoxyclav, cefotaxime, ceftriaxone, ceftazidime and gentamicin and nalidixic acid and produced plasmid-mediated CTX-M-15 type ESBLs and CMY-2 AmpC type enzymes. The other 5 E. coli that were non-ESBL-producing were multiply resistant to ampicillin, nitrofurantoin, cefoxitin, nalidixic acid. Resistance to fluoroquinolones resulted from a combination of the presence of qnrA, qnrB, ciprofloxacin acetylating enzyme designated aac(6’)-1b-cr, and mutations in the two amino acid substitutions; 83 Serine (TCG) to Leucine (TTG) and 87 Aspartic acid (GAC) to Asparagine (AAC). Conclusion: Antibiogram patterns and PFGE of E. coli showed that these were community acquired UTI caused by pockets of clonally-related and some discreet strain types. Plasmid-mediated CTX-M-15 beta-lactamases and CMY-2 AmpC enzymes and fluoroquinolone resistant E. coli are becoming increasingly prevalent in hospitals in Kenya, posing a major challenge in the management of UTIs.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S396-S396
Author(s):  
Nicole Harrington ◽  
Megan Doran ◽  
Stephen May ◽  
Julianne Care ◽  
Jillian Laude ◽  
...  

Abstract Background Complicated urinary tract infections (cUTI) including pyelonephritis may result in bacteremia, increasing the rate of morbidity and mortality. The Infectious Diseases Society of America recommends a fluoroquinolone as empiric therapy or trimethoprim/sulfamethoxazole as definitive therapy for acute pyelonephritis (AP). Oral β-lactams (BL) are considered sub-optimal based on historical efficacy data with aminopenicillins and variable bioavailability. Increasing resistance and toxicity with preferred agents, justifies further evaluation of oral BL for E. coli bacteremia secondary to urinary source. Methods This was a single-center, retrospective cohort study of patients with E. coli bacteremia secondary to AP or cUTI who received oral step-down therapy with a BL or non-BL. The primary outcome was the rate of clinical success defined by microbiological cure, clinical cure, and infection-related readmission. Secondary outcomes were time to oral step-down, total days of therapy, length of hospital stay, incidence of therapy escalation, 30-day readmissions, and antibiotic-associated adverse events. Results A total of 46 patients were included, with 23 patients in each group. The difference in clinical success between the BL and non-BL groups was not statistically significant (91.3% vs. 100%, P = 0.489). The most frequent oral step-down agents prescribed were cephalexin and ciprofloxacin. The median time to oral step-down was significantly lower in the non-BL group (4.39 vs. 3.41 days, P = 0.038), and the median duration of therapy in each group was 15 days. No patients required therapy escalation after oral step-down or had infection-related readmission within 30 days of discharge. Conclusion The observed clinical success rate of 91.3% remains consistent with previous studies evaluating oral BL as step-down therapy for Enterobacteriaceae bloodstream infections. The results of this study support the safety and efficacy of oral BL as step-down therapy for E. coli bacteremia due to cUTI, although larger studies may be beneficial. Disclosures All authors: No reported disclosures.


2012 ◽  
Vol 56 (12) ◽  
pp. 6358-6365 ◽  
Author(s):  
Arif Hussain ◽  
Christa Ewers ◽  
Nishant Nandanwar ◽  
Sebastian Guenther ◽  
Savita Jadhav ◽  
...  

ABSTRACTEscherichia colisequence type 131 (O25b:H4), associated with the CTX-M-15 extended-spectrum beta-lactamases (ESBLs) and linked predominantly to the community-onset antimicrobial-resistant infections, has globally emerged as a public health concern. However, scant attention is given to the understanding of the molecular epidemiology of these strains in high-burden countries such as India. Of the 100 clinicalE. coliisolates obtained by us from a setting where urinary tract infections are endemic, 16 ST131E. coliisolates were identified by multilocus sequence typing (MLST). Further, genotyping and phenotyping methods were employed to characterize their virulence and drug resistance patterns. All the 16 ST131 isolates harbored the CTX-M-15 gene, and half of them also carried TEM-1; 11 of these were positive forblaOXAgroups 1 and 12 foraac(6′)-Ib-cr. At least 12 isolates were refractory to four non-beta-lactam antibiotics: ciprofloxacin, gentamicin, sulfamethoxazole-trimethoprim, and tetracycline. Nine isolates carried the class 1 integron. Plasmid analysis indicated a large pool of up to six plasmids per strain with a mean of approximately three plasmids. Conjugation and PCR-based replicon typing (PBRT) revealed that the spread of resistance was associated with the FIA incompatibility group of plasmids. Pulsed-field gel electrophoresis (PFGE) and genotyping of the virulence genes showed a low level of diversity among these strains. The association of ESBL-encoding plasmid with virulence was demonstrated in transconjugants by serum assay. None of the 16 ST131 ESBL-producingE. colistrains were known to synthesize carbapenemase enzymes. In conclusion, our study reports a snapshot of the highly virulent/multiresistant clone ST131 of uropathogenicE. colifrom India. This study suggests that the ST131 genotypes from this region are clonally evolved and are strongly associated with the CTX-M-15 enzyme, carry a high antibiotic resistance background, and have emerged as an important cause of community-acquired urinary tract infections.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S717-S718
Author(s):  
Alexander C Branton ◽  
Catherine H Vu ◽  
Venugopalan Veena ◽  
Barbara A Santevecchi ◽  
Reuben Ramphal ◽  
...  

Abstract Background Carbapenems (CBP) are considered first-line for infections caused by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). However, recent literature suggests that cefepime (FEP) and piperacillin-tazobactam (TZP) may produce similar outcomes vs. CBPs for the treatment of ESBL-E urinary tract infections (UTIs). The goal of this study was to determine if non-carbapenem (NCBP) therapy with FEP or TZP is as effective as CBPs for the treatment of ESBL-E UTIs. Methods This was a retrospective observational study of patients admitted to the hospital from January 1st, 2016 to June 30th, 2020 with a urine culture positive for ESBL-E. Patients were included if they received a study antibiotic (meropenem, ertapenem, TZP, or FEP). Patients were excluded if they had any of the following: absence of pyuria, prior receipt of study antibiotic, CBP-resistant organism isolated in urine culture, polymicrobial urine culture, end-stage renal disease, or concomitant gram-negative infection. The primary outcome was clinical cure defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days, and resistance within 30 days. Results A total of 133 patients were included based on definitive therapy received; 69 (52%) received CBP and 64 (48%) received NCBP therapy. Of the total patient population, 17 (13%) were admitted to the intensive care unit, 84 (63%) had a complicated UTI, and 64 (48%) had pyelonephritis. Baseline characteristics were similar between the two groups. There was no difference in clinical cure between the CBP and NCBP therapy groups (96% vs. 97%, p = 1.0). Additionally, no differences in secondary outcomes were observed. Subgroup analyses were performed in patients with specific pathogens, uncontrolled genitourinary source, complicated UTI, and pyelonephritis. These analyses did not reveal any differences in primary or secondary outcomes between the two groups. Conclusion FEP and TZP may be reasonable CBP-sparing alternatives for the treatment of ESBL-E UTIs as clinical and microbiological outcomes were similar with these NCBP agents vs. CBPs in this study population. Disclosures Venugopalan Veena, PharmD, Melinta (Other Financial or Material Support, Received a stipend for participation in a drug registry)Merck (Other Financial or Material Support, Received a stipend for participation in a drug registry)


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S793-S793
Author(s):  
Ryan Lee ◽  
Thuong Tran ◽  
Susanna Tan

Abstract Background The prevalence of multidrug resistant gram-negative urinary tract infections (UTIs) is increasing, often requiring intravenous antimicrobial therapy. Oral fosfomycin is a recommended alternative agent for the treatment of cystitis caused by extended spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli). The primary objective of this study is to evaluate the efficacy of fosfomycin in the treatment of UTIs at the Veterans Affairs Long Beach Healthcare System. The secondary objective is to assess the incidence of adverse drug reactions associated with fosfomycin. Methods This is a retrospective, single-center, cohort study. Patients who received fosfomycin between June 1st, 2015 – June 30th, 2020 were included. Data collection was completed by chart review through the Computerized Patient Record System (CPRS). Descriptive analysis was used to evaluate data. Treatment outcomes were analyzed using a composite of clinical and microbiological cure. Clinical cure was defined as resolution of UTI symptoms. Microbiological cure was defined as urine sterilization within 1 month after completing treatment course with fosfomycin. Results A total of 62 unique patients were evaluated in this study. The mean age was 71.9 years. 56 patients (90.3%) were male, 31 patients (50.0%) had an indwelling catheter present at the time of treatment, and 48 patients (77.4%) had the presence of genitourinary tract pathology that may increase the risk of developing UTIs. Majority of patients (50%) had a urine culture result positive for E. coli prior to treatment, of which 43.5% were ESBL-producing. 60 patients (96.8%) received more than 1 dose of Fosfomycin. Out of 29 patients who were eligible to be evaluated for clinical outcomes, 20 patients (68.9%) met a positive composite outcome of either microbiological cure, clinical cure, or both. 4 patients (6.5%) experienced an adverse drug reaction of diarrhea that was self-limited. Conclusion Fosfomycin is an effective and well-tolerated antimicrobial agent that may be considered for treatment of complicated UTIs without evidence of pyelonephritis or bacteremia caused by multi-drug resistant organisms in the veteran population. Disclosures All Authors: No reported disclosures


Author(s):  
Belén Gutiérrez-Gutiérrez ◽  
Elena Pérez-Nadales ◽  
Salvador Pérez-Galera ◽  
Mario Fernández-Ruiz ◽  
Jordi Carratalà ◽  
...  

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to ESBL-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with non-severe bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem vs. meropenem and clinical cure at day 14 (principal outcome) was studied by logistic regression. Propensity score-matched and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29, 95% CI 0.51-3.22; P=0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14: 1.18, 95%CI 0.43-3.29; P=0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95%CI, 40.4-59.1%) when hospital stay was considered. It ranged from 59-67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost were considered besides outcomes. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat non-severe B-UTI due to ESBL-E in KT recipients and may have some advantages.


2016 ◽  
Vol 6 (1) ◽  
pp. 93
Author(s):  
Mahnaz Milani

<p class="1Body">Knowledge of antimicrobial resistance patterns in <em>E. coli</em>, the predominant pathogen associated with urinary tract infections (UTI) is important as a guide in selecting empirical antimicrobial therapy. To describe the antimicrobial susceptibility of <em>E. coli</em> associated with UTI in a major university hospital in Tehran (Iran), seventy-six clinical isolates of <em>E. coli</em> were studied for susceptibility to Beta-lactam antibiotics by the disc diffusion method and Minimal Inhibitory Concentrations determination. All isolates were resistant to ampicillin, amoxicillin and oxacillin. Resistance to the other tested antibiotics was shown to be 93.4% to cefradine, 76.3% to carbenicillin, 47.3% to cefazoline, 50% to cefalexin and 32.8% to cephalothin while 1.3% expressed resistance to cefoxitime, and 2.6% were resistant to ceftizoxime and ceftriaxone. Substrate hydrolysis by ultra violet spectroscopy showed that 87.4% harbored penicillinases, 9% produced cephlosporinases and 3.6% degraded both substrates. Clavulanic acid inhibited enzyme activity in 82.9%, of which 78.95% was penicillinases (group IIa) and 3.95% was cephalosporinases (group IIb) of the Bush classification system. These results indicate that <em>E. coli</em> can posses a variety of Beta-lactamases that are responsible for Beta-lactam resistance. Members of the family Enterobacteriaceae, particularly Escherichia coli is the most common causes of urinary tract infections in hospitals and societies. Beta-lactam antibiotics, particularly the third and fourth generation of cephalosporins are effective in treating these infections.</p>


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