Community-acquired Pyelonephritis Research Articles

P-1343. Extended Spectrum Beta Lactamases (ESBL) and New Delhi Metallo Protein (NDM) genes co-occurrence in Phenotypic ESBL Enterobacteriaceae (ESBL-E) isolates causing community-acquired pyelonephritis

Abstract Background Multidrug resistance Enterobacteriaceae causing community-acquired pyelonephritis is an emerging threat; most isolates are EBSL, as per Indian data. After the results of the MERINO trial, most guidelines favors Carbapenem for treating community-acquired pyelonephritis. Overuse of carbapenem may lead to Carbapenem resistance Enterobacteriaceae (CRE) in the community. We analyzed the ESBL and CRE genes in the clinically significant urinary isolates with phenotypic ESBL -E from patients with community-acquired pyelonephritis.Table 1Demographic characteristics of patients with community-acquired acute pyelonephritis caused by phenotypic ESBL -E. Methods Patients with a diagnosis of community-acquired acute pyelonephritis with age ≥ 18 years and urine culture showing the growth of Enterobacteriaceae with phenotypic ESBL-E are included in the study. If urine culture grew more than one organism in Enterobacteriaceae, other GNBs were excluded. The phenotypic ESBL detection was based on resistance to a third-generation cephalosporin (Cefotaxime, Cefpodoxime, Ceftazidime) and a monobactam (Aztreonam). These positive isolates were further processed using the combination disk method. A ≥5mm increase in zone diameter for either antimicrobial agent tested in combination with clavulanate vs the zone diameter of the agent when tested alone was considered ESBL (Clinical and Laboratory Standards Institute (CLSI) Performance standards for antimicrobial susceptibility tests). Simultaneously, multiplexed Real-time PCR (TRUPCR® UTI AST Panel Kit, Europe) was done to detect ESBL genes (CTX-M, TEM, SHV) and CRE genes (OXA-48, KPC, NDM, VIM, IMP) in these isolates.Table 2:Detection of NDM genes with ESBL genes in patients with community-acquired acute pyelonephritis caused by phenotypic ESBL -E. Results A total of 38 isolates with phenotypic ESBL in patients diagnosed with community-acquired pyelonephritis were processed for RT-PCR, and 30 were detected with ESBL and CRE genes. The demographic and clinical characteristics are shown in Table 1. The most common ESBL gene was CTX-M 29 (.96.7%) followed by TEM 25 (83.3%). Multiple ESBL genes were detected in 24(80%) isolates. Among CRE genes, the NDM genes were detected in 15 (50%) isolates with other ESBL genes (Table 2). Conclusion The presence of CRE genes in phenotypic ESBL -E in community-acquired acute pyelonephritis could be due to the injudicious use of carbapenem. This may imply that CRE will be spread in the community in the future, making it difficult to manage this infection. Disclosures All Authors: No reported disclosures

Effect of Inappropriate Treatment in Hospitalized Patients with Pyelonephritis Treated with Cefuroxime: A Cohort Study.

The aim of this study was to evaluate the effect of inappropriate therapy in adult patients with community-acquired pyelonephritis caused by Escherichia coli receiving empirical treatment with cefuroxime during hospital stay and readmission. A retrospective cohort study was performed. Inappropriate treatment was considered treatment for a nonsusceptible isolate according to the results of the urine culture. Adjustment for confounding factors was performed with propensity score-derived inverse probability of treatment weighting. Between 2013 and 2020, 747 patients were included, 102 (13.7%) of whom received inappropriate therapy. Compared to appropriate therapy, inappropriate therapy was associated with a shorter length of stay in the adjusted analysis (Hazard Ratio = 0.34; 95% CI = 0.23-0.49). After 735 patients were discharged from the hospital, 66 were readmitted in the following 30 days. In comparison with appropriate therapy, inappropriate antimicrobial therapy was not related to readmission (OR 1.47; 95% CI = 0.35-2.79). Inappropriate therapy was not related to a longer hospital stay or readmission due to pyelonephritis after adjusting for confounders and covariates.

Exposure to Non-Antimicrobial Drugs and Risk of Infection with Antibiotic-Resistant Enterobacteriaceae.

Antimicrobial resistance (AMR) has consistently been linked to antibiotic use. However, the roles of commonly prescribed non-antimicrobial drugs as drivers of AMR may be under-appreciated. Here, we studied a cohort of patients with community-acquired pyelonephritis and assessed the association of exposure to non-antimicrobial drugs at the time of hospital admission with infection with drug-resistant organisms (DRO). Associations identified on bivariate analyses were tested using a treatment effects estimator that models both outcome and treatment probability. Exposure to proton-pump inhibitors, beta-blockers, and antimetabolites was significantly associated with multiple resistance phenotypes. Clopidogrel, selective serotonin reuptake inhibitors, and anti-Xa agents were associated with single-drug resistance phenotypes. Antibiotic exposure and indwelling urinary catheters were covariates associated with AMR. Exposure to non-antimicrobial drugs significantly increased the probability of AMR in patients with no other risk factors for resistance. Non-antimicrobial drugs may affect the risk of infection with DRO through multiple mechanisms. If corroborated using additional datasets, these findings offer novel directions for predicting and mitigating AMR.

Factors Associated with Acute Community-Acquired Pyelonephritis Caused by Extended-Spectrum β-Lactamase-Producing Escherichia coli.

This study aimed to identify the factors associated with the presence of extended-spectrum ß-lactamase-(ESBL) in patients with acute community-acquired pyelonephritis (APN) caused by Escherechia coli (E. coli), with a view of optimising empirical antibiotic therapy in this context. We performed a retrospective analysis of patients with community-acquired APN and confirmed E. coli infection, collecting data related to demographic characteristics, comorbidities, and treatment. The associations of these factors with the presence of ESBL were quantified by fitting multivariate logistic models. Goodness-of-fit and predictive performance were measured using the ROC curve. We included 367 patients of which 51 presented with ESBL, of whom 90.1% had uncomplicated APN, 56.1% were women aged ≤55 years, 33.5% had at least one mild comorbidity, and 12% had recently taken antibiotics. The prevalence of ESBL-producing E. coli was 13%. In the multivariate analysis, the factors independently associated with ESBL were male sex (OR 2.296; 95% CI 1.043–5.055), smoking (OR 4.846, 95% CI 2.376–9.882), hypertension (OR 3.342, 95% CI 1.423–7.852), urinary incontinence (OR 2.291, 95% CI 0.689–7.618) and recurrent urinary tract infections (OR 4.673, 95% CI 2.271–9.614). The area under the ROC curve was 0.802 (IC 95% 0.7307–0.8736), meaning our model can correctly classify an individual with ESBL-producing E. coli infection in 80.2% of cases.

Cefepime/Sulbactam — A New Innovative Antibiotic for In-Hospital Treatment of Severe Infections and the Implementation of Carbapenem-Replacement Strategy to Contain Antibiotic Resistance

Cefepime/sulbactam is a combined antibiotic consisting of the 4 th generation cephalosporin cefepime and the beta-lactamase inhibitor sulbactam in 1:1 ratio. Cefepime/sulbactam antibiotic was developed in Russia in 2006, it had passed preclinical and clinical studies, was approved for medical use, and has been produced in Russia since 2019. Cefepime has a wide spectrum of antimicrobial activity against gram-positive and gram-negative microorganisms, sulbactam adds two clinically important pathogens to the antimicrobial spectrum of cefepime —Acinetobacter baumanniiandBacteroides fragilis. In addition, sulbactam protects cefepime from hydrolysis by class A broad- and extended-spectrum beta-lactamases, and cefepime itself is stable against class C chromosomal beta-lactamases and partially stable to OXA-type class D carbapenemases.In vitrostudies have shown that most clinical strains of ESBL-producingKlebsiella pneumoniae,Escherichia coli,Proteusspp. are sensitive to cefepime/sulbactam, as well as some strains ofK.pneumoniaeandA.baumanniithat are resistant to carbapenems as a result of the production of class D carbapenemases. The efficacy and safety of cefepime/sulbactam have been determined in three clinical studies. Clinical and bacteriological efficacy of the drug was 97.9% and 97.6% in patients with acute community-acquired pyelonephritis. In the MAXI-19 multicenter study, the clinical efficacy of cefepime/sulbactam in patients with intra-abdominal infections, nosocomial pneumonia, and ventilator-associated pneumonia was 78.4, 90.3, and 80.7%, respectively. A comparative study examined the efficacy of cefepime/sulbactam and carbapenems in severe nosocomial infections (84% of patients had sepsis or septic shock). Clinical efficacy of cefepime/sulbactam and carbapenems was high and did not significantly differ (71% vs. 62%), as well as the bacteriological efficacy — 87% vs. 73%, while typical hospital pathogens characterized by MDR or XDR were identified in the majority of patients (most often —K.pneumoniae,A.baumannii,E.coli). During treatment with carbapenems, carbapenem-resistant bacteria were detected significantly more often (74.5%, most oftenA.baumannii— 44.7%,K.pneumoniae— 38.3%), compared to cefepime/sulbactam (20.0%,P.aeruginosaandK.pneumoniae, both at 15.5%), P=0.0001. The risk of superinfection was also significantly higher with carbapenems than with cefepime/sulbactam (53.3% vs. 22.2%, P=0.001). For severe infections, cefepime/sulbactam was administered at a dose of 4 g (2 g + 2 g) every 12 hours or 2 g (1 g + 1 g) every 8 hours. Currently, cefepime/sulbactam should be considered as a reliable option for the treatment of severe infections in the hospital as a carbapenem-replacement strategy to reduce the risks of selection of carbapenem-resistant gram-negative bacteria.

Rapid detection of amoxicillin-susceptible Escherichia coli in fresh uncultured urine: a new tool to limit the use of broad-spectrum empirical therapy of community-acquired pyelonephritis

Because of the high prevalence of amoxicillin resistance among uropathogens, amoxicillin is not recommended as an empirical treatment of urinary tract infections (UTIs). Quick detection of an amoxicillin-susceptible Escherichia coli (ASEC) would allow prescribing amoxicillin without preliminary broad-spectrum empirical treatment in uncomplicated pyelonephritis. To quickly diagnose UTIs due to ASEC, we developed a real-time PCR that detects in fresh uncultured urine the E. coli-specific gene yccT as well as the blaTEM and blaCTX-M genes. The ASEC rapid test was considered positive if the PCR was positive for the yccT gene but negative for blaTEM and blaCTX-M. The test was compared with culture and susceptibility testing. Among 200 patients with a suspected community-acquired UTI, 61 (30.5%) had a monobacterial UTI due to ASEC. The ASEC rapid test result was obtained in 3 h 13 [95% confidence interval (CI) 3 h 12–3 h 15] and was positive for 43 patients (21.5%). Specificity and sensitivity were 97.8% (95% CI 95.8–99.8%) and 65.6% (95% CI 59.0–72.1%), respectively. Positive and negative predictive values were 93.0% (95% CI 89.5–96.5%) and 86.6% (95% CI 81.9–91.3%), respectively. Owing to its high specificity and positive predictive value, the ASEC rapid test allows the diagnosis of UTI due to ASEC only 3 h after urine sampling. A positive ASEC rapid test may be used to treat uncomplicated pyelonephritis with amoxicillin from the start, without preliminary broad-spectrum empirical treatment. The ASEC rapid test is a promising tool to spare fluoroquinolones and third-generation cephalosporins in UTIs.

Community-Acquired Pyelonephritis in Pregnancy Caused by KPC-Producing Klebsiella pneumoniae

Community-Acquired Pyelonephritis in Pregnancy Caused by KPC-Producing Klebsiella pneumoniae

Recurrence of urinary tract infections in adult patients with community-acquired pyelonephritis caused by E. coli: a 1-year follow-up.

In a prospective study, 42 women were followed for recurrence of urinary tract infections (UTIs) for 1 y after an index episode of community-acquired pyelonephritis caused by Escherichia coli. Altogether, 26 repeat episodes were detected. Of these, 20 occurred at least 1 month after the index episode and were regarded as recurrences. In all, 40%, (17 of 42) of the women had recurrences. An earlier history of UTI increased the risk of recurrence: 52%, of the 29 women with previous UTI had at least 1 recurrence, compared with 15%, of the 13 patients without previous UTI. E. coli caused the majority (73%) of the recurrences. Genotype comparisons by RAPD-PCR analysis between E. coli isolates from a patient showed that 75%. of the original and recurrent strains were genetically non-identical. Of the 54 E. coli strains, 42 were carrying genes coding for G adhesins of P fimbriae: 40 isolates carried class II, I class III and 1 carried both class II and III G adhesin genes. Each of the virulence-associated factors (genes for G adhesins, MRHA, haemolysin, type 1C fimbriae, and O and K antigens) was evenly distributed among E. coli isolates of index episodes, independent of the recurrences. The index isolates, however, had more virulence-associated factors than did the isolates from the recurrences which were mainly due to lower UTIs.

Symptomatic pyelonephritis in elderly men.

A prospective study was carried out of the clinical, laboratory, radiologic and therapeutic features of acute, symptomatic, bacterial pyelonephritis as experienced by 12 consecutive elderly, noncatheterized men who required hospitalization. In spite of the advanced ages of the men and the inordinate frequency of bacteremia and septic shock, no patient died. "Appropriate" antibiotic therapy, supportive treatment, and, as importantly, a lack of associated "imminently" or "ultimately" fatal illnesses contributed to the 100 per cent survival rate. Guidelines are provided for the diagnostic evaluation and antibiotic therapy of community-acquired pyelonephritis in elderly men.