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Abstract Background ZTI-01 (fosfomycin for injection) is an epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has broad in vitro spectrum of activity, including multidrug-resistant Gram-negative pathogens, and is being developed for treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States. Methods Hospitalized adults with suspected or microbiologically confirmed cUTI/AP were randomized 1:1 to 6 g ZTI-01 q8h or 4.5 g intravenous (IV) piperacillin-tazobactam (PIP-TAZ) q8h for a fixed 7-day course (no oral switch); patients with concomitant bacteremia could receive up to 14 days. Results Of 465 randomized patients, 233 and 231 were treated with ZTI-01 and PIP-TAZ, respectively. In the microbiologic modified intent-to-treat (m-MITT) population, ZTI-01 met the primary objective of noninferiority compared with PIP-TAZ with overall success rates of 64.7% (119/184 patients) vs 54.5% (97/178 patients), respectively; treatment difference was 10.2% (95% confidence interval [CI]: −0.4, 20.8). Clinical cure rates at test of cure (TOC, day 19–21) were high and similar between treatments (90.8% [167/184] vs 91.6% [163/178], respectively). In post hoc analysis using unique pathogens typed by pulsed-field gel electrophoresis, overall success rates at TOC in m-MITT were 69.0% (127/184) for ZTI-01 versus 57.3% (102/178) for PIP-TAZ (difference 11.7% 95% CI: 1.3, 22.1). ZTI-01 was well tolerated. Most treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mild and transient. Conclusions ZTI-01 was effective for treatment of cUTI including AP and offers a new IV therapeutic option with a differentiated MOA for patients with serious Gram-negative infections. Clinical Trial Registration NCT02753946 ZEUS, a Phase 2/3 trial, studied ZTI-01 (fosfomycin for injection) in the treatment of hospitalized adults with complicated urinary tract infection and acute pyelonephritis versus piperacillin-tazobactam. ZTI-01 was non-inferior to piperacillin-tazobactam and was well tolerated.

Background. The global emergence of carbapenem-resistant Enterobacteriaceae highlights the urgent need to reduce carbapenem dependence. The phase 3 RECAPTURE program compared the efficacy and safety of ceftazidime-avibactam and doripenem in patients with complicated urinary tract infection (cUTI), including acute pyelonephritis. Methods. Hospitalized adults with suspected or microbiologically confirmed cUTI/acute pyelonephritis were randomized 1:1 to ceftazidime-avibactam 2000 mg/500 mg every 8 hours or doripenem 500 mg every 8 hours (doses adjusted for renal function), with possible oral antibiotic switch after ≥5 days (total treatment duration up to 10 days or 14 days for patients with bacteremia). Results. Of 1033 randomized patients, 393 and 417 treated with ceftazidime-avibactam and doripenem, respectively, were eligible for the primary efficacy analyses; 19.6% had ceftazidime-nonsusceptible baseline pathogens. Noninferiority of ceftazidimeavibactam vs doripenem was demonstrated for the US Food and Drug Administration co-primary endpoints of (1) patient-reported symptomatic resolution at day 5: 276 of 393 (70.2%) vs 276 of 417 (66.2%) patients (difference, 4.0% [95% confidence interval {CI}, −2.39% to 10.42%]); and (2) combined symptomatic resolution/microbiological eradication at test of cure (TOC): 280 of 393 (71.2%) vs 269 of 417 (64.5%) patients (difference, 6.7% [95% CI, .30% to 13.12%]). Microbiological eradication at TOC (European Medicines Agency primary endpoint) occurred in 304 of 393 (77.4%) ceftazidime-avibactam vs 296 of 417 (71.0%) doripenem patients (difference, 6.4% [95% CI, .33% to 12.36%]), demonstrating superiority at the 5% significance level. Both treatments showed similar efficacy against ceftazidime-nonsusceptible pathogens. Ceftazidime-avibactam had a safety profile consistent with that of ceftazidime alone. Conclusions. Ceftazidime-avibactam was highly effective for the empiric treatment of cUTI (including acute pyelonephritis), and may offer an alternative to carbapenems in this setting. Clinical Trials Registration. NCT01595438; NCT01599806.

Background and Objectives: Acute and obstructive pyelonephritis (AOP) management, despite advancements in diagnostic imaging and antimicrobial therapy, is characterized by delayed recognition and increasing antimicrobial resistance. This review aimed to summarize current evidence regarding the clinical characteristics, microbiological spectrum, biomarkers, and imaging findings associated with AOP. Materials and Methods: A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251162736). Literature searches were performed across the PubMed, Scopus, and Web of Science databases for articles published between January 2014 and 31 March 2025 using the term “acute obstructive pyelonephritis”. Inclusion criteria comprised original full-text English-language studies, published in the last 10 years and conducted in adults, reporting clinical, laboratory, microbiological, and imaging characteristics. Exclusion criteria are letters to the editor, expert opinions, case reports, conference or meeting abstracts, reviews, and redundant publications; having unclear or incomplete data; and being performed on cell cultures or on mammals. The quality of included studies was assessed using the Newcastle–Ottawa Scale. Results: Twenty-three studies met the inclusion criteria. AOP predominantly affected elderly patients with comorbidities, especially diabetes mellitus and urinary tract obstruction. Predictors of septic shock included thrombocytopenia, hypoalbuminemia, elevated procalcitonin (>1.12 µg/L), presepsin, and a neutrophil-to-lymphocyte ratio ≥ 8.7. Escherichia coli remained the leading pathogen (60–95%) with extended-spectrum β-lactamase (ESBL) rates between 20 and 70%, followed by Klebsiella pneumoniae. CT demonstrated 71–100% sensitivity for detecting obstructive complications, confirming its superiority over ultrasound, while MRI provided comparable diagnostic accuracy in selected cases. Source control through double-J stenting or percutaneous drainage significantly improved survival. Conclusions: AOP requires prompt recognition and early decompression to prevent sepsis-related mortality. Biomarkers such as procalcitonin, presepsin, and neutrophil to lymphocyte ratio enhance risk stratification, while CT remains the gold-standard imaging modality. The increasing prevalence of ESBL-producing pathogens underscores the need for antimicrobial stewardship and individualized therapeutic strategies guided by local resistance data.

In patients with complicated urinary tract infection, clinical and microbiologic treatment success was significantly better with cefepime–taniborbactam (β-lactam and β-lactamase inhibitor) than with meropenem.

PurposeEmphysematous pyelonephritis (EPN) is an acute, severe necrotising infection of the kidney. There has been a shift from early nephrectomy to conservative methods. We conducted a meta-analysis to assess the impact of risk factors and treatment choices on outcomes in EPN.MethodsWe conducted a database search of all studies in English, reporting more than 12 patients of EPN from 1980 to 2020. We compiled the demographics, clinical presentations, risk factors, critical diagnostic results, treatment modalities and outcomes, including mortality.ResultsWe identified 37 observational studies, 32 retrospective and 5 prospective. The studies reported on 1146 patients, of which 790(68.9%) were female, and 946 (82.5%) were diabetic. In addition, 184 (16.1%) patients had stones, and 235 (20.5%) had obstructive uropathy. Fever and flank pain were the most frequent symptoms. The most common clinical features were pyuria, fever, flank tenderness, and tachycardia. E. coli, Klebsiella pneumoniae and Proteus were the most frequent organisms isolated. X-ray KUB and ultrasound were used as initial diagnostic modalities, but CT scan was the usual diagnostic and confirmatory investigation. Confusion, shock, thrombocytopenia, sepsis, emergency nephrectomy and hyponatremia were significantly associated with mortality. In particular, confusion and hyponatremia were associated with a sevenfold increase in mortality risk. There was no evidence that diabetes, stones, obstructive uropathy, AKI or proteinuria was associated with higher mortality. Nevertheless, 143 of the total 1146 patients died (12.5%). While 26% of the patients who had upfront emergency nephrectomy died, only 9.7% and 10% of patients with medical management and medical management plus minimally invasive treatments died. However, patients that failed medical and minimally invasive treatments and needed salvage emergency nephrectomy had a mortality of upwards of 27%.ConclusionThe risk factors for mortality in emphysematous pyelonephritis are shock, thrombocytopenia, confusion, hyponatremia and emergency nephrectomy. Conservative and minimally invasive treatment should be the initial management strategy for emphysematous pyelonephritis as they carry lesser mortality risks. The presence of risk factors may help predict the subset of patients who need aggressive treatment and minimally invasive treatment modalities or early nephrectomy.

Xanthogranulomatous pyelonephritis is a rare condition in paediatric patients, mostly described in middle-aged female patients. We present a 7-year-old female with juvenile idiopathic arthritis, who was found to have a kidney mass with a concurrent Escherichia coli urinary tract infection. Surgical excision was done out of concern for possible malignancy. Histology confirmed the diagnosis of xanthogranulomatous pyelonephritis and persistent E. coli infection.

Background Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and is associated with long-term complications. We aimed to assess the effect of adjuvant dexamethasone treatment on reducing kidney scarring after acute pyelonephritis (APN) in children. Methods Multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial (RCT) where children from 1 month to 14 years of age with proven APN were randomly assigned to receive a 3-day course of either an intravenous corticosteroid (dexamethasone 0.30 mg per kg/day) twice daily or placebo. The late technetium 99 m-dimercaptosuric acid scintigraphy (> 6 months after acute episode) was performed to assess kidney scar persistence. Kidney scarring risk factors (vesicoureteral reflux, kidney congenital anomalies, or urinary tract dilatation) were also assessed. Results Ninety-one participants completed the follow-up and were finally included (dexamethasone n  = 49 and placebo n  = 42). Both groups had similar baseline characteristics. Twenty participants showed persistent kidney scarring after > 6 months of follow-up without differences in incidence between groups (22% and 21% in the dexamethasone and placebo groups, p  = 0.907). Renal damage severity in the early DMSA (β = 0.648, p  = 0.023) and procalcitonin values (β = 0.065 p  = 0.027) significantly modulated scar development. Vesicoureteral reflux grade showed a trend towards significance (β = 0.545, p  = 0.054), but dexamethasone treatment showed no effect. Conclusion Dexamethasone showed no effect on reducing the risk of scar formation in children with APN. Hence, there is no evidence for an adjuvant corticosteroid treatment recommendation in children with APN. However, the study was limited by not achieving the predicted sample size and the expected scar formation. Trial registration Clinicaltrials.gov, NCT02034851. Registered in January 14, 2014. Graphical abstract “A higher resolution version of the Graphical abstract is available as Supplementary information.”

Acute pyelonephritis is one of the most serious bacterial illnesses during childhood. Escherichia coli is responsible in most cases, however other organisms including Klebsiella, Enterococcus, Enterobacter, Proteus , and Pseudomonas species are being more frequently isolated. In infants, who are at major risk of complications such as sepsis and meningitis, symptoms are ambiguous and fever is not always useful in identifying those at high risk. A diagnosis of acute pyelonephritis is initially made on the basis of urinalysis; dipstick tests for nitrites and/or leukocyte esterase are the most accurate indicators of infection. Collecting a viable urine sample for urine culture using clean voided methods is feasible, even in young children. No gold standard antibiotic treatment exists. In children appearing well, oral therapy and outpatient care is possible. New guidelines suggest less aggressive imaging strategies after a first infection, reducing radiation exposure and costs. The efficacy of antibiotic prophylaxis in preventing recurrence is still a matter of debate and the risk of antibiotic resistance is a warning against its widespread use. Well-performed randomized controlled trials are required in order to better define both the imaging strategies and medical options aimed at preserving long-term renal function.

Decisions regarding disposition and treatment in patients with pyelonephritis should be guided by assessment of the likelihood of pathogen resistance to antimicrobial agents and by patient factors (e.g., illness severity, coexisting conditions, and psychosocial situation).

See the retraction notice BIO Web of Conferences 84 , 00001 (2024), https://doi.org/10.1051/bioconf/20248400001