piperacillin--tazobactam-drug-combination and Pyelonephritis

To evaluate efficacy and adverse events of ceftolozane/tazobactam in complicated UTI including acute pyelonephritis.. Databases that include PubMed, Embase, Scopus, and TRIP were searched. All randomized controlled trials and cohort studies were considered for the study. Statistical analysis was done using a fixed effects model, and results were expressed in proportion for dichotomous data and risk ratio for continuous data with 95% confidence intervals (CI).. A clinical cure of ceftolozane/tazobactam was found to be 92% with 95% CI of 90-94 while that of piperacillin/tazobactam was only 78% (95% CI, 74-82) in patients with complicated UTI. Microbiological eradication was still higher in the ceftolozane/tazobactam group (83%, 95% CI 81-88) when compared with piperacillin/tazobactam (63% 95% CI, 58.77-65.2). Ceftolozane/tazobactam was more effective in the treatment of complicated urinary tract infections other than acute pyelonephritis as compared to piperacillin/tazobactam (RR = 1.21, 95% CI, 1.07-1.23). Serious adverse events were found comparable in both groups (RR = 1.15, 95% CI, 0.64-2.09).. The analysis showed that ceftolozane/tazobactam has better clinical outcomes including cure rates and low resistance for the treatment of complicated urinary tract infection.

Topics: Anti-Bacterial Agents; Cephalosporins; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Tazobactam; Urinary Tract Infections

Kaye KS, Belley A, Barth P, et al.

Topics: Anti-Bacterial Agents; Cefepime; Humans; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Urinary Tract Infections

Cefepime/enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination and a potential empirical therapy for resistant gram-negative infections.. To evaluate whether cefepime/enmetazobactam was noninferior to piperacillin/tazobactam for the primary outcome of treatment efficacy in patients with complicated urinary tract infections (UTIs) or acute pyelonephritis.. A phase 3, randomized, double-blind, active-controlled, multicenter, noninferiority clinical trial conducted at 90 sites in Europe, North and Central America, South America, and South Africa. Recruitment occurred between September 24, 2018, and November 2, 2019. Final follow-up occurred November 26, 2019. Participants were adult patients aged 18 years or older with a clinical diagnosis of complicated UTI or acute pyelonephritis caused by gram-negative urinary pathogens.. Eligible patients were randomized to receive either cefepime, 2 g/enmetazobactam, 0.5 g (n = 520), or piperacillin, 4 g/tazobactam, 0.5 g (n = 521), by 2-hour infusion every 8 hours for 7 days (up to 14 days in patients with a positive blood culture at baseline).. The primary outcome was the proportion of patients in the primary analysis set (patients who received any amount of study drug with a baseline gram-negative pathogen not resistant to either treatment and ≥105 colony-forming units [CFU]/mL in urine culture or the same pathogen present in concurrent blood and urine cultures) who achieved overall treatment success (defined as clinical cure combined with microbiological eradication [<103 CFU/mL in urine] of infection). Two-sided 95% CIs were computed using the stratified Newcombe method. The prespecified noninferiority margin was -10%. If noninferiority was established, a superiority comparison was also prespecified.. Among 1041 patients randomized (mean age, 54.7 years; 573 women [55.0%]), 1034 (99.3%) received study drug and 995 (95.6%) completed the trial. Among the primary analysis set, the primary outcome occurred in 79.1% (273/345) of patients receiving cefepime/enmetazobactam compared with 58.9% (196/333) receiving piperacillin/tazobactam (between-group difference, 21.2% [95% CI, 14.3% to 27.9%]). Treatment-emergent adverse events occurred in 50.0% (258/516) of patients treated with cefepime/enmetazobactam and 44.0% (228/518) with piperacillin/tazobactam; most were mild to moderate in severity (89.9% vs 88.6%, respectively). A total of 1.7% (9/516) of participants who received cefepime/enmetazobactam and 0.8% (4/518) of those who received piperacillin/tazobactam did not complete the assigned therapy due to adverse events.. Among patients with complicated UTI or acute pyelonephritis caused by gram-negative pathogens, cefepime/enmetazobactam, compared with piperacillin/tazobactam, met criteria for noninferiority as well as superiority with respect to the primary outcome of clinical cure and microbiological eradication. Further research is needed to determine the potential role for cefepime/enmetazobactam in the treatment of complicated UTI and pyelonephritis.. ClinicalTrials.gov Identifier: NCT03687255.

Topics: Acute Disease; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cefepime; Double-Blind Method; Drug Combinations; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Urinary Tract Infections

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.. 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.. 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.. 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.. NCT02753946.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Load; Drug Resistance, Bacterial; Female; Fosfomycin; Humans; Injections; Male; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Treatment Outcome; Urinary Tract Infections; Young Adult

Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections.. To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis.. Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region.. Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment.. Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated.. Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam.. Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage.. clinicaltrials.gov Identifier: NCT02166476.

Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Boronic Acids; Drug Combinations; Female; Humans; Intention to Treat Analysis; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Pyelonephritis; Thienamycins; Urinary Tract Infections; Urine

Tazobactam/piperacillin (TAZ/PIPC) was given intravenously to 15 children with acute bacterial infections including 1 with purulent tonsillitis, 11 with pneumonia, 3 with acute pyelonephritis (2 cases are omitted from evaluation because of Mycoplasma pneumonia and intramuscular injection of gammaglobulin) Daily dosages per kg bodyweight ranging from 132 to 156 mg were given in 3 divided doses per day for 4 to 7 days. Clinical responses were excellent in 7 (54%), good in 6 (46%), fair and poor in 0, with an overall efficacy rate of 100%. Good bacterial responses were obtained in all of the 8 cases from which pathogens were identified. Any side effect was not observed. The above results suggest that TAZ/PIPC is a useful new antibiotic for the treatment of bacterial infections in children.

Topics: Acute Disease; Bacteria; Child; Child, Preschool; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Infant; Infusions, Intravenous; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Pyelonephritis; Tonsillitis

Topics: beta-Lactamases; Carbapenems; Enterobacteriaceae; Humans; Piperacillin, Tazobactam Drug Combination; Pyelonephritis

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin-tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs.. A monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae.. Of the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01).. In terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Retrospective Studies; Urinary Tract Infections

We studied the performance of aminoglycosides in treating bloodstream infections (BSIs) of urinary source caused by ESBL-producing Enterobacteriaceae (ESBL-EB).. In a retrospective study of 193 patients with a clinical diagnosis of urinary tract infection, pyelonephritis or urosepsis and blood and urine cultures positive for ESBL-EB, patients were grouped according to whether they were treated with an aminoglycoside, a carbapenem or piperacillin/tazobactam. Multivariate analysis was used to define risk factors for mortality with inverse probability of treatment weighting used to minimize confounding. The primary efficacy outcome was 30 day mortality. The primary safety outcome was acute kidney injury (AKI) at 14 days.. Mean age was 79.3 years. Dementia, chronic kidney disease and the presence of a urinary catheter were common. Thirty-two (16.6%) patients died and risk factors for mortality included age, high Charlson score, presentation with severe sepsis/septic shock and infection with bacteria other than Escherichia coli. Aminoglycosides were non-inferior compared with other antibiotics regarding 30 day mortality [13.0% versus 21.2%, respectively; adjusted risk difference=10.29% (-0.82% to 21.41%)], but did not reach non-inferiority for bacteriuria recurrence [48.9% versus 44.7%, respectively; adjusted risk difference=-8.72% (-30.87% to 13.43%)]. AKI developed at a similar rate in both treatment groups: 12.0% versus 10.6%, respectively [OR=1.14 (0.46-2.81)]. Aminoglycosides were more efficacious in E. coli infections compared with other ESBL-EB.. We demonstrated the efficacy and safety of aminoglycosides in treating BSI of urinary source caused by ESBL-EB. This carbapenem-sparing approach can assist in avoiding excessive carbapenem use without compromising outcomes.

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Humans; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Retrospective Studies; Urinary Tract Infections

Limited data exist regarding the efficacy of piperacillin-tazobactam (TZP) for the management of nonbacteremic pyelonephritis caused by extended-spectrum β-lactamase (ESBL)-producing organisms.. We conducted a multicenter observational study comparing clinical outcomes of adults hospitalized with ESBL-producing pyelonephritis who were receiving TZP versus carbapenems, using an inverse probability of treatment weighted propensity score analysis. Patients were eligible for inclusion if all of the following criteria were met: (1) urine cultures growing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis at ≥50 000 colony-forming units/mL; (2) identification of an ESBL gene; (3) pyuria (≥10 white blood cells per high powered field in the urine); and (4) dysuria and fever plus at least 1 of the following symptoms: emesis, rigors, hypotension, or flank pain.. There were 186 patients included in the propensity score-weighted cohort; 45 (24%) received TZP and 141 (76%) received a carbapenem. Of these 186 patients, 27% were admitted to the intensive care unit, 48% were immunocompromised, and 45% had underlying urologic abnormalities. There were no differences between the 2 groups in the proportion of patients (20% vs 25%) with recurrent cystitis or pyelonephritis with the same ESBL-producing organism within 30 days (odds ratio, 0.75; 95% confidence interval, .31-1.81; P = .52). There were no differences in the resolution of clinical symptoms by Day 7 or in 30-day mortality. There was 1 (2%) patient in the TZP arm and 11 (8%) patients in the carbapenem arm who had incident carbapenem-resistant organisms isolated within 30 days (P = .09).. TZP may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Escherichia coli Infections; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Retrospective Studies

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; beta-Lactamases; Carbapenems; Humans; Piperacillin, Tazobactam Drug Combination; Pyelonephritis

Topics: beta-Lactamases; Carbapenems; Humans; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis

Topics: beta-Lactamases; Humans; Piperacillin, Tazobactam Drug Combination; Pyelonephritis

To determine clinical outcomes associated with aminoglycosides versus other antimicrobial agents as empirical treatment of hospitalized patients with pyelonephritis.. An institutional programme promoting aminoglycosides as empirical treatment of pyelonephritis was implemented in 2016. We reviewed the hospital records of patients with pyelonephritis from January 2017 to April 2019. The primary outcome was death within 30 days of index culture. Initial treatment with aminoglycoside-based regimens was compared with non-aminoglycoside antibiotics. Propensity score matching was performed to adjust for between-group differences in baseline covariates.. The study cohort included 2026 patients, 715 treated with aminoglycosides and 1311 treated with non-aminoglycoside drugs (ceftriaxone, n = 774; piperacillin/tazobactam, n = 179; carbapenems, n = 161; and fluoroquinolones, n = 133); 589 patients (29%) had bloodstream infections. Treatment with aminoglycosides was associated with a higher likelihood of in vitro activity against clinical isolates (OR = 2.0; P < 0.001). Death at 30 days occurred in 55 (7.6%) versus 145 (11%) patients treated with aminoglycosides and non-aminoglycoside drugs, respectively (adjusted HR = 0.78; P = 0.013). Aminoglycosides were either superior or similar to comparator drugs in all patient subgroups, stratified according to age, glomerular filtration rate, bacteraemia, haemodynamic shock and infection with third-generation cephalosporin-resistant Enterobacteriaceae. The incidence of acute kidney injury was similar for aminoglycosides and comparators (2.5% versus 2.9%, respectively; P = 0.6).. Within the context of an institutional programme, initial empirical treatment of pyelonephritis with aminoglycosides was associated with higher rates of in vitro activity and lower overall mortality compared with non-aminoglycoside drugs, without excess nephrotoxicity.

Topics: Aminoglycosides; Anti-Bacterial Agents; Fluoroquinolones; Humans; Piperacillin, Tazobactam Drug Combination; Pyelonephritis

Topics: Anti-Bacterial Agents; Comorbidity; Diabetes Mellitus; Diabetic Ketoacidosis; Drug Therapy, Combination; Emphysema; Humans; Hypertension; Kidney Transplantation; Male; Middle Aged; Norepinephrine; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Pyelonephritis; Tomography, X-Ray Computed; Transplantation, Homologous; Vancomycin

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) is a frequent cause of acute pyelonephritis (APN), requiring carbapenem therapy. However, alternatives to carbapenems are needed due to the emergence of carbapenemase-producing micro-organisms. The purpose of this study was to compare the clinical efficacy of piperacillin/tazobactam (TZP) versus ertapenem in the treatment of adult patients with APN caused by ESBL-Ec. A retrospective observational study of APN caused by ESBL-Ec susceptible to TZP was performed at a university-affiliated hospital in the Republic of Korea between February 2011 and June 2013. All adult patients initially treated with in vitro-active TZP were compared with those treated with ertapenem to evaluate antibiotic clinical efficacy. The primary endpoint was treatment failure, defined as a composite of in-hospital mortality, change of initial antibiotic regimen and microbiological eradication failure. During the study period, 68 patients prescribed TZP and 82 patients prescribed ertapenem were eligible for inclusion in the study. There was no significant difference between the two treatment groups in the occurrence of in-hospital mortality, change of initial antibiotic regimen or microbiological eradication failure. In the multivariate analyses, predictors associated with treatment failure included septic shock [odds ratio (OR) = 4.27, 95% confidence interval (CI) 1.66-10.99] and recent administration of immunosuppressive agents (OR = 2.84, 95% CI 1.02-7.91). However, the type of antibiotic was not associated with treatment failure. TZP could be an effective alternative to ertapenem for the treatment of APN caused by ESBL-Ec, sparing carbapenem consumption in the multidrug-resistant era.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Hospitals, University; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Republic of Korea; Retrospective Studies; Survival Analysis; Treatment Failure; Young Adult

The emergence of resistant Escherichia coli to fluoroquinolones (FQs) is of growing concern, yet the latest guidelines for the treatment of pyelonephritis still recommend FQs as first-line treatment. Our primary objective was to determine the impact of discordant prescribing of FQs in E coli pyelonephritis on hospital length of stay (LOS) and early clinical response (ECR).. We retrospectively compared discordant and concordant prescribing of FQs for LOS and ECR. We also compared FQs, ceftriaxone, piperacillin/tazobactam, and carbapenems for these clinical outcomes.. Forty-nine patients included in the comparison between discordant (n = 9) and concordant (n = 40) prescribing of FQs. There was significantly lower ECR in patients with discordant prescribing of FQs (38 of 40, 95% vs 5 of 9, 55.6%, P = .0074) and a trend toward longer LOS (4 [2.3] days vs 3 [2.0] days, P = .0571). Illness severity, estimated using Simplified Acute Physiology Score (SAPS II) score, was similar between groups (P = .717).. There was a significantly decreased ECR and a trend toward increased LOS when FQs were used in FQ-resistant E coli. Regarding alternative treatment for E coli pyelonephritis, ceftriaxone was as effective as concordant FQs and significantly better than discordant FQs.

Topics: Adult; Anti-Bacterial Agents; Carbapenems; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Fluoroquinolones; Guidelines as Topic; Humans; Length of Stay; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Retrospective Studies; Treatment Outcome

Topics: Acute Disease; Anti-Bacterial Agents; Catheterization, Central Venous; Diagnosis, Differential; Drug Administration Routes; Escherichia coli; Fatigue; Female; Flank Pain; Fluid Therapy; Humans; Levofloxacin; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Systemic Inflammatory Response Syndrome; Tomography, X-Ray Computed; Treatment Outcome