piperacillin--tazobactam-drug-combination and Kidney-Diseases

Observational studies have suggested an increased risk of nephrotoxicity when piperacillin-tazobactam is added to vancomycin, although the data are confliciting.. To perform a meta-analysis of identified studies to assess if adding piperacillin-tazobactam to vancomycin increases the incidence of nephrotoxicity.. A systematic review of PubMed, EMBASE, Cochrane Central, and Google Scholar was conducted to identify studies. Studies selected for meta-analysis were full length reports, retrospective or prospective, and designed specifically to assess if the combining piperacillin-tazobactam with vancomycin increases nephrotoxicity.. Six observational trials involving 963 patients were identified and analyzed. Five trials were retrospective and one was prospective. Vancomycin/piperacillin-tazobactam was compared to vancomycin alone in 2 trials, to vancomycin/cefepime in 3 trials, and vancomycin/cefepime or meropenem in one. Meta-analysis showed a statistical increase in the incidence of nephrotoxicity when piperacillin-tazobactam/vancomycin is compared to the control group (2.26 95% CI 1.41-3.63, p= 0.0007). No differences were noted between groups in patients requiring renal replacement.. Adding piperacillin-tazobactam to vancomycin increases the risk of nephrotoxicity when compared to vancomycin alone or vancomycin with either cefepime or meropenem.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Kidney Diseases; Observational Studies as Topic; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Retrospective Studies; Vancomycin

The effect of different antibiotics on the outcome of surgical care in the management of diabetic foot was investigated. We randomly allocated 100 patients with diabetic foot into one of four groups. Each patient's infection was graded (Wagner classification). All patients were offered the same surgical care but each group was assigned a different antibiotic. Hospital stay for the four groups ranged from 7 to 14 days. Five patients experienced complications from septicaemia; 15 patients underwent amputation; and five patients experienced temporary renal impairment. Careful consideration to the type of antibiotic used is essential.

Topics: Amikacin; Amputation, Surgical; Anti-Bacterial Agents; Ceftazidime; Chemotherapy, Adjuvant; Debridement; Diabetic Foot; Drug Combinations; Drug Monitoring; Humans; Imipenem; Kidney Diseases; Length of Stay; Lincomycin; Metronidazole; Patient Selection; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Severity of Illness Index; Treatment Outcome; Wound Healing; Wound Infection

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Incidence; Kidney Diseases; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Vancomycin; Young Adult

A drug combination that has gained recent attention for an additive risk of nephrotoxicity is vancomycin plus piperacillin-tazobactam. Clinicians need to better understand whether tubular cell stress occurs with piperacillin-tazobactam administration to establish whether renal injury associated with this combination is a valid clinical concern.. An evaluation of the pharmacokinetics of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding-protein 7 (IGFBP7) for patients receiving vancomycin alone, piperacillin-tazobactam alone, and vancomycin plus piperacillin-tazobactam in combination was conducted to understand the impact on acute kidney cell stress and compare the rates of dialysis or death at 9 months among these three drug exposure types.. A secondary analysis of the prospective, multicenter Sapphire study (ClinicalTrials.gov identifier NCT01209169) including 35 intensive care units (ICUs) in North America and Europe was performed. Critically ill adult patients at risk for acute kidney injury (AKI) were included. Urinary [TIMP-2]∙[IGFBP7] was measured serially. Patients who received vancomycin alone, piperacillin-tazobactam alone, or vancomycin plus piperacillin-tazobactam were grouped according to their maximum AKI stage within 3 days of the first drug dose.. Of 723 critically ill adults admitted to the ICU, 46% received either piperacillin-tazobactam (n = 110), vancomycin (n = 156), or both (n = 67). The urinary [TIMP-2]∙[IGFBP7] was highest on day 1 for the combination group. AKI stage 2/3 occurred more frequently in patients receiving the drug combination than in those receiving piperacillin-tazobactam alone (p = 0.03) but not vancomycin alone (p = 0.29). Risk of death or dialysis at 9 months was greatest for vancomycin plus piperacillin-tazobactam (48%) and similar for patients receiving vancomycin alone (29%) or piperacillin-tazobactam alone (35%) (p = 0.03 for unadjusted and p = 0.048 after adjusting for covariates).. After exposure to piperacillin-tazobactam and vancomycin in combination, there was a greater release of AKI biomarkers in patients who develop AKI than with piperacillin-tazobactam or vancomycin monotherapy and the combination is associated with possible increased long-term adverse outcomes.

Topics: Anti-Bacterial Agents; Biomarkers; Critical Illness; Drug Therapy, Combination; Humans; Kidney Diseases; Piperacillin, Tazobactam Drug Combination; Vancomycin

Tazobactam/piperacillin (TAZ/PIPC) is widely used in the treatment of infectious disease. In this study, three hundred and sixty-three patients who were treated with the recommended dose of TAZ/PIPC were investigated for the proportion of time above the minimum inhibitory concentration (%TAM) and the frequency of renal and liver dysfunction. Of the whole patient population, 5.23%, exhibited increased creatinine levels, 9.37% and 8.82% exhibited increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, respectively. The patients who exhibited high serum creatinine (SCr) levels before administration, exhibited significant increases of AST (p=0.0121). The patients who exhibited low albumin levels before administration, exhibited significant decreases in renal function (p=0.0041). In the case of a breakpoint (BP) of 64 μg/mL, the arrival probabilities of %TAM of 30% and 50% were 99.4% and 76.9%, respectively. We suggested that the dose of TAZ/PIPC should be adjusted according to the interview form finding and a %TAM>50% (maximal bactericidal action).

Topics: Aged; Aged, 80 and over; Alanine Transaminase; Aspartate Aminotransferases; Biomarkers; Chemical and Drug Induced Liver Injury; Creatinine; Drug Administration Schedule; Female; Humans; Incidence; Kidney Diseases; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

Early administration of appropriate empiric antibiotics is essential for achieving the best possible outcomes in sepsis. Yet the choice of antibiotic therapy has become more challenging due to recent reports of nephrotoxicity with the combination of vancomycin and piperacillin/tazobactam, the "workhorse" regimen at many institutions. In this article we assess the evidence for nephrotoxicity and its possible mechanisms, provide recommendations for risk mitigation, address the advantages and disadvantages of alternative antibiotic choices, and suggest areas for future research.

Topics: Anti-Bacterial Agents; Combined Modality Therapy; Drug Therapy, Combination; Humans; Kidney; Kidney Diseases; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Vancomycin

Antibiotic computerized decision support systems (CDSSs) were developed to guide antibiotic decisions, yet prescriptions of CDSS-recommended antibiotics have remained low. Our aim was to identify predictors of patients' receipt of empiric antibiotic therapies recommended by a CDSS when the prescribing physician had an initial preference for using broad-spectrum antibiotics.. We conducted a prospective cohort study in a 1 500-bed tertiary-care hospital in Singapore. We included all patients admitted from October 1, 2011 through September 30, 2012, who were prescribed piperacillin-tazobactam or carbapenem for empiric therapy and auto-triggered to receive antibiotic recommendations by the in-house antibiotic CDSS. Relevant data on the patient, prescribing and attending physicians were collected via electronic linkages of medical records and administrative databases. To account for clustering, we used multilevel logistic regression models to explore factors associated with receipt of CDSS-recommended antibiotic therapy.. One-quarter of the 1 886 patients received CDSS-recommended antibiotics. More patients treated for pneumonia (33.2%) than sepsis (12.1%) and urinary tract infections (7.1%) received CDSS-recommended antibiotic therapies. The prescribing physician - but not the attending physician or clinical specialty - accounted for some (13.3%) of the variation. Prior hospitalization (odds ratio [OR] 1.32, 95% CI, 1.01-1.71), presumed pneumonia (OR 6.77, 95% CI, 3.28-13.99), intensive care unit (ICU) admission (OR 0.38, 95% CI, 0.21-0.66), and renal impairment (OR 0.70, 95% CI, 0.52-0.93) were factors associated with patients' receipt of CDSS-recommended antibiotic therapies.. We observed that ICU admission and renal impairment were negative predictors of patients' receipt of CDSS-recommended antibiotic therapies. Patients admitted to ICU and those with renal impairment might have more complex clinical conditions that require a physician's assessment in addition to antibiotic CDSS.

Topics: Academic Medical Centers; Aged; Anti-Bacterial Agents; Carbapenems; Cohort Studies; Decision Support Systems, Clinical; Drug Therapy, Computer-Assisted; Drug Utilization; Female; Guideline Adherence; Humans; Inappropriate Prescribing; Intensive Care Units; Kidney Diseases; Male; Middle Aged; Patient Admission; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Singapore

Neutropenic fever is a common complication of myelosuppressive therapy in pediatric oncology patients. Piperacillin-tazobactam (PIP/TAZO) is a broad spectrum antibiotic used for empiric treatment of neutropenic fever. We describe four cases of suspected PIP/TAZO induced nephrotoxicity occurring in children with pediatric malignancies admitted to the hospital and treated for fever ± neutropenia. All patients exhibited acute renal injury shortly after PIP/TAZO administration with one of these cases having biopsy evidence of acute interstitial nephritis. These findings are suggestive of PIP/TAZO induced nephrotoxicity in pediatric oncology patients with fever ± neutropenia and that PIP/TAZO should be used judiciously in this population.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Kidney Diseases; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prognosis

This study aimed to clarify the efficacy, safety, and pharmacokinetics of piperacillin–tazobactam (PIPC– TAZ) in late elderly Japanese patients. This is the first antimicrobial pilot study in late elderly patients with nursing and healthcare associated pneumonia. After PIPC–TAZ administration, PIPC concentrations in plasma were measured chromatographically and the pharmacokinetic parameters were estimated. Efficacy, safety, and bacteriological evaluations were also carried out. The mean age was 85.0 years old and most of the patients were late elderly. Chest X-rays, body temperature, white blood cell count, and C reactive protein all improved significantly, and a high efficacy ratio of 90.9% was observed. Serious nephrotoxicity was observed in 4 cases (18.2%) after administration of PIPC–TAZ. Creatinine clearance (meanS.D.) measured before PIPC–TAZ therapy was significantly lower in the nephrotoxicity group (32.54.4 mL/min) than in the non-nephrotoxicity group (46.116.7 mL/min), although the ages were not different between the 2 groups. In the pharmacokinetic parameters for PIPC, total clearance was slightly lower in the nephrotoxicity group than in the non-nephrotoxicity group. However, no significant difference was observed in plasma PIPC levels between the 2 groups. In patients with renal impairment, especially with a creatinine clearance of <40 mL/ min, renal impairment was found to be an influencing factor for severe nephrotoxicity following PIPC–TAZ administration. In conclusion, the results suggest that physicians should pay close attention in order to avoid possible toxicity, and that deliberate administration planning and careful follow-up are required in late elderly patients with comprised organ dysfunction.

Topics: Aged; Aged, 80 and over; Aging; Anti-Bacterial Agents; Asian People; Cross Infection; Female; Humans; Kidney Diseases; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial

Days of therapy (DOTs) are an important measure to quantify antimicrobial use but may not reflect patients' true antimicrobial exposure. Three methods of calculating DOTs were compared to determine whether including "exposure days," when antimicrobials are given less frequently than daily due to renal dysfunction, makes a difference.

Topics: Adult; Anti-Infective Agents; Ceftriaxone; Drug Dosage Calculations; Humans; Kidney Diseases; Ofloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Time Factors; Tobramycin; Vancomycin

Renal absceeses in childhood are rare and require hospitalization, antibiotic therapy and drainage.. Two cases of renal abscess in childhood are described. In both cases there was no history of either antecedent skin infection or urinary tract infection or reflux. Flank pain and fever had a sudden onset.. The diagnosis was made in the first case by ultrasound and gadolinium-enhnaced magnetic resonance, in the second case ultrasound and computerized axial tomography were used. The patients were successfully treated at home with antibiotic therapy but without drainage.. Renal abscesses must be suspected in children with loin pain, fever and leukocytosis. They may heal even without hospitalization and drainage.

Topics: Abscess; Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Drainage; Female; Hospitalization; Humans; Kidney; Kidney Diseases; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Radiography; Staphylococcal Infections; Ultrasonography