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JAMA Oct 2023Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been...
IMPORTANCE
Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial.
OBJECTIVE
To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction.
DESIGN, SETTING, AND PARTICIPANTS
The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022.
INTERVENTIONS
Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam.
MAIN OUTCOMES AND MEASURES
The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days.
RESULTS
There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]).
CONCLUSIONS AND RELEVANCE
Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05094154.
Topics: Humans; Adult; Female; Middle Aged; Male; Anti-Bacterial Agents; Cefepime; Coma; Piperacillin; Drug Therapy, Combination; Retrospective Studies; Piperacillin, Tazobactam Drug Combination; Sepsis; Acute Kidney Injury; Kidney; Delirium
PubMed: 37837651
DOI: 10.1001/jama.2023.20583 -
Critical Care Medicine Sep 2023As causative pathogens are not usually identified at the time of initiating antibiotics in sepsis, carbapenems are commonly used as an initial treatment. To reduce... (Observational Study)
Observational Study
OBJECTIVES
As causative pathogens are not usually identified at the time of initiating antibiotics in sepsis, carbapenems are commonly used as an initial treatment. To reduce indiscriminate use of carbapenems, the efficacy of alternative empiric regimens, such as piperacillin-tazobactam and the fourth-generation cephalosporins, should be elucidated. This study aimed to evaluate survival effect associated with carbapenems as initial therapy for sepsis compared with these antibiotics.
DESIGN
Multicenter retrospective observational study.
SETTING
Tertiary hospitals in Japan.
PATIENTS
Adult patients diagnosed as having sepsis from 2006 to 2019.
INTERVENTIONS
Administration of carbapenems as initial antibiotic therapy.
MEASUREMENTS AND MAIN RESULTS
This study used data of adult patients with sepsis extracted from a large-scale database in Japan. Patients were divided into two groups as follows: patients receiving carbapenems and patients receiving noncarbapenem broad-spectrum beta-lactam antibiotics as initial treatment. In-hospital mortality was compared between the groups by a logistic regression model adjusted by an inverse probability treatment weighting using propensity scores. To evaluate heterogeneity of effects according to patient characteristics, we also fitted logistic models in several subgroups. Among 7,392 patients with sepsis, 3,547 patients received carbapenems, and 3,845 patients received noncarbapenem agents. The logistic model showed no significant association between carbapenem therapy and lower mortality (adjusted OR 0.88, p = 0.108). Subgroup analyses suggested that there were significant survival benefits associated with carbapenem therapy in patients with septic shock, in ICUs, or with mechanical ventilation ( p for effect modifications: < 0.001, 0.014, and 0.105, respectively).
CONCLUSIONS
Compared with the noncarbapenem broad-spectrum antibiotics, carbapenems as an initial therapy for sepsis were not associated with significantly lower mortality.
Topics: Adult; Humans; Anti-Bacterial Agents; Carbapenems; Monobactams; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Hospital Mortality; Treatment Outcome
PubMed: 37232855
DOI: 10.1097/CCM.0000000000005932 -
International Journal of Infectious... Mar 2024Pseudomonas fluorescens (P. fluorescens) is not generally considered a bacterial pathogen in humans; however, multiple culture-based and culture-independent studies have...
Pseudomonas fluorescens (P. fluorescens) is not generally considered a bacterial pathogen in humans; however, multiple culture-based and culture-independent studies have identified it in the indigenous microbiota of multiple body sites. We herein report a rare case of pneumonia caused by P. fluorescens. A man in his 80 s with chronic obstructive pulmonary disease and diabetes mellitus was diagnosed with stage II rectal cancer. He underwent laparoscopic surgery, and on the 6th postoperative day, he developed a high fever. Chest computed tomography revealed infiltration in the left lower lung. Gram staining of the sputum showed Gram-negative rods phagocytosed by neutrophils, suggesting postoperative nosocomial pneumonia. The patient was started on tazobactam/piperacillin, and his pneumonia quickly improved. Later, only P. fluorescens was detected in a sputum culture. It was susceptible to common antipseudomonal agents. Gram staining of P. fluorescens appears to show a slightly thicker and larger morphology in comparison to Pseudomonas aeruginosa. Although there have been reports of opportunistic infections caused by P. fluorescens in immunosuppressed patients, including those with advanced cancer, most have been bloodstream infections, with very few reports of pneumonia alone. Clinicians should be aware that patients, who are not necessarily immunosuppressed, may develop pneumonia caused by P. fluorescens.
Topics: Male; Humans; Pseudomonas fluorescens; Pseudomonas Infections; Pneumonia; Pneumonia, Bacterial; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Anti-Bacterial Agents
PubMed: 38218379
DOI: 10.1016/j.ijid.2024.01.007 -
Critical Care (London, England) Jun 2023In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to...
BACKGROUND
In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time.
METHODS
A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides.
RESULTS
A total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%).
CONCLUSIONS
We observed numerous changes in practice since the ADMIN-ICU 2015 survey was conducted. Beta-lactams are more commonly administered as extended infusions, and therapeutic drug monitoring use has increased, which align with emerging evidence.
Topics: Humans; Adult; Anti-Bacterial Agents; Vancomycin; Meropenem; Cross-Sectional Studies; Piperacillin, Tazobactam Drug Combination; Surveys and Questionnaires; Intensive Care Units; Aminoglycosides; Critical Illness; Piperacillin
PubMed: 37331935
DOI: 10.1186/s13054-023-04527-1 -
Journal of Intensive Care Medicine Dec 2023Prior studies suggest associations between receipt of piperacillin-tazobactam and development of acute kidney injury and receipt of anti-pseudomonal cephalosporins and...
Prior studies suggest associations between receipt of piperacillin-tazobactam and development of acute kidney injury and receipt of anti-pseudomonal cephalosporins and neurotoxicity. We compared clinically-relevant renal and neurologic outcomes in critically ill patients who received piperacillin-tazobactam versus anti-pseudomonal cephalosporins. We conducted a secondary analysis of data from the Isotonic Solutions and Major Adverse Renal Events Trial examining patients who received piperacillin-tazobactam or an anti-pseudomonal cephalosporin within 24 h of intensive care unit admission. We performed multivariable analysis using a proportional odds model to examine the association between the first antibiotic received and the outcomes of Major Adverse Kidney Events within 30 days (MAKE30) and days alive and free of delirium and coma to day 28. 3199 were included in the study; 2375 (74%) receiving piperacillin-tazobactam and 824 (26%) receiving anti-pseudomonal cephalosporin. After adjustment for prespecified confounders, initial receipt of piperacillin-tazobactam, compared to anti-pseudomonal cephalosporins, was not associated with higher incidence of MAKE30 (adjusted odds ratio, 1.03; 95% CI, 0.83-1.27; = .80) but was associated with a greater number of days alive and free of delirium and coma (adjusted odds ratio, 1.18; 95% CI, 1.00-1.38; = .04). In a sensitivity analysis adjusting for baseline receipt of medications which may impact neuro function, this finding was not significant. Among critically ill adults, receipt of piperacillin-tazobactam was not associated with an increased incidence of death, renal replacement therapy, or persistent renal dysfunction or a greater number of days alive and free of delirium and coma. Randomized trials are needed to inform the choice of antibiotics for empiric treatment infection in critically ill adults.
Topics: Adult; Humans; Acute Kidney Injury; Anti-Bacterial Agents; Cephalosporins; Coma; Critical Illness; Delirium; Drug Therapy, Combination; Piperacillin, Tazobactam Drug Combination; Clinical Trials as Topic
PubMed: 37357717
DOI: 10.1177/08850666231184177 -
Therapeutic Drug Monitoring Oct 2023Recently, several studies have assessed the effects of therapeutic drug monitoring of frequently prescribed beta-lactam antibiotics, for which they were quantified in...
BACKGROUND
Recently, several studies have assessed the effects of therapeutic drug monitoring of frequently prescribed beta-lactam antibiotics, for which they were quantified in human plasma samples. Beta-lactams are considered unstable, leading to extra challenges in quantification. Therefore, to ensure sample stability and minimize sample degradation before analysis, stability studies are crucial. This study investigated the stability of 10 frequently used beta-lactam antibiotics in human plasma at relevant storage conditions for clinical use.
METHODS
Amoxicillin, benzylpenicillin, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, imipenem, meropenem, and piperacillin were analyzed using ultraperformance convergence chromatography tandem mass spectrometry and liquid chromatography tandem mass spectrometry. Their short-term and long-term stabilities were investigated by measuring quality control samples at low and high concentrations against freshly prepared calibration standards. Measured concentrations at each time point were compared with the concentrations at T = 0. Antibiotics were considered stable if recovery results were between 85% and 115%.
RESULTS
Short-term stability results indicated ceftriaxone, cefuroxime, and meropenem to be stable up to 24 hours at room temperature. All evaluated antibiotics, except imipenem, were stable on ice in a cool box for 24 hours. Amoxicillin, benzylpenicillin, and piperacillin were stable for 24 hours at 4-6°C. Cefotaxime, ceftazidime, cefuroxime, and meropenem were stable at 4-6°C up to 72 hours. Ceftriaxone and flucloxacillin were stable for 1 week at 4-6°C. Long-term stability results showed that all antibiotics were stable up to 1 year at -80°C, except imipenem and piperacillin, which were stable for 6 months at -80°C.
CONCLUSIONS
Plasma samples for amoxicillin, benzylpenicillin, cefotaxime, ceftazidime, flucloxacillin, and piperacillin may be stored for a maximum of 24 hours in a cool box. Refrigeration is suitable for plasma samples of amoxicillin, benzylpenicillin, meropenem, and piperacillin for up to 24 hours and cefotaxime, ceftriaxone, ceftazidime and cefuroxime for 72 hours. Plasma samples for imipenem should be frozen directly at -80°C. For long-term storage, plasma samples can be stored at -80°C for a maximum of 6 months for imipenem and piperacillin and 12 months for all other evaluated antibiotics.
Topics: Humans; Meropenem; Ceftazidime; Floxacillin; Cefuroxime; Ceftriaxone; Anti-Bacterial Agents; Piperacillin; Monobactams; Tandem Mass Spectrometry; Imipenem; Cefotaxime; Amoxicillin
PubMed: 37199408
DOI: 10.1097/FTD.0000000000001100 -
Antimicrobial Agents and Chemotherapy Jul 2023We conducted antimicrobial susceptibility testing of 267 isolates for 16 antibiotics from 2017 to 2022. The highest susceptibility was found for...
We conducted antimicrobial susceptibility testing of 267 isolates for 16 antibiotics from 2017 to 2022. The highest susceptibility was found for piperacillin-tazobactam (70%) and ceftazidime-avibactam (62%). Between 30% and 49% of strains were susceptible to tigecycline, ceftazidime, and meropenem. We applied species-specific Achromobacter xylosoxidans breakpoints for piperacillin-tazobactam, meropenem, and trimethoprim-sulfamethoxazole and EUCAST pharmacokinetic/pharmacodynamic (PK/PD) breakpoints for the others. A. xylosoxidans was the most frequently isolated species, followed by Achromobacter insuavis and Achromobacter ruhlandii.
Topics: Humans; Meropenem; Cystic Fibrosis; Microbial Sensitivity Tests; Anti-Bacterial Agents; Achromobacter; Piperacillin; Tazobactam
PubMed: 37310234
DOI: 10.1128/aac.00379-23 -
BJS Open May 2024Pancreatoduodenectomy is associated with an increased incidence of surgical-site infections, often leading to a significant rise in morbidity and mortality. This trend... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatoduodenectomy is associated with an increased incidence of surgical-site infections, often leading to a significant rise in morbidity and mortality. This trend underlines the inadequacy of traditional antibiotic prophylaxis strategies. Hence, the aim of this meta-analysis was to assess the outcomes of antimicrobial prophylaxis, comparing piperacillin/tazobactam with traditional antibiotics.
METHODS
Upon registering in PROSPERO, the international prospective register of systematic reviews (CRD42023479100), a systematic search of various databases was conducted over the interval 2000-2023. This inclusive search encompassed a wide range of study types, including prospective and retrospective cohorts and RCTs. The subsequent data analysis was carried out utilizing RevMan 5.4.
RESULTS
A total of eight studies involving 2382 patients who underwent pancreatoduodenectomy and received either piperacillin/tazobactam (1196 patients) or traditional antibiotics (1186 patients) as antibiotic prophylaxis during surgery were included in the meta-analysis. Patients in the piperacillin/tazobactam group had significantly reduced incidences of surgical-site infections (OR 0.43 (95% c.i. 0.30 to 0.62); P < 0.00001) and major surgical complications (Clavien-Dindo grade greater than or equal to III) (OR 0.61 (95% c.i. 0.45 to 0.81); P = 0.0008). Subgroup analysis of surgical-site infections highlighted significantly reduced incidences of superficial surgical-site infections (OR 0.34 (95% c.i. 0.14 to 0.84); P = 0.02) and organ/space surgical-site infections (OR 0.47 (95% c.i. 0.28 to 0.78); P = 0.004) in the piperacillin/tazobactam group. Further, the analysis demonstrated significantly lower incidences of clinically relevant postoperative pancreatic fistulas (grades B and C) (OR 0.67 (95% c.i. 0.53 to 0.83); P = 0.0003) and mortality (OR 0.51 (95% c.i. 0.28 to 0.91); P = 0.02) in the piperacillin/tazobactam group.
CONCLUSION
Piperacillin/tazobactam as antimicrobial prophylaxis significantly lowers the risk of postoperative surgical-site infections, major surgical complications (complications classified as Clavien-Dindo grade greater than or equal to III), clinically relevant postoperative pancreatic fistulas (grades B and C), and mortality, hence supporting the implementation of piperacillin/tazobactam for surgical prophylaxis in current practice.
Topics: Humans; Pancreaticoduodenectomy; Antibiotic Prophylaxis; Piperacillin, Tazobactam Drug Combination; Surgical Wound Infection; Anti-Bacterial Agents; Piperacillin
PubMed: 38869238
DOI: 10.1093/bjsopen/zrae066 -
Pharmaceutics Nov 2023Outpatient parenteral antimicrobial therapy (OPAT) is a useful treatment strategy against and other multidrug-resistant bacteria. However, it is hindered by the lack of...
Outpatient parenteral antimicrobial therapy (OPAT) is a useful treatment strategy against and other multidrug-resistant bacteria. However, it is hindered by the lack of stability data for the administration of antibiotics under OPAT conditions. Our objective was to investigate the stability of nine antipseudomonal and broad-spectrum beta lactam antibiotics (aztreonam, cefepime, cefiderocol, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, meropenem/vaborbactam, and piperacillin/tazobactam) to allow the spread of OPAT programs. All the antibiotics were diluted in 500 mL 0.9% sodium chloride and stored at 4, 25, 32, and 37 °C for 72 h in two different devices (infusion bags and elastomeric pumps). The solutions were considered stable if the color, clearness, and pH remained unchanged and if the percentage of intact drug was ≥90%. All the antimicrobials remained stable 72 h under refrigerated conditions and at least 30 h at 25 °C. At 32 °C, all the antibiotics except for meropenem and meropenem/vaborbactam remained stable for 24 h or more. At 37 °C, only aztreonam, piperacillin/tazobactam, cefepime, cefiderocol, and ceftolozane/tazobactam were stable for at least 24 h. The stability results were the same in the two devices tested. All the antibiotics studied are actual alternatives for the treatment of antipseudomonal or multidrug-resistant infections in OPAT programs, although the temperature of the devices is crucial to ensure antibiotic stability.
PubMed: 38140046
DOI: 10.3390/pharmaceutics15122705 -
Radiology Case Reports Jun 2024A 51-year-old woman presented to her local emergency department with acute onset right-sided flank pain and nausea. Her blood results on admission were largely...
A 51-year-old woman presented to her local emergency department with acute onset right-sided flank pain and nausea. Her blood results on admission were largely unremarkable aside from leucocytosis and neutrophilia. Two days after admission, she developed the following: stage 3 AKI with oliguria, anaemia, thrombocytopenia, and acute derangement of liver function tests. A computed tomography of the kidney ureter bladder demonstrated a right-sided 4 mm obstructing vesicoureteric junction stone with associated hydronephrosis and hydroureter. She was transferred to a tertiary care centre; gram negative sepsis was confirmed with a Proteus on blood culture and laboratory findings were in keeping with DIC. She was treated with Tazobactam/Piperacillin and intravenous fluids. In addition, further imaging showed improving right-sided hydronephrosis and left renal cortical necrosis. The aetiology of this presentation was sepsis complicated by disseminated intravascular coagulation. The coagulopathy likely contributed to the unilateral renal cortical necrosis. Cortical necrosis usually affects both kidneys, and is typically a complication of sepsis, shock, or obstetrical trauma. To our knowledge, there are only 2 reported cases of unilateral renal cortical necrosis and contralateral hydronephrosis with renal colic and septic shock. Potential pathogenetic mechanisms are discussed.
PubMed: 38577129
DOI: 10.1016/j.radcr.2024.02.108