Preventing Pneumonia in High-risk Patients After Esophageal Cancer Surgery: Mini-tracheostomy and Tazobactam/Piperacillin.

BACKGROUND/AIM: We evaluated the usefulness of prophylactic mini-tracheostomy (PMT) and perioperative administration of tazobactam/piperacillin (TAZ/PIPC) in high-risk patients after esophagectomy. PATIENTS AND METHODS: We retrospectively studied 89 consecutive high-risk patients who underwent esophagectomy for esophageal cancer between January 2013 and December 2021. We defined patients with two or more of the following factors as high risk: age ≥70 years, performance status ≥1, respiratory dysfunction, liver dysfunction, cardiac dysfunction, renal dysfunction, diabetes mellitus, albumin <3.5 g/dl, and Brinkman index >600. Standard management was administered to the first 50 patients (standard group). PMT and TAZ/PIPC were administered to the next 39 patients (combination group). Patient characteristics and short-term outcomes were compared before and after propensity-score matching. RESULTS: Before propensity-score matching, 24-hour urine creatinine clearance, retrosternal route, 3-field lymph node dissection, and open abdominal approach were more common, postoperative pneumonia (13% vs. 36%, p=0.045) and complications of grade ≥3b (2.6% vs. 22%, p=0.01) were less frequent, and the postoperative hospital stay was shorter (median: 23 vs. 28 days, p=0.022) in the combination group than in the standard group. In propensity-score matching, patient characteristics, except for 24-h creatinine clearance and reconstructive route, were matched for 23 paired patients. Postoperative pneumonia (8.7% vs. 39%, p=0.035) and complications of grade ≥3b (0% vs. 26%, p=0.022) were less frequent and postoperative hospital stay was shorter (median: 22 vs. 25 days, p=0.021) in the combination group than in the standard group. CONCLUSION: PMT with TAZ/PIPC can potentially prevent postoperative pneumonia in high-risk patients after esophagectomy.

Mortality of Patients With Sepsis Administered Piperacillin-Tazobactam vs Cefepime.

Importance: Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents. Objective: To examine the use of piperacillin-tazobactam compared with cefepime in 90-day mortality in patients treated empirically for sepsis, using instrumental variable analysis of a 15-month piperacillin-tazobactam shortage. Design, Setting, and Participants: In a retrospective cohort study, hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including a piperacillin-tazobactam shortage period from June 12, 2015, to September 18, 2016, were examined. Adult patients with suspected sepsis treated with vancomycin and either piperacillin-tazobactam or cefepime for conditions with presumed equipoise between piperacillin-tazobactam and cefepime were included in the study. Data analysis was conducted from December 17, 2022, to April 11, 2023. Main Outcomes and Measures: The primary outcome was 90-day mortality. Secondary outcomes included organ failure-free, ventilator-free, and vasopressor-free days. The 15-month piperacillin-tazobactam shortage period was used as an instrumental variable for unmeasured confounding in antibiotic selection. Results: Among 7569 patients (4174 men [55%]; median age, 63 [IQR 52-73] years) with sepsis meeting study eligibility, 4523 were treated with vancomycin and piperacillin-tazobactam and 3046 were treated with vancomycin and cefepime. Of patients who received piperacillin-tazobactam, only 152 (3%) received it during the shortage. Treatment groups did not differ significantly in age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration. In an instrumental variable analysis, piperacillin-tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9%-8.1%) and 2.1 (95% CI, 1.4-2.7) fewer organ failure-free days, 1.1 (95% CI, 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01-2.01) fewer vasopressor-free days. Conclusions and Relevance: Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime. These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.

Comparing cefazolin/ metronidazole, piperacillin-tazobactam, or c efoxitin as surgical antibiotic prophylaxis in patients undergoing pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. OBJECTIVE: To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). METHODS: Consecutive adult patients at one institution who underwent PD from November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. RESULTS: Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. CONCLUSION: PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PD at our center.

The Impact of Antibiotic Strategy on Outcomes in Surgically Managed Necrotizing Enterocolitis.

BACKGROUND: We sought to evaluate postoperative antibiotic practices in a large population of patients with necrotizing enterocolitis (NEC) and determine whether any regimens were associated with better outcomes. METHODS: The Pediatric Health Information Systems (PHIS) database was queried to identify patients who underwent an intestinal resection for acute NEC between July, 2016 and June, 2021. Data regarding post-resection antibiotic therapy, cutaneous or intraabdominal infection, and fungal or antibiotic-resistant infection were collected. RESULTS: 130 infants at 38 children's hospitals met inclusion criteria. Postoperative antibiotics were administered for a median of 13 days. The most frequently used antibiotics were vancomycin and piperacillin/tazobactam. Antibiotic duration greater than five days was not associated with a lower incidence of infection. No antibiotic was associated with a lower incidence of any of the complications assessed, although ampicillin was associated with more infections, overall. The incidence of fungal infection and treatment with a parenteral anti-fungal medication was greater with vancomycin. No antibiotic combination was used enough to be assessed. CONCLUSIONS: Administration of antibiotics for more than five days after resection for NEC was not associated with better infectious outcomes and no single antibiotic demonstrated superior efficacy. Consistent with prior studies, fungal infections were more frequent with vancomycin. TYPE OF STUDY: Retrospective database study, level 3B. LEVEL OF EVIDENCE: II.

Is the fluoroquinolone combination necessary for empirical antibiotic regimen in severe community-acquired pneumonia?

OBJECTIVES: This study aimed to assess whether superior clinical outcomes can be attained through piperacillin/tazobactam (TZP)+fluoroquinolone (FQ) combination therapy for severe community-acquired pneumonia (CAP) compared to TZP monotherapy. METHODS: This retrospective study was conducted at a tertiary care hospital in Korea. Adult inpatients diagnosed with pneumonia within 48 hours of hospitalization were included. Severe CAP was defined as a CURB-65 score of ≥ 3 or based on the 2007 guidelines of the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) definition. Only patients who received either TZP and FQ combination or TZP as initial empirical therapy were included. RESULTS: The final analysis included 145 patients; 57.9% received combination therapy and 42.1% received monotherapy. In the combination therapy group, body mass index (20.67 ± 3.28 vs. 22.26 ± 4.80, p = 0.030) and asthma prevalence (0 vs. 8.3%, p = 0.022) were significantly higher; initial symptoms, clinical severity, and causative pathogens were not significantly different between groups. White blood cell counts (12,641.64 ± 6,544.66 vs. 12,491.67 ± 10,528.24, p = 0.008), and C-reactive protein levels (18.78 ± 11.47 vs. 26.58 ± 14.97, p < 0.001) were significantly higher in the combination therapy group. Clinical outcomes, including all-cause in-hospital mortality rate (26.2 vs. 33.3%, p = 0.358), were not significantly different between the groups. Multivariate analysis identified no significant association between FQ combination and all-cause in-hospital mortality. CONCLUSION: In patients with severe CAP, there were no differences in the clinical outcomes, including mortality, between the TZP and FQ combination therapy and TZP monotherapy. FQ combination was not significantly associated with in-hospital mortality.

Effect modification of dosing strategy (AUC or trough) on AKI associated with vancomycin in combination with piperacillin/tazobactam or cefepime and meropenem.

Piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) and vancomycin (VAN) are commonly used in combination for sepsis. Studies have shown an increased risk of acute kidney injury (AKI) with TZP and VAN compared to FEP or MEM. VAN guidelines recommend area under the curve (AUC) monitoring over trough (Tr) to minimize the risk of AKI. We investigated the association of AKI and MAKE-30 with the two VAN monitoring strategies when used in combination with TZP or FEP/MEM. Adult patients between 2015 and 2019 with VAN > 72 hours were included. Patients with AKI prior to or within 48 hours of VAN or baseline CrCl of ≤30 mL/min were excluded. Four cohorts were defined: FEP/MEM/Tr, FEP/MEM/AUC, TZP/Tr, and TZP/AUC. A Cox Proportional Hazard Model was used to model AKI as a function of the incidence rate of at-risk days, testing monitoring strategy as a treatment effect modification. Multivariable logistic regression was used to model MAKE-30. Overall incidence of AKI was 18.6%; FEP/MEM/Tr = 115 (14.6%), FEP/MEM/AUC = 52 (14.9%), TZP/Tr = 189 (26%), and TZP/AUC = 96 (17.1%) (P < 0.001). Both drug group [(TZP; P = 0.0085)] and monitoring strategy [(Tr; P = 0.0007)] were highly associated with the development of AKI; however, the effect was not modified with interaction term [(TZP*Tr); 0.085)]. The odds of developing MAKE-30 were not different between any group and FEP/MEM/AUC. The effect of VAN/TZP on the development of AKI was not modified by the VAN monitoring strategy (AUC vs trough). MAKE-30 outcomes were not different among the four cohorts.

Risk and Time-to-Onset of Acute Kidney Injury With Vancomycin Plus Piperacillin-tazobactam Combination: Analysis Using JADER.

BACKGROUND/AIM: Pharmacovigilance data and clinical studies have indicated a risk of acute kidney injury (AKI) associated with concomitant administration of vancomycin and piperacillin-tazobactam. However, no pharmacovigilance studies have evaluated time-to-onset and outcomes of AKI related to this combination. Therefore, this study used a pharmacovigilance database to investigate the incidence, time-to-onset, and outcomes of AKI in patients treated with intravenous vancomycin plus piperacillin-tazobactam or other antipseudomonal antibiotics. PATIENTS AND METHODS: From data in the Japanese Adverse Drug Event Report (JADER) database, we calculated the reporting odds ratios (RORs) and 95% confidence intervals (CIs), time-to-onset, and outcomes of AKI following intravenous administration of vancomycin plus piperacillin-tazobactam or other antipseudomonal antibiotics and with other vancomycin regimens, including monotherapy. RESULTS: The JADER database contained 4,471 reports of intravenous vancomycin treatment, including 517 reports of AKI. The adjusted RORs (95%CIs) of AKI in cases with co-administration of intravenous vancomycin and piperacillin-tazobactam was 2.58 (2.06-3.24). The median time-to-onset for AKI in vancomycin plus piperacillin-tazobactam was 6.0 (interquartile range=3.0-10.3). Weibull shape parameter analysis showed that the pattern of onset of AKI in vancomycin plus piperacillin-tazobactam represented a wear out failure, predicting an increasing hazard with time. For the outcome of AKI, there was no significant difference between all vancomycin regimen and the piperacillin-tazobactam combination groups. CONCLUSION: Concomitant use of intravenous vancomycin and piperacillin-tazobactam may increase the incidence of AKI but may not affect the outcome. This combination does not necessarily have to be avoided, but long-term use is not advisable.

Towards optimizing cefepime/tazobactam (WCK 4282) exposure to achieve efficacy against piperacillin/tazobactam-resistant ESBL infections: dose recommendations for various renal functions, including intermittent haemodialysis, in healthy individuals.

OBJECTIVES: WCK 4282 is a novel combination of cefepime 2 g and tazobactam 2 g being developed for the treatment of infections caused by piperacillin/tazobactam-resistant ESBL infections. The dosing regimen for cefepime/tazobactam needs to be optimized to generate adequate exposures to treat infections caused by ESBL-producing pathogens resistant to both cefepime and piperacillin/tazobactam. METHODS: We developed pharmacokinetic population models of cefepime and tazobactam to evaluate the optimal dose adjustments in patients, including those with augmented renal clearance as well as various degrees of renal impairment, and also for those on intermittent haemodialysis. Optimal doses for various degrees of renal function were identified by determining the PTA for a range of MICs. To cover ESBL-producing pathogens with an cefepime/tazobactam MIC of 16 mg/L, a dosing regimen of 2 g q8h infused over 1.5 h resulted in a combined PTA of 99% for the mean murine 1 log10-kill target for the cefepime/tazobactam combination. RESULTS: We found that to adjust for renal function, doses need to be reduced to 1 g q8h, 500 mg q8h and 500 mg q12h for patients with CLCR of 30-59, 15-29 and 8-14 mL/min (as well as patients with intermittent haemodialysis), respectively. In patients with high to augmented CLR (estimated CLCR 120-180 mL/min), a prolonged 4 h infusion of standard dose is required. CONCLUSIONS: The suggested dosing regimens will result in exposures of cefepime and tazobactam that would be adequate for infections caused by ESBL-producing pathogens with a cefepime/tazobactam MICs up to 16 mg/L.

Cálculo de los Días de Terapia Antimicrobiana (DOT) en Cuidados Intensivos Pediátricos: una propuesta de metodología basada en el sistema informático de dispensación de medicamentos / Days of Antimicrobial Therapy (DOT) calculation in Pediatric Intensive Care: a methodology proposal based on the electronic records from the pharmacy dispensation system

INTRODUCCIÓN: El método recomendado para la medición de consumo de antimicrobianos (AMB) en pediatría es el cálculo del indicador Días de Terapia estandarizado por ocupación (DOT-std). Sin embargo, en hospitales que no cuentan con fichas electrónicas, obtener el numerador de los días de terapia (DOT) requiere revisión directa de las indicaciones del paciente, dificultando su aplicabilidad. OBJETIVOS: Validar el sistema de registros electrónicos de dispensación de medicamentos desde farmacia como fuente para el cálculo de DOT y DOT-std en la Unidad de Cuidados Intensivos Pediátrica (UCIP). MATERIALES Y MÉTODOS: Se revisaron las prescripciones de AMB desde la ficha clínica (método manual) y se compararon con los registros de dispensación de AMB a la UCIP (método informático) obtenidos del sistema de medicamentos de farmacia. Se evaluó la concordancia entre los DOT obtenidos mediante el Coeficiente de Correlación Intraclase. RESULTADOS: Los AMB más utilizados fueron vancomicina, meropenem y piperacilina/tazobactam. En 9 de 12 AMB se encontró concordancia significativa entre ambos métodos. CONCLUSIONES: Tras un proceso de validación local, los registros del sistema informático de dispensación de medicamentos desde farmacia podrían utilizarse para el cálculo de DOT en pediatría en hospitales que no cuenten con una ficha electrónica que permita su cálculo directo.

BACKGROUND: The recommended indicator for measuring antimicrobial (AMB) consumption in pediatric patients is the Days of Therapy indicator (DOT), which is then standardized by hospital occupancy rates (DOT-std). However, in hospitals that do not have electronic health records, obtaining the DOT requires a direct review of each pharmacological indication, which is not feasible in the long term. AIMS: To validate electronic records from the pharmacy dispensation system as a source for calculating DOT and estimating DOT-std in a Pediatric Intensive Care Unit (PICU). METHODS: AMB prescriptions at the PICU of a university hospital were directly reviewed (manual method) and compared with AMB dispensation records (computer method) obtained from the hospital pharmacy system. The Intraclass Correlation Coefficient was used to evaluate the agreement between the DOT obtained by both methods. RESULTS: The most used AMB were vancomycin, meropenem, and piperacillin/tazobactam. A significant agreement between the DOT obtained by using manual and computer methods was found in 9 of 12 evaluated AMB. CONCLUSIONS: After a local validation process, the electronic records of the pharmacy drug dispensation system could be considered a valid source for calculating DOT in PICUs in hospitals where electronic health records with prescription data are not yet available.

Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial.

Importance: Cefepime/enmetazobactam is a novel ß-lactam/ß-lactamase inhibitor combination and a potential empirical therapy for resistant gram-negative infections. Objective: 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. Design, Setting, and Participants: 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. Interventions: 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). Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03687255.

Bloodstream Infections in Children With Cancer: Pathogen Distribution and Antimicrobial Susceptibility Patterns Over a 10-Year Period.

Bloodstream infections (BSIs) adversely affect clinical outcome in children with cancer. Over 1 decade, this retrospective cohort study describes pathogen distribution in BSIs and antimicrobial susceptibility against empirical antibiotics frequently prescribed in children with cancer. The antibiotic efficacy was evaluated through the determination of minimal inhibitory concentrations for piperacillin-tazobactam and meropenem and by disk diffusion for remaining antibiotics. From 2004 to 2013, 398 BSIs occurred in 196 children with cancer (median age: 5.4 y), resulting in 457 bacteria. Overall, 266 (58.2%) were Gram-positive, and 191 (41.8%) were Gram-negative with a significant Gram-positive increase over time (P=0.032). Coagulase-negative staphylococci (74, 16.2%), viridans group streptococci (67, 14.7%), Escherichia coli (52, 11.4%), and Staphylococcus aureus (39, 8.5%) were the most common pathogens. Susceptibility to piperacillin-tazobactam (95.9%, P=0.419) and meropenem (98.9%, P=0.752) was stable over time, and resistance was observed among viridans group streptococci against piperacillin-tazobactam (18%) and meropenem (7%) and among Enterobacterales against piperacillin-tazobactam (3%). Vancomycin showed 98% Gram-positive activity, gentamicin 82% Gram-negative activity and ampicillin, cefotaxime, and cefuroxime were active in 50%, 72%, and 69% of pathogens, respectively, and BSI-related mortality was 0%. In conclusion, over 1 decade, we report an increase in Gram-positive BSIs, and stable, low-resistance rates against currently recommended empirical antibiotics, piperacillin-tazobactam and meropenem.

Lowered Risk of Nephrotoxicity through Intervention against the Combined Use of Vancomycin and Tazobactam/Piperacillin: A Retrospective Cohort Study.

The combined use of vancomycin (VCM) and tazobactam/piperacillin (TAZ/PIPC) is a major risk factor for nephrotoxicity. We sought to evaluate interventions against the combined use of VCM and TAZ/PIPC. This retrospective cohort study involved patients who considered the combined use of VCM and TAZ/PIPC as a treatment. Patients that had either or both antimicrobials replaced were assigned to the intervention group, whereas those who were continued on combination therapy were assigned to the comparison group. The primary endpoint was the incidence of acute kidney injury (AKI). The survival rate of patients on day 30 was evaluated as the secondary endpoint. The comparison and intervention groups were composed of 65 and 68 patients, respectively, and the incidence rates of AKI were 44.6% and 17.6%, respectively. Cox proportional hazard analysis identified the intervention as the only independent factor against AKI development, with a hazard ratio of 0.282 (95% confidence interval [CI], 0.141 to 0.565). For the incidence of AKI of grade greater than 1, the hazard ratio was 0.114 (95% CI, 0.025 to 0.497). The survival rates on day 30 in the comparison and intervention groups were 92.3% and 91.2%, respectively, with a relative risk of 0.988 (95% CI, 0.892 to 1.094). The trough VCM concentration was not associated with the incidence of AKI in patients receiving the combination therapy. This study demonstrated that intervention against the combined use of VCM and TAZ/PIPC can lower the risk of nephrotoxicity. IMPORTANCE The combined use of vancomycin (VCM) and tazobactam/piperacillin (TAZ/PIPC) is a major risk factor for nephrotoxicity. We retrospectively evaluated interventions against the combined use of VCM and TAZ/PIPC. Patients for whom either or both antimicrobials were replaced were assigned to the intervention group (65 patients), whereas those who were continued on combination therapy were assigned to the comparison group (68 patients). The primary endpoint was the incidence of acute kidney injury (AKI). The incidence rates of AKI in the intervention and comparison groups were 44.6% and 17.6%, respectively. Cox proportional hazard analysis identified intervention as the only independent factor against AKI development, with a hazard ratio of 0.282 (95% confidence interval [CI], 0.141 to 0.565). In conclusion, this study demonstrated that intervention against the combined use of VCM and TAZ/PIPC can lower the risk of nephrotoxicity.

Prolapse Surgery: What Kind of Antibiotic Prophylaxis Is Necessary?

INTRODUCTION: The aim of this study was to assess whether antibiotic prophylaxis or therapy is sufficient for laparoscopic or vaginal prolapse surgery with mesh. METHODS: This is a single-center prospective study. The study was divided into 3 groups. Protocol A: metronidazole (15 mg/kg) and piperacillin-tazobactam (2 g) 1 h before surgery and, for postoperative treatment, gentamycin (160 mg) 1 h before surgery in a single dose. Metronidazole and piperacillin-tazobactam were administered until hospital discharge. Protocol B: gentamycin and piperacillin-tazobactam in the same manner as group A. Protocol C: clindamycin (600 mg) and gentamicin (160 mg) 1 h before surgery in a single dose. RESULTS: We included 87 consecutive patients who underwent prolapse surgery involving mesh prostheses: 57 by the laparoscopic approach and 30 by the vaginal route. Of these, 30 patients were included in protocol A, 30 in protocol B, and 27 in protocol C. There were no statistically significant differences among the 3 protocols regarding any postoperative complications, except for urinary tract infections that were more in the vaginal approach than in the laparoscopic route, in protocol A (p = 0.002). CONCLUSIONS: One-shot prophylaxis can be successfully used in prolapse surgery regardless of the surgical approach.

Evaluating and Mitigating Risk of Acute Kidney Injury with the Combination of Vancomycin and Piperacillin-Tazobactam in Children.

The antibiotic combination of vancomycin (VAN) and piperacillin-tazobactam (PTZ) has been associated with an increased risk of acute kidney injury (AKI) in both adult and pediatric patients. In this review, we highlight some of the limitations of existing pediatric studies evaluating the combination of VAN/PTZ, focusing on AKI risk in specific pediatric patient populations. We also review the variability in defining AKI in children and provide guidance to clinicians for use of prospective surveillance and stewardship in mitigating the risk of AKI in pediatric patients treated with combination of VAN/PTZ. Based on review of available pediatric studies, if the combination of VAN/PTZ is selected as an empirical antibiotic combination, it should be used in those at low risk for AKI and should be used with extreme caution in patients with additional nephrotoxic risks. Systems should be in place to monitor the use of VAN/PTZ and associated renal function in those receiving this antibiotic combination.

Continuous Infusion of Piperacillin/Tazobactam and Meropenem in ICU Patients Without Renal Dysfunction: Are Patients at Risk of Underexposure?

BACKGROUND AND OBJECTIVES: Morbidity and mortality from serious infections are common in intensive care units (ICUs). The appropriateness of the antibiotic treatment is essential to combat sepsis. We aimed to evaluate pharmacokinetic/pharmacodynamic target attainment of meropenem and piperacillin/tazobactam administered at standard total daily dose as continuous infusion in critically ill patients without renal dysfunction and to identify risk factors of non-pharmacokinetic/pharmacodynamic target attainment. RESULTS: We included 118 patients (149 concentrations), 47% had microorganism isolation. Minimum inhibitory concentration (MIC) [median (interquartile range, IQR) values in isolated pathogens were: meropenem: 0.05 (0.02-0.12) mg/l; piperacillin: 3 (1-4) mg/l]. Pharmacokinetic/pharmacodynamic target attainments (100%fCss≥1xMIC, 100%fCss≥4xMIC and 100%fCss ≥ 8xMIC, respectively) were: 100%, 96.15%, 96.15% (meropenem) and 95.56%, 91.11%, 62.22% (piperacillin) for actual MIC; 98.11%, 71.70%, 47.17% (meropenem, MIC 2 mg/l), 95.83%, 44.79%, 6.25% (piperacillin, MIC 8 mg/l), 83.33%, 6.25%, 1.04% (piperacillin, MIC 16 mg/l) for EUCAST breakpoint of Enterobacteriaceae spp. and Pseudomonas spp. Multivariable linear analysis identified creatinine clearance (CrCL) as a predictive factor of free antibiotic concentrations (fCss) of both therapies (meropenem [ß = - 0.01 (95% CI - 0.02 to - 0.0; p = 0.043)] and piperacillin [ß = - 0.01 (95% CI - 0.02 to 0.01, p < 0.001)]). Neurocritical status was associated with lower piperacillin fCss [ß = - 0.36 (95% CI - 0.61 to - 0.11; p = 0.005)]. CONCLUSION: Standard total daily dose of meropenem allowed achieving pharmacokinetic/pharmacodynamic target attainments in ICU patients without renal dysfunction. Higher doses of piperacillin/tazobactam would be needed to cover microorganisms with MIC > 8 mg/l. CrCL was the most powerful factor predictive of fCss in both therapies.

Third generation cephalosporins and piperacillin/tazobactam have distinct impacts on the microbiota of critically ill patients.

Effective implementation of antibiotic stewardship, especially in critical care, is limited by a lack of direct comparative investigations on how different antibiotics impact the microbiota and antibiotic resistance rates. We investigated the impact of two commonly used antibiotics, third-generation cephalosporins (3GC) and piperacillin/tazobactam (TZP) on the endotracheal, perineal and faecal microbiota of intensive care patients in Australia. Patients exposed to either 3GC, TZP, or no ß-lactams (control group) were sampled over time and 16S rRNA amplicon sequencing was performed to examine microbiota diversity and composition. While neither treatment significantly affected diversity, numerous changes to microbiota composition were associated with each treatment. The shifts in microbiota composition associated with 3GC exposure differed from those observed with TZP, consistent with previous reports in animal models. This included a significant increase in Enterobacteriaceae and Enterococcaceae abundance in endotracheal and perineal microbiota for those administered 3GC compared to the control group. Culture-based analyses did not identify any significant changes in the prevalence of specific pathogenic or antibiotic-resistant bacteria. Exposure to clinical antibiotics has previously been linked to reduced microbiota diversity and increased antimicrobial resistance, but our results indicate that these effects may not be immediately apparent after short-term real-world exposures.

Comparison of teicoplanin versus vancomycin in combination with piperacillin-tazobactam or meropenem for the risk of acute kidney injury.

We compared the rates of acute kidney injury (AKI), 7-day and 30-day mortalities, and resolution of AKI at discharge in combination therapies involving either teicoplanin (TEI) or vancomycin (VAN) with piperacillin-tazobactam (TZP) or meropenem (MER). In a single-center, retrospective cohort study, adult patients (>18 years) who had a baseline serum creatinine level within 24 h of admission and who received study antibiotics for at least 48 h were included. The primary outcome was AKI incidence after therapy per RIFLE criteria. Multivariate logistic regression and propensity score match analyses were employed for statistical comparisons. Data from 379 patients were evaluated. In multivariate analysis (MVA) of the whole cohort, TZP-VAN combination was associated with significantly higher rate of AKI as compared with TZP-TEI (aOR: 3.21, 95% CI, 1.36-7.57; p = 0.008) or with MER-VAN (aOR: 2.28, 95% CI, 1.008-5.18; p = 0.048). In MVA of the matched cohorts, TZP-VAN as compared with TZP-TEI and MER-VAN was associated with 3.96 times (95% CI, 1.48-10.63, p = 0.006) and 3.11 times (95% CI, 1.12-8.62; p = 0.028) increased risk of AKI, respectively. No differences between MER-TEI and MER-VAN combinations were detected. Seven-day and 30-day mortalities and resolution rates of AKI were similar in all comparisons. Teicoplanin can be preferred instead of VAN when combination with TZP is used particularly for patients with high AKI risk.

Acute Cholecystitis, Sepsis, and Disseminated Intravascular Coagulation Caused by Edwardsiella tarda in an Elderly Woman.

Edwardsiella tarda is a gram-negative bacillus associated with gastrointestinal diseases. It is rarely responsible for sepsis; however, the fatality is very high. Only two cases of E. tarda infections in patients over 90 years of age have been reported; these are not cases of sepsis associated with acute cholecystitis. We report a case of acute cholecystitis, sepsis, and disseminated intravascular coagulation (DIC) caused by E. tarda in a super-elderly woman aged over 90 years. There could be a possibility for recovery from sepsis and DIC if antimicrobial treatment responsiveness is ensured in the super-elderly.