Are Antibiotics of Value for a Whipple Procedure?

Pancreatoduodenectomy is a complex surgical procedure with a high rate of morbidity, of which surgical-site infections (SSIs) make a large portion. Reduction of SSI rates is critical to decrease hospital lengths of stay, readmissions, delays in adjuvant therapies, and financial health care burden. Current clinical guidelines recommend the administration of cefoxitin as surgical prophylaxis prior to pancreatoduodenectomy. In April 2023, a randomized controlled trial was published in JAMA which showed that piperacillin-tazobactam as perioperative surgical prophylaxis prior to pancreatoduodenectomy decreased 30 day SSI rates (primary outcome), clinically relevant postoperative pancreatic fistula, postoperative sepsis, and Clostridium difficile infection rates.

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.

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.

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.

[Potential Nephrotoxicity of Combination of Vancomycin and Piperacillin-Tazobactam: Recommendations from the AG ABS of the DGPI supported by experts of the GPN]. / Potentielle Nephrotoxizität der Kombinationstherapie von Vancomycin und Piperacillin-Tazobactam: Empfehlungen der AG ABS der DGPI unter Beteiligung von Experten der GPN.

The combination of vancomycin and piperacillin/tazobactam (V+P/T) is used for empirical antibiotic treatment of severe infections, especially in immunocompromised patients and those colonized with multidrug-resistant bacteria. Nephrotoxicity is a frequently observed adverse effect of vancomycin. Its risk can be reduced by therapeutic drug monitoring and adjusted dosing. Piperacillin/tazobactam (P/T) rarely causes interstitial nephritis. The results of retrospective cohort studies in children predominantly show a low, clinically irrelevant, additive nephrotoxicity (defined as an increase in creatinine in the serum) of both substances. Due to the limitations of the existing publications, the ABS working group of the DGPI and experts of the GPN do not recommend against the use of P/T plus vancomycin. Preclinical studies and a prospective study with adult patients, which evaluated different renal function tests as well as clinical outcomes, do not support previous findings of additive nephrotoxicity. Time-restricted use of V+P/T can minimize exposure and the potential risk of nephrotoxicity. Local guidelines, developed in collaboration with the antibiotic stewardship team, should define the indications for empirical and targeted use of P/T and V+P/T. When using combination therapy with V+P/T, kidney function should be monitored through clinical parameters (volume status, balancing, blood pressure) as well as additional laboratory tests such as serum creatinine and cystatin C.

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.

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.

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.

A NSQIP-based randomized clinical trial evaluating choice of prophylactic antibiotics for pancreaticoduodenectomy.

Surgical site infection after pancreaticoduodenectomy is often caused by pathogens resistant to standard prophylactic antibiotics, suggesting that broad-spectrum antibiotics may be more effective prophylactic agents. This article describes the rationale and methodology underlying a multicenter randomized trial evaluating piperacillin-tazobactam compared with cefoxitin for surgical site infection prevention following pancreaticoduodenectomy. As the first US randomized surgical trial to utilize a clinical registry for data collection, this study serves as proof of concept for registry-based clinical trials.

Pharmacokinetics and Pharmacodynamics of High-Dose Piperacillin-Tazobactam in Obese Patients.

BACKGROUND AND OBJECTIVE: Standard piperacillin-tazobactam (P-T) dosing may be suboptimal in obesity, but high-dose regimens have not been studied. We prospectively evaluated the pharmacokinetics and pharmacodynamics of standard- and high-dose P-T in obese adult inpatients. METHODS: Those receiving standard-dose P-T with BMI ≥ 30 kg/m2 weighing 105-139 kg or ≥ 140 kg were given up to 6.75 g or 9 g every 6 h, respectively. Patients were monitored closely for safety. Elimination phase blood samples were drawn for 28 patients on standard and high doses to calculate the pharmacokinetic values using a one-compartment model. The likelihood of pharmacodynamic target attainment (100% fT > 16/4 mg/L) on various P-T regimens was calculated using each patient's own pharmacokinetic values. RESULTS: Piperacillin and tazobactam half-lives ranged from 0.5-10.6 to 0.9-15.0 h, while volumes of distribution ranged from 13.6-54.8 to 11.5-60.1 L, respectively. Predicted dose requirements for target attainment ranged from 2.25 g every 6 h in hemodialysis patients to a 27 g/24-h continuous infusion in a patient with a short P-T half-life. An amount of 4.5 g every 6 h would have met the target for only 1/12 (8%) patients with creatinine clearance ≥ 80 mL/min and 13/28 (46%) for all enrolled patients. One patient (3%) experienced an adverse event deemed probably related to high-dose P-T. CONCLUSION: Some patients required high P-T doses for target attainment, but dosing requirements were highly variable. Doses up to 6.75 g or 9 g every 6 h may be tolerable; however, studies are needed to see if high dosing, prolonged infusions, or real-time therapeutic drug monitoring improves outcomes in obese patients. CLINICAL TRIAL REGISTRATION (CLINICALTRIALS.GOV): NCT01923363.

Meropenem versus piperacillin/tazobactam for febrile neutropenia in pediatric patients: efficacy of piperacillin/tazobactam as a 1-h drip infusion four times a day.

Although survival of children with hematological diseases and cancer has increased dramatically, febrile neutropenia (FN) is a frequently observed complication and is sometimes life-threatening in pediatric cancer patients. A prospective, randomized study was performed to clarify the usefulness of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) for pediatric patients with FN. Ninety-nine patients with 394 episodes were randomly assigned to receive MEPM or PIPC/TAZ. MEPM was administered at 120 mg/kg/day as a 1-h drip infusion 3 times a day. On the other hand, PIPC/TAZ was administered at 360 mg/kg/day as a 1-h drip infusion 4 times a day. MEPM was effective in 69.5% of the 200 episodes, and PIPC/TAZ was effective in 77.2% of the 193 episodes. Compared with our previous study of MEPM 120 mg/kg/day as a 1-h drip infusion 3 times a day versus PIPC/TAZ 337.5 mg/kg/day as a 1-h drip infusion 3 times a day, the success rate of the MEPM group was not different. However, the success rate of the PIPC/TAZ group was higher than in the previous study (p = 0.001). In particular, the success rate in patients ≥ 15 years of age was improved in the PIPC/TAZ group of the present study compared with the previous study (p = 0.005).

Analysis of blood stream infections, antibiograms and clinical outcomes in haematological patients with febrile neutropenia: data from a tertiary care haematology institute in India.

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

[Antibiotic stewardship - recent developments]. / Aktuelle Entwicklungen im Bereich Antibiotic Stewardship.

Both in hospitals and outpatient settings, fewer fluoroquinolones have been prescribed in Germany in recent years. The consumption of cephalosporins also decreased somewhat in favor of penicillin derivatives. The aminoglycosides, which have only rarely been prescribed, can now be used again as a suitable alternative - but only parenterally - due to their relatively favorable activity and low resistance rates among typical urinary tract infection pathogens. In acute severe infection such as sepsis, addition, e. g. of tobramycin, to a suitable betalactam of a single dose has been discussed as a useful option, but the evidence for such a recommendation is weak. There is little news about the rational use of antibiotics in hematology-oncology patients. In the case of fever and neutropenia, the initial empirical regimens of choice remain piperacillin-tazobactam or a pseudomonas-active carbapenem as monotherapy. These betalactams should be given with extended infusion times, e. g. over 4 hours. Linezolid should be considered as a reserve drug and not be used empirically, but only in targeted therapy. With regard to an alleged penicillin allergy, the risk of true allergic reactions can be differentiated by careful taking of the history; on that ground patient subgroups can be defined that may be re-exposed without further allergological examinations.

Reducing acute kidney injury in pediatric oncology patients: An improvement project targeting nephrotoxic medications.

BACKGROUND: Nephrotoxic medication exposure and associated acute kidney injury (AKI) occur commonly in hospitalized children. At Cincinnati Children's Hospital Medical Center, there is an initiative to increase awareness of nephrotoxic medication exposure and decrease rates of associated AKI. The oncology service utilized these data in a quality improvement project to drive reductions in AKI rates. METHODS: Three interventions were implemented targeted at decreasing the incidence of nephrotoxic exposure, as well as protecting against the conversion of exposures to AKI episodes. Cefepime replaced piperacillin-tazobactam for febrile neutropenia, vancomycin stewardship limited empiric courses to 72 hours, and nephroprotection for intravenous contrast administration was standardized for defined high-risk patients. RESULTS: The study cohort comprised 42 520 noncritically ill patient days admitted to the oncology service at Cincinnati Children's Hospital Medical Center. A total of 273 unique patients were exposed to combination nephrotoxic medications, leading to 111 AKI episodes. The rate of nephrotoxic medication exposure within the oncology service decreased by 49% from 16.08 to 8.17 per 1000 patient days. Episodes of AKI associated with nephrotoxic medication exposure decreased by 45% from 3.48 to 1.92 per 1000 patient days. CONCLUSION: Interventions to decrease AKI took a three-pronged approach. Collectively, this approach was proven successful with significant reductions in both rates of nephrotoxic medication exposure and associated AKI among hospitalized oncology patients.

[Combinatorial Vancomycin and Piperacillin/Tazobactam Results in Elevated Vancomycin Trough Concentration and Acute Kidney Injury: A Case Report].

In the hospital, antibiotics are widely used to treat infections. We report a case of acute kidney injury (AKI) caused by an antibiotic drug combination. A 30-year-old Japanese male presented with lung metastases, pneumothorax, empyema, and methicillin-resistant Staphylococcus aureus (MRSA) infection. The patient received a combination of vancomycin and piperacillin/tazobactam, which resulted in elevated vancomycin trough concentration and subsequently in AKI. Renal function was restored upon vancomycin and piperacillin/tazobactam cessation. Though this patient had AKI most likely due to the combined use of two agents as has been reported in many cases, vancomycin trough concentration showed an unexpected abnormal increase when halting vancomycin treatment. This is the first report indicating a drug-drug interaction between vancomycin and piperacillin/tazobactam with unexpected abnormal vancomycin trough concentration, leading to AKI, additionally we think that there was a situation that he stressed against the kidney by a history of medications caused renal dysfunction and co-administration. We suggest that when using vancomycin in combination with piperacillin/tazobactam, the trough concentration of vancomycin must be confirmed simultaneously with renal function and evaluation, and that the combination of these two drugs should be minimized.

Prospective evaluating the appropriate use of piperacillin /tazobactam in cardiac center of a tertiary care hospital.

BACKGROUND: The appropriate use of Piperacillin/Tazobactam (Pip/Taz), including the correct dose, escalating and or de-escalation according to the microbiological culture is essential to reduce the antibiotic resistance. Resistant to antimicrobials in a major global problem and contributes significantly to morbidity, mortality and cost of care. Guidelines exists to ensure appropriate use of Pip/Taz. Antibiotics Stewardship guidelines (https://apps.who.int/iris/bitstream/handle/10665/329404/9789241515481-eng.pdf) provides a detailed recommendation with regards to initiation, monitoring and escalation and de-escalation based on final culture results. Appling such guidelines ensures a more proper utilization of the empiric uses of antibiotics used in the hospital-based setting. Use of Pip/Taz in cases of suspected infection postoperatively is common practice in the cardiac surgery ward where this study was conducted. METHODS: This was a prospective cohort study involving all patients who were admitted to the cardiac surgery unit of a tertiary care center. All patient prescribed at least 1 day of Pip/Taz as an empirical therapy were included and prospectively observed. We aimed to evaluate the use of Pip/Taz and its appropriateness based on Antibiotics Stewardship guidelines (ASG). Any deviation from the guidelines in initiation, escalation, de-escalation based on culture and sensitivity results was considered inappropriate use. Four patients died (1.3%) early as result of complications for surgery but included in the analysis. The study was conducted from October 2017 to October 2018. RESULTS: Of the 300 patients who received Pip/Taz Cultures were done in 250 patients (83%). The overall appropriate use of Pip/Taz was seen in 166 patients (55.3%). CONCLUSION: The empirical use of Pip/Taz in the surgical cardiac unit was largely inappropriate and not entirely driven by the culture test results. Interventions are needed to optimize the use of Pip/Taz including appropriate culture and sensitivity driven use and timely de-escalation or de-escalation when indicated. This will prevent emergence of resistance and reduce the patient toxicity and financial costs.

Antimicrobial utilization and antimicrobial resistance in patients with haematological malignancies in Japan: a multi-centre cross-sectional study.

BACKGROUND: Infection is a major complication for patients with haematological malignancies. It is important to better understand the use of antimicrobial agents and antibiotic resistance for appropriate treatment and prevention of drug resistance. However, very few multi-centre analyses have focused on the use of antimicrobial agents and antibiotic resistance have been carried out in Japan. This study aimed to describe the characteristics of the use of antimicrobial agents and antibiotic resistance in patients with haematological malignancies. METHODS: We conducted a cross-sectional study using administrative claims data and antimicrobial susceptibility data in Japan. We included patients diagnosed with haematological malignancies, who were hospitalized in a haematology ward between 1 April 2015 and 30 September 2017 in 37 hospitals. Descriptive statistics were used to summarize patient characteristics, antimicrobial utilization, bacterial infections, and antibiotic resistance. RESULTS: In total, 8064 patients were included. Non-Hodgkin lymphoma (50.0%) was the most common malignancy. The broad-spectrum antibiotics displayed a following antimicrobial use density (AUD): cefepime (156.7), carbapenems (104.8), and piperacillin/tazobactam (28.4). In particular, patients with lymphoid leukaemia, myeloid leukaemia, or myelodysplastic syndromes presented a higher AUD than those with Hodgkin lymphoma, non-Hodgkin lymphoma, or multiple myeloma. The most frequent bacterial species in our study cohort was Escherichia coli (9.4%), and this trend was also observed in blood specimens. Fluoroquinolone-resistant E. coli (3.6%) was the most frequently observed antibiotic-resistant strain, while other antibiotic-resistant strains were rare. CONCLUSIONS: Broad-spectrum antibiotics were common in patients with haematological malignancies in Japan; however, antibiotic-resistant bacteria including carbapenem-resistant or multidrug-resistant bacteria were infrequent. Our results provide nationwide, cross-sectional insight into the use of antimicrobial agents, prevalence of bacteria, and antibiotic resistance, demonstrating differences in antimicrobial utilization among different haematological diseases.

The pharmacokinetics of meropenem and piperacillin-tazobactam during sustained low efficiency haemodiafiltration (SLED-HDF).

OBJECTIVE: We analysed the pharmacokinetics of meropenem and piperacillin-tazobactam in patients undergoing a standardised session of sustained low efficiency haemodiafiltration (SLED-HDF) to inform the dosing of these drugs in an acute setting. PARTICIPANTS: Six stable patients with end-stage kidney disease. METHODS: An open-label pilot pharmacokinetic study of meropenem and piperacillin-tazobactam. SLED-HDF was undertaken for 4 h. Plasma drug concentrations were measured pre- and post-filter and in the effluent at multiple time points. The pharmacokinetic data was analysed using non-compartmental methods. The fraction of time that individual plasma concentration profiles were predicted to remain above the MIC break-points for commonly isolated gram-negative pathogens during a prolonged SLED-HDF session was assessed using two targets; fT > MIC (fraction of time above the MIC) and the more aggressive fT > 4 × MIC (fraction of time above 4 × MIC). RESULTS: Meropenem total and SLED-HDF clearance ranged from 141 to 180 mL/min and 126-205 mL/min, respectively. Piperacillin total and SLED-HDF clearance values ranged from 131 to 252 mL/min and 135-162 mL/min, respectively. Our results suggest that prolonged SLED-HDF (12 h) will only maintain a sufficient meropenem and piperacillin-tazobactam plasma concentration to achieve a target of fT > MIC for gram-negative pathogens (MIC 2 mg/L-meropenem, 8 mg/L-piperacillin-tazobactam) for less than 40% of the time. Plasma concentrations would be inadequate to achieve the more aggressive target of 100 % fT > 4xMIC target recommended for critically unwell patients. CONCLUSIONS: The pharmacokinetic data obtained from this pilot study demonstrate significant quantities of meropenem and piperacillin are removed during a SLED-HDF session. This may lead to subtherapeutic concentrations of piperacillin and meropenem over the duration of HDF session. TRIAL REGISTRATION: Australasian Clinical Trials Registry Network (ACTRN12616000078459).