Piperacillin-tazobactam Research Articles

Visible mucosal changes of pseudomembranous colitis in a sigmoid colostomy.

We visited an 82-year-old man who was receiving palliative home care for acute myelogenous leukemia. He had a sigmoid colostomy because of rectal cancer. Two weeks previously, he had received piperacillin–tazobactam for 7 days for cellulitis. We noticed stomal swelling, with irregularly

Evaluation of the safety of piperacillin-tazobactam extended infusion in pediatric cystic fibrosis patients.

Patients with cystic fibrosis (CF)may be treated with piperacillin-tazobactam (PZT)for acute pulmonary exacerbations. Extending the infusion of PZT is one strategy to increase efficacy. Direct comparison, with respect to the incidence of acute kidney injury (AKI),between these two strategies has not been evaluated in pediatric patients with CF. The primary objective of this study was to compare the incidence of AKI in pediatric CF patients receiving extended infusion (EI) PZT versus traditional infusion (TI). This IRB-approved, retrospective analysis included patients ages 30 days to 18 years that received PZT for at least 48 h between January 1, 2008, and January 1, 2020. PZT was infused over 30 min(TI group) or 4 h(EI group). Two hundred and four patients were included (TI: 109, EI: 95). Median age was 8 years (4-13) and 7 years (3-12) in the TI and EI groups (p = 0.15). The groups did not differ significantly in their baseline characteristics. There were 12 (11%) AKIs in the TI group and 8 (8.4%) in the EI group (p = 0.53). There was one occurrence of serum sickness in the TI group and none in the EI group. The incidence of thrombocytopenia was similar between the two groups. Median treatment duration was 8 days (5-11) and 9 days (5-13) for the TI and EI groups, respectively (p = 0.24). There was no significant increase in AKI in pediatric patients with CF receiving PZT by EI compared withTI. EI may be utilized to optimize the pharmacokinetics of PZT in pediatric CF patients.

First publication of endemic channels as part of a pediatric Antimicrobial Stewardship Program: when to turn on the alarms? Recommendations of a pediatric ASP program

BackgroundPediatric Antimicrobial Stewardship Programs (ASP) consider DOT a fundamental measure to quantify the impact of ASP. Novel strategies have been described, but no endemic channels (EC) have been reported to compare antibiotic use within historical patterns. This report describes the process of constructing an EC and analyzing its interpretation.MethodsThis was a descriptive study of the construction, implementation, and analysis of EC. The median and quartile method, as well as the geometric mean (GM) and confidence interval (CI) methods using DOT for the last 4 years were used. ECs have also been elaborated on in critical services (PICU).ResultsGM and CI method seem to be more sensitive in identifying changes in antimicrobial use. Ceftriaxone increased its use starting in December 2021, reaching the warning zone in March 2022 in relation to increased cases of bacterial and complicated pneumonia. Piperacillin–tazobactam showed an important increase in PICU during the first 8 months of 2021, reaching the alert zone until August 2021; thereafter, its use decreased, and this variation was related to a modification in the presentation of complicated appendicitis during the COVID 19 pandemic restrictions. The use of ampicillin-sulbactam has increased since January 2022 because of a change in local guidelines regarding its use in appendicitis and peritonitis. The changes identified in each EC allowed ASP to take different conducts.ConclusionEC allowed us to construct a new tool to measure ASP impact, internal comparison of antibiotic use facilitated taking timely interventions. EC could be useful for all pediatric and adult ASP.

In vitro resistance pattern of Citrobacter infections: A retrospective study

Background: Citrobacter infections are associated with a high mortality rate of about 33-48% if infected patients develop bacteremia. This is partly due to high prevalence of intrinsic resistance, extended spectrum beta lactamases and inducible chromosomal Amp C beta lactamases in Citrobacter spp. thus limiting the therapeutic options. We undertook this study to throw light on the current scenario of infection with this organism. Materials and methods: This retrospective study was conducted over a period of 1 year in Microbiology laboratory of a tertiary care teaching hospital in Eastern part of India. From various samples, 146 clinically significant Citrobacter spp. identified by standard biochemical tests and susceptibility testing performed by Kirby Bauer’s disc diffusion method were included in this study. Results: Majority of patients age ranged of 41-50 year. The highest number (70/146, 47.9%) of Citrobacter spp. was isolated from pus and wound swabs followed by urine (46/146, 31.5%) and out of these, 51.4% strains were of Citrobacter koseri whereas 48.6% were of Citrobacter fruendii. Of Citrobacter isolates 36.6% were ESBL producers. They showed 54.1%, 37.9%, 47.1%, 39.8% and 58.5% resistance to imipenem, netilmycin, piperacillin tazobactam, minocycline and levofloxacin respectively. We also found 9.6% and 28.4% strains of Citrobacter spp. being resistant to colistin and tigecycline respectively. Conclusion: Citrobacter spp. showed high degree of resistance to carbapenem and there were colistin resistance strains as well. This study reiterates the emerging resistance in these supposedly low virulence microbes which may pose future challenge in infection control activities.

1988. Piperacillin-tazobactam plus Ceftriaxone for Enterococcus faecalis endocarditis: A Single Center Experience

Abstract Background Enterococcus faecalis is a leading cause of Infective Endocarditis (IE). IE guidelines recommend combination of penicillin (PCN) or ampicillin (AMP) with ceftriaxone (CTX) in susceptible strains. OPAT allows for antibiotic continuation at home; however outpatient AMP is limited due to frequent dosing and instability. Piperacillin-tazobactam (PTZ) has similar but not identical activity against penicillin binding proteins (PBP) compared to AMP and PCN, suggesting that PTZ may be a substitute in OPAT. This study compares outcomes in those with E. faecalis IE discharged with either PTZ or PCN with CTX. Results of primary outcomes including death at 90 days and readmission at 90 days for those discharged on either PTZ or PCN in combination with CTX for E. faecalis endocarditis Results of non infectious complications and changes in antibiotic therapy in both groups post discharge Methods This single center retrospective study took place from 2016 - 2020. Adults > 18 years with AMP susceptible E. faecalis IE diagnosed using Duke’s criteria and blood or tissue cultures were included, with cultures confirming PCN susceptibility. Primary endpoint was failure of therapy at 90 days, defined as death due to any cause or infection relapse. Secondary outcomes were duration of antibiotics, change in regimen and non-infectious complications. Results Overall, 34 patients were identified, 17 in each group. Average age was 60–80 years, majority having a high Charleston comorbidity index. One did not have available AMP susceptibility but was PCN susceptible. 19 were managed surgically (65% PTZ group, 47% PCN group). Average total antibiotic course was 8.2 and 7.3 weeks in PTZ and PCN groups, with average OPAT course being 4.5 and 4.4 weeks. Primary endpoint was met in 18% patients in the PTZ group and 24% in the PCN group. Of the PCN group, 1 was admitted 4 months later due to an E. faecalis device infection, outside of primary endpoint. Nearly 80% completed antibiotic therapy with 29% in the PTZ group and 35% in the PCN group readmitted for non-infectious complications, including metabolic imbalances, stroke, volume overload and gastro-intestinal bleed. Hyperkalemia was seen in the PCN group with 3 patients requiring readmission. Seizures were not reported with combined PCN and ceftriaxone. Conclusion Similar outcomes were seen using either PTZ or PCN with CTX for treatment of enterococcal IE. Discharging patients on PCN is not always a feasible option. In these instances, PTZ could be considered as an alternative OPAT agent despite dissimilar mechanism of action compared to AMP and PCN. Disclosures All Authors: No reported disclosures.

Infectious complications of non-surgical biliary tract manipulation in paediatric patients. Role of antibiotic prophylaxis

BackgroundInfections related to non-surgical manipulation of the biliary tract (NSMBT) are common events despite periprocedural antibiotic prophylaxis (PAP). Since June 2017, our local protocol has indicated a 24-h regimen of intravenous piperacillin–tazobactam for this purpose. ObjectiveWe aimed to describe the incidence and characteristics of NSMBT-related paediatric infections, define risk factors for their development, and analyse adherence to our PAP protocol. Materials and methodsEpidemiological, clinical, and microbiological data were collected in consecutive NSMBT procedures performed in paediatric patients (<18 years) in our centre (2010–2019). Results113 procedures in 37 patients, median age 4 years (IQR 1–8), were included. Main underlying diseases were biliary atresia (32%) and cancer (14%). Sixty-eight percent had undergone liver transplant and 70% hepaticojejunostomy. In 44 procedures (39%), the intervention was performed during the course of infection and previously prescribed antibiotic treatment was maintained. In the other 69, PAP was specifically indicated for NSMBT; antibiotic adequacy increased from 35% to 100% after June 2017. In total, 32 NSMBT-related infections (28%) occurred, mainly in the first 24h post-procedure (72%); no deaths happened. Causative pathogens were Gram-negative rods (64%), Gram-positive cocci (28%), and Candida spp. (8%). Main related risk factors were hepaticojejunostomy, biliary obstruction, and liver transplant. ConclusionsNSMBT in children entails a significant infection risk, even under antibiotic prophylaxis, being hepaticojejunostomy the main risk factor. Infectious complications mainly occurred immediately after the procedure. After establishing a PAP protocol, 100% of interventions received appropriate prophylaxis, decreasing antibiotic exposure time and potentially, the length of hospital stay.

Fatal Case of Autochthonous Strongyloides stercoralis Hyperinfection in an Immunosuppressed Calabrian Patient

Strongyloides stercoralis is an intestinal nematode that can induce disseminated infection in immunocompromised patients. It is most commonly acquired in tropical and subtropical countries; however, foci of the infection have also been reported in temperate geographic areas. In non-endemic areas, the diagnosis of an S. stercoralis infection is challenging due to the variety of clinical symptoms. Herein, we report the case of a patient, born and raised in the Calabria region of Southern Italy, who presented with melanoma and S. stercoralis hyperinfection, which is characterized by dyspnea, productive cough, inappetence, marked asthenia, weight loss, and Klebsiella pneumoniae bacteremia. He worked as a farmer and never traveled to another country known to be endemic for S. stercoralis. Despite the prompt identification of the parasite with sputum microscopy and the initiation of therapy with ivermectin and piperacillin–tazobactam, the patient later died. This case underscores the continued risk for S. stercoralis infection even in geographic areas that were previously considered non-endemic for the nematode and indicates that the geographic distribution of S. stercoralis may be expanding in Italy.

Piperacillin/tazobactam and risk of acute kidney injury in adults hospitalized with infection without vancomycin: a multi-centre real-world data analysis

There is uncertainty about whether piperacillin/tazobactam (PT) increases the risk of acute kidney injury (AKI) in patients without concomitant use of vancomycin. This study compared the risk of hospital-acquired AKI (HA-AKI) among adults treated with PT or antipseudomonal β-lactams (meropenem, ceftazidime) without concomitant use of vancomycin. This real-world study analysed the data from China Renal Data System and assessed the risk of HA-AKI in adults hospitalized with infection after exposure to PT, meropenem or ceftazidime in the absence of concomitant vancomycin. The primary outcome was any stage of HA-AKI according to the Kidney Disease Improving Global Outcomes guidelines. A multi-variable Cox regression model and different propensity score (PS) matching models were used. Among the 29,441 adults [mean (standard deviation) age 62.44 (16.84) years; 17,980 females (61.1%)] included in this study, 14,721 (50%) used PT, 9081 (31%) used meropenem and 5639 (19%) used ceftazidime. During a median follow-up period of 8 days, 2601 (8.8%) develped HA-AKI. The use of PT was not associated with significantly higher risk of HA-AKI compared with meropenem [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.97-1.19], ceftazidime (aHR 1.09, 95% CI 0.92-1.30) or both agents (aHR 1.07, 95% CI 0.97-1.17) after adjusting for confounders. Results were consistent in stratified analyses, PS matching using logistic regression or random forest methods to generate a PS, and in an analysis restricting outcomes to AKI stage 2-3. Without concomitant use of vancomycin, the risk of AKI following PT therapy is comparable with that of meropenem or ceftazidime among adults hospitalized with infection.

Detection of Beta-Lactamases (ESBL and MBL) Producing Gram-Negative Pathogens in National Public Health Laboratory of Nepal.

Background Bacterial resistance to antibiotics has increased in recent years. Resistance to β-lactams in Gram-negative bacteria has been reported to be associated with extended spectrum beta-lactamases and metallo-beta-lactamases. This study was aimed at determining the distribution and antibiotic susceptibility patterns of Gram-negative pathogens producing extended spectrum beta lactamases and metallo-beta lactamases. Method and Methodology. This cross-sectional study was conducted at the National Public Health Laboratory during a period of six months. All clinical specimens were obtained and processed for the identification of Gram-negative pathogens by culture, morphological, and biochemical tests. Antibiotic susceptibility testing of the isolates was performed by the Kirby Bauer disc diffusion and the isolates were tested for ESBL and MBL by the combined disk method. Results Out of 4266 clinical specimens, 197 (4.6%) were found to be Gram-negative bacterial isolates. 47 (23.9%) isolates were ESBL producers. The most predominant organisms were Escherichia coli (53%), Klebsiella pneumonia (23%), and Pseudomonas spp. (13%). 16 (8.2%) were positive for MBL producers, and 6(3.1%) were both ESBL and MBL producers. The MBL activity was seen in E. coli (38%), followed by Pseudomonas spp. (31%), and K. pneumoniae (19%). The ESBL producers showed a higher degree of sensitivity towards imipenem and amikacin, followed by piperacillin tazobactam. MBL producers showed sensitivity towards amikacin only. Conclusion The prevalence of ESBL and MBL producing Gram-negative bacteria was found to be high in bacterial infections in Nepal. Routine laboratory testing for ESBL and MBL is needed in order to optimize antibiotic management and reduce the risk of spread of infections caused by ESBL and MBL producers.

Prevalence of S. aureus and/or MRSA from seafood products from Indian seafood products

Compared to the clinical sector, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the food sector is relatively low. However, their presence in seafood is a significant public health concern. In India, fish and fishery products are maximally manually handled compared to other food products. In this study, 498 fish samples were collected under various conditions (fresh, chilled or dressed) and representatives from their surroundings. These samples were screened for the prevalence of Staphylococcus aureus, determining its antimicrobial resistance, MRSA and genetic profile. It is observed that 15.0% and 3.0% of the total samples were screened positive for S. aureus and MRSA, respectively. The S. aureus strain MRSARF-10 showed higher resistance to linezolid, co-trimoxazole, cefoxitin, ofloxacin, gentamicin, rifampicin, ampicillin/sulbactam and Piperacillin–tazobactam. This MRSA, spa type t021 and SCCmec type V strain isolated from dried ribbon fish (Family Trachipteridae) carried virulence factors for exoenzymes such as aureolysin, serine, toxin genes and a novel MLST ST 243, as revealed from its draft-genome sequence. This highly pathogenic, multidrug-resistant and virulent S. aureus novel strain is circulating in the environment with chances of spreading among the seafood workers and the environment. It is further suggested that Good Hygienic Practices recommended by World Health Organization need to be followed during the different stages of seafood processing to provide pathogen-free fish and fishery products to the consumers.

Impact of Respiratory Viral Panel Results on Piperacillin-Tazobactam Use in a Medical Intensive Care Unit: A Single-Center Retrospective Study

PurposeIn critically ill patients with acute respiratory infection, antibiotic stewardship can be challenging given the acuity and complexities of such patients, and the associated high mortality. This study determined the impact of respiratory viral panel (RVP) testing on piperacillin-tazobactam (PT) use in patients admitted to a medical intensive care unit (MICU). MethodsThis retrospective chart review used data from adults admitted to a MICU between January 1, 2017, and January 31, 2018, and with findings from at least one RVP available. FindingsRVP testing was performed on samples from 90 patients admitted to the MICU. RVP was positive in 41% (37/90) of patients, and 53.3% (48/90) received PT during their MICU stay. PT was discontinued in 25.5% (23/90) of patients, 16.2% (6/37) with a positive RVP and 32.1% (17/53) with a negative RVP. Overall mortality was significantly lower in the positive RVP group versus the negative RVP group (odds ratio = 0.28; P = 0.001). In a multivariate Cox proportional hazards model (adjusted for acute kidney injury and culture positivity), the risk for PT discontinuation was significantly less in patients with a positive RVP compared to those with a negative RVP (primary outcome). Overall mortality rate and median length of stay were significantly lower in patients with a positive RVP compared to those in patients with a negative RVP (secondary outcomes). The 30-day hospital readmission rate and the risk for AKI were not significantly different between those with positive versus negative RVP. ImplicationsReasons for these observations are currently unclear, but deserve further exploration in future studies. It is hypothesized that the treating providers were concerned about the presence of concurrent bacterial infections along with the diagnosed viral infections given that the patients were critically ill. This suggests that RVP results did not impact PT-prescribing practices in the MICU, and thus that the routine use of RVP solely for guiding antimicrobial-stewardship practices may not be effective.

Intra-abdominal abscesses: Microbiological epidemiology and empirical antibiotherapy

PurposeData on the microbiological epidemiology of Intra-Abdominal Abscesses (IAAs) are very scarce. We aimed to study the microbiological epidemiology of these infections in order to optimize empirical antibiotic therapy. Patients and methodsBetween January 2015 and December 2020, we retrospectively analyzed all IAAs files in our hospital. Clinical and microbiological data such as antibiotic susceptibilities were collected. ResultsWe studied 243 IAA cases. All in all, 139 (57.2%) IAAs were healthcare-associated and 201 (82.7%) were drained. The highest risk situations for IAAs were appendicitis (n = 69) and diverticulitis (n = 37). Out of the 163 microbiologically documented infections, 136 (81.9%) were polymicrobial. Enterobacterales (n = 192, 36.1%), Enterococcus sp. (n = 84, 17.6%) and anaerobes (n = 66, 16.1%) were the most frequently identified bacteria. Gram-negative bacteria were susceptible to amoxicillin–acid clavulanic, piperacillin–tazobactam, cefotaxime, meropenem in 55.2%, 84.9%, 77.6% and 99.5% of cases, respectively. Concerning Gram-positive bacteria, the susceptibility rate was 81.8% for amoxicillin–clavulanic acid, piperacillin–tazobactam and meropenem, and decreased to 63.4% for cefotaxime. ConclusionThis study highlights the polymicrobial profile of IAAs and their low susceptibility to amoxicillin and clavulanic acid. The piperacillin–tazobactam association remained the most appropriate empirical antibiotic therapy.

Prevalence of Antibiotic Resistant Bacteria among the Clinical Samples from Different Hospitals of Peshawar, Pakistan

Background: Majority of the microorganisms are responsible for causing diseases which can be fatal if left untreated. In Pakistan this might be very critical because of the misuse and/or improper use of antibiotics. Objective: The current study was designed to point out the challenges of antibiotic resistance in Peshawar Pakistan. Methods: A total of 100 samples, 25 each from blood, pus, skin, urine were collected from four different hospitals of Peshawar, Pakistan. The samples were grown on culture media after collection. Results: Out 100 samples, 46 samples showed growth on culture medium. Four main isolates namely Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. S. aureus and E. coli were found in all tested samples blood, pus, skin, urine. P. aeruginosa was found in pus and K. pneumonia in urine only. The identified strains were subjected to sensitivity testing against 7 different antibiotics i.e., ampicillin, piperacillin tazobactam, doxycycline, aztreonam, ciprofloxacin, levofloxacin and teicoplanin. Conclusion: All of the bacterial species were found resistant against the applied antibiotics except aztreonam. Keywords: Prevalence, antibiotics sensitivity, S. aureus, E. coli, K. pneumonia, P. aeruginosa

Piperacillin-Tazobactam Plus Vancomycin-Associated Acute Kidney Injury in Adults: Can Teicoplanin or Other Antipseudomonal Beta-Lactams Be Remedies?

Numerous observational studies and meta-analyses have suggested that combination therapy consisting of piperacillin–tazobactam (TZP) and vancomycin (VAN) augments acute kidney injury (AKI) risk when compared to viable alternatives, such as cefepime–vancomycin (FEP–VAN) and meropenem–VAN. However, the exact pathophysiological mechanisms of this phenomenon are still unclear. One major limitation of the existing studies is the utilization of serum creatinine to quantify AKI since serum creatinine is not a sufficiently sensitive and specific biomarker to truly define the causal relationship between TZP–VAN exposure and nephrotoxicity. Even so, some preventive measures can be taken to reduce the risk of AKI when TZP–VAN is preferred. These measures include limiting the administration of TZP–VAN to 72 h, choosing FEP–VAN in place of TZP–VAN in appropriate cases, monitoring the VAN area under the curve level rather than the VAN trough level, avoiding exposure to other nephrotoxic agents, and minimizing the prescription of TZP–VAN for patients with a high risk of AKI. More data are needed to comment on the beneficial impact of the extended-infusion regimen of TZP on nephrotoxicity. Additionally, TZP and teicoplanin can be reasonable alternatives to TZP–VAN for the purpose of lowering AKI risk. However, the data are scarce to advocate this practice convincingly.

Evaluate the drug resistance pattern in various antibiotics with biofilm-producing capability of Klebsiella pneumoniae

Aim: Objective of study was to evaluate the drug resistance pattern in various antibiotics with the biofilm-producing capability of Klebsiella pneumoniae. Methods: Klebsiella pneumoniae was isolated for identification from total of 83 OPD and IPD patients by analysing colony morphology, microscopic examination, and performed biochemical testing. Antibiotics susceptibility Tests and biofilm-producing capacity was done by the Kirby-Bauer disk diffusion method and adherence quantitative assays. Chi-square test was used and P &lt; 0.05 was measured as statistically significant. Results: Out of 83 isolates, 47 (56.6%) were Biofilm Producer and 36 (43.4%) were non-biofilm producers by tissue culture method, and tube method 62.7% and 37.3% respectively. Among biofilm producer and non-biofilm producer isolates, Klebsiella pneumoniae had the most Resistant to Ceftazidime (100%) &amp; (61.0%), followed by Ceftriaxone (56.0%) &amp; (95.7%) respectively. The association between biofilm and antibiotic resistance was checked to be statistically significant for aminoglycosides, fluoroquinolones, Cephalosporin’s, Imipenem, Meropenem, Amoxyclav, and Piperacillin Tazobactam. No resistance was observed against Colistin and Polymyxin B. Conclusion: The strain Klebsiella pneumoniae isolated from different samples showed drug resistance to all broad-spectrum antibiotics whereas there is no drug resistance was found with narrow-spectrum drugs. This study supports the use of narrow-spectrum antibiotics for most of infections.

Intravenous route for folate supplementation in a patient with celiac disease treated by pemetrexed-based chemotherapy for non-small-cell lung cancer.

Oral folic acid supplementation is essential for patients treated with pemetrexed, to prevent the risk of severe hematologic toxicity. In case of intestinal absorption disorder, no recommendations exist for intravenous folic acid supplementation. We describe a 74-year-old patient with multimetastatic non-small-cell lung adenocarcinoma, receiving first-line chemotherapy with carboplatin AUC5, pemetrexed 500 mg/m2 and pembrolizumab 200 mg intravenously every 3 weeks. The patient presented neglected celiac disease, resulting in malabsorption syndrome with iron and folic acid deficiency. The question was how to administer folic acid supplementation during the pemetrexed-based chemotherapy. Intravenous injection of 200 mg levoleucovorin on day 1 of cycle 1 of pemetrexed-based chemotherapy was administered and well tolerated. During the second cycle, the levoleucovorin perfusion was not renewed by omission. The patient was hospitalized for 7 days because of febrile aplasia. Piperacillin-tazobactam was started, and then switched to amoxicillin-clavulanate plus ciprofloxacin. After this episode of post-chemotherapy febrile aplasia, it was decided to systematically supplement the patient with intravenous levoleucovorin, with blood folate concentration monitoring at each cycle. At 16 months after start of treatment, the patient was in complete remission, indicating that the immune-chemotherapy was effective, with no further febrile neutropenia. This case report highlights intravenous levoleucovorin supplementation as an alternative to oral folic acid if needed during pemetrexed-antifolate-based chemotherapy.

Association of vancomycin plus piperacillin–tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study

PurposeAlthough dozens of studies have associated vancomycin + piperacillin–tazobactam with increased acute kidney injury (AKI) risk, it is unclear whether the association represents true injury or a pseudotoxicity characterized by isolated effects on creatinine secretion. We tested this hypothesis by contrasting changes in creatinine concentration after antibiotic initiation with changes in cystatin C concentration, a kidney biomarker unaffected by tubular secretion.MethodsWe included patients enrolled in the Molecular Epidemiology of SepsiS in the ICU (MESSI) prospective cohort who were treated for ≥ 48 h with vancomycin + piperacillin–tazobactam or vancomycin + cefepime. Kidney function biomarkers [creatinine, cystatin C, and blood urea nitrogen (BUN)] were measured before antibiotic treatment and at day two after initiation. Creatinine-defined AKI and dialysis were examined through day-14, and mortality through day-30. Inverse probability of treatment weighting was used to adjust for confounding. Multiple imputation was used to impute missing baseline covariates.ResultsThe study included 739 patients (vancomycin + piperacillin–tazobactam n = 297, vancomycin + cefepime n = 442), of whom 192 had cystatin C measurements. Vancomycin + piperacillin–tazobactam was associated with a higher percentage increase of creatinine at day-two 8.04% (95% CI 1.21, 15.34) and higher incidence of creatinine-defined AKI: rate ratio (RR) 1.34 (95% CI 1.01, 1.78). In contrast, vancomycin + piperacillin–tazobactam was not associated with change in alternative biomarkers: cystatin C: − 5.63% (95% CI − 18.19, 8.86); BUN: − 4.51% (95% CI − 12.83, 4.59); or clinical outcomes: dialysis: RR 0.63 (95% CI 0.31, 1.29); mortality: RR 1.05 (95%CI 0.79, 1.41).ConclusionsVancomycin + piperacillin–tazobactam was associated with creatinine-defined AKI, but not changes in alternative kidney biomarkers, dialysis, or mortality, supporting the hypothesis that vancomycin + piperacillin–tazobactam effects on creatinine represent pseudotoxicity.

Diagnosis and Treatment-Spectrum Beta-Lactamase and Multidrug Resistance Bacterial

Multidrug-resistant (MDR) is a condition resistant to at least one type of antibiotic from 3 classes of antibiotics. Extended-Spectrum Beta Lactamases are globular proteins that consist of alpha-helices and beta-pleated sheets. β-lactamase hydrolyze broad-spectrum cephalosporin with oxyimino side chain. ESBL hydrolyze antibiotics group penicillin, cephalosporin first, second, third, fourth generation, and monobactam aztreonam. Multidrug resistance occurs through two mechanisms, bacteria accumulate multiple genes encoding resistance to one antibiotic, and due to increased expression of genes encoding multidrug effluent pump, enzymatic inactivation and target structure change. Multidrug-resistant (MDR) caused by extended-spectrum resistance beta-lactamase (ESBL) can be detected by phenotyping and genotyping methods. Treatment for MDR ESBLs other than carbapenems can be β-lactam/β-lactamase inhibitor combinations (BLBLIs), namely piperacillin/tazobactam (PZT).

Risk of Neutropenia in Adults Treated with Piperacillin-Tazobactam or Cefazolin: A Retrospective Cohort Study.

Neutropenia is an adverse effect associated with the use of several antibiotics, including piperacillin-tazobactam (P/T). Previous findings have suggested that the risk of neutropenia in children is significantly higher with P/T than with ticarcillin-clavulanate. To compare the risk of neutropenia associated with P/T and with cefazolin in an adult population and to describe the characteristics of neutropenia episodes observed. This descriptive retrospective study involved patients aged 18 years or older who received a minimum of 10 days of treatment with P/T or cefazolin between January 2009 and December 2013. Patients who experienced neutropenia (absolute neutrophil count < 1.5 × 109/L) were compared, using univariate and multivariate logistic regression models, between those who received P/T and those who received cefazolin. A total of 207 patients were included (104 who received P/T and 103 who received cefazolin). Ten episodes of neutropenia were observed, 5 with each antibiotic (4.8% and 4.9%, respectively; odds ratio 0.99, 95% confidence interval 0.278-3.527). The mean cumulative dose of piperacillin was 290.4 g among patients who experienced neutropenia and 247.0 g among all patients treated with P/T, and the mean treatment duration was 24.0 days and 21.0 days, respectively. The average time before the onset of neutropenia was slightly longer with P/T than with cefazolin (22.0 versus 17.2 days, p = 0.38). Although these results require confirmation in a larger clinical trial (to lessen possible attribution bias), the risk of neutropenia appeared to be similar between P/T and cefazolin.

Expert clinical pharmacological advice may make an antimicrobial TDM program for emerging candidates more clinically useful in tailoring therapy of critically ill patients

BackgroundTherapeutic drug monitoring (TDM) may represent an invaluable tool for optimizing antimicrobial therapy in septic patients, but extensive use is burdened by barriers. The aim of this study was to assess the impact of a newly established expert clinical pharmacological advice (ECPA) program in improving the clinical usefulness of an already existing TDM program for emerging candidates in tailoring antimicrobial therapy among critically ill patients.MethodsThis retrospective observational study included an organizational phase (OP) and an assessment phase (AP). During the OP (January–June 2021), specific actions were organized by MD clinical pharmacologists together with bioanalytical experts, clinical engineers, and ICU clinicians. During the AP (July–December 2021), the impact of these actions in optimizing antimicrobial treatment of the critically ill patients was assessed. Four indicators of performance of the TDM-guided real-time ECPA program were identified [total TDM-guided ECPAs July–December 2021/total TDM results July–December 2020; total ECPA dosing adjustments/total delivered ECPAs both at first assessment and overall; and turnaround time (TAT) of ECPAs, defined as optimal (< 12 h), quasi-optimal (12–24 h), acceptable (24–48 h), suboptimal (> 48 h)].ResultsThe OP allowed to implement new organizational procedures, to create a dedicated pathway in the intranet system, to offer educational webinars on clinical pharmacology of antimicrobials, and to establish a multidisciplinary team at the morning bedside ICU meeting. In the AP, a total of 640 ECPAs were provided for optimizing 261 courses of antimicrobial therapy in 166 critically ill patients. ECPAs concerned mainly piperacillin–tazobactam (41.8%) and meropenem (24.9%), and also other antimicrobials had ≥ 10 ECPAs (ceftazidime, ciprofloxacin, fluconazole, ganciclovir, levofloxacin, and linezolid). Overall, the pre–post-increase in TDM activity was of 13.3-fold. TDM-guided dosing adjustments were recommended at first assessment in 61.7% of ECPAs (10.7% increases and 51.0% decreases), and overall in 45.0% of ECPAs (10.0% increases and 35.0% decreases). The overall median TAT was optimal (7.7 h) and that of each single agent was always optimal or quasi-optimal.ConclusionsMultidisciplinary approach and timely expert interpretation of TDM results by MD Clinical Pharmacologists could represent cornerstones in improving the cost-effectiveness of an antimicrobial TDM program for emerging TDM candidates.