Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.

BACKGROUND: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.

The clinical efficacy of cefoperazone-sulbactam versus piperacillin-tazobactam in the treatment of severe community-acquired pneumonia.

The objective was to compare the clinical efficacy of cefoperazone-sulbactam with piperacillin-tazobactam in the treatment of severe community-acquired pneumonia (SCAP). The retrospective study was conducted from March 1, 2018 to May 30, 2019. Clinical outcomes were compared for patients who received either cefoperazone-sulbactam or piperacillin-tazobactam in the treatment of SCAP. A total of 815 SCAP patients were enrolled. Among them, 343 received cefoperazone-sulbactam, and 472 received piperacillin-tazobactam. Patients who received cefoperazone-sulbactam presented with higher Charlson Comorbidity Index scores. (6.20 ± 2.77 vs 5.72 ± 2.61; P = .009). The clinical cure rates and effectiveness for patients receiving cefoperazone-sulbactam and piperacillin-tazobactam were 84.2% versus 80.3% (P = .367) and 85.4% versus 83.3% (P = .258), respectively. In addition, the overall mortality rate of the cefoperazone-sulbactam group was 16% (n = 55), which was also comparable to the piperacillin-tazobactam group (17.8%, n = 84, P = .572). The primary clinical outcomes for patients receiving cefoperazone-sulbactam were superior compared to those receiving piperacillin-tazobactam after adjusting disease severity status. The clinical efficacy of cefoperazone-sulbactam in the treatment of adult patients with SCAP is comparable to that of piperacillin-tazobactam. After adjusting for disease severity, cefoperazone-sulbactam tended to be superior to piperacillin-tazobactam.

Outcomes of surgical treatment of diverticular abscesses after failure of antibiotic therapy.

Management of diverticular abscess (DA) is still controversial. Antibiotic therapy is indicated in abscesses ≤ 4 cm, while percutaneous drainage/surgery in abscesses > 4 cm. The study aims to assess the role of antibiotics and surgical treatments in patients affected by DA. We retrospectively analyzed 100 consecutive patients with DA between 2013 and 2020, with a minimum follow-up of 12 months. They were divided into two groups depending on abscess size ≤ or > 4 cm (group 1 and group 2, respectively). All patients were initially treated with intravenous antibiotics. Surgery was considered in patients with generalized peritonitis at admission or after the failure of antibiotic therapy. The primary endpoint was to compare recurrence rates for antibiotics and surgery. The secondary endpoint was to assess the failure rate of each antibiotic regimen resulting in surgery. In group 1, 31 (72.1%) patients were conservatively treated and 12 (27.9%) underwent surgery. In group 2, percentages were respectively 50.9% (29 patients) and 49.1% (28 patients). We observed 4 recurrences in group 1 and 6 in group 2. Recurrence required surgery in 3 patients/group. We administered amoxicillin-clavulanic acid to 74 patients, piperacillin-tazobactam to 14 patients and ciprofloxacin + metronidazole to 12 patients. All patients referred to surgery had been previously treated with amoxicillin-Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation clavulanic acid. No percutaneous drainage was performed in a hundred consecutive patients. Surgical treatment was associated with a lower risk of recurrence in patients with abscess > 4 cm, compared to antibiotics. Amoxicillin-clavulanic acid was associated with a higher therapeutic failure rate than piperacillin-tazobactam/ciprofloxacin + metronidazole.

Piperacillin-tazobactam dosing in anuric acute kidney injury patients receiving continuous renal replacement therapy.

INTRODUCTION: To determine appropriate dosing of piperacillin-tazobactam in critically ill patients receiving continuous renal replacement therapy (CRRT). METHODS: The databases of PubMed, Embase, and ScienceDirect were searched. We used the Medical Subject Headings of "piperacillin-tazobactam," "CRRT," and "pharmacokinetics" or related terms or synonym to identify the studies for reviews. A one-compartment pharmacokinetic model was conducted to predict piperacillin levels for the initial 48 h of therapy. The pharmacodynamic target was 50% of free drug level above the minimum inhibitory concentration (MIC) and 4 times of the MIC. The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. RESULTS: Our simulation study reveals that the dosing regimen of piperacillin-tazobactam 12 g/day is appropriate for treating Pseudomonal infection with KDIGO recommended effluent rate of 25-35 mL/kg/h. The MIC values of each setting were an important factor to design piperacillin-tazobactam dosing regimens. CONCLUSION: The Monte Carlo simulation can be a useful tool to evaluate drug dosing in critically ill acute kidney injury patients receiving CRRT when limited pharmacokinetic data are a concern. Clinical validation of these results is needed.

Association between emergency department sepsis order set design and delay to second dose piperacillin-tazobactam administration.

BACKGROUND: Delay to first antibiotic dose in patients with sepsis has been associated with increased mortality. Second dose antibiotic delay has also been linked to worsened patient outcomes. Optimal methods to decrease second dose delay are currently unclear. The primary objective of this study was to evaluate the association between updating an emergency department (ED) sepsis order set design from one-time doses to scheduled antibiotic frequencies and delay to administration of second piperacillin-tazobactam dose. METHODS: This retrospective cohort study was conducted at eleven hospitals in a large, integrated health system and included adult patients treated in the ED with at least one dose of piperacillin-tazobactam ordered through an ED sepsis order set over a two year period. Patients were excluded if they received less than two doses of piperacillin-tazobactam. Midway through the study period, the enterprise-wide ED sepsis order set was updated to include scheduled antibiotic frequencies. Two patient cohorts receiving piperacillin-tazobactam were compared: those in the year before the order set update and those in the year post-update. The primary outcome was major delay, defined as an administration delay >25% of the recommended dosing interval, which was evaluated with multivariable logistic regression and interrupted time series analysis. RESULTS: 3219 patients were included: 1222 in the pre-update group and 1997 in the post-update group. The proportion of patients who experienced major second dose delay was significantly lower in the post-update group (32.7% vs 25.6%, p < 0.01; adjusted OR 0.64, 95% CI 0.52 to 0.78). No between-group difference was detected in the slope of monthly major delay frequency, but there was a significant level change (post-update change -10%, 95% CI -17.9% to -1.9%). CONCLUSIONS: Including scheduled antibiotic frequencies in ED sepsis order sets is a pragmatic mechanism to decrease delays in second antibiotic doses.

Implementation of an Electronic Alert to Improve Timeliness of Second Dose Antibiotics for Patients With Suspected Serious Infections in the Emergency Department: A Quasi-Randomized Controlled Trial.

STUDY OBJECTIVE: Delays in the second dose of antibiotics in the emergency department (ED) are associated with increased morbidity and mortality in patients with serious infections. We analyzed the influence of clinical decision support to prevent delays in second doses of broad-spectrum antibiotics in the ED. METHODS: We allocated adult patients who received cefepime or piperacillin/tazobactam in 9 EDs within an integrated health care system to an electronic alert that reminded ED clinicians to reorder antibiotics at the appropriate interval vs usual care. The primary outcome was a median delay in antibiotic administration. Secondary outcomes were rates of intensive care unit (ICU) admission, hospital mortality, and hospital length of stay. We included a post hoc secondary outcome of frequency of major delay (>25% of expected interval for second antibiotic dose). RESULTS: A total of 1,113 ED patients treated with cefepime or piperacillin/tazobactam were enrolled in the study, of whom 420 remained under ED care when their second dose was due and were included in the final analysis. The clinical decision support tool was associated with reduced antibiotic delays (median difference 35 minutes, 95% confidence interval [CI], 5 to 65). There were no differences in ICU transfers, inpatient mortality, or hospital length of stay. The clinical decision support tool was associated with decreased probability of major delay (absolute risk reduction 13%, 95% CI, 6 to 20). CONCLUSIONS: The implementation of a clinical decision support alert reminding clinicians to reorder second doses of antibiotics was associated with a reduction in the length and frequency of antibiotic delays in the ED. There was no effect on the rates of ICU transfers, inpatient mortality, or hospital length of stay.

Cefepime, not Piperacillin/Tazobactam use, for empirical treatment of bloodstream infections caused by Enterobacter spp.: Results from a population pharmacokinetic/pharmacodynamic analysis.

OBJECTIVE: There is a paucity of published data to evaluate the efficacy and safety of imipenem, cefepime and piperacillin/tazobactam dosing regimens against bloodstream infections caused by Klebsiella aerogenes (BSIs-Kae) and Enterobacter cloacae complex (BSIs-Ecc) in patients with various degrees of renal function. METHODS: Pathogens were isolated from China's blood bacterial resistant investigation network. The dosing regimens of imipenem, cefepime and piperacillin were simulated with intermittent infusion and extended infusion. Monte Carlo simulation was performed to calculate the probability of target attainment and a cumulative fraction of response (CFR) against BSIs-Kae/Ecc. RESULTS: In total, 203 BSIs-Kae, and 785 BSIs-Ecc were isolated from the surveillance network. Imipenem showed the highest in vitro activity against BSIs-Kae/Ecc, followed by cefepime (85%) and piperacillin/tazobactam (70-80%). The MIC90 values of imipenem, cefepime and piperacillin/tazobactam aginst BSIs-Kae and BSIs-Ecc were 1/1 mg/L, 16/16 mg/L, and 64/128 mg/L, respectively. The simulation results showed imipenem achieved the highest CFRs in patients with normal or decreased renal function, with values of 91-99%, followed by FEP (88-96%), without risk of excessive dosing. However, the intermittent and extended dosing regimens of piperacillin/tazobactam were unlikely to provide adequate exposure for empirical management of BSIs-Kae/Ecc (CFRs, 50-80%), regardless of renal function. Besides, the traditional intermittent piperacillin/tazobactam dosing regimens were highly likely to contribute to suboptimal therapeutic exposure when MIC was close to clinical breakpoints. CONCLUSIONS: Cefepime, not piperacillin/tazobactam, can be a reasonable carbapenem-sparing option in empirically treating BSIs-Kae/Ecc.

Efficacy and Safety Analysis of Piperacillin Tazobactam in Combination With High Frequency Chest Wall Oscillation in Patients With COPD Coupled With Pneumonia.

Context: Chronic obstructive pulmonary disease (COPD) is a common, chronic inflammatory disease of the airway, and acute exacerbation of COPD (AE-COPD) refers to the manifestations of inflammation in the lungs that appear within a short period of time. Some patients contract pneumonia, and they can be prone to recurrent attacks of AE-COPD combined with pneumonia. The efficacy of conventional treatments isn't generally satisfactory. Objective: The study intended to investigate the effectiveness and safety of piperacillin tazobactam in combination with the use of high-frequency chest-wall oscillation (HFCWO) to produce expectoration for the treatment of pneumonia in patients with AE-COPD and to provide a reference for clinical treatment. Design: The research team designed a prospective, randomized controlled trial. Setting: The study took place at the Sixth Hospital of Wuhan of the Affiliated Hospital of Jianghan University in Wuhan, China. Participants: Participants were 92 patients who had been admitted to the hospital between January 2020 and November 2021 with AE-COPD combined with pneumonia. Intervention: Using the random number table method, the research team randomly assigned participants to one of two groups, an intervention group or a control group, each with 46 participants. The control group received conventional treatment with oxygen, antibiotics, antispasmodics, antiasthmatic drugs, and phlegmolytic drugs as well as HFCWO for sputum removal. In addition to those treatments, the intervention group received piperacillin tazobactam. Outcome measures: The research team measured the treatment's efficacy at one day postintervention. At baseline and at one day postintervention, the study also measured pulmonary function, laboratory indexes, and blood-gas-analysis indexes. In addition, the research team identified the time of disappearance of clinical symptoms, including the disappearance of cough, sputum, dyspnea, and pulmonary rales; calculated the length of hospital stay, and evaluated the treatment's safety. Results: Postintervention, the intervention group's clinical efficacy was significantly higher than that of the control group (P < .05), and the group's cough, coughing of sputum, dyspnea, disappearance time of pulmonary rales, and hospitalization times were all significantly lower than those in the control group (P < .05). The FEV1, FVC, FEV1% and FEV1/FVC levels were higher in both groups postintervention than at baseline and were significantly higher in the intervention group than in the control group (P < .05). Postintervention, the levels of IL-2, IL-10, TNF-α, CRP and PCT were lower in both groups than at baseline, and the intervention group's levels were significantly lower than those in the control group (P < .05). Postintervention, the PaCO2 level decreased and PaO2 and SaO2 levels increased in both groups compared to baseline; the intervention group's PaCO2 level was lower and PaO2 and SaO2 levels were higher than those in the control group. During the treatment, no adverse reactions occurred in the control group, and one participant had a decreased appetite in the intervention group; the incidence of adverse reactions in that group was 2.17% (1/46). That participant received no special treatment, and the condition improved after stopping the drug. Conclusion: Piperacillin tazobactam combined with HFCWO for sputum evacuation can effectively treat patients with pneumonia in acute exacerbation of COPD, with high safety. The treatment is worthy of clinical application.

Antibiotic Stewardship in Treatment of Osteoarticular Infections Based on Local Epidemiology and Bacterial Growth Times.

Incubation for 14 days is recommended for the culture of microorganisms from osteoarticular infections (OAI), but there are no recommendations for postoperative antibiotic stewardship concerning empirical antimicrobial therapy (EAT), while prolonging broad-spectrum EAT results in adverse effects. The aim of this study was to describe the local OAI epidemiology with consideration of bacterial growth times to determine which antibiotic stewardship intervention should be implemented in cases of negative culture after 2 days of incubation. We performed a 1-year, single-center, noninterventional cohort study at the Pitié-Salpêtrière hospital OAI reference center. Samples were taken as part of the local standard of care protocol for adult patients who underwent surgery for OAI (native or device related) and received EAT (i.e., piperacillin-tazobactam plus daptomycin [PTD]) following surgery. The time to culture positivity was monitored daily. Overall, 147 patients were recruited, accounting for 151 episodes of OAI, including 112 device-related infections. Microbiological cultures were positive in 144 cases, including 42% polymicrobial infections. Overall, a definitive microbiological result was obtained within 48 h in 118 cases (78%) and within 5 days in 130 cases (86%). After 5 days, only Gram-positive bacteria were recovered, especially Cutibacterium acnes, Staphylococcus spp., and Streptococcus spp. Overall, 90% of culture-positive OAI were correctly treated with the locally established EAT. EAT guidance for OAI was in agreement with our local epidemiology. Our results supported antibiotic stewardship intervention consisting of stopping piperacillin-tazobactam treatment at day 5 in cases of negative culture. IMPORTANCE Osteoarticular infections (OAI) remain challenging to diagnose and to treat. One of the issues concerns postoperative empirical antimicrobial therapy (EAT), which is usually a combination of broad-spectrum antibiotics. This EAT is maintained up to 2 weeks, until the availability of the microbiological results (identification and drug susceptibility testing of the microorganisms responsible for the OAI). Our results provide new data that will help to improve OAI management, especially EAT. Indeed, we have shown that antibiotic stewardship intervention consisting of stopping the antibiotic targeting Gram-negative bacteria included in the EAT could be implemented in cases where culture is negative after 5 days of incubation. The benefits of such an antibiotic stewardship plan include improved patient outcomes, reduced adverse events (including Clostridioides difficile infection), improvement in rates of susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care.

Activity of newest generation ß-lactam/ß-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa.

Multidrug resistant (MDR) P. aeruginosa accounts for 35% of all P. aeruginosa isolated from respiratory samples of patients with cystic fibrosis (CF). The usefulness of ß-lactam antibiotics for treating CF, such as carbapenems and later generation cephalosporins, is limited by the development of antibacterial resistance. A proven treatment approach is the combination of a ß-lactam antibiotic with a ß-lactamase inhibitor. New ß-lactam/ß-lactamase inhibitor combinations are available, but data are lacking regarding the susceptibility of MDR CF-associated P. aeruginosa (CFPA) to these new combination therapies. In this study we determined MIC values for three new combinations; imipenem-relebactam (I-R), ceftazidime-avibactam (CZA), and ceftolozane-tazobactam (C/T) against MDR CFPA (n = 20). The MIC90 of I-R, CZA, and C/T was 64/4, 32/4, and 16/8 (all µg/mL), respectively. The susceptibility of isolates to imipenem was not significantly improved with the addition of relebactam (p = 0.68). However, susceptibility to ceftazidime was significantly improved with the addition of avibactam (p < 0.01), and the susceptibility to C/T was improved compared to piperacillin/tazobactam (p < 0.05) These data provide in vitro evidence that I-R may not be any more effective than imipenem monotherapy against MDR CFPA. The pattern of susceptibility observed for CZA and C/T in the current study was similar to data previously reported for non-CF-associated MDR P. aeruginosa.

Simultaneous infusion of two incompatible antibiotics: Impact of the choice of infusion device and concomitant simulated fluid volume support on the particulate load and the drug mass flow rates.

Vancomycin and piperacillin/tazobactam are known to be incompatible. The objectives of the present study were to evaluate the impact of their simultaneous infusion on mass flow rates and particulate load and identify preventive strategies. We assessed both static conditions and a reproduction of an infusion line used in a hospital's critical care unit. A high-performance liquid chromatography/UV diode array system and static and dynamic laser diffraction particle counters were used. The mass flow rates were primarily influenced by the choice of the infusion device and the presence of simulated fluid volume support. Drug incompatibility also appeared to affect vancomycin's mass flow rate, and the dynamic particulate load increased during flow rate changes - especially in the infusion set with a large common volume line and no concomitant simulated fluid volume support. Only discontinuation of the piperacillin/tazobactam infusion was associated with a higher particulate load in the infusion set with a large common volume line and no concomitant simulated fluid volume support. A low common volume line and the use of simulated fluid volume support were associated with smaller fluctuations in the mass flow rate. The clinical risk associated with a higher particulate load must now be assessed.

Antibiotic therapy does not alter mitochondrial bioenergetics in lymphocytes of patients with septic shock - A prospective cohort study.

Antibiotics may trigger alterations in mitochondrial function, which has been explored in cells culture, and in animal model of sepsis. This study sought to evaluate whether antibiotic therapy affects mitochondrial bioenergetics in a 68-patients clinical study. We studied mitochondrial respiratory rates at two time points: the first day of antibiotic administration and three days after. The Δbasal, ΔCI, ΔCII respiration, and ΔBCE respiratory rates were not different between patients administered with polymyxin, vancomycin, amoxicillin-clavulanate, and azithromycin compared to those who were not administered. Specific beta-lactams are associated with specific modifications in mitochondrial respiratory endpoints - patients who used meropenem had higher delta C2 values compared to those who did not (p = 0.03). Patients who used piperacillin-tazobactam had lower delta C1 (p = 0.03) values than those who did not, but higher delta C2 values (p = 0.02). These mitochondrial metabolic signatures in isolated lymphocytes challenges the proposed effects of antibiotics in mitochondrial bioenergetics of cell cultures, but at current status have an uncertain clinical significance.

Population pharmacokinetics of piperacillin in critically ill children including those undergoing continuous kidney replacement therapy.

OBJECTIVES: Despite that piperacillin-tazobactam combination is commonly used in critically ill children, increasing evidence suggests that the current dosing schedules are not optimal for these patients. The aim of this work is to develop a population pharmacokinetic model for piperacillin to evaluate the efficacy of standard dosing in children with and without continuous kidney replacement therapy (CKRT) and to propose alternative dosing schemes maximizing target attainment. METHODS: Four hundred twenty-nine piperacillin concentrations measured in different matrices, obtained from 32 critically ill children (19 without CKRT, 13 with CKRT) receiving 100 mg/kg of piperacillin/tazobactam every 8 hours (increased to 12 hours after the fourth dose) were modelled simultaneously using the population approach with NONMEM 7.4. The percentage of patients with 90% fT > MIC and target attainment (percentage of dosing interval above MIC) were estimated for different intermittent and continuous infusions in the studied population. RESULTS: Piperacillin pharmacokinetic was best described with a two-compartment model. Renal, nonrenal, and hemofilter clearances were found to be influenced by the glomerular filtration rate, height (renal clearance), weight (nonrenal clearance), and filter surface (hemofilter clearance). Only seven (37%) children without CKRT and seven (54%) with CKRT achieved 90% fT > MIC with the current dosing schedule. Of the alternative regimens evaluated, a 24-hour continuous infusion of 200 mg/kg (CKRT) and 300 mg/kg (no CKRT) provided 100% fT > MIC (percent of time free drug remains above the minimum inhibitory concentration) (≤16 mg/L) and target attainments ≥90% across all evaluated MICs. DISCUSSION: In children with and without CKRT, standard dosing failed to provide an adequate systemic exposure, while prolonged and continuous infusions showed an improved efficacy.

Pharmacokinetics of piperacillin and tazobactam in critically Ill patients treated with continuous kidney replacement therapy: A mini-review and population pharmacokinetic analysis.

WHAT IS KNOWN AND OBJECTIVE: Timely and appropriate dosing of antibiotics is essential for the treatment of bacterial sepsis. Critically ill patients treated with continuous kidney replacement therapy (CKRT) often have physiologic derangements that affect pharmacokinetics (PK) of antibiotics and dosing may be challenging. We sought to aggregate previously published piperacillin and tazobactam (pip-tazo) pharmacokinetic data in critically ill patients undergoing CKRT to better understand pharmacokinetics of pip-tazo in this population and better inform dosing. METHODS: The National Library of Medicine Database was searched for original research containing piperacillin or tazobactam clearance (CL) or volume of distribution (V) estimates in patients treated with CKRT. The search yielded 77 articles, of which 26 reported suitable estimates of CL or V. Of the 26 articles, 10 for piperacillin and 8 for tazobactam had complete information suitable for population pharmacokinetic modelling. Also included in the analysis was piperacillin and tazobactam PK data from 4 critically ill patients treated with CKRT in the Military Health System, 2 with burn and 2 without burn. RESULTS AND DISCUSSION: Median and range of literature reported PK parameters for piperacillin (CL 2.76 L/hr, 1.4-7.92 L/hr, V 31.2 L, 16.77-42.27 L) and tazobactam (CL 2.34 L/hr, 0.72-5.2 L/hr, V 36.6 L, 26.2-58.87 L) were highly consistent with population estimates (piperacillin CL 2.7 L/hr, 95%CI 1.99-3.41 L/hr, V 25.83 22.07-29.59 L, tazobactam CL 2.49 L/hr, 95%CI 1.55-3.44, V 30.62 95%CI 23.7-37.54). The proportion of patients meeting pre-defined pharmacodynamic (PD) targets (median 88.7, range 71%-100%) was high despite significant mortality (median 44%, range 35%-60%). High mortality was predicted by baseline severity of illness (median APACHE II score 23, range 21-33.25). Choice of lenient or strict PD targets (ie 100%fT >MIC or 100%fT >4XMIC) had the largest impact on probability of target attainment (PTA), whereas presence or intensity of CKRT had minimal impact on PTA. WHAT IS NEW AND CONCLUSION: Pip-tazo overexposure may be associated with increased mortality, although this is confounded by baseline severity of illness. Achieving adequate pip-tazo exposure is essential; however, risk of harm from overexposure should be considered when choosing a PD target and dose. If lenient PD targets are desired, doses of 2250-3375 mg every 6 h are reasonable for most patients receiving CKRT. However, if a strict PD target is desired, continuous infusion (at least 9000-13500 mg per day) may be required. However, some critically ill CKRT populations may need higher or lower doses and dosing strategies should be tailored to individuals based on all available clinical data including the specific critical care setting.

Changing Patterns of Causative Pathogens over Time and Efficacy of Empirical Antibiotic Therapies in Acute Cholangitis with Bacteremia.

Background/Aims: To select appropriate empirical antibiotics, updates on the changes in pathogens are essential. We aimed to investigate the changes in pathogens and their antibiotic susceptibility in acute cholangitis (AC) with bacteremia over a period of 15 years. Furthermore, the efficacy of empirical antibiotic therapies and the risk factors predicting antibiotic-resistant pathogens (ARPs) were analyzed. Methods: A total of 568 patients with AC and bacteremia who were admitted to Daegu Catholic University Medical Center from January 2006 to December 2020 were included. Their medical records were retrospectively reviewed. In addition, the data were grouped and analyzed at 3-year intervals under the criteria of Tokyo Guideline 2018. Results: During the study period, 596 pathogens were isolated from blood cultures of 568 patients. The three most common pathogens were Escherichia coli (50.5%), Klebsiella species (24.5%), and Enterococcus species (8.1%). The proportion of vancomycin-resistant Enterococci (VRE) has increased since the mid-2010 (0.0% to 4.3%, p=0.007). There was emergence of carbapenem-resistant Enterobacteriaceae (CRE) in 2018 to 2020, albeit not statistically significant (1.3%, p=0.096). Risk factors predicting ARP were healthcare-associated infection, history of previous biliary intervention, and the severity of AC. For patients with these aforementioned risk factors, imipenem was the most effective antibiotic and piperacillin-tazobactam was also effective but to a lesser degree (susceptibility rates of 92.1% and 75.0%, respectively). Conclusions: The proportion of VRE has increased and CRE has emerged in AC. In addition, healthcare-associated infection, history of previous biliary intervention, and the severity of AC were independent risk factors predicting ARP. For patients with these risk factors, the administration of imipenem or piperacillin-tazobactam should be considered.

Vigilancia del consumo de antimicrobianos en 10 instituciones de salud entre 2013 y 2020 en Colombia / Antibiotic consumption surveillance in 10 health institutions between 2013 and 2020 in Colombia

INTRODUCCIÓN: El uso de antimicrobianos es el principal factor de resistencia bacteriana. OBJETIVO: Determinar el consumo de antimicrobianos en instituciones de salud de Santiago de Cali entre 2013 y 2020. MATERIAL Y MÉTODO: Se empleó la Dosis Diaria Definida por 100 camas-día. Se definieron como criterios de inclusión las instituciones que tuvieran como mínimo 9 reportes anuales y que el reporte fuese superior a 95%. En este caso quedaron incluidas 10 instituciones. RESULTADOS: El consumo en Unidades de Cuidados Intensivos (UCI) fue mayor que en servicios diferentes a UCI. Se consumió más ceftriaxona e imipenem en servicios diferentes a UCI, mientras que meropenem, piperacilina/tazobactam y vancomicina lo fueron en UCI. En servicios diferentes a UCI, dos instituciones aumentaron el consumo para ceftriaxona, ciprofloxacina y piperacilina/tazobactam y una para vancomicina, mientras que en UCI en una institución el consumo aumentó para piperacilina/tazobactam. CONCLUSIÓN: El sistema brindó herramientas de vigilancia prospectiva que mostraron necesidades de intervención en instituciones.

BACKGROUND: The use of antibiotics is the main factor of microbial resistance. Aim: To determine the consumption of antibiotics in health care institutions in Santiago de Cali between 2013 and 2020. METHODS: The methodology of the Defined Daily Dose per 100 beddays was employed. Institutions that had at least 9 annual reports and that the report is greater than 95% were defined as inclusion criteria. In this case, 10 institutions were included. RESULTS: Consumption in Intensive Care Units (ICU) was higher than in other units. Ceftriaxone and imipenem were more consumed in units other than ICU, whereas meropenem, piperacillin/tazobactam and vancomycin were more consumed in the ICU. In units other than ICU, two institutions increased the consumption of ceftriaxone, ciprofloxacin and piperacillin/tazobactam and one the consumption of vancomycin, whereas in the ICU, one institution increased the consumption of piperacillin/tazobactam. The endemic range identified that vancomycin located itself in the epidemic zone in one institution. CONCLUSION: The system provided tools for prospective surveillance that showed the need for intervention in institutions.

Therapeutic drug monitoring of meropenem and piperacillin-tazobactam in the Singapore critically ill population - A prospective, multi-center, observational study (BLAST 1).

PURPOSE: To determine percentage of patients with sub-therapeutic beta-lactam exposure in our intensive care units (ICU) and to correlate target attainment with clinical outcomes. MATERIALS AND METHODS: Multi-centre, prospective, observational study was conducted in ICUs from three hospitals in Singapore from July 2016 to May 2018. Adult patients (≥21 years) receiving meropenem or piperacillin-tazobactam were included. Four blood samples were obtained during a dosing interval to measure and determine attainment of therapeutic targets: unbound beta-lactam concentration above (i) minimum inhibitory concentration (MIC) at 40% (meropenem) or 50% (piperacillin) of dosing interval (40-50%fT > MIC) and (ii) 5 × MIC at 100% of dosing interval (100%fT > 5 × MIC). Correlation to clinical outcomes was evaluated using Cox regression. RESULTS: Beta-lactam levels were highly variable among 61 patients, with trough meropenem and piperacillin levels at 21.5 ± 16.8 mg/L and 101.6 ± 81.1 mg/L respectively. Among 85 sets of blood samples, current dosing practices were able to achieve 94% success for 40-50%fT > MIC and 44% for 100%fT > 5 × MIC. Failure to achieve 40-50%fT > MIC within 48 h was significantly associated with all-cause mortality (HR: 9.0, 95% CI: 1.8-45.0), after adjustment for APACHE II score. Achievement of 100%fT > 5 × MIC within 48 h was significantly associated with shorter length of hospital stay. CONCLUSION: Current dosing practices may be suboptimal for ICU patients. Beta-lactam TDM may be useful.

Comparative activity of newer ß-lactam/ß-lactamase inhibitor combinations against Pseudomonas aeruginosa from patients hospitalized with pneumonia in European medical centers in 2020.

Pseudomonas aeruginosa isolates were consecutively collected from patients with pneumonia in 29 medical centers in 2020 and susceptibility tested by broth microdilution method. Ceftazidime-avibactam (95.5% susceptible), imipenem-relebactam (94.3% susceptible), and ceftolozane-tazobactam (93.3% susceptible) were the most active compounds after colistin (99.5% susceptible). Susceptibility rates for the ß-lactam/ß-lactamase inhibitor combinations (BL/BLIs) varied against isolates resistant to piperacillin-tazobactam, meropenem, imipenem, and/or ceftazidime. Ceftazidime-avibactam was the most active BL/BLI against resistant subsets from Western Europe, whereas imipenem-relebactam was slightly more active than other BL/BLIs against resistant subsets from Eastern Europe. Susceptibility rates were markedly lower in Eastern Europe than Western Europe.

Antibiogram and molecular characterization of multi-drug resistant microorganisms isolated from urinary tract infections.

Bacteria are the commonest etiological factor among the microbes that cause UTIs. The most prevalent bacteria identified in the lab are Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa. Antibiotics are the empiric therapy for such infections but the reoccurrence rate is becoming high owing to the development of resistance due to their irrational and indiscriminate use across the globe. This study was designed on UTI cases of OPD, Medical, Nephrology, Surgical, Main OT, Urology and ICU wards of Allied hospital Faisalabad. 11 antibiotics were used which showed that E. coli is sensitive to Amikacin, Gentamicin, Imipenem, Piperacillin tazobactam, and Polymyxin B. Klebsiella pneumonia showed sensitivity for Amikacin, Gentamicin, Nitrofurantoin, Imipenem, Polymyxin B, Piperacillin tazobactam and Trimethoprim-sulfamethoxazole. While Pseudomonas aurignosa showed resistance to Amikacin, Ciprofloxacin, Gentamicin, Piperacillin tazobactam, Imipenem, and Polymyxin B. E. coli exhibited the highest sensitivity for Piperacillin tazobactam, Klebsiella pneumonia for Imipenem and Pseudomonas aurignosa for Ciprofloxacin. Further, the isolated DNA samples of these microorganisms were confirmed by gel electrophoresis and subjected to molecular characterization by performing trace file and phylogenetic tree analysis.