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Background Ceftolozane/tazobactam and ceftazidime/avibactam are commonly used in patients with MDR- Pseudomonas aeruginosa (PSA) pneumonia (PNA). This study compared outcomes between non-COVID-19 hospitalized patients with MDR-PSA PNA who received ceftolozane/tazobactam or ceftazidime/avibactam. Methods The study included non-COVID-19 adult hospitalized patients with MDR-PSA PNA in the PINC AI Healthcare Database (2016–22) who received ceftolozane/tazobactam or ceftazidime/avibactam within 3 days of index culture for ≥2 days. Outcomes were mortality, recurrent MDR-PSA PNA, discharge destination, post-index culture day length of stay (LOS) and costs (in US dollars, USD), and hospital readmission. Results The final sample included 197 patients (117 ceftolozane/tazobactam, 80 ceftazidime/avibactam). No significant differences were observed in mortality and post-index culture LOS and costs between groups. In the multivariable analyses, patients who received ceftolozane/tazobactam versus ceftazidime/avibactam had lower recurrent MDR-PSA PNA (7.9% versus 18.0%, P  = 0.03) and 60 day PNA-related readmissions (11.1% versus 28.5%, P  = 0.03) and were more likely to be discharged home (25.8% versus 9.8%, P  = 0.03). Compared with ceftazidime/avibactam patients, ceftolozane/tazobactam patients had lower adjusted median total antibiotic costs (5052 USD versus 8099 USD, P  = 0.003) and lower adjusted median comparator (ceftolozane/tazobactam or ceftazidime/avibactam) antibiotic costs (3938 USD versus 6441 USD, P  = 0.005). In the desirability of outcome ranking (DOOR) analysis, a ceftolozane/tazobactam-treated patient was more likely to have a more favourable outcome than a ceftazidime/avibactam-treated patient [DOOR probability: 59.6% (95% CI: 52.5%–66.8%)]. Conclusions Early treatment with ceftolozane/tazobactam may offer some clinical and cost benefits over ceftazidime/avibactam in patients with MDR-PSA PNA. Further large-scale studies are necessary to comprehensively understand the outcomes associated with these treatments for MDR-PSA PNA. [ABSTRACT FROM AUTHOR]

Objectives We aimed to compare the stability of the newly developed β-lactams (cefiderocol) and β-lactam/β-lactamase inhibitor combinations (ceftazidime/avibactam, ceftolozane/tazobactam, aztreonam/avibactam, cefepime/taniborbactam, cefepime/zidebactam, imipenem/relebactam, meropenem/vaborbactam, meropenem/nacubactam and meropenem/xeruborbactam) against the most clinically relevant mechanisms of mutational and transferable β-lactam resistance in Pseudomonas aeruginosa. Methods We screened a collection of 61 P. aeruginosa PAO1 derivatives. Eighteen isolates displayed the most relevant mechanisms of mutational resistance to β-lactams. The other 43 constructs expressed transferable β-lactamases from genes cloned in pUCP-24. MICs were determined by reference broth microdilution. Results Cefiderocol and imipenem/relebactam exhibited excellent in vitro activity against all of the mutational resistance mechanisms studied. Aztreonam/avibactam, cefepime/taniborbactam, cefepime/zidebactam, meropenem/vaborbactam, meropenem/nacubactam and meropenem/xeruborbactam proved to be more vulnerable to mutational events, especially to overexpression of efflux operons. The agents exhibiting the widest spectrum of activity against transferable β-lactamases were aztreonam/avibactam and cefepime/zidebactam, followed by cefepime/taniborbactam, cefiderocol, meropenem/xeruborbactam and meropenem/nacubactam. However, some MBLs, particularly NDM enzymes, may affect their activity. Combined production of certain enzymes (e.g. NDM-1) with increased MexAB-OprM-mediated efflux and OprD deficiency results in resistance to almost all agents tested, including last options such as aztreonam/avibactam and cefiderocol. Conclusions Cefiderocol and new β-lactam/β-lactamase inhibitor combinations show promising and complementary in vitro activity against mutational and transferable P. aeruginosa β-lactam resistance. However, the combined effects of efflux pumps, OprD deficiency and efficient β-lactamases could still result in the loss of all therapeutic options. Resistance surveillance, judicious use of new agents and continued drug development efforts are encouraged. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to present real-life data on the use, effectiveness, and safety of administering Ceftolozane/Tazobactam (C/T) through elastomeric pumps (EP) in the outpatient setting. Methods: This case series study was conducted from January 2022 to July 2023 in a large University Hospital in Rome, Italy. Patients receiving continuous infusion of C/T via EP were included up to a follow-up period of 90 days after the end of antibiotic therapy. The primary endpoint was the infection's clinical cure rate. Secondary endpoints were adverse events attributable to continuous home infusion of Ceftolozane/Tazobactam via elastomeric pumps. Results: Seven patients received C/T continuously infused via EP and were included in the final analysis. Three patients suffered from prosthetic joint infection (n = 3/7; 43%), two patients from osteomyelitis (n = 2/7; 29%), one patient from otomastoiditis (n = 1/7; 15%) and one from pneumonia (n = 1/7; 15%). All infection were sustained by P. aeruginosa. Five strains had MDR-type susceptibility profiles (n = 5/7; 71%) and two of these were DTR (n = 2/7; 29%). The infection cure rate reached 86% (n = 6/7). Two patients reported a complication related to the vascular catheter for drug infusion (n = 2/7; 29%). Conclusions: Continuous infusion of Ceftolozane/Tazobactam by elastomeric pumps has been shown to be safe and effective in practice representing a viable option of intravenous treatment in outpatient setting for infection sustained by P. aeruginosa especially for multidrug-resistant strains. [ABSTRACT FROM AUTHOR]

Background: Open abdomen with vacuum-assisted wound closure therapy (OA/VAC) is frequently used in critically ill patients although the impact of OA/VAC on antibiotics pharmacokinetics (PK) remains unknown. We thus aimed to characterize the PK of piperacillin–tazobactam (PTZ) in critically ill patients with OA/VAC and assess the optimal dosing regimens based on pharmacodynamics (PD) target attainment. Methods: Over a 15-month study period, 45 patients with OA/VAC treated with PTZ administered continuously and adapted to 24 h creatinine clearance (CLCR) underwent measurements of free concentrations in their plasma, urine, VAC exudate, and peritoneal fluid. Population PK modeling was performed considering the effect of covariates, and Monte Carlo simulations were employed to determine the probability of target attainment (PTA) for the PK/PD targets (100% fT > 16 mg/L) in the plasma and at the peritoneal site at steady state. Results: Piperacillin concentrations were described using a two-compartment model, with age and total body weight as significant covariates for central volume of distribution (V1) and estimated renal function for clearance (CL). Tazobactam concentrations were described using a two-compartment model with estimated renal function as a significant covariate. The central volume of distributions V1 of piperacillin and tazobactam were 21.2 and 23.2 L, respectively. The VAC-induced peritoneal clearance was negligible compared to renal clearance. Most patients achieved the desirable PK/PD target when using a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day. Conclusions: Despite a wide inter-individual variability, the influence of OA/VAC on piperacillin and tazobactam PK parameters is not straightforward. The use of a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day is needed to reach a PTA > 85%. [ABSTRACT FROM AUTHOR]

Introduction: Drug incompatibilities are among the most common medication errors in intensive care units. A precipitate can form and block the catheter or cause an adverse event in the patient. Intensive care units have implemented various strategies for limiting the occurrence of these incompatibilities, which have already been studied in vitro under standardized conditions. The objective of the present in vitro study was to continue these assessments by determining the impact of the infusion line geometry and the drugs' position in the infusion set-up on the prevention of vancomycin–piperacillin/tazobactam incompatibility. Methods: Infusion lines with a different common volume, a multilumen medical infusion device, a dilute vancomycin solution, and separate infusions of incompatible drugs were evaluated separately. The infusion line outlet was connected to a dynamic particle counter. Results: Reducing the common volume, using multilumen medical devices, or spacing out the two incompatible drugs on the infusion line did not prevent the occurrence of a significant particulate load. Only dilution of the vancomycin solution was associated with a significantly lower particulate load and the absence of drug incompatibility. Conclusions: Our results show that under specific conditions, it is possible to reduce particulate contamination considerably. [ABSTRACT FROM AUTHOR]

Some antibiotics that are frequently employed are β-lactams. In light of the hydrolytic process of β-lactamase, found in Gram-negative bacteria, inhibitors of β-lactamase (BLIs) have been produced. Examples of first-generation β-lactamase inhibitors include sulbactam, clavulanic acid, and tazobactam. Many kinds of bacteria immune to inhibitors have appeared, and none cover all the β-lactamase classes. Various methods have been utilized to develop second-generation β-lactamase inhibitors possessing new structures and facilitate the formation of diazabicyclooctane (DBO), cyclic boronate, metallo-, and dual-nature β-lactamase inhibitors. This review describes numerous promising second-generation β-lactamase inhibitors, including vaborbactam, avibactam, and cyclic boronate serine-β-lactamase inhibitors. Furthermore, it covers developments and methods for synthesizing MβL (metallo-β-lactamase inhibitors), which are clinically effective, as well as the various dual-nature-based inhibitors of β-lactamases that have been developed. Several combinations are still only used in preclinical or clinical research, although only a few are currently used in clinics. This review comprises materials on the research progress of BLIs over the last five years. It highlights the ongoing need to produce new and unique BLIs to counter the appearance of multidrug-resistant bacteria. At present, second-generation BLIs represent an efficient and successful strategy. [ABSTRACT FROM AUTHOR]

Purpose: Carbapenem resistant Pseudomonas aeruginosa (CR-PA) is escalating worldwide and leaves clinicians few therapeutic options in recent years, β-lactam/β-lactamase inhibitor combinations (ceftolozane-tazobactam, ceftazidime-avibactam) and a new siderophore cephalosporin (cefiderocol) have been approved for the treatment of P. aeruginosa infection and have shown potent activity against isolates defined as carbapenem resistant. The aim of this study was to determine the phenotypic profile of these agents against CR-PA in the emerging setting of carbapenemases. Methods: CR-PA clinical isolates were collected from three teaching hospitals in different geographical regions between January 2017-December 2021. All isolates were subjected to phenotypic carbapenemase testing using modified carbapenem inactivation method. MICs were determined by reference broth microdilution and evaluated according to EUCAST standards, while genotypic profiling was determined using PCR methods. Results: 244 CR-PA sourced most frequently from the respiratory tract (32.2%), blood (20.4%) and urine (17.5%) were evaluated. Of all isolates, 32 (13.1%) were phenotypically and 38 (15.6%) were genotypically defined as carbapenemase-positive. The most common carbapenemase was GES (63.1%), followed by VIM (15.8%). The MIC50/90(S%) of ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol in all CR-PA isolates were 4 and 32 (80%), 1 and > 64 (69%) and 0.25 and 1 mg/L (96%), respectively. Cefiderocol was also the most active agent in carbapenemase-positive isolates (90%). Conslusion: While ceftolozane/tazobactam and ceftazidime/avibactam remained highly active against CR-PA devoid of carbapenemases, cefiderocol provided potent in vitro activity irrespective of carbapenemase production. When considering the potential clinical utility of newer agents against CR-PA, regional variations in carbapenemase prevalence must be considered. [ABSTRACT FROM AUTHOR]

We evaluated the activity of piperacillin in relation to increasing tazobactam concentration against ESBL-producing Enterobacterales collected from patients with bacteraemia. Increasing tazobactam concentration (4, 12 or 24 mg/L) exerted a reduction of piperacillin MICs under the clinical breakpoint in a concentration-dependent manner (0%, 60% and 90% of clinical isolates). Also, activity of piperacillin/tazobactam based at higher achievable serum concentrations (123/14 mg/L) is needed to reduce the bacterial growth in 92% of ESBL-producers. Changes in the piperacillin MIC in relation to increasing tazobactam suggest that realtime TDM could be used for driven antimicrobial therapy with piperacillin/tazobactam in BSI due to ESBL strains. [ABSTRACT FROM AUTHOR]

Background: Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low. Methods: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator‐initiated, international, parallel‐group, randomised, open‐label, adaptive clinical trial with an integrated feasibility phase. We will randomise adult, critically ill patients with sepsis to empirical treatment with meropenem or piperacillin/tazobactam for up to 30 days. The primary outcome is 30‐day all‐cause mortality. The secondary outcomes are serious adverse reactions within 30 days; isolation precautions due to resistant bacteria within 30 days; days alive without life support and days alive and out of hospital within 30 and 90 days; 90‐ and 180‐day all‐cause mortality and 180‐day health‐related quality of life. EMPRESS will use Bayesian statistical models with weak to somewhat sceptical neutral priors. Adaptive analyses will be conducted after follow‐up of the primary outcome for the first 400 participants concludes and after every 300 subsequent participants, with adaptive stopping for superiority/inferiority and practical equivalence (absolute risk difference <2.5%‐points) and response‐adaptive randomisation. The expected sample sizes in scenarios with no, small or large differences are 5189, 5859 and 2570 participants, with maximum 14,000 participants and ≥99% probability of conclusiveness across all scenarios. Conclusions: EMPRESS will compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis. Due to the pragmatic, adaptive design with high probability of conclusiveness, the trial results are expected to directly inform clinical practice. [ABSTRACT FROM AUTHOR]

We investigated the activity of cefiderocol/β-lactamase inhibitor combinations against clinical strains with different susceptibility profiles to cefiderocol to explore the potentiality of antibiotic combinations as a strategy to contain the major public health problem of multidrug-resistant (MDR) pathogens. Specifically, we evaluated the synergistic activity of cefiderocol with avibactam, sulbactam, or tazobactam on three of the most "Critical Priority" group of MDR bacteria (carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii). Clinical isolates were genomically characterized by Illumina iSeq 100. The synergy test was conducted with time-kill curve assays. Specifically, cefiderocol/avibactam, /sulbactam, or /tazobactam combinations were analyzed. Synergism was assigned if bacterial grow reduction reached 2 log10 CFU/mL. We reported the high antimicrobial activity of the cefiderocol/sulbactam combination against carbapenem-resistant Enterobacterales, P. aeruginosa, and A. baumannii; of the cefiderocol/avibactam combination against carbapenem-resistant Enterobacterales; and of the cefiderocol/tazobactam combination against carbapenem-resistant Enterobacterales and P. aeruginosa. Our results demonstrate that all β-lactamase inhibitors (BLIs) tested are able to enhance cefiderocol antimicrobial activity, also against cefiderocol-resistant isolates. The cefiderocol/sulbactam combination emerges as the most promising combination, proving to highly enhance cefiderocol activity in all the analyzed carbapenem-resistant Gram-negative isolates, whereas the Cefiderocol/tazobactam combination resulted in being active only against carbapenem-resistant Enterobacterales and P. aeruginosa, and cefiderocol/avibactam was only active against carbapenem-resistant Enterobacterales. [ABSTRACT FROM AUTHOR]

Objectives To investigate clinical outcomes of patients with Pseudomonas endocarditis and identify factors associated with treatment failure. Methods Adult patients meeting definitive Duke's criteria for Pseudomonas endocarditis at 11 hospitals were identified between May 2000 and February 2024. Failure was defined as death or microbiological failure by day 42. First-line therapy consisted of cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam alone or in combination. Results Forty-eight patients met inclusion criteria; 29% were persons who inject drugs and 13% were organ transplant recipients. Pseudomonas aeruginosa was the causative species in 98% of cases. Patients who experienced 42 day cure were more likely to be initially managed with first-line β-lactam agents compared with those who experienced clinical failure (97% versus 62%, P  = 0.004). Treatment with first-line β-lactams was associated with shorter time to treatment initiation and a lower likelihood of infection due to MDR Pseudomonas spp. In the univariate model, patients who experienced 90 day mortality were more likely to have prosthetic valve endocarditis (57% versus 24%, P  = 0.02), an intracardiac complication (36% versus 9%, P  = 0.04) and a higher median (IQR) Pitt bacteraemia score [2.5 (2–3.8) versus 1 (0–2), P  = 0.048]. Combination therapy did not improve clinical outcomes but did increase the rate of adverse effects resulting in drug discontinuation compared with monotherapy, (21% versus 0%, P  = 0.08). Conclusions This is the largest study of Pseudomona s endocarditis to date. We identified improved clinical outcomes when cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam were used for initial treatment. We did not identify a clinical benefit for combination treatment. [ABSTRACT FROM AUTHOR]

Background and Objective: Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal. This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF). Methods: Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cleff) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days. Results: HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (β = − 8.90 (95% CI − 12.9 to − 4.87), p < 0.001) and tazobactam (β = − 8.29 (95% CI − 13.5 to − 3.08), p = 0.002) and Cleff for each antibiotic (meropenem β = − 10,206 (95% CI − 14,787 to − 5787), p = 0.001); tazobactam (β = − 4551 (95% CI − 7781 to − 1322), p = 0.012); piperacillin (β = − 3913 (95% CI − 6388 to − 1437), p = 0.002), even if the carryover effect influenced the Cleff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (β = − 38.1 (95% CI − 47.9 to − 28.3), p < 0.001) and tazobactam (β = − 4.45 (95% CI − 6.17 to − 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type. Conclusion: MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM. [ABSTRACT FROM AUTHOR]

This is the first case report of decubitus infection and bacteremia due to Veillonella parvula (V. parvula). A patient in his 70s with pre-existing diabetes mellitus was admitted with decubitus infection, and tazobactam/piperacillin treatment was initiated. Tazobactam/piperacillin-resistant V. parvula was detected in the blood and decubitus site cultures. The antimicrobial treatment was changed to clindamycin and cefmetazole. Antimicrobial therapy was administered for 28 days. The patient was transferred to a convalescent hospital. V. parvula occasionally causes infection in immunocompromised patients with underlying diseases, such as diabetes. An appropriate evaluation by culture test is important for diagnosis, treatment, and recurrence prevention. Tazobactam/piperacillin is often used in the treatment of multi-bacterial infections such as decubitus infections. V. parvula may be resistant to tazobactam/piperacillin, and this possibility should be taken into account when administering treatment. [ABSTRACT FROM AUTHOR]

Pulmonary infections complicate chronic lung diseases requiring attention to both the pathophysiology and complexity associated with infection management. Patients with cystic fibrosis (CF) struggle with continuous bouts of pulmonary infections, contributing to lung destruction and eventual mortality. Additionally, CF patients struggle with airways that are highly viscous, with accumulated mucus creating optimal environments for bacteria colonization. The unique physiology and altered airway environment provide an ideal niche for bacteria to change their phenotype often becoming resistant to current treatments. Colonization with multiple pathogens at the same time further complicate treatment algorithms, requiring drug combinations that can challenge CF patient tolerance to treatment. The goal of this research initiative was to explore the utilization of a microparticle antibiotic delivery system, which could provide localized and sustained antibiotic dosing. The outcome of this work demonstrates the feasibility of providing efficient localized delivery of antibiotics to manage infection using both preclinical in vitro and in vivo CF infection models. The studies outlined in this manuscript demonstrate the proof-of-concept and unique capacity of polymerized cyclodextrin microparticles to provide site-directed management of pulmonary infections. [ABSTRACT FROM AUTHOR]

Objective: Piperacillin/tazobactam (PIP/TAZ) is used for the treatment of lower respiratory tract bacterial infections in children. This study was performed to evaluate if the current dosing regimen results in therapeutic drug concentrations. Patients and methods: Patients suspected or proven to have lower respiratory tract bacterial infection and administrated PIP/TAZ intravenously for a duration of no less than 0.5 h, q6h-q12h daily, were enrolled. Blood samples were collected, and PIP concentrations were determined by high-performance liquid chromatography. The individual predicted concentration of PIP was evaluated using the individual empirical Bayesian estimate method. The evaluated PK/PD targets included (1) 70% time when the predicted free drug concentration exceeds the minimum inhibitory concentration (fT > MIC) and (2) 50% fT > 4× MIC. Probability of target attainment (PTA) was assessed by the proportion of patients who reached the PK/PD targets. The PIP concentrations between different groups of patients were compared. Results: A total of 57 samples were collected from 57 patients with a median age of 2.26 years (0.17-12.58). For the PK/PD targets of 70% fT > MIC and 50% fT > 4× MIC for Pseudomonas aeruginosa and Klebsiella pneumoniae, the PTA was all 0. The median Cmin of PIP was significantly higher in infants than in children, and the median Cmin after administration in q8h was significantly higher than that after administration in q12h. Conclusion: The current dose regimen of PIP/TAZ leads to extremely low plasma concentrations in most children with lower respiratory tract bacterial infections. More optimized dosing regimens or better alternative therapies need to be further explored. [ABSTRACT FROM AUTHOR]

Purpose: The current study evaluated the in vitro activities of ceftolozane/tazobactam (C/T), imipenem/relebactam (IMI/REL), and comparators against recent (2017–2021) clinical isolates of gram-negative bacilli from two countries in southern Europe. Methods: Nine clinical laboratories (two in Greece; seven in Italy) each collected up to 250 consecutive gram-negative isolates per year from lower respiratory tract, intraabdominal, urinary tract, and bloodstream infection samples. MICs were determined by the CLSI broth microdilution method and interpreted using 2022 EUCAST breakpoints. β-lactamase genes were identified in select β-lactam-nonsusceptible isolate subsets. Results: C/T inhibited the growth of 85–87% of Enterobacterales and 94–96% of ESBL-positive non-CRE NME (non-Morganellaceae Enterobacterales) isolates from both countries. IMI/REL inhibited 95–98% of NME, 100% of ESBL-positive non-CRE NME, and 98–99% of KPC-positive NME isolates from both countries. Country-specific differences in percent susceptible values for C/T, IMI/REL, meropenem, piperacillin/tazobactam, levofloxacin, and amikacin were more pronounced for Pseudomonas aeruginosa than Enterobacterales. C/T and IMI/REL both inhibited 84% of P. aeruginosa isolates from Greece and 91–92% of isolates from Italy. MBL rates were estimated as 4% of Enterobacterales and 10% of P. aeruginosa isolates from Greece compared to 1% of Enterobacterales and 3% of P. aeruginosa isolates from Italy. KPC rates among Enterobacterales isolates were similar in both countries (7–8%). OXA-48-like enzymes were only identified in Enterobacterales isolates from Italy (1%) while GES carbapenemase genes were only identified in P. aeruginosa isolates from Italy (2%). Conclusion: We conclude that C/T and IMI/REL may provide viable treatment options for many patients from Greece and Italy. [ABSTRACT FROM AUTHOR]

Background: Critically ill patients in intensive care units (ICU) are frequently administered broad‐spectrum antibiotics (e.g., carbapenems or piperacillin/tazobactam) for suspected or confirmed infections. This retrospective cohort study aimed to describe the use of carbapenems and piperacillin/tazobactam in two international, prospectively collected datasets. Methods: We conducted a post hoc analysis of data from the "Adjunctive Glucocorticoid Therapy in Patients with Septic Shock" (ADRENAL) trial (n = 3713) and the "Antimicrobial de‐escalation in the critically ill patient and assessment of clinical cure" (DIANA) study (n = 1488). The primary outcome was the proportion of patients receiving initial antibiotic treatment with carbapenems and piperacillin/tazobactam. Secondary outcomes included mortality, days alive and out of ICU and ICU length of stay at 28 days. Results: In the ADRENAL trial, carbapenems were used in 648 out of 3713 (17%), whereas piperacillin/tazobactam was used in 1804 out of 3713 (49%) participants. In the DIANA study, carbapenems were used in 380 out of 1480 (26%), while piperacillin/tazobactam was used in 433 out of 1488 (29%) participants. Mortality at 28 days was 23% for patients receiving carbapenems and 24% for those receiving piperacillin/tazobactam in ADRENAL and 23% and 19%, respectively, in DIANA. We noted variations in secondary outcomes; in DIANA, patients receiving carbapenems had a median of 13 days alive and out of ICU compared with 18 days among those receiving piperacillin/tazobactam. In ADRENAL, the median hospital length of stay was 27 days for patients receiving carbapenems and 21 days for those receiving piperacillin/tazobactam. Conclusions: In this post hoc analysis of ICU patients with infections, we found widespread initial use of carbapenems and piperacillin/tazobactam in international ICUs, with the latter being more frequently used. Randomized clinical trials are needed to assess if the observed variations in outcomes may be drug‐related effects or due to confounders. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cefepime and piperacillin/tazobactam are antimicrobials recommended by IDSA/ATS guidelines for the empirical management of patients admitted to the intensive care unit (ICU) with community-acquired pneumonia (CAP). Concerns have been raised about which should be used in clinical practice. This study aims to compare the effect of cefepime and piperacillin/tazobactam in critically ill CAP patients through a targeted maximum likelihood estimation (TMLE). A total of 2026 ICU-admitted patients with CAP were included. Among them, (47%) presented respiratory failure, and (27%) developed septic shock. A total of (68%) received cefepime and (32%) piperacillin/tazobactam-based treatment. After running the TMLE, we found that cefepime and piperacillin/tazobactam-based treatments have comparable 28-day, hospital, and ICU mortality. Additionally, age, PTT, serum potassium and temperature were associated with preferring cefepime over piperacillin/tazobactam (OR 1.14 95% CI [1.01–1.27], p = 0.03), (OR 1.14 95% CI [1.03–1.26], p = 0.009), (OR 1.1 95% CI [1.01–1.22], p = 0.039) and (OR 1.13 95% CI [1.03–1.24], p = 0.014)]. Our study found a similar mortality rate among ICU-admitted CAP patients treated with cefepime and piperacillin/tazobactam. Clinicians may consider factors such as availability and safety profiles when making treatment decisions. [ABSTRACT FROM AUTHOR]

Background A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates. Objectives We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic. Methods We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90 day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups. Results Sixty-two patients were included in our analysis. Overall, median age was 63 years (IQR 49.5–71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0 days (IQR 9.0–16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30–1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%. Conclusions These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone. [ABSTRACT FROM AUTHOR]

Background Pancreatoduodenectomy is associated with an increased incidence of surgical-site infections, often leading to a significant rise in morbidity and mortality. This trend underlines the inadequacy of traditional antibiotic prophylaxis strategies. Hence, the aim of this meta-analysis was to assess the outcomes of antimicrobial prophylaxis, comparing piperacillin/tazobactam with traditional antibiotics. Methods Upon registering in PROSPERO, the international prospective register of systematic reviews (CRD42023479100), a systematic search of various databases was conducted over the interval 2000–2023. This inclusive search encompassed a wide range of study types, including prospective and retrospective cohorts and RCTs. The subsequent data analysis was carried out utilizing RevMan 5.4. Results A total of eight studies involving 2382 patients who underwent pancreatoduodenectomy and received either piperacillin/tazobactam (1196 patients) or traditional antibiotics (1186 patients) as antibiotic prophylaxis during surgery were included in the meta-analysis. Patients in the piperacillin/tazobactam group had significantly reduced incidences of surgical-site infections (OR 0.43 (95% c.i. 0.30 to 0.62); P < 0.00001) and major surgical complications (Clavien–Dindo grade greater than or equal to III) (OR 0.61 (95% c.i. 0.45 to 0.81); P = 0.0008). Subgroup analysis of surgical-site infections highlighted significantly reduced incidences of superficial surgical-site infections (OR 0.34 (95% c.i. 0.14 to 0.84); P = 0.02) and organ/space surgical-site infections (OR 0.47 (95% c.i. 0.28 to 0.78); P = 0.004) in the piperacillin/tazobactam group. Further, the analysis demonstrated significantly lower incidences of clinically relevant postoperative pancreatic fistulas (grades B and C) (OR 0.67 (95% c.i. 0.53 to 0.83); P = 0.0003) and mortality (OR 0.51 (95% c.i. 0.28 to 0.91); P = 0.02) in the piperacillin/tazobactam group. Conclusion Piperacillin/tazobactam as antimicrobial prophylaxis significantly lowers the risk of postoperative surgical-site infections, major surgical complications (complications classified as Clavien–Dindo grade greater than or equal to III), clinically relevant postoperative pancreatic fistulas (grades B and C), and mortality, hence supporting the implementation of piperacillin/tazobactam for surgical prophylaxis in current practice. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is one of the most common causes of mastitis worldwide. This study aimed to determine the prevalence and antimicrobial resistance (AMR) patterns of S. aureus in mastitic milk samples collected from camel farms in Matrouh Governorate, Egypt. A total of 200 mastitic camel milk samples were evaluated for S. aureus using both conventional culture-based and molecular-based methods. Antibiotic susceptibility testing of S. aureus isolates was conducted using disc diffusion and agar dilution methods, with antibiotic resistance genes identified through polymerase chain reaction with specific primers. Out of samples tested, 60 (30.00%) were positive for S. aureus. The isolates displayed the highest of resistance against piperacillin-tazobactam (55.00%) followed by trimethoprim-sulfamethoxazole (45.00%) and amoxicillin (40.00%). Half of the isolates were multidrug-resistant (MDR). The AMR genes included methicillin-resistant gene (mecA), ß-lactamase gene (blaZ), tetracycline resistance gene (tetK), erythromycin resistance gene (ermB) and vancomycin resistant gene (vanA) were detected in 100%, 100%, 95.00%, 90.00% and 20.00% of the isolates, respectively. In conclusion, the presence of MDRS aureus as a cause of clinical camel mastitis is a significant veterinary and public health concern. These findings highlight the importance of proper antibiotic use in Egyptian camel farms and the need for molecular techniques to fully understand the genetic profile of antimicrobial-resistant S. aureus isolates. [ABSTRACT FROM AUTHOR]