Effectiveness of ceftazidime-avibactam versus ceftolozane-tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the USA (CACTUS): a multicentre, retrospective, observational study.

Background: Ceftolozane-tazobactam and ceftazidime-avibactam are preferred treatment options for multidrug-resistant Pseudomonas aeruginosa infections; however, real-world comparative effectiveness studies are scarce. Pharmacokinetic and pharmacodynamic differences between the agents might affect clinical response rates. We aimed to compare the effectiveness of ceftolozane-tazobactam and ceftazidime-avibactam for treatment of invasive multidrug-resistant P aeruginosa infections.

A Comparison of Different Strategies for Optimizing the Selection of Empiric Antibiotic Therapy for Pneumonia Caused by Gram-Negative Bacteria in Intensive Care Units: Unit-Specific Combination Antibiograms Versus Patient-Specific Risk Factors.

Background: Guidelines suggest dual antipseudomonal therapy for empiric treatment of pneumonia caused by gram-negative bacteria in intensive care unit (ICU) patients. Additionally, consideration of local susceptibility data and patient-specific risk factors for resistance is recommended for selecting optimal empiric regimens. However, data assessing how to best do this are lacking, and it is unclear whether a local susceptibility data-based or a patient-specific risk factor-based approach will better drive appropriate empiric treatment.

Piperacillin/Tazobactam Susceptibility Test Interpretive Criteria for Enterobacterales: Recommendations From the United States Committee on Antimicrobial Susceptibility Testing.

The in vitro susceptibility testing interpretive criteria (STIC) for piperacillin/tazobactam (TZP) against Enterobacterales were recently updated by the US Food and Drug Administration, Clinical and Laboratory Standards Institute, and European Committee on Antimicrobial Susceptibility Testing. The United States Committee on Antimicrobial Susceptibility Testing (USCAST) also recently reviewed TZP STIC for Enterobacterales and arrived at different STIC for Enterobacterales. Here, we explain our recommendations and rationale behind them.

The Growing Threat of NDM-Producing Escherichia coli With Penicillin-Binding Protein 3 Mutations in the United States-Is There a Potential Role for Durlobactam?

We report identification of 5 patients with infections caused by NDM-5-producing Escherichia coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane β-lactamase inhibitor, demonstrated minimum inhibitory concentrations ranging from 0.5 to 2 µg/mL supporting future investigations into a potential role in clinical management.

Population pharmacokinetic/pharmacodynamic target attainment analysis of IV fosfomycin for the treatment of MDR Gram-negative bacterial infections.

Background: IV fosfomycin is used against MDR Gram-negative bacilli (GNB) but has dose-limiting side effects, especially in patients with impaired kidney function.

Objectives: To determine the optimal dosage of IV fosfomycin for patients with varying degrees of kidney function.

Methods: Adult patients receiving IV fosfomycin for treatment of GNB were eligible.

A comparison of strategies for identifying patients at risk for carbapenem-resistant or extended β-lactam-resistant Pseudomonas aeruginosa.

Objectives: To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-β-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures.

Methods: This retrospective study analysed hospitalized patients with positive P.

Nut Cracked? Does the ACORN Trial End the Debate Surrounding Vancomycin and Piperacillin-Tazobactam Combination Therapy and Increased Risk for Acute Kidney Injury?

Observational data published over the past decade have suggested that concomitant receipt of piperacillin-tazobactam with vancomycin significantly increases the risk for vancomycin-associated acute kidney injury. Importantly, however, there is significant controversy surrounding this association, and debate continues about the veracity of the risk. Given this ongoing debate, the recently published "Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial" is of tremendous interest to the infectious diseases community.

Impact of Reducing Time-to-Antibiotics on Sepsis Mortality, Antibiotic Use, and Adverse Events.

Shorter time-to-antibiotics is lifesaving in sepsis, but programs to hasten antibiotic delivery may increase unnecessary antibiotic use and adverse events. We sought to estimate both the benefits and harms of shortening time-to-antibiotics for sepsis. We conducted a simulation study using a cohort of 1,559,523 hospitalized patients admitted through the emergency department with meeting two or more systemic inflammatory response syndrome criteria (2013-2018).

An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections.

Background: Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode.

Methods: We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan.

State of the Management of Infections Caused by Multidrug-Resistant Gram-Negative Organisms.

In the past decade, the prevalence of multidrug-resistant gram-negative (MDR-GN) bacterial infections has increased significantly, leading to higher rates of morbidity and mortality. Treating these infections poses numerous challenges, particularly when selecting appropriate empiric therapy for critically ill patients for whom the margin for error is low. Fortunately, the availability of new therapies has improved the treatment landscape, offering safer and more effective options.

Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms.

Background: Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) , XDR , and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections.

Methods: The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial.

Which trial do we need? Combination antimicrobial therapy for hospital-acquired bacterial pneumonia caused by Pseudomonas aeruginosa.

Meropenem therapy will be open-label, while tobramycin or placebo will be administered in a double-blind fashion. The primary trial endpoint will be a composite hierarchical outcome of 1) 28-day all-cause mortality, 2) ventilator-free days, and 3) modified time to clinical stability, evaluated using a win ratio methodology (see below). Secondary trial outcomes will include frequency of safety events (acute kidney injury), resolution of circulatory shock, recurrent HABP, and emergence of meropenem resistance both during treatment and in cases of recurrent infection.

Case Commentary: When Voldemort Meets Sauron: Treatment Considerations for Emerging Dual-Carbapenemase-Producing Extensively Drug-Resistant Pseudomonas aeruginosa.

Infections caused by extensively drug-resistant Pseudomonas aeruginosa are difficult to treat due to limited effective treatment options. In this issue, a patient with a corneal infection caused by a Verona integron-encoded metallo-β-lactamase (VIM)- and Guiana extended-spectrum β-lactamase (GES)-coproducing P. aeruginosa strain associated with the recent artificial tears-related outbreak in the United States is described.

A population pharmacokinetic model of polymyxin B based on prospective clinical data to inform dosing in hospitalized patients.

Objectives: To develop a population pharmacokinetic (PK) model with data from the largest polymyxin B-treated patient population studied to date to optimize its dosing in hospitalized patients.

Methods: Hospitalized patients receiving intravenous polymyxin B for ≥48 hours were enrolled. Blood samples were collected at steady state and drug concentrations were analysed by liquid chromotography tandem mass spectrometry (LC-MS/MS).

Clinical Outcomes With Extended Versus Intermittent Infusion of Anti-Pseudomonal Beta-Lactams in Patients With Gram-Negative Bacteremia.

Background: Administration of doses via an extended infusion (EI) is an important strategy to optimize beta-lactams. Available data on the impact of EI on outcomes largely focus on clinical cure or mortality in critically ill patients or those with resistant pathogens. The potential benefits of EI extend beyond these populations and outcomes, and further study is warranted.

Cefiderocol, a Siderophore Cephalosporin, as a Treatment Option for Infections Caused by Carbapenem-Resistant Enterobacterales.

Carbapenem-resistant Enterobacterales (CRE) remain a significant public health threat, and, despite recent approvals, new antibiotics are needed. Severe infections caused by CRE, such as nosocomial pneumonia and bloodstream infections, are associated with a relatively high risk of morbidity and mortality. The recent approval of ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, plazomicin, eravacycline and cefiderocol has broadened the armamentarium for the treatment of patients with CRE infections.

Pharmacists as important prescribers of coronavirus disease 2019 (COVID-19) antivirals.

Although pharmacists are key members of the healthcare team, they are currently ineligible to independently prescribe the oral coronavirus disease 2019 (COVID-19) antivirals. We report the roles pharmacists have undertaken during the COVID-19 pandemic and provide evidence for the support of independent oral COVID-19 antiviral prescribing.

Quantifying the breadth of antibiotic exposure in sepsis and suspected infection using spectrum scores.

A retrospective cohort study. Studies to quantify the breadth of antibiotic exposure across populations remain limited. Therefore, we applied a validated method to describe the breadth of antimicrobial coverage in a multicenter cohort of patients with suspected infection and sepsis.

Less Is More? Antibiotic Treatment Duration in Pseudomonas aeruginosa Ventilator-Associated Pneumonia.

Recommended antimicrobial treatment durations for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa have evolved over the past few decades. In this Viewpoint, we provide a narrative review of landmark trials investigating antimicrobial treatment durations for VAP caused by P. aeruginosa, and appraise iterations of expert consensus guidelines based on these data.

Temporal Trends in Antimicrobial Prescribing During Hospitalization for Potential Infection and Sepsis.

Importance: Some experts have cautioned that national and health system emphasis on rapid administration of antimicrobials for sepsis may increase overall antimicrobial use even among patients without sepsis.

Objective: To assess whether temporal changes in antimicrobial timing for sepsis are associated with increasing antimicrobial use, days of therapy, or broadness of antimicrobial coverage among all hospitalized patients at risk for sepsis.

Design, Setting, And Participants: This is an observational cohort study of hospitalized patients at 152 hospitals in 2 health care systems during 2013 to 2018, admitted via the emergency department with 2 or more systemic inflammatory response syndrome (SIRS) criteria.