Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial.

Importance: Extended-spectrum ß-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum ß-lactamase producers. Objectives: To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae. Design, Setting, and Participants: Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. Main Outcomes and Measures: The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. Results: Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group. Conclusions and relevance: Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting. Trial Registration: anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.

Implementing the First Outpatient Parenteral Antimicrobial Therapy (OPAT) Program to Utilize Disposable Elastomeric Pumps in the Gulf Region: Results From a Tertiary Teaching Hospital in the Kingdom of Saudi Arabia.

Objectives To describe the implementation process, safety, and efficacy outcomes, as well as cost-effectiveness, of the first outpatient parenteral antimicrobial therapy (OPAT) program to utilize disposable elastomeric pumps in the Kingdom of Saudi Arabia and the entire Gulf region. Methods This OPAT program was initiated in May 2018 and was administered through a multidisciplinary team that included the home medicine department, pharmacy department, nursing department, and the infectious diseases service. The device used was the Intermate® (Baxter, Deerfield, Illinois) elastomeric pump. After consultation with an infectious diseases physician, eligible patients were discharged home to complete the remainder of their antimicrobial treatment, which was self-administered via the elastomeric devices. Results From May 2018 to December 2019, 47 patients received 55 courses of OPAT via the new program. A total of 2,869 pumps were used during that period to provide 927 days of antimicrobial therapy in the home setting. Most patients completed the program successfully with no reported significant OPAT-related complications such as catheter-related infections. Four patients were re-admitted for relapse of infections and one patient was re-admitted for colistin-induced nephrotoxicity. No mortality was reported for any patient during OPAT treatment and 30 days after program completion. Conclusions The implementation of this novel OPAT program was safe, effective, and offered significant cost-savings to our institution. The entire process was very dynamic and was centered around proper patient selection and education as well as excellent communication between patients and the entire multidisciplinary team involved in the program. We hope that these results will encourage other institutions in the region to implement similar OPAT programs to alleviate the existing bed crisis due to the ongoing COVID-19 pandemic.

Prevalence of infections and antimicrobial use in the acute-care hospital setting in the Middle East: Results from the first point-prevalence survey in the region.

OBJECTIVES: Community-acquired (CAIs) and healthcare-associated (HAIs) infections are associated with significant morbidity and mortality. Data related to the epidemiology of these infections in the Middle East is scarce. The aim of this study is to estimate the prevalence of infections and antimicrobial use in the acute hospital setting in this region. METHODS: A multicentre Point-Prevalence Survey was conducted in seven Middle Eastern countries: Egypt, Kingdom of Saudi Arabia, United Arab Emirates, Lebanon, Oman, Kuwait and Bahrain. Data were collected by the infection control and infectious diseases teams of the respective hospitals. Study surveys were completed in one day (03 April 2018). RESULTS: The overall point prevalence of infection was 28.3%; HAI and CAI point prevalence was 11.2% and 16.8%, respectively. The majority of patients with an infection (98.2%) were receiving antimicrobial therapy. There were high levels of resistance to antimicrobials among Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae and other Klebsiella sp. CONCLUSIONS: Our findings indicate that the point prevalence of both HAI and CAI is high in a sample of Middle Eastern countries. These findings along with the increased use of antimicrobials represent a significant public health problem in the region; particularly in light of the growing regional antimicrobial resistance.

Use of Ceftolozane/tazobactam for the Treatment of Multidrug-resistant Pseudomonas aeruginosa Pneumonia in a Pediatric Patient with Combined Immunodeficiency (CID): A Case Report from a Tertiary Hospital in Saudi Arabia.

Infections, with multidrug-resistant Pseudomonas aeruginosa, are a major concern in the pediatric intensive care unit, especially in immunocompromised patients. Some of these strains are resistant to all beta-lactams, including carbapenems, leaving very limited treatment options remaining. These options include aminoglycosides and colistin, both of which have poor pharmacokinetic profiles with significant toxicities. Newer beta-lactam/beta-lactamase inhibitor combinations offer additional novel options to treat such infections, given their good pharmacokinetic profiles and activity against multi-drug resistant strains. Ceftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination approved in 2014. The drug demonstrates good activity against multidrug-resistant P. aeruginosa strains, including those resistant to all other antibiotics. Ceftolozane/tazobactam is currently approved in adult patients 18 years and older only. There are very limited data on its pharmacokinetic profile and clinical utility in the pediatric population. We report the use of ceftolozane/tazobactam to successfully treat pneumonia caused by multidrug-resistant P. aeruginosa in a pediatric patient with combined immunodeficiency syndrome.