The Association of Antibiotic Stewardship With Fluoroquinolone Prescribing in Michigan Hospitals: A Multi-hospital Cohort Study

By Valerie M Vaughn, Tejal Gandhi, Anna Conlon, Vineet Chopra, Anurag N Malani, Scott A Flanders. Published in Clinical Infectious Diseases. To be published October 15, 2019.   

 

Fluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown. This study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship. There were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003). Hospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing.

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Mycoplasma pneumoniae Carriage With De Novo Macrolide-Resistance and Breakthrough Pneumonia.

By Ammar Saadoon Alishlash, Thomas Prescott Atkinson, Charles Schlappi, Sixto M. Leal Jr, Ken B. Waites, Li Xiao. Published in Pediatrics. Published October 1, 2019.  

 

Mycoplasma pneumoniae pneumonia is prevalent in children and can be followed by upper airway carriage for months. Treatment of M pneumoniae pneumonia with macrolides is widespread and can lead to the development of macrolide resistance. The clinical consequences of chronic M pneumoniae carriage are unknown. In this article, we describe a child with acute lymphoblastic leukemia who developed macrolide-susceptible M pneumoniae pneumonia confirmed by nasopharyngeal secretions polymerase chain reaction and culture with good response to azithromycin. Five months later, the patient developed another M pneumoniae pneumonia that was diagnosed with positive macrolide-resistant M pneumoniae polymerase chain reaction and culture from the bronchoalveolar lavage. The child responded well to fluoroquinolones and eventually was discharged from the hospital. The M pneumoniae recovered from the second pneumonia is a novel strain and is genetically identical to the M pneumoniae that caused the first pneumonia, apart from the macrolide-resistance 23S ribosomal RNA gene. Both isolates are identical in both P1 (subtype 2 with a novel variant, 2bv) and multiple-locus variable number tandem repeat analysis type (53662). This is indicative of chronic M pneumoniae carriage with de novo macrolide-resistance mutation and subsequent breakthrough pneumonia that is reported for the first time here. Children with immunosuppression may be at increased risk of life-threatening macrolide-resistant pneumonia after M pneumoniae carriage. Further studies are required to evaluate the impact of this phenomenon. This will then guide strategies to limit the associated morbidity, such as testing for macrolide resistance, treatment of M pneumoniae pneumonia in high-risk children with bactericidal antibiotics (such as fluoroquinolones), and possibly eradication protocols of M pneumoniae carriage to prevent subsequent life-threatening infections.

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Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia

By Elizabeth Alexander, Lisa Goldberg, Anita F. Das, Gregory J. Moran, Christian Sandrock, Leanne B. Gasink, Patricia Spera, Carolyn Sweeney, Susanne Paukner, Wolfgang W. Wicha, Steven P. Gelone, Jennifer Schranz. JAMA. September 27, 2019.

 

Is 5-day oral lefamulin noninferior to 7-day oral moxifloxacin in the management of community-acquired bacterial pneumonia? In this randomized clinical trial that included 738 patients, the early clinical response at 96 hours (within a 24-hour window) after the first dose of study drug was 90.8% in the lefamulin group and 90.8% in the moxifloxacin group, a difference that met the noninferiority margin of 10%. This study demonstrated the noninferiority of oral lefamulin to oral moxifloxacin for the treatment of community-acquired bacterial pneumonia.

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View the accompanying editorial ‘Lefamulin—A New Antibiotic for Community-Acquired Pneumonia’ by Preeti N. Malani.

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Passage Adaptation Correlates With the Reduced Efficacy of the Influenza Vaccine

By Hui Chen, Jacob Josiah Santiago Alvarez, Sock Hoon Ng, Rasmus Nielsen, Weiwei Zhai

Clinical Infectious Diseases. October 1, 2019.

 

As a dominant seasonal influenza virus, H3N2 virus rapidly evolves in humans and is a constant threat to public health. Despite sustained research efforts, the efficacy of H3N2 vaccine has decreased rapidly. Even though antigenic drift and passage adaptation (substitutions accumulated during vaccine production in embryonated eggs) have been implicated in reduced vaccine efficacy (VE), their respective contributions to the phenomenon remain controversial.

We utilized mutational mapping, a powerful probabilistic method for studying sequence evolution, to analyze patterns of substitutions in different passage conditions for an unprecedented amount of H3N2 hemagglutinin sequences (n = 32 278).

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Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial

By Dafna Yahav, Erica Franceschini, Fidi Koppel, Adi Turjeman, Tanya Babich, Roni Bitterman, Ami Neuberger, Nesrin Ghanem-Zoubi, Antonella Santoro, Noa Eliakim-Raz, Barak Pertzov, Tali Steinmetz, Anat Stern, Yaakov Dickstein, Elias Maroun, Hiba Zayyad, Jihad Bishara, Danny Alon, Yonatan Edel, Elad Goldberg, Claudia Venturelli, Cristina Mussini, Leonard Leibovici, Mical Paul, Bacteremia Duration Study Group

Clinical Infectious Diseases. October 1, 2019.

 

Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited.

This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%.

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