Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia

Vaughn, Valerie M.; Flanders, Scott A.; Snyder, Ashley; Conlon, Anna; Rogers, Mary A.M.; Malani, Anurag N.; McLaughlin, Elizabeth; Bloemers, Sarah; Srinivasan, Arjun; Nagel, Jerod; Kaatz, Scott; Osterholzer, Danielle; Thyagarajan, Rama; Hsaiky, Lama; Chopra, Vineet; Gandhi, Tejal

doi:10.7326/m18-3640

Cited by 172 publications

(147 citation statements)

References 39 publications

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“…Likewise, in the ODAPE trial patients who received a longer course of antibiotics had a trend towards developing more adverse effects, which was not statistically significant most likely due to the insufficient sample size. In a multicenter study of 6481 patients hospitalized with pneumonia (73% with CAP), each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge (mostly diarrhea, gastrointestinal distress and mucosal candidiasis) [8]. On the other hand, the prevalence of residual pleural thickening at 3 months from diagnosis was about 65%, a figure comparable with that reported in other studies [16].…”

Section: Discussionsupporting

confidence: 74%

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Two vs. three weeks of treatment with amoxicillin-clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial

Porcel

Ferreiro

Руми

et al. 2020

Pleura and Peritoneum

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Two vs. three weeks of treatment with amoxicillin-clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial Abstract Background: The optimal duration of antibiotic treatment for complicated parapneumonic effusions (CPPEs) has not been properly defined. Our aim was to compare the efficacy of amoxicillin-clavulanate for 2 vs. 3 weeks in patients with CPPE (i.e. those which required chest tube drainage). Methods: In this non-inferiority, randomized, doubleblind, controlled trial, patients with community-acquired CPPE were recruited from two centers in Spain and, after having obtained clinical stability following 2 weeks of amoxicillin-clavulanate, they were randomly assigned to placebo or antibiotic for an additional week. The primary objective was clinical success, tested for a non-inferiority margin of <10%. Secondary outcomes were the proportion of residual pleural thickening of >10 mm at 3 months, and adverse events. The study was registered with EudraCT, number 2014-003137-25. We originally planned to randomly assign 284 patients. Results: After recruiting 55 patients, the study was terminated early owing to slow enrolment. A total of 25 patients were assigned to 2 weeks and 30 patients to 3 weeks of amoxicillin-clavulanate. Clinical success occurred in the 25 (100%) patients treated for 2 weeks and 29 (97%) treated for 3 weeks (difference 3%, 95% CI −3 to 9.7%). Respective between-group differences in the rate of residual pleural thickening (−12%, 95%CI −39 to 14%) and adverse events (−7%, 95%CI −16 to 2%) did not reach statistical significance. Conclusions: In this small series of selected adult patients with community-acquired CPPE, amoxicillinclavulanate treatment could be safely discontinued by day 14 if clinical stability was obtained.

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Section: Discussionsupporting

confidence: 74%

“…About 5-7 days of antibiotics are considered effective enough for most CAP [7], though more than 70% of patients hospitalized with CAP eventually receive antibiotic treatment exceeding this recommended duration [8]. Conversely, the optimal duration of therapy for CPPE is unknown.…”

Section: Introductionmentioning

confidence: 99%

Two vs. three weeks of treatment with amoxicillin-clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial

Porcel

Ferreiro

Руми

et al. 2020

Pleura and Peritoneum

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“…Pneumonia is a primary cause of morbidity and mortality among adults, leading to more than one million hospitalizations every year and high rates of intensive care unit (ICU) admission in the US [1]. The mainstay of pneumonia management is early and appropriate antimicrobial therapy targeting the causative pathogens, balanced with preventing antibiotic overuse and emergence of resistance [2]. Thus, timely and accurate identification of causal pathogens is imperative yet remains challenging due to reliance on culture-based methods with low sensitivity and long turnaround times (48~72 h to actionable results [3]).…”

Section: Introductionmentioning

confidence: 99%

Metagenomic identification of severe pneumonia pathogens in mechanically-ventilated patients: a feasibility and clinical validity study

et al. 2019

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Background: Metagenomic sequencing of respiratory microbial communities for pathogen identification in pneumonia may help overcome the limitations of culture-based methods. We examined the feasibility and clinical validity of rapid-turnaround metagenomics with Nanopore™ sequencing of clinical respiratory specimens. Methods: We conducted a case-control study of mechanically-ventilated patients with pneumonia (nine culturepositive and five culture-negative) and without pneumonia (eight controls). We collected endotracheal aspirates and applied a microbial DNA enrichment method prior to metagenomic sequencing with the Oxford Nanopore MinION device. For reference, we compared Nanopore results against clinical microbiologic cultures and bacterial 16S rRNA gene sequencing. Results: Human DNA depletion enabled in depth sequencing of microbial communities. In culture-positive cases, Nanopore revealed communities with high abundance of the bacterial or fungal species isolated by cultures. In four cases with resistant clinical isolates, Nanopore detected antibiotic resistance genes corresponding to the phenotypic resistance in antibiograms. In culture-negative pneumonia, Nanopore revealed probable bacterial pathogens in 1/5 cases and Candida colonization in 3/5 cases. In controls, Nanopore showed high abundance of oral bacteria in 5/8 subjects, and identified colonizing respiratory pathogens in other subjects. Nanopore and 16S sequencing showed excellent concordance for the most abundant bacterial taxa. Conclusions: We demonstrated technical feasibility and proof-of-concept clinical validity of Nanopore metagenomics for severe pneumonia diagnosis, with striking concordance with positive microbiologic cultures, and clinically actionable information obtained from sequencing in culture-negative samples. Prospective studies with real-time metagenomics are warranted to examine the impact on antimicrobial decision-making and clinical outcomes.

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“…Excessive outpatient antibiotic therapy for treatment of pneumonia is associated with increased risk for adverse effects. 2 As such, we wanted to share additional outcomes related to our multicenter evaluation of an antimicrobial stewardship initiative focused on duration of therapy (DOT) for >600 patients with community-acquired pneumonia (CAP), 3 which is consistent with the findings by Dyer et al 3 and highlights the widespread need to focus on stewardship practices across phases of care.…”

mentioning

confidence: 84%

Improving antibiotic use through antimicrobial stewardship interventions upon discharge

Nguyen

Huang

Nagel

2019

Infect. Control Hosp. Epidemiol.

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Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia

Cited by 172 publications

References 39 publications

Two vs. three weeks of treatment with amoxicillin-clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial

Two vs. three weeks of treatment with amoxicillin-clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial

Metagenomic identification of severe pneumonia pathogens in mechanically-ventilated patients: a feasibility and clinical validity study

Improving antibiotic use through antimicrobial stewardship interventions upon discharge

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