Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia: A Multihospital Cohort Study

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

Annals of Internal Medicine, August 6, 2019

 

Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration.The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care–associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability of treatment.

Two thirds (67.8% [4391 of 6481]) of patients received excess antibiotic therapy. Antibiotics prescribed at discharge accounted for 93.2% of excess duration. Patients who had respiratory cultures or nonculture diagnostic testing, had a longer stay, received a high-risk antibiotic in the prior 90 days, had community-acquired pneumonia, or did not have a total antibiotic treatment duration documented at discharge were more likely to receive excess treatment. Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge.

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Early Clinical Response in Community-acquired Bacterial Pneumonia: From Clinical Endpoint to Clinical Practice

By Julio A Ramirez,  Evan Tzanis,  Marla Curran,  Robert Noble,  Surya Chitra,  Amy Manley, Courtney Kirsch,  Paul C McGovern

Clinical Infectious Diseases, August 1, 2019

 

Early clinical response (ECR) is a new endpoint to determine whether a drug should be approved for community-acquired bacterial pneumonia in the United States. The Omadacycline for Pneumonia Treatment In the Community (OPTIC) phase III study demonstrated noninferiority of omadacycline to moxifloxacin using this endpoint. This study describes the performance of the ECR endpoint and clinical stability relative to a posttreatment evaluation (PTE) of clinical success.

ECR was defined as symptom improvement 72–120 hours after the first dose of study drug (ECR window), no use of rescue antibiotics, and patient survival. Clinical success at PTE was an investigator assessment of success. Clinical stability was defined based on vital sign stabilization, described in the American Thoracic Society and Infectious Diseases Society of America community-acquired pneumonia treatment guidelines.

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Risk Factors for Unnecessary Antibiotic Therapy: A Major Role for Clinical Management

By Pierre-Marie Roger,  Eve Montera,  Diane Lesselingue,  Nathalie Troadec,  Patrick Charlot, Agnès Simand,  Agnès Rancezot,  Olivier Pantaloni,  Thomas Guichard, Véronique Dautezac,  Cécile Landais,  Frédéric Assi,  Thierry Levent,  Collaborators

Clinical Infectious Diseases, To be Published August 1, 2019

 

Assessment of antimicrobial use places an emphasis on therapeutic aspects of infected patients. Our aim was to determine the risk factors for unnecessary antibiotic therapy (UAT).

This was a prospective, multicenter study evaluating all curative antibiotic therapies prescribed over 2 consecutive days through the same electronic medical records. Each item that could participate in these prescriptions was collected from the computerized file (reason for hospitalization, comorbid conditions, suspected or definitive diagnosis of infection, microbial analyses). UAT was defined as the recognition of noninfectious sydromes (NIS), nonbacterial infections, use of redundant antimicrobials, and continuation of empirical broad-spectrum antimicrobials.

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Comparison of 3 Days Amoxicillin Versus 5 Days Co-Trimoxazole for Treatment of Fast-breathing Pneumonia by Community Health Workers in Children Aged 2–59 Months in Pakistan: A Cluster-randomized Trial

By Salim Sadruddin,  Ibad ul Haque Khan,  Matthew P Fox,  Abdul Bari,  Attaullah Khan, Donald M Thea,  Amanullah Khan,  Inamullah Khan,  Ijaz Ahmad,  Shamim A Qazi

Clinical Infectious Diseases, To be Published August 1, 2019

 

Globally, most deaths due to childhood pneumonia occur at the community level. Some countries are still using oral co-trimoxazole, despite a World Health Organization recommendation of oral amoxicillin for the treatment of fast-breathing pneumonia in children at the community level.

We conducted an unblinded, cluster-randomized, controlled-equivalency trial in Haripur District, Pakistan. Children 2–59 months of age with fast-breathing pneumonia were treated with oral amoxicillin suspension (50 mg/kg/day) for 3 days in 14 intervention clusters and oral co-trimoxazole suspension (8 mg trimethoprim/kg and 40 mg sulfamethoxazole/kg/day) for 5 days in 14 control clusters by lady health workers (LHW). The primary outcome was treatment failure by day 4 for intervention clusters and by day 6 for control clusters. The analysis was per protocol.

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Procalcitonin-guided Antibiotic Treatment in Patients With Positive Blood Cultures: A Patient-level Meta-analysis of Randomized Trials

By Marc A Meier,  Angela Branche,  Olivia L Neeser,  Yannick Wirz,  Sebastian Haubitz, Lila Bouadma,  Michel Wolff,  Charles E Luyt,  Jean Chastre,  Florence Tubach, Mirjam Christ-Crain,  Caspar Corti,  Jens-Ulrik S Jensen,  Rodrigo O Deliberato, Kristina B Kristoffersen,  Pierre Damas,  Vandack Nobre,  Carolina F Oliveira, Yahya Shehabi,  Daiana Stolz,  Michael Tamm,  Beat Mueller,  Philipp Schuetz

Clinical Infectious Diseases, To be Published August 1, 2019

 

Whether procalcitonin (PCT)–guided antibiotic management in patients with positive blood cultures is safe remains understudied. We performed a patient-level meta-analysis to investigate effects of PCT-guided antibiotic management in patients with bacteremia.

We extracted and analyzed individual data of 523 patients with positive blood cultures included in 13 trials, in which patients were randomly assigned to receive antibiotics based on PCT levels (PCT group) or a control group. The main efficacy endpoint was duration of antibiotic treatment. The main safety endpoint was mortality within 30 days.

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