Subsequent Antibiotic Use Research Articles

A CHALLENGE TO APPROPRIATE ANTIBIOTIC USE IN CHILDREN WITH RESPIRATORY INFECTIONS: A 5-YEAR SINGLE-INSTITUTION EXPERIENCE

We have studied the rate of emergence of antibiotic-resistant Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae) and the subsequent antibiotic use in host patients of those isolates at the Department of Pediatrics, Soma General Hospital, Fukushima. Moreover, we carried out several studies investigating the risks and benefits of antibiotic-free treatment for children with respiratory infections. In this report, we summarize our research and suggest better treatment options for pediatric patients with respiratory infections. We investigated the necessity of antibiotic use in the treatment of pediatric inpatients with respiratory syncytial virus (RSV) infection, and tested our hypothesis that antibiotic-free treatment for common cold will reduce the number of resistant S. pneumoniae strains in the pediatric nasopharynx. Therefore, we restricted prescribing antibiotics for pediatric patients with respiratory infections. The rates of resistant S. pneumoniae and H. influenzae and the medication history of the host patients before and after the intervention were compared. We found that most of the RSV-infected patients recovered without antibiotic treatment, and that the antibiotic-free treatment inhibited the emergence of antibiotic-resistant strains. The rate of penicillin-resistant S. pneumoniae decreased but the rate of ampicillin-resistant H. influenzae did not change significantly during the study. We concluded that patients with respiratory infections can be treated without antibiotics, under careful examination and observation. Continued monitoring of such new interventions as well as recommending their use to other caregivers and physicians will help inhibit the spread of resistant strains.

The Risk for Outpatient Antibiotic-Treated Infections Following a Course of Oral Corticosteroids Among Children with Asthma

Short courses of oral corticosteroids are widely used to treat asthma. The objective of this study was to assess if one course of oral corticosteroids increases asthmatic children's risk for infections treated with outpatient antibiotics. Using New York State Medicaid claims data on asthmatic children 2–15 years old, we made cohorts of oral corticosteroid users and nonusers. We determined the percentage of children who filled antibiotic prescriptions in the 30 days after index dates. Index dates were dates oral steroids were started (for steroid users) or matched dates (for nonusers). Odds ratios were adjusted for age, month of index date, and prior antibiotic use. Among children not receiving antibiotics on index dates, antibiotic prescriptions were filled in the next 30 days for 438 (20%) of 2145 steroid nonusers and 130 (19%) of 698 steroid users (p = 0.30); compared to nonusers, steroid users had an adjusted odds ratio of subsequent antibiotic use of 0.92 (95% confidence interval [CI] 0.73–1.15). Among children receiving antibiotics on index dates, antibiotic prescriptions were filled in the next 30 days for 116 (26%) of 451 steroid nonusers and 50 (19%) of 260 steroid users (p = 0.05); compared to nonusers, steroid users had an adjusted odds ratio of subsequent antibiotic use of 0.65 (95% Cl 0.53–0.97). We conclude that one course of oral corticosteroids does not increase asthmatic children's risk for infections treated with outpatient antibiotics.

Risk for infection following oral corticosteroid use in children with asthma♦ 44

To assess if one course of oral steroids increases the risk for bacterial infection in children with asthma, we used New York Medicaid data for children 2-15 yo with asthma. We made cohorts of oral steroid users and non-users, and determined the percentage of children in each cohort with antibiotic prescriptions filled in the 30 days after index dates. Index dates were dates oral steroids were started (for steroid users) or matched dates (for steroid non-users). Analyses adjusted for age, month of index date, and recent antibiotic use. Among children who did not receive antibiotics on their index dates, antibiotic prescriptions were filled in the next 30 days for 438 (20%) of 2,145 steroid non-users and 130 (19%) of 698 steroid users (p=NS); compared to non-users, oral steroid users had an adjusted odds ratio of subsequent antibiotic use of 0.92 (95% CI 0.73, 1.15). Among children who received antibiotics on their index dates, antibiotic prescriptions were filled in the next 30 days for 116 (26%) of 451 steroid non-users and 50 (19%) of 260 steroid users (p=0.05); compared to non-users, oral steroid users had an adjusted odds ratio of subsequent antibiotic use of 0.65 (95% CI 0.44, 0.97). Among children with asthma, one course of oral steroids is not associated with an increased use of antibiotics in the 30 days after the course is initiated, suggesting it does not increase the risk for bacterial infections. Compared to asthmatic children given antibiotics without oral steroids, asthmatic children given antibiotics when oral steroids are started have a lower rate of antibiotic use in the next 30 days, probably because of differences in the infections initially treated.

Acute Asthma: Admission Chest Radiography in Hospitalized Adult Patients

The utility of admission chest radiography has been controversial in the management of adult patients admitted to the hospital with acute asthma. We reviewed the impact of admission chest radiography on in-hospital management of 54 adult patients with acute asthma. Each patient was admitted after a failed 12-h course of bronchodilator therapy in the emergency ward. Major radiographic abnormalities were found in 20 (34 percent) of 58 occasions. These abnormalities included focal parenchymal opacities, IIM, enlarged cardiac silhouette, pulmonary vascular congestion, new solitary pulmonary nodule and pneumothorax. Subsequent antibiotic use correlated with radiographic focal opacities or IIM, even in afebrile patients, but did not correlate with elevated blood leukocyte count. Based on the evidence of in-hospital alteration of management independent of elevated blood leukocyte count and body temperature, we recommend that chest radiographs be obtained for all adult patients admitted because of acute asthma.

A case of meningomyelocele in a kindred with multiple cases of spondylolisthesis and spina bifida occulta.

<h3>Background</h3> The use of immune checkpoint inhibitors (ICI) has increased significantly in the past five years, along with the number of available drugs and regimens. ICIs have dramatically increased survival in cancer patients, however, there has been data to show that they have reduced efficacy in the presence of antibiotics.¹ Antibiotic use prior and during ICI therapy was associated with worsening clinical outcomes in patients with renal cell carcinoma,² melanoma,³ and non-small-cell-lung-cancer.⁴ Specifically, exposure within 60 days of initiation of ICIs in NSCLC seemed most detrimental, however, some studies have suggested that antibiotics disrupt intestinal microflora for up to six months.^{5 6} Therefore, we hypothesized that the duration of the antibiotic effect on ICI efficacy may be present for a longer duration. <h3>Methods</h3> The electronic medical record was queried at the University of Cincinnati Medical Center for the administration of ICIs and antibiotics. Data was collected on the use, type, and duration of antibiotics before ICI use after administration with relevant demographic and clinicopathologic variables including treatment type, cancer type, staging information, and clinical course including subsequent antibiotic use. Univariant (Fischer’s Exact) and multivariant analysis (multiple logistic regression) were conducted and survival analysis was determined according to log-rank testing. <h3>Results</h3> 217 patients were examined. The median age was 64 (range 22-93), 38% were female, 73% had ECOG 0-1, and 77% were white. Cancer types included melanoma 24%, non-small cell lung cancer (NSCLC) 34%, small cell lung cancer 2%, renal cancer 11%, urothelial cancer 10%, head and neck cancers 11%, and 16% other primaries. 20% remained on ICI at the time of data entry. The most common ICIs were pembrolizumab, nivolumab, followed by ipilimumab-nivolumab, ipilimumab, and durvalumab. 81 patients of 218 received antibiotics within 6 months of receiving checkpoint inhibitors. Of antibiotics administered, the most common classes were cephalosporins (86%), fluoroquinolones (28%), and glycopeptides (23%) with substantial overlap. Overall survival and progression-free survival was improved for those who did not receive antibiotics prior to ICI therapy (median OS 6.5 vs. 2.3 years, HR 0.36, p&lt;0.0001; median PFS 1.1 vs 0.5 years, HR 0.6, p=0.0027) (figure 1 and 2 respectively). Linear regression showed no significant association between antibiotic use prior to ICI use and age, sex, race, ICI type, or ECOG status. <h3>Conclusions</h3> This data adds to the growing body of knowledge that the use of antibiotics prior to ICI treatment leads to inferior overall and progression-free survival. <h3>Acknowledgements</h3> We would like to thank the Roman Jandarov, UC Cancer Center, the University of Cincinnati Division of Hematology and Oncology, Department of Internal Medicine of the University of Cincinnati, and the University of Cincinnati Medical Center for their continued support. <h3>Ethics Approval</h3> IRB 2019-0610 <h3>References</h3> Pinato DJ, Gramenitskaya D, Altmann DM, Boyton RJ, Mullish BH, Marchesi JR, et al. Antibiotic therapy and outcome from immune-checkpoint inhibitors. <i>J Immunother Cancer</i> 2019;<b>7</b>:287. Ueda K, Yonekura S, Ogasawara N, Matsunaga Y, Hoshino R, Kurose H, et al. The impact of antibiotics on prognosis of metastatic renal cell carcinoma in japanese patients treated with immune checkpoint inhibitors. <i>Anticancer Res</i> 2019;<b>39</b>:6265–71. Elkrief A, El Raichani L, Richard C, Messaoudene M, Belkaid W, Malo J, et al. Antibiotics are associated with decreased progression-free survival of advanced melanoma patients treated with immune checkpoint inhibitors. <i>Oncoimmunology</i> 2019;8:e1568812. Ruiz-Patiño A, Barrón F, Cardona AF, Corrales L, Mas L, Martín C, et al. Antibiotics impair immune checkpoint inhibitor effectiveness in Hispanic patients with non-small cell lung cancer (AB-CLICaP). <i>Thorac Cancer</i> 2020;(9):2552-2560. Pinato DJ, Howlett S, Ottaviani D, Urus H, Patel A, Mineo T, et al. Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer. <i>JAMA Oncol</i> 2019;5(12):1774-1778. Panda S, Khader IE, Casellas F, Vivancos JL, Cors MG, Santiago A, et al. Short-term effect of antibiotics on human gut microbiota. <i>PLoS ONE</i> 2014;9.