Author: Marija Kusulja, MD
Time to Antibiotic for Pediatric Oncology Patients With Febrile Neutropenia at Regional Emergency Departments
This study evaluated time to antibiotic in 205 pediatric patients with oncology diagnosis (389 admissions), comparing groups treated in regular emergency department (26.7%) and those treated at pediatric emergency departments (73.3%). The observed outcome was need for aggressive medical care within 24 hours of admission, including more than one fluid bolus, intensive care unit admission, inotrope treatment and mechanical ventilation
The results of the study show that time to antibiotic was significantly greater in patients who presented at a non-pediatric emergency department. Additional analysis showed that presentation at a non-pediatric emergency department was the only factor associated with delay in antibiotic, although there was no association between the delay of antibiotic and the need for aggressive medical care.
In conclusion, pediatric oncology patients who present with febrile neutropenia at a non-pediatric emergency department have delayed antibiotic administration compared to the same patients who present at a pediatric emergency department.
Reference: Wadhwa A, Oakley J, Richman J, Bhatia S, Kutny MA. Time to Antibiotic for Pediatric Oncology Patients With Febrile Neutropenia at Regional Emergency Departments [published online ahead of print, 2020 Jun 16]. Pediatr Emerg Care. 2020;10.1097/PEC.0000000000002160. doi:10.1097/PEC.0000000000002160
Association of Azithromycin Use With Cardiovascular Mortality
The goal of this retrospective cohort study was to estimate cardiovascular risks in outpatient treated with azithromycin from 1998 to 2014. The study compared 7.8 million azithromycin exposures (22.2%) with 6 million amoxicillin exposures among 2.9 million patients aged 30 to 74 years, 61.8% of whom were women.
The results showed that azithromycin was associated with a significantly higher risk of cardiovascular death (HR 1.82, 95% CI, 1.23-2.67), an increased risk of non-cardiovascular death (HR 2.18, 95% CI, 1.44-3.26) and increased all-cause mortality (HR 2, 95% CI, 1.51-2.63) within 5 days of antibiotic exposure. There was no significant increase in sudden cardiac death (HR 1.59, 95% CI, 0.9-2.81), nor was there a significant increase in either observed outcome 6-10 days after exposure.
In conclusion, outpatient azithromycin prescription was associated with an increased risk of death, both cardiovascular and all-cause.
Reference: Zaroff JG, Cheetham TC, Palmetto N, et al. Association of Azithromycin Use With Cardiovascular Mortality. JAMA Netw Open. 2020;3(6):e208199. doi:10.1001/jamanetworkopen.2020.8199
Systematic or Test-Guided Treatment for Tuberculosis in HIV-Infected Adults
This study was conducted in order to compare test-guided and empirical treatment of tuberculosis in HIV-infected adults, the observed outcomes were all-cause death and invasive bacterial disease within 24 and 48 weeks following randomization. The study asigned ART-naive HIV-infected patients with CD4+ lower than 100 cells/mm3 from Ivory Coast, Uganda, Cambodia and Vietnam to two groups: 525 patients underwent Xpert MTB/RIF test, urinary lipoarabinomannan test and chest radiography to decide whether to initiate antituberculotic therapy, and 522 patients received systematic empirical treatment with rifampicin, isoniazid, ethambutol and pyrazinamide for 2 months, followed by rifampicin and isoniazid for 4 months.
The results show no superiority of empirical treatment for tuberculosis, with no increased rate of death nor invasive bacterial disease after 24 and 48 weeks of treatment; however, the patient in this group had a significantly higher incidence of drug-related adverse events.
Reference: François-Xavier Blanc, M.D., Ph.D., Anani D. Badje, M.D., Ph.D., Maryline Bonnet, M.D., Ph.D., Delphine Gabillard, M.Sc., Eugène Messou, M.D., Conrad Muzoora, M.D., et al. Systematic or Test-Guided Treatment for Tuberculosis in HIV-Infected Adults. N Engl J Med 2020; 382:2397-2410. DOI: 10.1056/NEJMoa1910708
Combination therapy with rifampicin or fosfomycin in patients with Staphylococcus aureus bloodstream infection at high risk for complications or relapse: results of a large prospective observational cohort
The goal of this study was to deduce whether patient with Staphylococcus aureus bloodstream infections at high risk for complications or relapse (patients with native valve infective endocarditis, osteoartricular infections, and those with implanted foreign devices) may benefit from combination therapy including rifampicin or fosfomycin.
The study included 313 patients who received combination therapy with either rifampicin (242) or fosfomycin (58), and 265 patients in control group. The combination therapy group had a lower rate of death or bloodstream infection-related late complications within 180 days (HR 0.65, 95% CI, 0.46-0.92), a result most prominent in patients with implanted foreign devices. There were no significant differences in outcome between patients receiving rifampicin and fosfomycin.
In conclusion, in patients with implanted foreign devices and S. aureus blood stream infection, combination therapy involving rifampicin or fosfomycin was associated with a better long-term outcome.
Reference: Rieg S, Ernst A, Peyerl-Hoffmann G, Joost I, Cam Jp, Hellmich M et al. Combination therapy with rifampicin or fosfomycin in patients with Staphylococcus aureus bloodstream infection at high risk for complications or relapse: results of a large prospective observational cohort, Journal of Antimicrobial Chemotherapy, dkaa144, https://doi.org/10.1093/jac/dkaa144
Mortality in Escherichia coli bloodstream infections: antibiotic resistance still does not make it
The objective of this study was to ascertain the role that host characteristics, bacterial virulence and antibiotic resistance play in the outcome of patients with E. coli blood stream infections.
The study included 545 patients of mean age 68.5± 16.5 years (52.5% male), with a mean Charlson comorbidity index of 5.6± 3.1; 19.6% patients presented with sepsis and 12.8% patients presented with septic shock. The most common portal of entry was urinary tract (51.9%), followed by digestive tract (41.9%). Upon NextSeq technology analysis it was revealed that 18% of isolates were third-generation cephalosporin resistant, most of which were ESBL producers. In hospital death at 28 days was 9.5%, with pulmonary port of entry [adjusted OR (aOR) 6.54, 95% CI 2.23–19.2], iha_17 virulence gene (aOR 4.41, 95% CI 1.23–15.74), high Charlson comorbidity index (aOR 1.14, 95% CI 1.04–1.26) and healthcare-associated infections (aOR 1.98, 95% CI 1.04–3.76) each independently associated with death outcome. Antibiotic resistance did not have a significant impact on mortality.
In conclusions, host factors, portal of entry and bacterial characteristics all play a major role in mortality associated with E. coli blood stream infections.
Reference: de Lastours V, Laouénan C, Royer G, Carbonnelle E, Lepeule R, Esposito-Farèse M et al. Mortality in Escherichia coli bloodstream infections: antibiotic resistance still does not make it, Journal of Antimicrobial Chemotherapy, dkaa161, https://doi.org/10.1093/jac/dkaa161
Oral fluconazole use in the first trimester and risk of congenital malformations: population based cohort study
The purpose of this cohort study was to assess the risk of congenital malformations connected to oral fluconazole exposure for the treatment of vulvovaginal candidiasis during the first trimester of pregnancy.
Out of almost 2 million publicly insured pregnancies in the USA traced through 2000-2014, 1.9% were exposed to oral fluconazole and 4.2% were exposed to topical azoles during the first trimester. The difference in pregnancies exposed to oral fluconazole and those exposed to topical azoles were: 52.1 vs 36.3 per 10.000 pregnancies for risk of musculoskeletal malformations (adjusted relative risk based on cumulative dose 1.29 [1.05-1.58]), 9.6 vs 8.3 per 10.000 pregnancies for risk of conotruncal malformations (adjusted relative risk based on cumulative dose 1.12 [0.71-1.77]) and 9.3 vs 10.6 per 10.000 pregnancies for risk of oral clefts (adjusted relative risk based on cumulative dose 0.99 [0.55-1.4]).
In conclusion, oral fluconazole use during the first trimester of pregnancy was associated with musculoskeletal malformations (12 incidents per 10.000 exposed pregnancies), while there was no association with conotruncal malformations and oral clefts.
Reference: Zhu Y, Bateman BT, Gray KJ, Hernandez-Diaz S, Mogun H, Straub L, et al. Oral fluconazole use in the first trimester and risk of congenital malformations: population based cohort study. BMJ 2020;369:m1494. doi: https://doi.org/10.1136/bmj.m1494
Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic HBV Infection: Systematic Review and Meta-analysis
This systematic review of 28 studies and a meta-analysis were performed in order to evaluate the association between HbsAg seroclearance and long-term clinical outcomes. The observed outcomes included hepatocellular carcinoma, liver decompensation, liver transplantation and all-cause mortality during follow up. The analysis included 1.486.081 person-years. The pooled risk ratios for HBsAg seroclearance group were 0.28 for liver decompensation (95% CI, 0.13-0.59), 0.3 for hepatocellular carcinoma (95% CI, 0.2-0.44), 0.22 for liver transplantation and/or death (95% CI, 0.13-0.39). The results were consistent in different types of studies, in all subpopulations. The conclusion of this meta-analysis is that there was a significant association between HBsAg seroclearance and positive patient outcomes, which supports the use of HBsAg seroclearance as primary endpoint in trials of patients with chronic HBV.
Reference: Anderson RT, Choi HSJ, Lenz O, et al. Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic HBV Infection: Systematic Review and Meta-analysis [published online ahead of print, 2020 May 27]. Clin Gastroenterol Hepatol. 2020;S1542-3565(20)30748-5. doi:10.1016/j.cgh.2020.05.041