A Decision Tree Using Patient Characteristics to Predict Resistance to Commonly Used Broad-Spectrum Antibiotics in Children With Gram-Negative Bloodstream Infections

Abstract Background As rates of multidrug-resistant gram-negative infections rise, it is critical to recognize children at high risk of bloodstream infections with organisms resistant to commonly used empiric broad-spectrum antibiotics. The objective of the current study was to develop a user-friendly clinical decision aid to predict the risk of resistance to commonly prescribed broad-spectrum empiric antibiotics for children with gram-negative bloodstream infections. Methods This was a longitudinal retrospective cohort study of children with gram-negative bacteria cared for at a tertiary care pediatric hospital from June 2009 to June 2015. The primary outcome was a bloodstream infection due to bacteria resistant to broad-spectrum antibiotics (ie, cefepime, piperacillin-tazobactam, meropenem, or imipenem-cilastatin). Recursive partitioning was used to develop the decision tree. Results Of 689 episodes of gram-negative bloodstream infections included, 31% were resistant to broad-spectrum antibiotics. The decision tree stratified patients into high- or low-risk groups based on prior carbapenem treatment, a previous culture with a broad-spectrum antibiotic resistant gram-negative organism in the preceding 6 months, intestinal transplantation, age ≥3 years, and ≥7 prior episodes of gram-negative bloodstream infections. The sensitivity for classifying high-risk patients was 46%, and the specificity was 91%. Conclusion A decision tree offers a novel approach to individualize patients’ risk of gram-negative bloodstream infections resistant to broad-spectrum antibiotics, distinguishing children who may warrant even broader antibiotic therapy (eg, combination therapy, newer β-lactam agents) from those for whom standard empiric antibiotic therapy is appropriate. The constructed tree needs to be validated more widely before incorporation into clinical practice.

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Which Type of Empiric Antibiotic Therapy is Appropriate? A 20-Year Retrospective Study of Bloodstream Infections in Childhood Cancer

Infectious Diseases and Therapy ◽

10.1007/s40121-021-00427-5 ◽

2021 ◽

Author(s):

Andreas Meryk ◽

Gabriele Kropshofer ◽

Caroline Bargehr ◽

Miriam Knoll ◽

Benjamin Hetzer ◽

...

Keyword(s):

Retrospective Study ◽

Antibiotic Therapy ◽

Childhood Cancer ◽

Bloodstream Infections ◽

Empiric Antibiotic Therapy ◽

Empiric Antibiotic

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Pattern of acquisition of hospital-associated pathogens in the ICU of an academic tertiary care hospital

Official Journal of the Association of Medical Microbiology and Infectious Disease Canada ◽

10.3138/jammi-2021-0025 ◽

2022 ◽

Author(s):

Shazia Damji ◽

Jerrold Perrott ◽

Salomeh Shajari ◽

Jennifer Grant ◽

Titus Wong ◽

...

Keyword(s):

Hospital Admission ◽

Median Time ◽

Broad Spectrum ◽

Health Authority ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Primary Objective ◽

Solid Organ ◽

Care Hospital ◽

Broad Spectrum Antibiotics

BACKGROUND: Among hospitalized patients, a 48-hour window from time of hospitalization defines nosocomial infections and guides empiric antibiotic selection. This time frame may lead to overuse of broad-spectrum antibiotics. Our primary objective was to determine the earliest and median time since hospital admission to acquire antibiotic-resistant pathogens among patients admitted to the intensive care unit (ICU) of an academic, tertiary care hospital. METHODS: Retrospective chart review was conducted for adult patients admitted to the ICU from home or another hospital within the same health authority in 2018, to identify the time to acquisition of hospital-associated pathogens: methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococci, extended-spectrum beta-lactamase (ESBL)–producing Enterobacterales, non-ESBL ceftriaxone-resistant Enterobacterales, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Patients transferred from hospitals outside the health authority, admitted to ICU after 14 days of hospitalization, who were solid organ or bone marrow transplant recipients, or who were otherwise immunocompromised were excluded. RESULTS: In 2018, 1,343 patients were admitted to this ICU; 820 met the inclusion criteria. Of these, 121 (14.76%) acquired a hospital-associated pathogen in the ICU. The probability of isolating a hospital-associated pathogen by 48 hours of hospital admission was 3%. The earliest time to isolate any of these pathogens was 29 hours, and the median was 9 days (interquartile range [IQR] 3.8–15.6 days). CONCLUSIONS: Most patients (85.3%) in this ICU never acquired a hospital-associated pathogen. The median time to acquire a hospital-associated pathogen among the remaining patients suggests that initiating empiric broad-spectrum antibiotics on the basis of a 48-hour threshold may be premature.

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51 Overuse of ceftriaxone in children with otitis media: experience at a Canadian tertiary care hospital

Paediatrics & Child Health ◽

10.1093/pch/pxaa068.050 ◽

2020 ◽

Vol 25 (Supplement_2) ◽

pp. e21-e21

Author(s):

Mila Arnautovich ◽

Ann-Christine Godard ◽

Jean-Francois Turcotte

Keyword(s):

Otitis Media ◽

Broad Spectrum ◽

Antibiotic Stewardship ◽

Tertiary Care ◽

Penicillin Allergy ◽

White Blood Count ◽

Oral Drugs ◽

Broad Spectrum Antibiotics ◽

Amoxicillin Clavulanate ◽

History Of

Abstract Background Acute otitis media (AOM) is extremely common. In fact, most children experience at least one ear infection before starting school. It is also recognized as the most frequent reason to administer antibiotics in children. However, many advocate for limited use of antibiotics in healthy children over 6 months of age using a watchful waiting approach. This applies even more for broad-spectrum antibiotics in the context of antibiotic stewardship. The Canadian Paediatric Society (CPS) recommends using parenteral ceftriaxone only when oral drugs are not tolerated or amoxicillin-clavulanate fails. Objectives This primary aim of this study was to describe the use of ceftriaxone in the treatment of children with AOM. Secondary aims were to assess length of therapy and complications as well as determine if the use of ceftriaxone met the criteria of refractory AOM suggested by the CPS. Design/Methods We performed a retrospective observational cohort study of children aged between the ages of 6 months and 5 years with a diagnosis of AOM at a single tertiary care center. All children were seen between March 2017 and February 2019 in a pediatric outpatient medical day unit and received at least one dose of ceftriaxone. Chart review was performed and multiples variables were included in the analysis. Patients with insufficient chart data or with a congenital ear anomaly were excluded. Results A total of 276 patients were included. Patients were aged 17.5 ± 9 months and a majority were boys (N=160). Most patients were fully immunized (N=252). A history of penicillin allergy was reported for 59 patients. Previous AOM was common (N=205) while tympanostomy tubes were rare (N=12). With regards to the diagnosis of AOM, a majority (N=153) had bilateral AOM. Diagnosis of AOM was based on inflammation (N=204), bulging tympanic membrane (N=158) or middle ear effusion (N=118). Fourteen patients had a tympanic perforation. Almost all patients were febrile (N=266). One patient had a positive blood culture (streptococcus pneumoniae) and one had a mastoiditis. Among those who underwent bloodwork (N=212), white blood count was 15.2 ± 6.7 x 109. With regards to antibiotics, most patients (N=218) were initially given oral antibiotics, with amoxicillin given as a first line therapy for 99 patients. A minority of patients received amoxicillin-clavulanate prior to receiving ceftriaxone (N=105). Reasons for the use of ceftriaxone included intolerance to oral drugs (N=18), failure of (or recent exposure to) amoxicillin-clavulanate (N=89) and a history of penicillin allergy (N=50). Most patients were treated with a course of three days with only 51 patients receiving one or two doses. Conclusion In our cohort, the use of ceftriaxone was not limited to nonresponsive AOM. In fact, a minority of patients received ceftriaxone in the setting of intolerance to oral drugs or failure of amoxicillin-clavulanate. This goes against current CPS recommendations and suggests an overuse of broad-spectrum antibiotics. Obviously, this needs to be addressed in the context of antibiotic stewardship.

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Time to First Culture Positivity for Gram-Negative Rods Resistant to Ceftriaxone in Critically Ill Adults

Journal of Intensive Care Medicine ◽

10.1177/0885066620963903 ◽

2020 ◽

Vol 36 (1) ◽

pp. 51-57

Author(s):

Kevin G. Buell ◽

Jonathan D. Casey ◽

Michael J. Noto ◽

Todd W. Rice ◽

Matthew W. Semler ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Critically Ill ◽

Broad Spectrum ◽

Research Question ◽

Blood Cultures ◽

Optimal Timing ◽

Gram Negative ◽

Broad Spectrum Antibiotics ◽

Critically Ill Adults ◽

Ill Adults

Background: The optimal timing for the de-escalation of broad-spectrum antibiotics with activity against Pseudomonas aeruginosa and resistant Gram-negative rods (GNRs) in critically ill adults remains unknown. Research Question: We tested the hypothesis that cultures will identify GNRs that ultimately demonstrate resistance to ceftriaxone within 48 hours, potentially allowing safe de-escalation at this time point. Study Design and Methods: We conducted a secondary analysis of data from the Isotonic Solutions and Major Adverse Renal Events Trial: a pragmatic, cluster-randomized, multiple-crossover trial comparing balanced crystalloids versus saline for intravenous fluid administration in 15,802 critically ill adults at 5 intensive care units (ICUs) at Vanderbilt University Medical Center in Nashville, TN, USA. The primary endpoint was the time-to-positivity of respiratory and blood cultures that ultimately demonstrated growth of GNRs resistant to ceftriaxone. Multivariable logistic regression modeling was used to examine risk factors for the growth of cultures after 48 hours. Results: A total of 524 respiratory cultures had growth of GNRs, of which 284 (54.2%) had resistance to ceftriaxone. A total of 376 blood cultures grew GNRs, of which 70 (18.6%) had resistance to ceftriaxone. At 48 hours, 87% of respiratory cultures and 85% of blood cultures that ultimately grew GNRs resistant to ceftriaxone had demonstrated growth. Age, gender, predicted risk of inpatient mortality and prior use of antibiotics did not predict the growth of cultures after 48 hours. Interpretation: Among a cohort of critically ill adults, 13% of respiratory cultures and 15% of blood cultures that ultimately grew GNRs resistant to ceftriaxone did not demonstrate growth until at least 48 hours after collection. Further work is needed to determine the ideal time for critically ill adults to de-escalate from broad-spectrum antibiotics targeting Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing gram-negative pathogens.

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Prolonged empirical antibiotic therapy is correlated with bloodstream infections and increased mortality in a tertiary care hospital in Ethiopia: bacteriology testing matters

JAC-Antimicrobial Resistance ◽

10.1093/jacamr/dlaa039 ◽

2020 ◽

Vol 2 (3) ◽

Cited By ~ 1

Author(s):

Makeda Semret ◽

Workeabeba Abebe ◽

Ling Yuan Kong ◽

Tinsae Alemayehu ◽

Temesgen Beyene ◽

...

Keyword(s):

Blood Culture ◽

Antibiotic Therapy ◽

Tertiary Care ◽

Empirical Therapy ◽

Bloodstream Infections ◽

Care Hospital ◽

Empirical Antibiotic Therapy ◽

Middle Income ◽

Risk Of Death ◽

Days Of Therapy

Abstract Background Hospital-associated infection (HAI) and antimicrobial resistance (AMR) are major health threats in low- and middle-income countries (LMICs). Because diagnostic capacity is lacking throughout most of Africa, patients are commonly managed with prolonged empirical antibiotic therapy. Our goal was to assess mortality in relation to HAI and empirical therapy in Ethiopia’s largest referral hospital. Methods Cohort study of patients with suspected HAI at Tikur Anbessa Specialized Hospital from October 2016 to October 2018. Blood culture testing was performed on an automated platform. Primary outcomes were proportion of patients with bloodstream infection (BSI), antibiotic resistance patterns and 14 day mortality. We also assessed days of therapy (DOT) pre- and post-blood culture testing. Results Of 978 enrolled patients, 777 had blood culture testing; 237 (30%) had a BSI. Enterobacteriaceae were isolated in 49%; 81% of these were cephalosporin resistant and 23% were also carbapenem resistant. Mortality at 14 days was 31% and 21% in those with and without BSI, respectively. Ceftriaxone resistance was strongly correlated with mortality. Patients with BSI had longer DOT pre-blood culture testing compared with those without BSI (median DOT 12 versus 3 days, respectively, P < 0.0001). After testing, DOT were comparable between the two groups (20 versus 18 days, respectively). Conclusions BSI are frequent and fatal among patients with suspected HAI in Ethiopia. Highly resistant blood isolates are alarmingly common. This study provides evidence that investing in systematic blood culture testing in LMICs identifies patients at highest risk of death and that empirical management is frequently inappropriate. Major investments in laboratory development are critical to achieve better outcomes.

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Pseudomonal breast infection

Annals of The Royal College of Surgeons of England ◽

10.1308/147870810x12659688851591 ◽

2010 ◽

Vol 92 (3) ◽

pp. e20-e22 ◽

Cited By ~ 4

Author(s):

DP Harji ◽

S Rastall ◽

C Catchpole ◽

R Bright-Thomas ◽

S Thrush

Keyword(s):

Septic Shock ◽

Pseudomonas Aeruginosa ◽

Antibiotic Therapy ◽

Broad Spectrum ◽

Abscess Formation ◽

Causative Organism ◽

Breast Infection ◽

Broad Spectrum Antibiotics

Breast infection and breast sepsis secondary to Pseudomonas aeruginosa is uncommon. We report two cases of pseudomonal breast infection leading to septic shock and abscess formation in women with non-responding breast infection. The management of breast infection is broad-spectrum antibiotics and ultrasound with aspiration of any collection. To treat breast infection effectively, the causative organism must be isolated to enable appropriate antibiotic therapy.

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Epidemiology of Inappropriate Empiric Antibiotic Therapy for Bacteremia Based on Discordant In vitro Susceptibilities: Risk factors and Taxon-level Variation in Burden and Outcome in 156 US hospitals, 2000–2014

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx162.032 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S13-S14

Author(s):

Sameer S Kadri ◽

Yi Ling Lai ◽

Emily Ricotta ◽

Jeffrey Strich ◽

Ahmed Babiker ◽

...

Keyword(s):

Risk Factors ◽

Antibiotic Therapy ◽

Empiric Antibiotic Therapy ◽

In Vitro Susceptibility ◽

Gram Negative ◽

Risk Of Death ◽

Risk Of Mortality ◽

Increased Risk ◽

Empiric Antibiotic

Abstract Background Discordance between in vitro susceptibility and empiric antibiotic therapy is inextricably linked to antibiotic resistance and decreased survival in bloodstream infections (BSI). However, its prevalence, patient- and hospital-level risk factors, and impact on outcome in a large cohort and across different pathogens remain unclear. Methods We examined in vitro susceptibility interpretations for bacterial BSI and corresponding antibiotic therapy among inpatient encounters across 156 hospitals from 2000 to 2014 in the Cerner Healthfacts database. Discordance was defined as nonsusceptibility to initial therapy administered from 2 days before pathogen isolation to 1 day before final susceptibility reporting. Discordance prevalence was compared across taxa; risk factors and its association with in-hospital mortality were evaluated by logistic regression. Adjusted odds ratios (aOR) were estimated for pathogen-, patient- and facility-level factors. Results Of 33,161 unique encounters with BSIs, 4,219 (13%) at 123 hospitals met criteria for discordant antibiotic therapy, ranging from 3% for pneumococci to 55% for E. faecium. Discordance was higher in recent years (2010–2014 vs. 2005–2009) and was associated with older age, lower baseline SOFA score, urinary (vs. abdominal) source and hospital-onset BSI, as well as ≥500-bed, Midwestern, non-teaching, and rural hospitals. Discordant antibiotic therapy increased the risk of death [aOR = 1.3 [95% CI 1.1–1.4]). Among Gram-negative taxa, discordant therapy increased risk of mortality associated with Enterobacteriaceae (aOR = 1.3 [1.0–1.6]) and non-fermenters (aOR = 1.7 [1.1–2.5]). Among Gram-positive taxa, risk of mortality from discordant therapy was significantly higher for S. aureus (aOR = 1.3 [1.1–1.6]) but unchanged for streptococcal or enterococcal BSIs. Conclusion The prevalence of discordant antibiotic therapy displayed extensive taxon-level variability and was associated with patient and institutional factors. Discordance detrimentally impacted survival in Gram-negative and S. aureus BSIs. Understanding reasons behind observed differences in discordance risk and their impact on outcomes could inform stewardship efforts and guidelines for empiric therapy in sepsis. Disclosures All authors: No reported disclosures.

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Multidrug Pump Inhibitors Uncover Remarkable Activity of Plant Antimicrobials

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.10.3133-3141.2002 ◽

2002 ◽

Vol 46 (10) ◽

pp. 3133-3141 ◽

Cited By ~ 294

Author(s):

George Tegos ◽

Frank R. Stermitz ◽

Olga Lomovskaya ◽

Kim Lewis

Keyword(s):

Broad Spectrum ◽

Plant Pathogens ◽

Bacterial Species ◽

Permeability Barrier ◽

Gram Negative Bacteria ◽

Human Pathogens ◽

Gram Negative ◽

Low Level ◽

Broad Spectrum Antibiotics ◽

Level Of Activity

ABSTRACT Plant antimicrobials are not used as systemic antibiotics at present. The main reason for this is their low level of activity, especially against gram-negative bacteria. The reported MIC is often in the range of 100 to 1,000 μg/ml, orders of magnitude higher than those of common broad-spectrum antibiotics from bacteria or fungi. Major plant pathogens belong to the gram-negative bacteria, which makes the low level of activity of plant antimicrobials against this group of microorganisms puzzling. Gram-negative bacteria have an effective permeability barrier, comprised of the outer membrane, which restricts the penetration of amphipathic compounds, and multidrug resistance pumps (MDRs), which extrude toxins across this barrier. It is possible that the apparent ineffectiveness of plant antimicrobials is largely due to the permeability barrier. We tested this hypothesis in the present study by applying a combination of MDR mutants and MDR inhibitors. A panel of plant antimicrobials was tested by using a set of bacteria representing the main groups of plant pathogens. The human pathogens Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica serovar Typhimurium were also tested. The results show that the activities of the majority of plant antimicrobials were considerably greater against the gram-positive bacteria Staphylococcus aureus and Bacillus megaterium and that disabling of the MDRs in gram-negative species leads to a striking increase in antimicrobial activity. Thus, the activity of rhein, the principal antimicrobial from rhubarb, was potentiated 100- to 2,000-fold (depending on the bacterial species) by disabling the MDRs. Comparable potentiation of activity was observed with plumbagin, resveratrol, gossypol, coumestrol, and berberine. Direct measurement of the uptake of berberine, a model plant antimicrobial, confirmed that disabling of the MDRs strongly increases the level of penetration of berberine into the cells of gram-negative bacteria. These results suggest that plants might have developed means of delivering their antimicrobials into bacterial cells. These findings also suggest that plant antimicrobials might be developed into effective, broad-spectrum antibiotics in combination with inhibitors of MDRs.

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