Faculty Opinions recommendation of Less is more: combination antibiotic therapy for the treatment of gram-negative bacteremia in pediatric patients.

Abstract Background The rise of antimicrobial resistance among gram-negative (GN) pathogens has been dramatic nationally. Delayed initiation of active antimicrobial agents has been associated with poor outcomes. We aimed at evaluating the prevalence and treatment of multi-drug-resistant gram-negative (MDR-GN) bacteremia in our pediatric patients. Methods All episodes of GN bacteremia from 2017–2018 at our institution were retrospectively reviewed. GN defined as MDR in our study were carbapenem-resistant organisms (CRO), extended-spectrum β-lactamase (ESBL) producers, and GN that were resistant to cefepime and ≥2 classes of non-cephalosporin antimicrobial agents. Stenotrophomonas maltophilia was excluded. Ineffective empirical treatment (IET) is defined as an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results. Results A total of 292 episodes of GN bacteremia were identified and 6 S. maltophilia were excluded. Of these, 29 bacteremic episodes in 26 patients were caused by MDR-GN organisms including 18 ESBL, 7 CRO, 1 ESBL and CRO, 3 non-ESBL/non-CRO cefepime-resistant MDR-GN. None of the CRO had carbapenemase genes detected. However, there was a patient with multiple sites of infection simultaneously with non-NDM CR Acinetobacter bacteremia and NDM-mediated CR-Klebsiella ventriculitis. The annual rate of MDR-GN bacteremia increased from 8% in 2017 to 12% in 2018. Almost half (48%) of episodes were community onset. Among these, all but one had underlying medical conditions with hospital exposure and most patients had central venous devices at the time of infection. 52% (15/29) episodes of MDR-GN bacteremia had IET. Despite IET, 47% (7/15) had negative blood cultures prior to initiation of effective therapy (6 ESBL and 1 P. aeruginosa). Various antibiotic regimens were used for CRO therapy as shown in Table 1. Conclusion In our institution, MDR-GN infection is increasing. As such, empiric meropenem is currently recommended in BMT or neutropenic patients with suspected sepsis. However, empiric meropenem must be used judiciously as its widely use will lead to more selection of MDR pathogens. It is essential to continue monitoring of these MDR-GN to guide appropriate empiric regimens. Disclosures All authors: No reported disclosures.

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Pharmacist-Driven Implementation of Fast Identification and Antimicrobial Susceptibility Testing Improves Outcomes for Patients with Gram-Negative Bacteremia and Candidemia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00578-20 ◽

2020 ◽

Vol 64 (9) ◽

Author(s):

Sahil Sheth ◽

Michael Miller ◽

Angela Beth Prouse ◽

Scott Baker

Keyword(s):

Targeted Therapy ◽

Antibiotic Therapy ◽

Antimicrobial Susceptibility ◽

Susceptibility Testing ◽

Antimicrobial Susceptibility Testing ◽

Gram Negative ◽

Fast Identification ◽

Intensity Score ◽

Gram Negative Bacteremia ◽

The Impact

ABSTRACT Bloodstream infections (BSI) are associated with increased morbidity and mortality, especially when caused by Gram-negative or fungal pathogens. The objective of this study was to assess the impact of fast identification-antimicrobial susceptibility testing (ID/AST) with the Accelerate Pheno system (AXDX) from May 2018 to December 2018 on antibiotic therapy and patient outcomes. A pre-post quasiexperimental study of 200 patients (100 pre-AXDX implementation and 100 post-AXDX implementation) was conducted. The primary endpoints measured were time to first antibiotic intervention, time to most targeted antibiotic therapy, and 14-day hospital mortality. Secondary endpoints included hospital and intensive care unit (ICU) length of stay (LOS), antibiotic intensity score at 96 h, and 30-day readmission rates. Of 100 patients with Gram-negative bacteremia or candidemia in each cohort, 84 in the preimplementation group and 89 in the AXDX group met all inclusion criteria. The AXDX group had a decreased time to first antibiotic intervention (26.3 versus 8.0, P = 0.003), hours to most targeted therapy (14.4 versus 9, P = 0.03), hospital LOS (6 versus 8, P = 0.002), and average antibiotic intensity score at 96 h (16 versus 12, P = 0.002). Both groups had a comparable 14-day mortality (0% versus 3.6%, P = 0.11). In this analysis of patients with Gram-negative bacteremia or candidemia, fast ID/AST implementation was associated with decreased hospital LOS, decreased use of broad-spectrum antibiotics, shortened time to targeted therapy, and an improved utilization of antibiotics within the first 96 h of therapy.

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52. Development and Implementation of a Short Duration of Antibiotic Therapy Algorithm for Uncomplicated Gram-Negative Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.097 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S48-S48

Author(s):

Esther Y Bae ◽

Fidelia Bernice ◽

Kathryn Dzintars ◽

Sara E Cosgrove ◽

Pranita D Tamma ◽

...

Keyword(s):

Antibiotic Therapy ◽

Clinical Outcomes ◽

Median Duration ◽

Intervention Period ◽

Therapy Algorithm ◽

Gram Negative ◽

Duration Of Therapy ◽

Number Of Patients ◽

Gram Negative Bacteremia ◽

The Impact

Abstract Background Recent literature suggests no difference in clinical outcomes between short (7 days) and prolonged course (14 days) antibiotic therapy for the treatment of uncomplicated Gram-negative bacteremia (GNB). Methods The objectives of the study were to develop and implement a treatment algorithm that identifies patients who are eligible for 7-day therapy for uncomplicated GNB and evaluate its impact on patient outcomes at The Johns Hopkins Hospital (JHH) in Baltimore. The algorithm was developed and implemented at JHH on 11/11/2019. From 11/11/2019 to 3/31/2020, the Infectious Diseases (ID) Pharmacy Resident and ID pharmacists reviewed cases of GNB on weekdays and contacted teams to provide algorithm-compliant treatment recommendations. To quantify the impact of the intervention on clinical outcomes, data from the same time period during the previous year (baseline) were collected and compared to those collected during the intervention. The primary outcome was duration of antibiotic therapy for GNB. Secondary outcomes included: duration of intravenous (IV) antibiotics, length of hospital stay (LOS), and recurrent bacteremia. Results A total of 345 patients with GNB were identified (142 baseline; 203 intervention) of which 59 and 55 patients met criteria for 7-day therapy, respectively. The Pitt bacteremia score (median 1), bacteremia source [urinary (43%), abdominal (23%)], and organisms [E. coli (48%) and Klebsiella spp. (33%)] were similar between the periods. More patients in the intervention period were treated for ≤8 days (60.0% vs. 37.3%; p=0.015), and the median duration of therapy was 2 days shorter (8 vs. 10 days; p=0.04). Median duration of IV antibiotic therapy (4 vs. 7 days; p=0.004) and median LOS (4 vs. 7 days; p=0.029) were also shorter in the intervention period. There were no differences in the rate of 30-day recurrent bacteremia between the periods (3.4% baseline vs. 1.8% intervention; p=0.60). Conclusion Our pharmacist-led intervention successfully shortened the duration of therapy, increased conversion from IV to PO therapy, and reduced LOS, without negatively impacting the number of patients with recurrent GNB. Disclosures All Authors: No reported disclosures

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Risk factors of initial inappropriate antibiotic therapy and the impacts on outcomes of neonates with gram-negative bacteremia

10.21203/rs.2.18553/v1 ◽

2019 ◽

Author(s):

Shih-Ming Chu ◽

Jen-Fu Hsu ◽

Mei-Yin Lai ◽

Hsuan-Rong Huang ◽

Ming-Chou Chiang ◽

...

Keyword(s):

Antibiotic Therapy ◽

Neonatal Intensive Care ◽

Medical Center ◽

Tertiary Care ◽

Generation Cephalosporin ◽

Resistant Bacteria ◽

Empirical Antibiotic Therapy ◽

Gram Negative ◽

Tertiary Care Medical Center ◽

Gram Negative Bacteremia

Abstract Background Timely appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia. However, the relevant data and significant impacts have not been well studied in the neonatal intensive care unit (NICU).Methods An 8-year (1 January 2007-31 December 2014) cohort study of all NICU patients with gram-negative bacteremia in a tertiary-care medical center was performed. Inadequate empirical antibiotic therapy was defined when a patient didn’t receive any antimicrobial agent to which the causative microorganisms were susceptible within 24 hour of blood culture sampling.Results Among 376 episodes of Gram-negative bacteremia, 75 (19.9%) received inadequate empirical antibiotic therapy. The cause of inadequate treatment was mostly due to the pathogen resistant to prescribed antibiotics (88.0%), and Pseudomonas aeruginosa (Odds ratio [OR]: 20.8, P < 0.001) and ESBL-producing bacteria (OR: 18.4, P < 0.001) had the highest risk. Previous exposure with 3rd generation cephalosporin was identified as the only independent risk factor (OR: 2.52, 95% CI: 1.18-5.37, P = 0.018). Empirically inadequately treated bacteremias were significantly more likely to have worse outcomes than those with adequate therapy, including more prolonged illness, higher rate of infectious complications (25.3% versus 9.3%, P < 0.001) and overall mortality (22.7% versus 11.0%, P = 0.013).Conclusions Inadequate empirical antibiotic therapy occurs in one-fifth of Gram-negative bacteremias in the NICU, and is associated with worse outcomes. Further effort to decrease emergence of antibiotic resistance and highly suspicion of infection by drug-resistant bacteria clinically is important to reduce rates of inadequacy.

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Hafnia alvei causing late onset sepsis in neonates: report of two cases and review of literature

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20180580 ◽

2018 ◽

Vol 5 (2) ◽

pp. 673

Author(s):

Laxman Basani ◽

Roja Aepala

Keyword(s):

Antibiotic Therapy ◽

Pediatric Patients ◽

Neonatal Period ◽

Late Onset ◽

Review Of Literature ◽

Term Neonates ◽

Gram Negative ◽

Hafnia Alvei ◽

Late Onset Sepsis ◽

Compromised Patients

Hafnia alvei, a Gram negative motile bacillus that belongs to Enterobacteriaceae family is rarely associated with infection in pediatric patients and is exceptionally rare in the neonatal period. H. alvei is ubiquitous in the environment, causing infections in debilitated and immuno-compromised patients with few cases being reported in neonates. We report two cases of late onset sepsis in term neonates caused by H. alvei that were successfully treated in our unit. To the best of our knowledge, infection due to H. alvei has not been reported in neonates from India. Hafnia alvei causes infection rarely in neonates. Because it can cause nosocomial outbreaks, awareness regarding this uncommon pathogen and initiation of appropriate antibiotic therapy improves the outcome and prevents mortality.

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Potential Excess Intravenous Antibiotic Therapy in the Setting of Gram-Negative Bacteremia

Pharmacy ◽

10.3390/pharmacy9030133 ◽

2021 ◽

Vol 9 (3) ◽

pp. 133

Author(s):

Ashley R. Selby ◽

Jaffar Raza ◽

Duong Nguyen ◽

Ronald G. Hall

Keyword(s):

Antibiotic Therapy ◽

Inpatient Setting ◽

Negative Consequences ◽

Intravenous Therapy ◽

Intravenous Antibiotic ◽

Gram Negative ◽

Source Of Infection ◽

Intravenous Antibiotic Therapy ◽

Gram Negative Bacteremia ◽

Wbc Count

(1) Background: Excessive intravenous therapy (EIV) is associated with negative consequences, but guidelines are unclear about when switching to oral therapy is appropriate. (2) Methods: This cohort included patients aged ≥18 years receiving ≥48 h of antimicrobial therapy for bacteremia due to Escherichia coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter, or Stenotrophomonas maltophilia from 1/01/2008–8/31/2011. Patients with a polymicrobial infection or recurrent bacteremia were excluded. Potential EIV (PEIV) was defined as days of intravenous antibiotic therapy beyond having a normal WBC count for 24 h and being afebrile for 48 h until discharge or death. (3) Results: Sixty-nine percent of patients had PEIV. Patients who received PEIV were more likely to receive intravenous therapy until discharge (46 vs. 16%, p < 0.001). Receipt of PEIV was associated with a longer mean time to receiving oral antimicrobials (8.7 vs. 3 days, p < 0.001). The only factors that impacted EIV days in the multivariable linear regression model were the source of infection (urinary tract) (coefficient −1.54, 95%CI −2.82 to −0.26) and Pitt bacteremia score (coefficient 0.51, 95%CI 0.10 to 0.92). (4) Conclusions: PEIV is common in inpatients with Gram-negative bacteremia. Clinicians should look to avoid PEIV in the inpatient setting.

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Pediatric Gram-Negative Bacteremia: Hidden Agenda

Journal of Child Science ◽

10.1055/s-0037-1618564 ◽

2018 ◽

Vol 08 (01) ◽

pp. e1-e6

Author(s):

Elham Bukhari ◽

Abdulkarim Alrabiaah

Keyword(s):

Pediatric Patients ◽

University Hospital ◽

Gram Negative ◽

Hidden Agenda ◽

Significant Difference ◽

Gram Negative Bacteremia ◽

Common Clinical Presentation ◽

Healthcare Associated ◽

Epidemiological Characteristics ◽

Community Onset

Background Recently, new types of community-onset bacteremia have been introduced as healthcare associated (HCA) in which the infection onset started outside the hospital and there were interactions with the healthcare system. Little data exist differentiating community-acquired (CA) and HCA bacteremia from hospital-acquired bacteremia (HA). Objectives This article determines differences in the epidemiological characteristics and bacteriology of community-onset (i.e., CA and HCA) and HA gram-negative bacteremia in Saudi pediatric patients. Methods We conducted a prospective cohort of all pediatric patients diagnosed with gram-negative bacteremia at the King Khalid University Hospital over a year (2015). We received daily electronic notifications of all blood culture positive cases for gram-negative bacilli. Results A total of 92 children were hospitalized with gram-negative bacteremia; among these 64 (71.1%) were with HA bacteremia, 20 (21.1%) with CA bacteremia, and 8 (7.8%) with HCA bacteremia. Urinary tract infection was common clinical presentation (50%) in the patients diagnosed with CA and HCA bacteremia. Up to 92% of HA bacteremia and 2% of CA bacteremia were presented with septic shock. The most common gram-negative bacteria causing bacteremia is Klebsiella pneumoniae, constituting almost 29.3% of all organisms, and was only isolated from HA bacteremia. The antimicrobial susceptibility among the 92 isolates showed that the organisms were nonextended spectrum β-lactamase (non-ESBL) in 90%, and 10% of the isolates were ESBL. There was a significant difference in the total frequency of isolates between CA and HA incidences, regardless of ESBL or non-ESBL (p < 0.001). Conclusion The most common type of gram-negative bacteremia is HA bacteremia followed by the CA and HCA bacteremia.

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Risk factors of initial inappropriate antibiotic therapy and the impacts on outcomes of neonates with gram-negative bacteremia

10.21203/rs.2.19683/v1 ◽

2019 ◽

Author(s):

Shih-Ming Chu ◽

Jen-Fu Hsu ◽

Mei-Yin Lai ◽

Hsuan-Rong Huang ◽

Ming-Chou Chiang ◽

...

Keyword(s):

Antibiotic Therapy ◽

Neonatal Intensive Care ◽

Medical Center ◽

Tertiary Care ◽

Generation Cephalosporin ◽

Resistant Bacteria ◽

Empirical Antibiotic Therapy ◽

Gram Negative ◽

Tertiary Care Medical Center ◽

Gram Negative Bacteremia

Abstract Background Timely appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia. However, the relevant data and significant impacts have not been well studied in the neonatal intensive care unit (NICU). Methods An 8-year (1 January 2007-31 December 2014) cohort study of all NICU patients with gram-negative bacteremia in a tertiary-care medical center was performed. Inadequate empirical antibiotic therapy was defined when a patient didn’t receive any antimicrobial agent to which the causative microorganisms were susceptible within 24 hour of blood culture sampling. Results Among 376 episodes of Gram-negative bacteremia, 75 (19.9%) received inadequate empirical antibiotic therapy. The cause of inadequate treatment was mostly due to the pathogen resistant to prescribed antibiotics (88.0%), and Pseudomonas aeruginosa (Odds ratio [OR]: 20.8, P < 0.001) and ESBL-producing bacteria (OR: 18.4, P < 0.001) had the highest risk. Previous exposure with 3rd generation cephalosporin was identified as the only independent risk factor (OR: 2.52, 95% CI: 1.18-5.37, P = 0.018). Empirically inadequately treated bacteremias were significantly more likely to have worse outcomes than those with adequate therapy, including more prolonged illness, higher rate of infectious complications (25.3% versus 9.3%, P < 0.001) and overall mortality (22.7% versus 11.0%, P = 0.013). Conclusions Inadequate empirical antibiotic therapy occurs in one-fifth of Gram-negative bacteremias in the NICU, and is associated with worse outcomes. Further effort to decrease emergence of antibiotic resistance and highly suspicion of infection by drug-resistant bacteria clinically is important to reduce rates of inadequacy.

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Risk Factors of Initial Inappropriate Antibiotic Therapy and the Impacts on Outcomes of Neonates with Gram-Negative Bacteremia

Antibiotics ◽

10.3390/antibiotics9040203 ◽

2020 ◽

Vol 9 (4) ◽

pp. 203

Author(s):

Shih-Ming Chu ◽

Jen-Fu Hsu ◽

Mei-Yin Lai ◽

Hsuan-Rong Huang ◽

Ming-Chou Chiang ◽

...

Keyword(s):

Antibiotic Therapy ◽

Neonatal Intensive Care ◽

Medical Center ◽

Tertiary Care ◽

Pathogen Resistance ◽

Optimal Timing ◽

Empirical Antibiotic Therapy ◽

Gram Negative ◽

Tertiary Care Medical Center ◽

Gram Negative Bacteremia

Background: Timely appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia. However, the relevant data and significant impacts have not been well studied in the neonatal intensive care unit (NICU). Methods: An 8-year (1 January 2007–31 December 2014) cohort study of all NICU patients with gram-negative bacteremia (GNB) in a tertiary-care medical center was performed. Inadequate empirical antibiotic therapy was defined when a patient did not receive any antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture sampling. Neonates with GNB treated with inadequate antibiotics were compared with those who received initial adequate antibiotics. Results: Among 376 episodes of Gram-negative bacteremia, 75 (19.9%) received inadequate empirical antibiotic therapy. The cause of inadequate treatment was mostly due to the pathogen resistance to prescribed antibiotics (88.0%). Bacteremia caused by Pseudomonas aeruginosa (Odds ratio [OR]: 20.8, P < 0.001) and extended spectrum β-lactamase (ESBL)-producing bacteria (OR: 18.4, P < 0.001) had the highest risk of inadequate treatment. Previous exposure with third generation cephalosporin was identified as the only independent risk factor (OR: 2.52, 95% CI: 1.18–5.37, P = 0.018). Empirically inadequately treated bacteremias were significantly more likely to have worse outcomes than those with adequate therapy, including a higher risk of major organ damage (20.0% versus 6.6%, P < 0.001) and infectious complications (25.3% versus 9.3%, P < 0.001), and overall mortality (22.7% versus 11.0%, P = 0.013). Conclusions: Inadequate empirical antibiotic therapy occurs in one-fifth of Gram-negative bacteremias in the NICU, and is associated with worse outcomes. Additional prospective studies are needed to elucidate the optimal timing and aggressive antibiotic regimen for neonates who are at risk of antibiotic-resistant Gram-negative bacteremia.

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