scholarly journals Fluoroquinolone Versus Nonfluoroquinolone Treatment of Bloodstream Infections Caused by Chromosomally Mediated AmpC-Producing Enterobacteriaceae

Antibiotics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 331
Author(s):  
Sarah Grace Gunter ◽  
Katie E. Barber ◽  
Jamie L. Wagner ◽  
Kayla R. Stover

Objectives: Chromosomally mediated AmpC-producing Enterobacteriaceae (CAE) display high susceptibility to fluoroquinolones; minimal clinical data exist supporting comparative clinical outcomes. The objective of this study was to compare treatment outcomes between fluoroquinolone and nonfluoroquinolone definitive therapy of bloodstream infections caused by CAE. Methods: This retrospective cohort assessed adult patients with positive blood cultures for CAE that received inpatient treatment for ≥48 h. The primary outcome was difference in clinical failure between patients who received fluoroquinolone (FQ) versus non-FQ treatment. Secondary endpoints included microbiological cure, infection-related length of stay, 90-day readmission, and all-cause inpatient mortality. Results: 56 patients were included in the study (31 (55%) received a FQ as definitive therapy; 25 (45%) received non-FQ). All non-FQ patients received a beta-lactam (BL). Clinical failure occurred in 10 (18%) patients, with 4 (13%) in the FQ group and 6 (24%) in the BL group (p = 0.315). Microbiological cure occurred in 55 (98%) patients. Median infection-related length of stay was 10 (6–20) days, with a significantly longer stay occurring in the BL group (p = 0.002). There was no statistical difference in 90-day readmissions between groups (7% FQ vs. 17% BL; p = 0.387); one patient expired. Conclusion: These results suggest that fluoroquinolones do not adversely impact clinical outcomes in patients with CAE. When alternatives to beta-lactam therapy are needed, fluoroquinolones may provide an effective option.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S111-S111
Author(s):  
Sydney Agnello ◽  
Shandra R Day ◽  
Lynn Wardlow ◽  
Erica E Reed ◽  
Jessica M Smith ◽  
...  

Abstract Background The preferred management of patients with MSSA bacteremia includes definitive therapy with intravenous anti-staphylococcal β-lactam antibiotics. In β-lactam allergic or intolerant patients, daptomycin has been targeted as a viable alternative. The objective of this study was to assess clinical outcomes of daptomycin compared with nafcillin or cefazolin for the treatment of MSSA bacteremia. Methods This was a retrospective cohort study of patients hospitalized from November 1, 2011 to October 31, 2018 at The Ohio State University Wexner Medical Center with MSSA bacteremia. Patients treated with nafcillin, cefazolin or daptomycin were included with 1:1:1 random selection. The primary outcome was a composite of clinical failure, defined as a change in therapy due to persistent/worsening signs and symptoms, bacteremia recurrence or persistence, or inpatient infection-related mortality. Secondary endpoints included 30-day infection-related mortality, duration of bacteremia, 30-day all-cause mortality and adverse events (AEs) necessitating a change in therapy. Results Among patients with MSSA bacteremia, 162 received at least one dose of daptomycin. Of those, 29 received at least 14 days of daptomycin and/or received daptomycin as definitive therapy and thus were included in the analysis. There was no difference in the primary outcome of composite clinical failure comparing daptomycin vs. nafcillin/cefazolin (P = 0.71). In addition, no difference was observed in 30-day infection-related mortality (P = 0.51), duration of MSSA bacteremia (P = 0.9), or 30-day all-cause mortality (P = 0.64). A higher number of AEs necessitating change in therapy were seen in the daptomycin group (P = 0.0002), reflecting initial β-lactam intolerance. Conclusion No difference in clinical failure was identified in patients treated with daptomycin vs. nafcillin/cefazolin suggesting that daptomycin may serve as a non-inferior alternative for treatment of MSSA bacteremia. A higher number of AEs occurred in the daptomycin group indicating β-lactam intolerance as a primary indication for daptomycin therapy. Given the small sample size, subsequent studies are needed to further evaluate the use of daptomycin in the treatment of MSSA bacteremia. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S126-S126
Author(s):  
Mary L Staicu ◽  
Tyler Baumeister ◽  
Maryrose R Laguio-Vila

Abstract Background AmpC beta-lactamase producing organisms are traditionally treated with carbapenem or fluoroquinolone antibiotics. Recent studies, however, describe similar clinical outcomes in patients that receive cefepime or piperacillin/tazobactam. We sought to assess outcomes in patients with bloodstream infections caused by AmpC-producing organisms that received beta-lactams compared non-beta-lactam therapy. Methods Data was obtained retrospectively from the electronic health record (EHR) from January 2012 to February 2020. The primary objective was 30-day mortality from the day of first positive blood cultures with Enterobacter spp., Citrobacter spp., or Serratia spp. in patients who received non-beta-lactam therapy (carbapenem, fluoroquinolone, trimethoprim/sulfamethoxazole) to those who received beta-lactam therapy (cefepime, piperacillin/tazobactam). Secondary objectives included 30-day recurrence of bacteremia, pathogen isolated, source of bacteremia, hospital length of stay, and duration of antimicrobial therapy. Results A total of 90 patients were included, 50 in the non-beta lactam group and 40 in the beta-lactam group. Demographics were similar between groups. Thirty-day mortality was significantly higher in the beta-lactam group (20% vs 2%, p=0.009). Enterobacter spp. was the most frequently identified pathogen (67%), most commonly isolated from a urinary (31%) or intra-abdominal source (22%). The average duration of antibiotic therapy was significantly higher in the non-beta lactam group (18 vs 12 days, p=0.001). In contrast, there was no significant difference found in hospital length of stay, recurrence of bacteremia, pathogen isolated or source of bacteremia between groups. Conclusion Beta-lactam therapy for the treatment of bloodstream infections caused by Amp-C producing organisms was associated with significantly greater 30-day mortality compared to patients that received non-beta-lactam therapy. Disclosures All Authors: No reported disclosures


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S137-S137
Author(s):  
Stephanie Wo ◽  
Yanina Dubrovskaya ◽  
Justin Siegfried ◽  
John Papadopoulos ◽  
Shin-Pung Jen

Abstract Background Viridans group streptococci (VGS) is an infrequent yet significant cause of bloodstream infections, and complicated cases may require prolonged antibiotic therapy. Ceftriaxone (CTX) and penicillin G (PCN G) are both considered first line options for VGS infections, but comparisons between these agents are limited. We evaluated the clinical outcomes amongst patients treated with CTX and PCN G for complicated VGS bacteremia. Methods This was a single-center, retrospective study of adult patients with ≥1 positive VGS blood culture who were treated with either CTX or PCN G/ampicillin (both included in PCN G arm) between January 2013 and June 2019. The primary outcome was a composite of safety endpoints, including hospital readmission due to VGS or an adverse event (AE) from therapy, Clostridioides difficile infections, treatment modification or discontinuation due to an antibiotic-related AE, and development of extended-spectrum beta lactamase resistance. Secondary outcomes included the individual safety endpoints, VGS bacteremia recurrence, hospital readmission, and all-cause mortality. Results Of 328 patients screened for inclusion, 94 patients met eligibility criteria (CTX n= 64, PCN G n=34). Median age was 68 years (IQR 56–81) and 68% were male. Study patients did not present with critical illness, as reflected by a median Pitt bacteremia score of 0 in the CTX and 1 in the PCN G arms, P=0.764. Streptococcus mitis was the most common VGS isolate and infective endocarditis (IE) was the predominant source of infection. CTX was not significantly associated with increased risk of the primary outcome (14% vs. 27%; P= 0.139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. Results were similar in the subgroup of patients with IE (12.5% vs. 23.5%). No secondary endpoints differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary outcome (OR 0.1; 95% CI 0.020–0.6771; P= 0.017). Conclusion Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate a higher rate of treatment failure, adverse events, or resistance. These findings warrant further exploration. Disclosures All Authors: No reported disclosures


2021 ◽  
Author(s):  
Elita Jauneikaite ◽  
Kate Honeyford ◽  
Oliver Blandy ◽  
Mia Mosavie ◽  
Max Pearson ◽  
...  

Background Escherichia coli bloodstream infections have increased rapidly in the UK, for reasons that are unclear. The relevance of highly fit, or multi-drug resistant lineages such as ST131 to overall E. coli disease burden remains to be fully determined. We set out to characterise the prevalence of E. coli multi-locus sequence types (MLST) and determine if these were associated with adverse outcomes in an urban population of E. coli bacteraemia patients. Methods We undertook whole genome sequencing of E. coli blood isolates from all patients with diagnosed E. coli bacteraemia in north-west London from July 2015 to August 2016 and assigned multi-locus sequence types to all isolates. Isolate sequence types were linked to routinely collected antimicrobial susceptibility, patient demographic, and clinical outcome data to explore relationships between the E. coli sequence types, patient factors, and outcomes. Findings A total of 551 E. coli genomes were available for analysis. More than half of these cases were caused by four E. coli sequence types: ST131 (21%), ST73 (15%), ST69 (9%) and ST95 (8%). E. coli genotype ST131-C2 was associated with non-susceptibility to quinolones and third-generation cephalosporins, and also to amoxicillin, augmentin, gentamicin and trimethoprim. An association between the ST131-C2 lineage and longer length-of-stay was detected, although multivariable regression modelling did not demonstrate an association between E. coli sequence type and mortality. However, a number of unexpected associations were identified, including gentamicin non-susceptibility, ethnicity, and sex that might influence mortality and length-of-stay, requiring further research. Interpretation Although E. coli sequence type was associated with antimicrobial non-susceptibility patterns and length-of-stay, we did not find that E. coli sequence type was associated with increased mortality. Where ST131 is prevalent, caution is required when pairing beta-lactam agents with gentamicin or using single agent aminoglycosides.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S97-S97
Author(s):  
Jeffrey W Jansen ◽  
Ryan P Moenster

Abstract Background Osteomyelitis (OM) in diabetics is frequently a polymicrobial infection that rarely involves Pseudomonas (4–5% of cases). Bone cultures have a low-positive yield of 34–50% and, as a result, many patients receive antimicrobial regimens which include antipseudomonal (AP) therapy. Methods A retrospective cohort analysis of adult Veterans with OM treated with AP compared with non-antipseudomonal (NAP) therapy was conducted. Patients managed by the VA St. Louis outpatient parenteral antimicrobial therapy (OPAT) service from 1/1/2009 to 7/31/2015 were identified and screened for inclusion. Patients with culture negative (CN) or non-pseudomonal superficial swab cultures (SCx) were included. Figure 1 presents the study profile and exclusion criteria. The primary outcome was clinical failure, defined as a composite of: (1) extension of antibiotics beyond 1 week of the planned duration, (2) recurrence of OM at the same anatomical site within 12 months, or (3) any unplanned surgery or amputation at the anatomical site within 12 months of ABx completion. Results Overall, 104 patients with 109 OM encounters were included; there were 29 CN encounters and 80 SCx encounters. Table 1 presents baseline demographics. The overall failure rate was 55/109 (50.5%). The results of the analysis are shown in Table 2. While not included in the primary analysis, Pseudomonas was isolated from 8/88 (9.1%) swab cultures and 5/33 (15%) deep cultures. Conclusion Empiric AP therapy did not improve clinical outcomes in patients with either CN or SCx OM. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Kellie Arensman ◽  
Maureen Shields ◽  
Maya Beganovic ◽  
Jessica L. Miller ◽  
Erik LaChance ◽  
...  

ABSTRACT Fluoroquinolones (FQs) are often preferred as oral step-down therapy for bloodstream infections (BSIs) due to favorable pharmacokinetic parameters; however, they are also associated with serious adverse events. The objective of this study was to compare clinical outcomes for patients who received an oral FQ versus an oral beta-lactam (BL) as step-down therapy for uncomplicated streptococcal BSIs. This multicenter, retrospective cohort study analyzed adult patients who completed therapy with an oral FQ or BL with at least one blood culture positive for a Streptococcus species from 1 January 2014 to 30 June 2019. The primary outcome was clinical success, defined as the lack of all-cause mortality, recurrent BSI with the same organism, and infection-related readmission at 90 days. A multivariable logistic regression model for predictors of clinical failure was conducted. A total of 220 patients were included, with 87 (40%) receiving an FQ and 133 (60%) receiving a BL. Step-down therapy with an oral BL was noninferior to an oral FQ (93.2% versus 92.0%; mean difference, 1.2%; 90% confidence interval [CI], −5.2 to 7.8). No differences were seen in 90-day mortality, 90-day recurrent BSI, 90-day infection-related readmission, or 90-day incidence of Clostridioides difficile-associated diarrhea. Predictors of clinical failure included oral step-down transition before day 3 (odds ratio [OR] = 5.18; 95% CI, 1.21, 22.16) and low-dose oral step-down therapy (OR = 2.74; 95% CI, 0.95, 7.90). Our results suggest that oral step-down therapy for uncomplicated streptococcal BSI with a BL is noninferior to an FQ.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lu Liu ◽  
Yali Tian

Abstract Background The acknowledgment that conservative oxygen therapy (COT) was related to better prognosis in the intensive care unit (ICU) was challenged recently. We conducted an updated meta-analysis aimed to determine whether liberal oxygen therapy (LOT) or COT is associated with better improve clinical outcomes. Methods We systematically searched the electronic databases (PubMed, Web of Science and Embase) up to May 2021 for randomized controlled trials (RCTs). The primary outcome was the mortality of the final follow-up time and secondary outcomes were ICU mortality, the ICU length of stay and the number of ventilator-free days. Results A total of 7 RCTs were included, with 2166 patients admitted to the ICU. There was no significant difference in the primary outcome between the LOT and COT. Additionally, LOT could not significantly increase ICU mortality and the ICU length of stay compared with COT. Conclusions The present study showed that COT was not significantly superior to LOT in clinical outcomes. Therefore, additional high-quality studies with novel designs are required to further elucidate this controversy.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S205-S205
Author(s):  
John M Boulos ◽  
Valeria Fabre ◽  
Kate Dzintars ◽  
Kate Dzintars ◽  
George Jones ◽  
...  

Abstract Background Shorter durations have shown similar clinical outcomes as longer durations for uncomplicated (source-controlled) Gram-negative bloodstream infections (BSI). There is limited data on the outcomes of patients with non-pneumococcal streptococcal BSI receiving shorter durations of therapy compared to usual durations. Methods This was a retrospective, multicenter study of adults hospitalized between January 2018 and March 2019 with ≥ 1 blood culture positive for Streptococcus spp. Exposed patients were those who received ≤ 10 days of antibiotics (i.e., short course therapy) and unexposed patients were those who received 11-21 days of antibiotics (i.e., prolonged course therapy). Patients were excluded if they had S. pneumoniae BSI, suspected contamination, did not receive or complete therapy, or treated for > 21 days. The primary outcome was a composite of recurrent bacteremia with the same pathogen, hospital readmission, or all-cause mortality, all within 30 days from completing therapy. The odds of achieving the primary outcome was compared between exposed and unexposed patients using multivariable logistic regression analysis. Results A total of 176 patients met eligibility criteria. 35 (20%) received a short course (median 8 days) and 141 (80%) received a prolonged course (median 15 days) of antibiotic therapy. Baseline characteristics were similar between short and long course groups. The most common pathogens were viridans group streptococci (22%) and S. agalactiae (23%). The most common BSI source was skin and soft tissue infection (SSTI) (40%). The primary outcome occurred in 26% (9/35) and 23% (33/141) of patients in the short course and prolonged course groups, respectively (p = 0.774). The proportion of patients in the short course and prolonged course groups who experienced recurrent BSI, hospital readmission, or all-cause mortality were also non-significant. After adjusting for receipt of an infectious diseases consult, Pitt bacteremia score, and SSTI source, the adjusted odds of meeting the composite outcome remained unchanged (aOR 1.41, 95% CI 0.55 – 3.61, p = 0.466). Table 1. Cohort Characteristics Table 2. Source/Microbiology Table 3. Outcomes Conclusion Approximately a week of antibiotic therapy may be associated with similar clinical outcomes as longer antibiotics courses in patients with uncomplicated streptococcal BSI. Disclosures Kate Dzintars, PharmD, Nothing to disclose Sara E. Cosgrove, MD, MS, Basilea (Individual(s) Involved: Self): Consultant Pranita Tamma, MD, MHS, Nothing to disclose


2017 ◽  
Vol 22 (4) ◽  
pp. 261-265
Author(s):  
Chad A. Knoderer ◽  
Lauren C. Karmire ◽  
Kristen R. Nichols

OBJECTIVES The primary objective of this study was to describe the clinical outcomes of continuous nafcillin infusion in pediatric patients. METHODS This was a retrospective case study performed at a freestanding, tertiary care children's hospital. Subjects were included if they were at least 30 days old and had received more than 1 dose of nafcillin by continuous infusion (CI) between January 1, 2009, and December 31, 2012. Clinical and microbiological data were extracted from the medical record. Documented adverse events potentially associated with nafcillin were recorded. Treatment success was defined by any one of the following outcomes without the presence of conflicting data: microbiological cure, prescriber-documented treatment success, or normalization of abnormal clinical or laboratory parameters. RESULTS Forty subjects with a median of 9 (interquartile range [IQR], 2.3–12) years of age were included. Median length of stay (in days) for all indications observed was 7 (IQR, 5–21.8) days. Extended lengths of stay, indicated by ≥10 days, were more common in cases of endocarditis, skin and soft tissue infection, and bacteremia. Adverse reactions were documented in 20% of patients. CONCLUSIONS In this pediatric study, overall treatment success was observed in 92.5% of patients. Microbiological cure was documented in 91.3% of patients by using follow-up cultures. Length of stay may be positively impacted by CI nafcillin. Continuously infused nafcillin appears to be an acceptable alternative to intermittently infused nafcillin in children. Further studies are needed to address the question of whether clinical outcomes of CI nafcillin are superior to those of conventional infusion.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S16-S17
Author(s):  
Lee Erik Connor ◽  
Yasir Hamad ◽  
Ige George

Abstract Background MSSA is a leading cause of bloodstream infection (BSI) and its incidence is on the rise. Standard of care (SOC) is prolonged parenteral therapy with nafcillin, oxacillin, or cefazolin. Ceftriaxone is active against MSSA and can be given conveniently as a daily infusion. Methods We conducted a retrospective analysis of hospitalized adults with MSSA BSI from December 2014 to May 2018, defined as ≥1 blood cultures positive for MSSA and discharged on outpatient parenteral antimicrobial therapy (OPAT) on either ceftriaxone, cefazolin, or oxacillin. We excluded patients with ESRD and polymicrobial infections. We collected demographics, comorbidities, outcome data, and treatment-related adverse events. The primary outcome was 90-day mortality with secondary outcomes of clinical failure and microbiologic failure. Clinical failure was defined as readmission for any infection within 90 days of discharge or a change in antibiotics from the planned course of therapy after discharge. Microbiologic failure was defined as reinfection with MSSA within 90 days of discharge from any site. Results In total, 167 patients had a BSI with MSSA. Of those patients, 66 (39.5%) were discharged on SOC and 101 (60.5%) on ceftriaxone. The two groups were similar in terms of their demographics (Table 1). The SOC group had more cases of endocarditis with 34 (51.5%) than ceftriaxone with 25 (24.8%) (P = 0.001). LOS for the SOC group had a median of 14.05 days whereas the ceftriaxone group had a median length of stay of 7.88 (P = 0.004). In the SOC group, 5 (7.6%) patients died compared with 8 (7.9%) patients in the ceftriaxone group within 90 days of the onset of bacteremia which was not statistically significant (P = 0.94) (Figure 1). There were 4 (6.1%) cases of microbiologic failure in SOC and 7 (6.9%) cases in the ceftriaxone group (P = 0.83). For clinical failures, the SOC had 6 (9.1%) cases compared with the 19 (18.8%) cases in the ceftriaxone group (P = 0.13). Conclusion Ceftriaxone was not statistically different when compared with SOC in terms of mortality, microbiologic failure, or clinical failure. Though clinical failures numerically were more frequent in the ceftriaxone group. Ceftriaxone maybe a reasonable and convenient option to SOC for patients with uncomplicated MSSA BSI discharged on OPAT, but further studies are needed. Disclosures All Authors: No reported Disclosures.


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