Appendicoliths, Antibiotic Treatment Failure, and Appendectomy—Is the Glass Half Full or Half Empty?

Introduction: Current guideline recommendations for optimal management of non-purulent skin and soft tissue infections (SSTIs) are based on expert consensus. There is currently a lack of evidence to guide emergency physicians on when to select oral versus intravenous antibiotic therapy. The primary objective was to identify risk factors associated with oral antibiotic treatment failure. A secondary objective was to describe the epidemiology of adult emergency department (ED) patients with non-purulent SSTIs. Methods: We performed a health records review of adults (age 18 years) with non-purulent SSTIs treated at two tertiary care EDs. Patients were excluded if they had a purulent infection or infected ulcers without surrounding cellulitis. Treatment failure was defined any of the following after a minimum of 48 hours of oral therapy: (i) hospitalization for SSTI; (ii) change in class of oral antibiotic owing to infection progression; or (iii) change to intravenous therapy owing to infection progression. Multivariable logistic regression was used to identify predictors independently associated with the primary outcome of oral antibiotic treatment failure after a minimum of 48 hours of oral therapy. Results: We enrolled 500 patients (mean age 64 years, 279 male (55.8%) and 126 (25.2%) with diabetes) and the hospital admission rate was 29.6%. The majority of patients (70.8%) received at least one intravenous antibiotic dose in the ED. Of 288 patients who had received a minimum of 48 hours of oral antibiotics, there were 85 oral antibiotic treatment failures (29.5%). Tachypnea at triage (odds ratio [OR]=6.31, 95% CI=1.80 to 22.08), chronic ulcers (OR=4.90, 95% CI=1.68 to 14.27), history of MRSA colonization or infection (OR=4.83, 95% CI=1.51 to 15.44), and cellulitis in the past 12 months (OR=2.23, 95% CI=1.01 to 4.96) were independently associated with oral antibiotic treatment failure. Conclusion: This is the first study to evaluate potential predictors of oral antibiotic treatment failure for non-purulent SSTIs in the ED. We observed a high rate of treatment failure and hospitalization. Tachypnea at triage, chronic ulcers, history of MRSA colonization or infection and cellulitis within the past year were independently associated with oral antibiotic treatment failure. Emergency physicians should consider these risk factors when deciding on oral versus intravenous antimicrobial therapy for non-purulent SSTIs being managed as outpatients.

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Assessing the Role of Pharyngeal Cell Surface Glycans in Group A Streptococcus Biofilm Formation

Antibiotics ◽

10.3390/antibiotics9110775 ◽

2020 ◽

Vol 9 (11) ◽

pp. 775

Author(s):

Heema K. N. Vyas ◽

Anuk D. Indraratna ◽

Arun Everest-Dass ◽

Nicolle H. Packer ◽

David M. P. De Oliveira ◽

...

Keyword(s):

Sialic Acid ◽

Cell Surface ◽

Treatment Failure ◽

Antibiotic Treatment ◽

Biofilm Formation ◽

Extracellular Polymeric Substances ◽

Group A Streptococcus ◽

Sialic Acid Residue ◽

Group A ◽

Terminal Mannose

Group A Streptococcus (GAS) causes 700 million infections and accounts for half a million deaths per year. Antibiotic treatment failure rates of 20–40% have been observed. The role host cell glycans play in GAS biofilm formation in the context of GAS pharyngitis and subsequent antibiotic treatment failure has not been previously investigated. GAS serotype M12 GAS biofilms were assessed for biofilm formation on Detroit 562 pharyngeal cell monolayers following enzymatic removal of all N-linked glycans from pharyngeal cells with PNGase F. Removal of N-linked glycans resulted in an increase in biofilm biomass compared to untreated controls. Further investigation into the removal of terminal mannose and sialic acid residues with α1-6 mannosidase and the broad specificity sialidase (Sialidase A) also found that biofilm biomass increased significantly when compared to untreated controls. Increases in biofilm biomass were associated with increased production of extracellular polymeric substances (EPS). Furthermore, it was found that M12 GAS biofilms grown on untreated pharyngeal monolayers exhibited a 2500-fold increase in penicillin tolerance compared to planktonic GAS. Pre-treatment of monolayers with exoglycosidases resulted in a further doubling of penicillin tolerance in resultant biofilms. Lastly, an additional eight GAS emm-types were assessed for biofilm formation in response to terminal mannose and sialic acid residue removal. As seen for M12, biofilm biomass on monolayers increased following removal of terminal mannose and sialic acid residues. Collectively, these data demonstrate that pharyngeal cell surface glycan structures directly impact GAS biofilm formation in a strain and glycan specific fashion.

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Antibiotic Treatment Failure and Associated Outcomes Among Adult Patients With Community-Acquired Pneumonia in the Outpatient Setting: A Real-world US Insurance Claims Database Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa065 ◽

2020 ◽

Vol 7 (3) ◽

Cited By ~ 1

Author(s):

Glenn Tillotson ◽

Thomas Lodise ◽

Peter Classi ◽

Donna Mildvan ◽

James A McKinnell

Keyword(s):

Health Care ◽

Treatment Failure ◽

Antibiotic Treatment ◽

Health Care Costs ◽

Outpatient Setting ◽

Community Acquired Pneumonia ◽

Failure Group ◽

Antibiotic Failure ◽

Care Costs ◽

Experienced Treatment

Abstract Background Antibiotic treatment failure is common among patients with community-acquired pneumonia (CAP) who are managed in the outpatient setting and is associated with higher mortality and increased health care costs. This study’s objectives were to quantify the occurrence of antibiotic treatment failure (ATF) and to evaluate clinical and economic outcomes between CAP patients who experienced ATF relative to those who did not. Methods Retrospective analysis of the MarketScan Commercial & Medicare Supplemental Databases was performed, identifying patients ≥18 years old, with a pneumonia diagnosis in the outpatient setting, and who received a fluoroquinolone, macrolides, beta-lactam, or tetracycline. ATF was defined as any of the following events within 30 days of initial antibiotic: antibiotic refill, antibiotic switch, emergency room visit, or hospitalization. Outcomes included 30-day all-cause mortality and CAP-related health care costs. Results During the study period, 251 947 unique patients met inclusion criteria. The mean age was 52.2 years, and 47.7% were male. The majority of patients received a fluoroquinolone (44.4%) or macrolide (43.6%). Overall, 22.1% were classified as ATFs. Among 18–64-year-old patients, 21.2% experienced treatment failure, compared with 25.7% in those >65 years old. All-cause mortality was greater in the antibiotic failure group relative to the non–antibiotic failure group (18.1% vs 4.6%, respectively), and the differences in 30-day mortality between antibiotic failure groups increased as a function of age. Mean 30-day CAP-related health care costs were also higher in the patients who experienced treatment failure relative to those who did not ($2140 vs $54, respectively). Conclusions Treatment failure and poor outcomes from outpatient CAP are common with current guideline-concordant CAP therapies. Improvements in clinical management programs and therapeutic options are needed.

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Cellulitis: Home or Inpatient Intravenous Therapy in a Veteran Population

Home Health Care Management & Practice ◽

10.1177/1084822319890102 ◽

2019 ◽

Vol 32 (3) ◽

pp. 127-133

Author(s):

Rebekah A. Wahking ◽

Bonnie Clark ◽

Tasha Cheatham-Wilson

Keyword(s):

Treatment Failure ◽

Antibiotic Treatment ◽

Inpatient Treatment ◽

Medical Center ◽

Retrospective Chart Review ◽

Primary Diagnosis ◽

Primary Objective ◽

Outpatient Parenteral Antimicrobial Therapy ◽

Inpatient Settings ◽

Inpatient Group

There are few studies describing outpatient parenteral antimicrobial therapy (OPAT) for cellulitis treatment. The Hospital in Home (HIH) program is a multidisciplinary team at the Cincinnati VA Medical Center (CVAMC) that provides acute care in patients’ homes similar to inpatient hospital care for a variety of indications, including cellulitis. Efficacy of OPAT for cellulitis treatment in the HIH program has not been directly compared with inpatient treatment. The primary objective of this retrospective review is to compare the rates of efficacy of intravenous (IV) antibiotics for cellulitis treatment for patients followed by HIH and inpatient settings. Treatment failure was defined as a change in IV antibiotic medications prescribed. A retrospective chart review was completed at CVAMC for patients enrolled in HIH ( n = 111) and patients who received inpatient treatment at CVAMC ( n = 111) with IV antibiotics for a primary diagnosis of cellulitis from January 1, 2014, through June 30, 2018. Six patients in the HIH group experienced IV antibiotic treatment failure compared with 11 in the inpatient group. The HIH group showed non-inferiority in rates of treatment failure compared with the inpatient group ( p = .21). OPAT with the HIH program appears to be non-inferior to inpatient IV antibiotic treatment for cellulitis infections. Tolerance issues and rates of adverse events do not appear to be worse in patients treated with OPAT in the Veteran population.

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The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated Streptococcus pyogenes Infections

mBio ◽

10.1128/mbio.00919-20 ◽

2020 ◽

Vol 11 (4) ◽

Author(s):

Jeffrey A. Freiberg ◽

Yoann Le Breton ◽

Janette M. Harro ◽

Devon L. Allison ◽

Kevin S. McIver ◽

...

Keyword(s):

Treatment Failure ◽

Antibiotic Treatment ◽

Streptococcus Pyogenes ◽

Bacterial Infections ◽

Bacterial Species ◽

Arginine Deiminase ◽

Antibiotic Tolerance ◽

Human Pathogen ◽

Biofilm Growth ◽

Content Type

ABSTRACT Bacterial biofilms are responsible for a variety of serious human infections and are notoriously difficult to treat due to their recalcitrance to antibiotics. Further work is necessary to elicit a full understanding of the mechanism of this antibiotic tolerance. The arginine deiminase (ADI) pathway is responsible for bacterial pH maintenance and is highly expressed during biofilm growth in multiple bacterial species. Using the group A Streptococcus (GAS) as a model human pathogen, the ADI pathway was demonstrated to contribute to biofilm growth. The inability of antibiotics to reduce GAS populations when in a biofilm was demonstrated by in vitro studies and a novel animal model of nasopharyngeal infection. However, disruption of the ADI pathway returned GAS biofilms to planktonic levels of antibiotic sensitivity, suggesting the ADI pathway is influential in biofilm-related antibiotic treatment failure and provides a new strategic target for the treatment of biofilm infections in GAS and potentially numerous other bacterial species. IMPORTANCE Biofilm-mediated bacterial infections are a major threat to human health because of their recalcitrance to antibiotic treatment. Through the study of Streptococcus pyogenes, a significant human pathogen that is known to form antibiotic-tolerant biofilms, we demonstrated the role that a bacterial pathway known for responding to acid stress plays in biofilm growth and antibiotic tolerance. This not only provides some insight into antibiotic treatment failure in S. pyogenes infections but also, given the widespread nature of this pathway, provides a potentially broad target for antibiofilm therapies. This discovery has the potential to impact the treatment of many different types of recalcitrant biofilm infections.

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