scholarly journals Why is preventing antibiotic resistance so hard? Analysis of failed resistance management

2020 ◽  
Vol 2020 (1) ◽  
pp. 102-108 ◽  
Author(s):  
Shiwei Zhou ◽  
Camilo Barbosa ◽  
Robert J Woods
Keyword(s):  
Antibiotic Resistance ◽  
Clinical Decision Making ◽  
Resistance Management ◽  
Clinical Decision ◽  
Source Control ◽  
Abdominal Infection ◽  
Resistance Evolution ◽  
Clinical Challenge ◽  
Intra Abdominal Infection ◽  
Emergence Of Resistance

Abstract We describe the case of a patient with pancreatitis followed by intra-abdominal infection in which source control was not achieved. Antimicrobial therapy led to the emergence of resistance in multiple organisms through multiple population dynamics processes. While the initial insult was not due to infection, subsequent infections with resistant organisms contributed to a poor outcome for the patient. Though resistance evolution was a known risk, it was difficult to predict the next organism that would arise in the setting of antibiotic pressure and its resistance profile. This case illustrates the clinical challenge of antibiotic resistance that current approaches cannot readily prevent. LAY SUMMARY Why is antibiotic resistance management so complex? Distinct evolutionary processes unfold when antibiotic treatment is initiated that lead, separately and together, to the undesired outcome of antibiotic resistance. This clinical case exemplifies some of those processes and highlights the dire need for evolutionary risk assessments to be incorporated into clinical decision making.

scholarly journals ALK inhibitors, resistance development, clinical trials

2018 ◽  
Vol 25 ◽  
pp. 59 ◽  
Author(s):  
J.M. Rothenstein ◽  
N. Chooback
Keyword(s):  
Clinical Trials ◽  
Patient Outcomes ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Current Treatment ◽  
Resistance Development ◽  
Ongoing Research ◽  
Alk Positive ◽  
Emergence Of Resistance ◽  
Key Questions

The treatment of advanced non-small-cell lung cancer (nsclc) has undergone a paradigm shift since the early 2000s. The identification of molecular subtypes of the disease, based on oncogenic drivers, has led to the development of personalized medicine and the ability to deliver molecularly targeted therapies to patients. In the 10 years that have elapsed since the discovery of the ALK gene in a patient with nsclc, several active drugs have moved rapidly from bench to bedside, and multiple others are currently in clinical trials. Those developments have led to important improvements in patient outcomes, while simultaneously raising key questions about the optimal treatment for ALK-positive nsclc. The inevitable emergence of resistance to alk-directed therapy is central to ongoing research and daily clinical practice for affected patients. In the present review, we highlight the current treatment landscape, the available and emerging clinical trials, and the evolving clinical decision-making in ALK-positive nsclc, with a focus on Canadian practice.

Carriage of antibiotic resistant bacteria flora and its role in the guidance of clinical decision making

2020 ◽  
Vol 78 (5) ◽  
Author(s):  
Darren W Wong
Keyword(s):  
Decision Making ◽  
Antibiotic Resistance ◽  
Antimicrobial Therapy ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Resistant Bacteria ◽  
Resistant Organism ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant

ABSTRACT There is considerable literature on the threat of antibiotic resistance and its impact on morbidity. However, an under-studied consideration is how carriage of these antibiotic resistant bacteria persist in an individual. The duration that a person harbors a resistant organism is critical in guiding future antimicrobial therapy. Key unexplored questions are the rate of clearance of these organisms and what drives their persistence. This paper attempts to examine these questions and offers some initial answers as well as avenues for further study.

Effects of pH on the Antibiotic Resistance of Bacteria Recovered from Diabetic Foot Ulcer Fluid

2018 ◽  
Vol 108 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Carla D. McArdle ◽  
Katie M. Lagan ◽  
David A. McDowell
Keyword(s):  
Antibiotic Resistance ◽  
Diabetic Foot ◽  
Bacterial Infections ◽  
Clinical Decision Making ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Clinical Decision ◽  
Wound Fluid ◽  
Ph Values ◽  
Diabetic Foot Infections

Background: This study investigated the resistance of bacteria isolated from diabetic foot ulcers (DFUs) to antibiotics frequently used in the management of the diabetic foot infections, at a range of pH values (pH 6.5, 7.5, and 8.5) known to exist in DFU wound fluid. This study aimed to determine whether changes (or atypical stasis) in wound fluid pH modulate the antibiotic resistance of DFU isolates, with potential implications in relation to the suppression/eradication of bacterial infections in DFUs. Methods: Thirty bacterial isolates were recovered from DFU wound fluid, including Staphylococcus spp, Staphylococcus aureus, Escherichia coli, Streptococcus spp, Pseudomonas spp, and Pseudomonas aeruginosa. The resistances of these isolates to a panel of antibiotics currently used in the treatment of infected or potentially infected DFUs, ie, ciprofloxacin, amoxicillin-clavulanate, doxycycline, and piperacillin-tazobactam, at the previously mentioned pH values were determined by a modification of the Kirby-Bauer assay. Results: The resistance of DFU isolates to clinically relevant antibiotics was significantly affected by the pH levels in DFU wound fluid. Conclusions: These findings highlight the importance of a more comprehensive understanding of the conditions in DFUs to inform clinical decision making in the selection and application of antibiotics in treating these difficult-to-heal wounds. The scale of the differences in the efficacies of antibiotics at the different pH values examined is likely to be sufficient to suggest reconsideration of the antibiotics of choice in the treatment of DFU infection.

scholarly journals Within-host dynamics explain patterns of antibiotic resistance in commensal bacteria

2017 ◽  
Author(s):  
Nicholas G. Davies ◽  
Stefan Flasche ◽  
Mark Jit ◽  
Katherine E. Atkins
Keyword(s):  
Antibiotic Resistance ◽  
Management Strategies ◽  
Resistance Management ◽  
Population Level ◽  
Antibiotic Consumption ◽  
Mathematical Framework ◽  
Host Immune Responses ◽  
Resistance Evolution ◽  
Resistant Strains ◽  
The Impact

The spread of antibiotic resistance, a major threat to human health, is poorly understood. Empirically, resistant strains gradually increase in prevalence as antibiotic consumption increases, but current mathematical models predict a sharp transition between full sensitivity and full resistance. In other words, we do not understand what drives persistent coexistence between resistant and sensitive strains of disease-causing bacteria in host populations. Without knowing what drives patterns of resistance, we cannot accurately predict the impact of potential strategies for managing resistance. Here, we show that within-host dynamics—bacterial growth, strain competition, and host immune responses—promote frequency-dependent selection for resistant strains, explaining patterns of resistance at the population level. By capturing these processes in a parsimonious mathematical framework, we resolve a long-standing conflict between theory and observation. Our models capture widespread coexistence for multiple bacteria-drug combinations across 30 European countries and explain associations between carriage prevalence and resistance prevalence among bacterial subtypes. A mechanistic understanding of resistance evolution is needed to accurately forecast the impact and effectiveness of resistance-management strategies.

Epidemiology and outcomes of source control procedures in critically ill patients with intra-abdominal infection

2019 ◽  
Vol 52 ◽  
pp. 258-264 ◽  
Author(s):  
Kirsten van de Groep ◽  
Tessa L. Verhoeff ◽  
Diana M. Verboom ◽  
Lieuwe D. Bos ◽  
Marcus J. Schultz ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Source Control ◽  
Abdominal Infection ◽  
Control Procedures ◽  
Intra Abdominal Infection

Does Initial Choice of Antimicrobial Therapy Affect Length of Stay for Patients with Complicated Intra-abdominal Infections?

2005 ◽  
Vol 71 (10) ◽  
pp. 816-820
Author(s):  
Samuel Eric Wilson ◽  
Robin S. Turpin ◽  
X. Henry Hu ◽  
Elizabeth Sullivan ◽  
Edward C. Mansley ◽  
...  
Keyword(s):  
Length Of Stay ◽  
Antimicrobial Therapy ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Regression Tree ◽  
Severity Of Illness ◽  
Source Control ◽  
Related Factors ◽  
Abdominal Infection ◽  
Intra Abdominal Infection

Outcomes for complicated intra-abdominal infection are influenced by operation for source control, patient-related factors, and medical management, including antibiotic treatment. We analyzed length of stay (LOS) at 33 hospitals for 2,150 patients discharged between February 2002 and June 2003, who were >18 years, had intra-abdominal infection, and received one of 6 first-line antimicrobials. A regression tree analysis selected important variables, their interactions, and their order of significance in explaining LOS. A linear mixed model evaluated the difference in LOS between treatment groups. Adjusted LOS was calculated by the least squares means from the model and was used to assess treatment differences. Mean LOS analyzed by initial antimicrobial therapy and stratified by diagnosis showed LOS for ampicillin/sulbactam and ertapenem to be significantly shorter from levofloxacin, ceftriaxone, and piperacillin/tazobactam (all P < 0.05). Adjusting for all other factors, the variables associated with severity (e.g., diagnosis, ICU stay, and comorbidities) had the greatest impact on adjusted LOS (all P < 0.001). Our findings indicate ampicillin/sulbactam and ertapenem were associated with shorter hospital stays, which may be explained by unaccounted for underlying severity of infection and/or by surgeons stratifying antimicrobial selection according to severity of illness.

scholarly journals Factor influencing outcome of source control in the management of complicated intra-abdominal infection in Cipto Mangunkusumo University Hospital

2019 ◽  
Vol 52 (5) ◽  
pp. 169
Author(s):  
ToarJean Maurice Lalisang ◽  
Yarman Mazni ◽  
WifantoSaditya Jeo ◽  
VaniaMyralda Giamour Marbun
Keyword(s):  
University Hospital ◽  
Source Control ◽  
Abdominal Infection ◽  
Intra Abdominal Infection

scholarly journals Improved Antimicrobial Host Defense in Mice following Poly-(1,6)-β-d-Glucopyranosyl-(1,3)-β-d-Glucopyranose Glucan Treatment by a Gender-Dependent Immune Mechanism

2011 ◽  
Vol 18 (12) ◽  
pp. 2043-2049 ◽  
Author(s):  
Courtni T. Newsome ◽  
Estefany Flores ◽  
Alfred Ayala ◽  
Stephen Gregory ◽  
Jonathan S. Reichner
Keyword(s):  
Host Defense ◽  
Cecal Ligation ◽  
Innate Immune ◽  
Source Control ◽  
Beta Glucan ◽  
Fungal Cell ◽  
Abdominal Infection ◽  
Female Mice ◽  
Beta Glucans ◽  
Intra Abdominal Infection

ABSTRACTClinical trials with biological modifiers targeting specific inflammatory mediators associated with severe sepsis have shown no or limited survival benefit. The approach taken in studies reported here was to limit the point source of intra-abdominal infection by potentiating innate immune function, thereby lessening the severity of sepsis and improving survival. Soluble beta-glucans, glucose polymers of the fungal cell wall, have been shown to stimulate innate immune host defense in animal and human studies when administered prior to an infectious challenge. We evaluated the effects of poly-(1,6)-β-d-glucopyranosyl-(1,3)-β-d-glucopyranose glucan (PGG glucan) on overall survival when administered intraperitoneally after the onset of polymicrobial infection by cecal ligation and puncture (CLP). Since gender-dependent differences in host immune response to infection have been reported, male and female mice were prospectively stratified for PGG glucan treatment. Outbred CD-1 mice were administered 10 mg/kg of body weight PGG glucan or the polysaccharide control, dextran, 1 h after CLP. Six hours after CLP, blood samples were obtained for cytokine measurements. Surprisingly, a gender-dependent effect on the response to PGG glucan was revealed. PGG glucan enhanced survival in female mice over a 10-day period, but survival in males was improved for only 24 h. In female mice, PGG glucan reduced interleukin-6 (IL-6) and IL-10 levels and reduced the bacterial burden in the liver. Ovariectomy abrogated the response to PGG glucan. Together, the translational potential of these findings is the indicated use of PGG glucan given locally, rather than intravenously, for improved source control during the management of sepsis. This therapy does not require prophylactic beta-glucan administration.

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