This study compared outcomes of patients with MDR/XDR Acinetobactor baumannii pneumonia treated with tigecycline or colistin. 70 patients received either tigecycline (n=30) or colistin (n=40). There were no significant differences in clinical outcomes between the two groups except nephrotoxicity, which only occurred in the colistin group. While the study indicates comparable efficacy, limitations include its small size, retrospective design, and exclusions. Further large randomized studies are still needed to properly evaluate tigecycline and optimal treatment combinations for MDR infections.
PEPTIC (Holden Young - Roseman University College of Pharmacy)HoldenYoung3
PEPTIC (Holden Young - Roseman University College of Pharmacy)
Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital
mortality among ICU patients receiving invasive mechanical ventilation (PEPTIC).
JAMA . 2020; 323(7):616-626
Comparative evaluation of 2g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections. Indian Journal Of Pharmacology. August 2015;Vol. 47; Issue 4
OMICS Publishing Group, Journal of Clinical Pharmacology & Biopharmaceutics (CPB) emphasizes the phases of drug development from absorption, disposition, metabolism, excretion interactions and rational design of drug products to deliver the drug at a specific rate to the body in order to optimize the therapeutic effect and minimize any adverse effects. The CPB acts as an interface between academics, those in research and developments, explicates the research on various developmental applications for contemporary drug development and utilization.
Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea ...Utai Sukviwatsirikul
Saccharomyces boulardii in the prevention of antibiotic-associated
diarrhoea in children: a randomized double-blind placebo-controlled
trial
M. KOTOWSKA, P. ALBRECHT & H. SZAJEWSKA
Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Warsaw, Poland
Accepted for publication 24 November 2004
PEPTIC (Holden Young - Roseman University College of Pharmacy)HoldenYoung3
PEPTIC (Holden Young - Roseman University College of Pharmacy)
Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital
mortality among ICU patients receiving invasive mechanical ventilation (PEPTIC).
JAMA . 2020; 323(7):616-626
Comparative evaluation of 2g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections. Indian Journal Of Pharmacology. August 2015;Vol. 47; Issue 4
OMICS Publishing Group, Journal of Clinical Pharmacology & Biopharmaceutics (CPB) emphasizes the phases of drug development from absorption, disposition, metabolism, excretion interactions and rational design of drug products to deliver the drug at a specific rate to the body in order to optimize the therapeutic effect and minimize any adverse effects. The CPB acts as an interface between academics, those in research and developments, explicates the research on various developmental applications for contemporary drug development and utilization.
Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea ...Utai Sukviwatsirikul
Saccharomyces boulardii in the prevention of antibiotic-associated
diarrhoea in children: a randomized double-blind placebo-controlled
trial
M. KOTOWSKA, P. ALBRECHT & H. SZAJEWSKA
Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Warsaw, Poland
Accepted for publication 24 November 2004
Optimal schedule of Bacillus Calmette-Guerin for non-muscle-invasive bladder ...Enrique Moreno Gonzalez
To explore the necessity of maintenance, efficacy of low-dose and superiority of various combination therapies of Bacillus Calmette-Guérin (BCG) in treatment of superficial bladder cancer (BCa).
The presentation is about the dose selection for laboratory animal toxicology drug testing, explaining staged and staggered approach of dose selection.
Traditionally, physicians recruited clinical trial subjects, but pharmaceutical companies have become ever more involved through centralized campaigns. Physicians are vital to a trial and the pharmaceutical effort helps shift some of the recruitment demands away from the site to allow them to focus on the subjects. Thus, it is practical to understand if different recruitment methods could change or skew the study population. This study determines if differences or similarities occurred between subjects recruited by physicians and pharmaceutical companies. It discovered that some of both occurred. The pharmaceutical company efforts helped recruit potential subjects from the general population that were similar to subjects recruited by the physicians, but this particular campaign was limited by language which affected recruitment of Hispanic subjects. The social impact of this study provides insight about pharmaceutical company recruitment. Since the National Library of Medicine has indicated that clinical trials should reflect the broader diseased population, the efforts of the pharmaceutical company can help support the physicians’ efforts by recruiting from the broader population. Together, both efforts can create a global good by allowing the trial to reflect the population of post-approval use. These findings still raise a question about the proper balance between the two recruitment groups so that the intended characteristics of the diseased population are maintained. Because differences between physician and pharmaceutical recruited subjects can exist, the potential of one group to bias the trial results exist. As such, some analysis by recruitment method can help ensure that variations in the study population are minimal without skewing the data to create positive study results.
Drug development for neglected parasitic diseases. Group of the University of Barcelona offers expertise from the design and synthesis of new therapeutic membrane active peptide-based antibiotics (AMP, NCE) to in vivo proof-of-concept and MoA (TEM, AFM, flow cytometry, fluorescence...).
Optimal schedule of Bacillus Calmette-Guerin for non-muscle-invasive bladder ...Enrique Moreno Gonzalez
To explore the necessity of maintenance, efficacy of low-dose and superiority of various combination therapies of Bacillus Calmette-Guérin (BCG) in treatment of superficial bladder cancer (BCa).
The presentation is about the dose selection for laboratory animal toxicology drug testing, explaining staged and staggered approach of dose selection.
Traditionally, physicians recruited clinical trial subjects, but pharmaceutical companies have become ever more involved through centralized campaigns. Physicians are vital to a trial and the pharmaceutical effort helps shift some of the recruitment demands away from the site to allow them to focus on the subjects. Thus, it is practical to understand if different recruitment methods could change or skew the study population. This study determines if differences or similarities occurred between subjects recruited by physicians and pharmaceutical companies. It discovered that some of both occurred. The pharmaceutical company efforts helped recruit potential subjects from the general population that were similar to subjects recruited by the physicians, but this particular campaign was limited by language which affected recruitment of Hispanic subjects. The social impact of this study provides insight about pharmaceutical company recruitment. Since the National Library of Medicine has indicated that clinical trials should reflect the broader diseased population, the efforts of the pharmaceutical company can help support the physicians’ efforts by recruiting from the broader population. Together, both efforts can create a global good by allowing the trial to reflect the population of post-approval use. These findings still raise a question about the proper balance between the two recruitment groups so that the intended characteristics of the diseased population are maintained. Because differences between physician and pharmaceutical recruited subjects can exist, the potential of one group to bias the trial results exist. As such, some analysis by recruitment method can help ensure that variations in the study population are minimal without skewing the data to create positive study results.
Drug development for neglected parasitic diseases. Group of the University of Barcelona offers expertise from the design and synthesis of new therapeutic membrane active peptide-based antibiotics (AMP, NCE) to in vivo proof-of-concept and MoA (TEM, AFM, flow cytometry, fluorescence...).
APRIL 2018, VOL. 22 NO. 2 CLINICAL JOURNAL OF ONCOLOGY NURSING.docxfestockton
APRIL 2018, VOL. 22 NO. 2 CLINICAL JOURNAL OF ONCOLOGY NURSING 175CJON.ONS.ORG
C
Nephrotoxicity
Evidence in patients receiving cisplatin therapy
Elizabeth A. Duffy, DNP, RN, CPNP, Wendy Fitzgerald, RN, MSN, PPCNP-BC, CPON®, Kelley Boyle, MSN, RN, PCNS-BC, and Radha Rohatgi, PharmD, BCOP
CISPLATIN IS A PLATINUM COMPOUND THAT HAS BEEN USED as a chemotherapeutic
agent for many different cancers, including ovarian, testicular, lung, cervical,
and bladder cancers (Ruggiero, Rizzo, Trombatore, Maurizi, & Riccardi, 2016;
Santoso, Lucci, Coleman, Shafer, & Hannigan, 2003). The primary dose-
limiting toxicity of cisplatin is nephrotoxicity, a well-known side effect
(Jones, Spunt, Green, & Springate, 2008; Miller, Tadagavadi, Ramesh, &
Reeves, 2010). Nephrotoxicity involves glomerular or tubular dysfunction
of the kidneys after exposure to medications, other treatments, or toxins
(Skinner, 2011). Nephrotoxicity associated with cisplatin is related to accu-
mulation of metabolites in the renal proximal tubule cells of the kidneys,
where about 90% of cisplatin undergoes urinary excretion (Ruggiero et al.,
2016). Accumulation of these metabolites causes direct inflammation; the
production of reactive oxygen species, which leads to oxidative cell damage;
and cell death (Miller et al., 2010; Ruggiero et al., 2016). Many methods are
available to measure kidney function and define nephrotoxicity or acute
kidney injury (see Table 1).
Most patients receiving cisplatin experience acute impairment of glo-
merular and tubular function in varying degrees. Toxicity is dependent on
individual cisplatin pharmacokinetics and is usually more severe with high
total cisplatin doses and when other potential nephrotoxic medications are
given concurrently (Skinner, 2011; Womer, Pritchard, & Barratt, 1985). In one
study, children aged 10 years or older at treatment had a lower glomerular
filtration rate 10 years after therapy compared to children aged younger than
10 years at treatment (Skinner et al., 2009).
Nephrotoxicity can be reversible, but for some individuals, it can result
in permanent kidney injury, chronic progressive renal failure, or renal tubule
function impairment (Skinner et al., 2009). Chronic and severe reductions
of renal function have several sequelae. The immediate impact may be dose
reduction or cessation of potentially lifesaving nephrotoxic chemotherapy,
thereby increasing the risk of relapse or progression of the cancer. In the
event of a disease relapse or progression, changes to renal function may limit
enrollment in phase 1 or 2 clinical trials because of inclusion parameters
related to baseline renal function.
Hydration and diuretics have been used in conjunction with cisplatin
administration for decades to improve the excretion of cisplatin and reduce
the incidence of nephrotoxicity. One method of promoting this excretion is
through osmotic diuresis with mannitol (Morgan et al., 2014). However, the
amount ...
Update on the evidence to support deprescribing, a presentation by David Erskine, Director – London & South East Medicine Information Service (July 2017).
UPDATED-Early Phase Drug Developmetn and Population PK and Its' ValueE. Dennis Bashaw
Presentation Given at Regional AAPS DDDI Meeting in Baltimore. Similar to previous talks BUT updated to include a discussion of BIA 10-2474 and extended discussion of risk
The dream of any physician and consequently every patient is to receive the right treatment in the right time with cost effectiveness. To achieve this goal, the 3 pillars: evidence based medicine, clinical research innovation & resources utilization should be integrated efficiently.
In this presentation, I'll try to comprehensively review the following:
1- How are we used to perform clinical trials in Oncology?
2- Does it fits in today’s needs?
3- Integration of biology knowledge in shaping drug development
4- New Clinical trial designs “Can they offer solution for accelerating drug development?”
5- The supporting infrastructure role in clinical trial execution
Meta-Analysis of Traditional Chinese Medicine Injection Combined with Paclita...semualkaira
To investigate the effect of traditional Chinese medicine injection combined with paclitaxel, cisplatin or carboplatin chemotherapy regimen (TP Chemotherapy Regimen) on lung cancer.
Similar to JC HO - Colistin V. Tige - NOWICKI (17)
Meta-Analysis of Traditional Chinese Medicine Injection Combined with Paclita...
JC HO - Colistin V. Tige - NOWICKI
1. Multi-Drug Resistance Journal Club – Diana Nicole Nowicki – 06/24/2016
1
BACKGROUND AND OVERVIEW
Article Title/Citation “Comparable efficacy of Tigecycline versus Colistin Therapy for Multidrug-Resistant and Extensively Drug-
Resistant Acinetobactor baumannii Pneumonia in Critically Ill Patients”
Kim WY, Moon JY, Huh JW, Choi SH, Lim CM, Koh Y, Chong YP, Hong SB. Comparable Efficacy of
Tigecycline versus Colistin Therapy for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter
baumannii Pneumonia in Critically Ill Patients. PLoS One. 2016 Mar 2;11(3):e0150642
Study objectives/purpose
(and research hypothesis, if
applicable)
1. Compare the clinical outcomes of patients with multi-drug resistance/extensively drug-resistant
Acinetobactor baumannii (MDR/XDRAB) pneumonia treated with either a tigecycline-based therapy or
colistin-based therapy.
2. Evaluate the efficacy of combination therapy versus monotherapy.
Brief background (why
issue is important, summary
of previous literature)
With the growth of multi-drug resistance organisms (MDROs), we have seen an increase in antimicrobial
stewardship programs, government-funded research, and ‘superbug’ occurrences worldwide (with the first
reported in U.S. in May 2016)1. Acinetobactor baumannii, an aerobic gram-negative bacillus that is ubiquitous in
nature, causes a range of infections. In the intensive care unit (ICU), especially mechanically ventilated (MV)
patients, MDR/XDRAB is associated with high mortality.2 Agents commonly used are meropenem, colistin,
polymyxins b, amikacin, rifampin, minocycline, sulbactam, zosyn and tigecycline.3
Agents Tigecycline Colistin
[aka polymyxins E; Colistimethate Sodium (CMS)]
Brand Tygacil® Coly-Mycin M
Class glycylcycline polymyxin
Hx 1st glycylcycline; Approved 2005 c. 1949; abandoned in 1980s d/t nephrotoxicity
Indications SSTI, IAIs, CAP, HAPa MDR Gram-negative bacilli infections, CF ppx a
Black Box Increase all-cause mortality -
MOA Binds to 30s ribosomal subunit
inhibiting protein synthesis
Inactive prodrug converts to CMS with multi-
targets that allows permeability of outer membrane
Dosing 100mg IV then 50mg IV Q12H IV 2.5-5 mg/kg/day (Consider loading dose)
Adjustments Sever hepatic impairment Renal impairment, RRT/HD
ADRs GI (N/V/D) Nephrotoxicity, neurotoxicity
MOR MDR efflux pump mechanism Gene amplification at high concentrations (mcr-1)
aoff-label use;
Definitions – CF ppx: Cystic fibrosis prophylaxis; RRT: renal replacement therapy; HD: hemodialysis
Funding sources Authors “received no specific funding for this work.”
METHODS
Study design and
methodology
Single-centered retrospective observational study at Asan Medical Center, a 2,680-bed university affiliated
hospital in Seoul, Korea. Reviewed medical records of patients admitted to the medical or cardiothoracic
ICU between January 2009 and December 2010. IRB approved study protocol. Patients records were
anonymized and de-identified prior to analysis.
Normal Renal Function Dosing Tigecycline Colistin
Loading Dose 100mg IV x 1 5mg/kg CBA IV x 1
Maintenance Dose 50 mg IV Q12h 150mg CBA IV Q12h
Definitions – CBA: Colistin Base Activity
Patient selection &
enrollment [inclusion/
exclusion criteria]
Inclusion Exclusion
≥ 20 yo who:
• Confirmed dx of HAP or VAP by
MDR/XDRAB
• Received tigecycline or colistin as
mono –or- combination therapy as
initial therapy for at least 3 days
• If multiple episodes in one patient,
only first episode was included
• Concomitant use of tigecycline and colistin
• “inadequate treatment” (< 3 days)
• Combination infection without
“appropriate Abx therapy” (empiric
therapy didn’t include “one effective Abx”)
Outcome measures/
endpoints
Primary Outcome: Clinical Success Rate = clinical cure (e.g. resolution of s/sx infection by end of therapy
or clinical improvement (e.g. partial resolution of s/sx of infection)
2. Multi-Drug Resistance Journal Club – Diana Nicole Nowicki – 06/24/2016
2
Outcome measures/
endpoints (ctd.)
Secondary Outcomes:
• Recurrence of infection (new episode of infection <72 h after preceding episode)
• Microbiological Success Rate (eradication of the pathogen (e.g., no growth of the pathogen in the
final culture of specimens during the entire hospitalization)
• Improvement in CPIS & radiologic score at day 7 compared with baseline
• Duration of MV, ICU and hospital stay
• Nephrotoxicity (In pts w/ normal renal function, nephrotoxicity was SCr >2 mg/dL, a 50%
reduction in the calculated CrCl compared w/ baseline, or initiation of RRT; In pts w/ preexisting
renal dysfunction, nephrotoxicity was increase of >50% baseline SCr or a 50% reduction in the
calculated CrCl compared with baseline)
• Mortality
• Clinical Failure
Statistical analyses Mann-Whitney U test [Continuous Variables], chi-square or Fisher’ s exact test [Categorical variables],
Hosmer-Leme show test [model calibration]. Two-tailed; P value < 0.05 was considered significant.
Univariate/multivariate analyses performed with SPSS version 22.0 for Windows (SPSS Inc., Chicago, IL)
RESULTS
Enrollment & baseline
characteristics
(Also see Table 1, page 5)
Of the 99 cases found, only 70 were used for this analysis. Tigecycline group was slightly older, colistin
group was larger (30 vs. 40 patients), while all other characteristics were similar. Concomitant use of
tigecycline and colistin was excluded, along with any patients that passed during 30-day period.
Summary of primary and
secondary outcomes
(Also see Table 2-3, page 6)
Appeared to be no statistical significance in any outcomes except for safety parameter, nephrotoxicity
occurred in colistin group and not tigecycline which was to be expected (0% and 20%, respectively;
p=0.009). More extensive hospital duration was apparent in colistin group but not significant per analysis
(19-58 days vs. 16-111 days, respectively; p = 0.44). Subgroup analysis on mono versus combination therapy
regimens based with tigecycline or colistin showed no significant difference in outcomes (ICU mortality 51%
vs. 31%, respectively; p=0.09).
AUTHORS’ DISCUSSION & CONCLUSIONS
Brief summary of authors’
main discussion points
and conclusions
• Assessed that the small population set and varying infection sites does not effectively project
tigecycline’s specific role in MDR/XDR treatment.
• They believe this study indicates comparable efficacy of tigecycline-based therapy to colistin-based
therapy in critically ill patients with MDR/XDRAB pneumonia.
• Study holds many limitations and further research must be conducted toward tigecycline.
STUDENT’S DISCUSSION & CONCLUSIONS
Study strengths Provided clear definitions.
Included causative pathogen of MDR/XDRAB pneumonia supported by microbiological data.
Routine susceptibility testing for tigecycline was performed for each isolate.
Universal healthcare system reporting.
Study limitations Poor study design (Non-randomized methods, size, not multi-center, no follow up, underpowered etc.)
Exclusions: Per-protocol – patients that died within 30 days were excluded (Monotherapy n=27 vs. Combo
n=21), combination therapy of tigecycline and colistin together (although mentioned in discussion), etc.
Did not provide dosing for renal adjustments, severity of CKD, or appear to analyze correlation to nephrotoxicity
and poor outcomes.
Applicability and impact
on
pharmacists/healthcare
providers
Need for further evaluation in appropriate therapy especially in high-risk mortality populations.
Supporting recommendation that colistin be used as adjunct therapy to prevent resistance, limit ADEs, and
provide synergistic antimicrobial effects with used in combination with other agents (mono-therapy does not
correlate to positive clinical outcomes).
Review proper dosing of colistin and CBA awareness.
Student Conclusions and
recommendations
Need quality RCTs/Prospective/Case Studies – although difficult with acute and severely ill patients
• Colistin Vs. Polymyxin b
• Further look into polymyxins b? (not available in Europe for human use, used in vet med)
• Best combinations with polymyxin.
Need to continue antimicrobial stewardship programs as resistance to these agents can happen quickly.
References
1. U.S. Department of Health and Human Services (HHS). Proactive Efforts by U.S. Federal Agencies Enable Early Detection of New Antibiotic Resistance.
HHS website. http://www.hhs.gov/blog/2016/05/26/early-detection-new-antibiotic-resistance.html. May 26, 2016. Accessed June 15, 2016.
2. Cheng A, Chuang YC, Sun HY, Sheng WH, Yang CJ, Liao CH, Hsueh PR, Yang JL, Shen NJ, Wang JT, Hung CC, Chen YC, Chang SC. Excess Mortality
Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter
baumannii Bacteremia: A Multicenter Prospective Observational Study. Crit Care Med. 2015 Jun;43(6):1194-204.
3. Fan B, Guan J, Wang X, Cong Y. Activity of Colistin in Combination with Meropenem, Tigecycline, Fosfomycin, Fusidic Acid, Rifampin or Sulbactam
against Extensively Drug-Resistant Acinetobacter baumannii in a Murine Thigh-Infection Model. PLoS One. 2016 Jun 17;11(6):e0157757.