This popular webinar is back for the third time soon, on March 5th, 2019.
The session will discuss on AUC based TDM for vancomycin. It will also highlight the pros and cons of using the current trough-only approach (supported by previous guidelines) vs. AUC method for vancomycin TDM.
Endorsed by ACCP, ESCMID, IDSA, ISAP, SCCM, and SIDP
This practice guideline provides consensus recommendations pertaining to the clinical use of the polymyxin antibiotics, colistin (polymyxin E) and polymyxin B, for the treatment of bacterial infections in adults.
Antibacterial Drug Enhancer Combinations and Non-traditional Products
Clinical development for non-developers Part 3
Fri, Mar 29, 2019 12:00 AM - 1:30 AM (local time)
The overall goal of this series of webinars is to provide, for the non-clinical developer, an understanding of the risks of development for various kinds of antibacterial products. The presentation will be followed by an interactive Q&A session.
It also penetrates the kidney tissues well,thus can be used in cases of pyelonephritis.
If you are faced with an isolate with a high MIC (>8 mg/L), think about the above and try to talk to your microbiologists reg. the use of fluconazole in this case as we can still use the drug if given in high dose. This is called dose-dependent susceptibility (or SDD).
In the field of Antibiotic Stewardship, data is an important tool that we can tap into in promoting ASP as well as its application in clinical practice, Data can also be used as metrics that allow us to benchmark our performance and track the effectiveness/ the lack of when come to ASP interventions.
We must also ensure that these data are highly visible and reachable by readers especially health care professionals. Below is a link to a webinar that provides viewers with useful tips in making one research visible.
In the collection of new and "advanced-articles" under Clinical Infectious Diseases (CID), there is this new paper published recently on an RCT performed in 3 centers in Israel and Italy. This trial tried to answer the million-dollar question on whether we should treat GNB bacteremia for 14 days or lesser (viz. 7 days).
So which one will you choose in your patient on the seventh day when your patient is well and afebrile for the past 48 hours prior?
This webinar reviews the basal requirements, indications and practical aspects for rational antibiotic TDM in the intensive-care setting, with a special focus on the beta-lactams that are the most widely used antibiotic class.
In the past therapeutic drug monitoring (TDM) has been employed only for antimicrobials with narrow therapeutic ranges, such as aminoglycosides. However, in recent years the knowledge about the altered pharmacokinetics in critically ill patients has led to a paradigm shift. Nowadays TDM of antibiotics is also advocated as a tool to guide dosage, ameliorating adequate drug exposure and therapeutic success in patients with severe infection, and at the same time minimizing the antimicrobial resistance.
Indian government bans 328 fixed combination drugs.
one such combination includes cefixime/azithromycin
Indian government delivered a massive blow to both local and international pharmaceutical companies following the ban on 328 combination drugs
We are not talking about normal FDCs (fixed drug combination) like amoxi-clav. Rather the combinations include the above, which were reported to be manufactured and marketed under 15 different names by companies in India (source; clinical infectious diseases news in Volume 67, Issue 12 -15 December 2018
The webinar will be delivered by Michael Paal of the Institute of Laboratory Medicine University Hospital, LMU Munich, Germany.
This webinar will review the basal requirements, indications and practical aspects for rational antibiotic therapeutic drug monitoring (TDM) in the intensive-care setting, with a special focus on the beta-lactams that are the most widely used antibiotic class. Quantification techniques and respective bottlenecks for affordable de-centralized testing will also be discussed.
It is an observational study, there is no intervention, no supplementary tests and all the data should be gathered from the patient's chart and what is available for their usual care. The study is sponsored by the ESICM Trials Group, and endorsed by the The ESICM Infection Section, the ESCMID Study Group for Infections in Critically Ill Patients – ESGCIP and the Asia Pacific association of Critical Care Medicine – APACCM.
We plan to include 10 consecutive patients (or for 3 months) from each ICU. The CRF will be electronic and the amount of required data has been kept to a minimum to facilitate data capture.
Your ICU can be part of this concerted effort of mapping out BSI incidence worldwide including the details on pathogens and treatment for BSI. Let's contribute to this cohort fellow Malaysian doctors. If you are interested in joining this study or would like to know more, please email the national coordinator for Malaysia, Helmi Bin Sulaiman at email@example.com.
In addition, please fill in the online form below if you would like to join us today!
Trialect has partnered with more than 200 faculty members from the United States to facilitate One-on-One online personalized grant tutoring by previous recipients of NIH or other Non-Profit grants. They can see your grant proposal with fresh eyes and help guide your students in the following
ECCMID (The European Congress of Clinical Microbiology and Infectious Diseases) is the largest, most comprehensive and most influential meeting in the fields of clinical microbiology, infectious disease and infection control.
A systemic review on bacteriophage-based therapy for infections caused by ESKAPE organisms was recently published in CID.
They (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are regarded as the most problematic bacteria, when comes to antibiotic resistance.
Thus, alternatives to antibiotic as the sole agent to combat these bugs are currently being pursued and these include phage cocktails.
It is believed that such cocktail may avoid development of antibiotic resistance in bacterial genomes.
According to the authors, it can also degrade biofilms that act as safe havens for bacteria to hide/slumber and they can resist antibiotic activity when given at normal and approved dosages within these sanctuaries.
The authors pooled 30 studies after sifting through 1,102 articles on phage therapy in this. A third of these cohorts were given antibiotic therapy in addition to phage and others received phage monotherapy only.The duration of phage therapy ranged from 1 day to 18 weeks.
The pooled efficacy of phage cocktails/treatment against ESKAPE organisms was reported to be at 87% in this review. With such high rate of success, perhaps more robust studies can be planned and carried out to study its efficacy against SOC.
Upon the direction of the ESCMID Executive Committee, a call is now open for proposals of Postgraduate Educational Courses and Technical Workshops, to be run in the second half of 2019.
In particular, ESCMID is seeking 4 courses, one from each of the following regions:
• Central and South America
• Eastern Europe
Support by ESCMID.
Selected courses will be administrated by the ESCMID executive office, and local organisers will receive a EUR 5000.- contribution towards organisation, as well as a further EUR 5000.- towards attendance grants for ESCMID Young Scientist Members.
The alphabet (fungal) soup of fungi and antifungal drugs
In November 2018, we had the chance of listening to a PKPD guru Deborah Marriott from St Vincent Sydney, Australia. She shared with us the ABC of fungal infections as well as antifungal treatments.
(I have attached the links to some of the studies used in the slides which were used to illustrate these in the link below)
These letters are;
A= Always consider fungus/fungal infections in your patients.
Especially in ICUs.
A big proportion/cases of fungal infections are unknown and will remain to be so in many patients.
Check out the paper in the link below.
B= Beware of fungal infections and incidence in your center
Different centers would have different fungi/candida species dominating the "fungal scene" in one's hospital. Candida auris of late has gained notoriety and Lockhart published a paper that narrates on "aurial infections" in India, Pakistan, South Africa as well as Venezuela.
C= consider biofilm.
Similar to bacteria, candida too can form biofilm and the MICs for candida in biofilm are multifold higher than the planktonic ones. Debby shared a few interesting papers in her talk on biofilm.
D= drug-drug interactions,
When one uses azole, one cannot run away from possible DDI. Azole interacts with meropenem, PPI and in one case, Debbie showed how a seemingly friendly beta lactam caused voriconazole to be metabolized extensively that the level was severely affected.
No two echinocandins are the same in term of exposure-response after dosing.
These papers and slides screamed PK as well as PD (to some extent).
In 2 large cohorts, micafungin and caspofungin levels were rendered insufficient in critically ill patients, which saw reductions in the areas under the curve for these echinocandins below the acceptable levels for these patients.
H and I point to the same thing which is G
You need G because of H, I as well as D really.
G = Go for TDM
Well this is so true especially for azole. Fluconazole levels for example may be low in patients with ATN and AKI. As ATN happens, patients would be excreting fluco too into their urine as there is no reabsorption happening in the renal tubules leading to the need for even higher dosages for patients with AKI.
Would you dare to do this?
I guess this is where TDM is very beneficial then.
H = hypoalbuminemia and increased Vd
Which also points to an increased risk of under dosing due to blunted dose-exposure response curve in patients receiving azole and echinocandins.
When your albumin is low, the holding power of plasma of the antifungal falters, leading to an increase in Vd as well as urinary excretion and liver metabolism.
I = Inflammation
In septic patients who receive azole (in this case voriconazole), patients may be exposed to supra-level(s) following inflammation
(surrogate marker used for inflammation in this study was CRP).
Why? Perhaps metabolism would get disrupted following an increase in inflammation leading to high level of voriconazole free drug in one's plasma.
In ID week, there would be these sessions that would be repeated in ID week every year. "What's-Hot-in-ID" is one of them.
In this, Stan Deresinski from Stanford University, located just down the road from where the ID week 2018 was held at (San Francisco), talked about the boy in the picture.
He was Leland Stanford Jr. and his parents named the university in remembrance of his passing. He died due to typhoid fever when the family went to Europe; their second grand tour, where he was first diagnosed with this in Greece and succumbed to the infection later in Florence, Italy.
Then there was no treatment available in the world.
He recounted this as a preamble to his first "HOT STORY", as well as a warning to all of us. The story was about the current outbreak of extensively drug resistant Salmonella in Pakistan, and the warning was the grim prospect of this becoming pan drug resistant soon and what then?
Another stories of Leland Stanford Juniors?
By now everyone has heard bits and pieces of this trial and Stan took a jab at this too. He was pro-carbapenem in this. He in his last slide for MERINO said, if anything MERINO favored pip tazo but yet pip tazo failed to prove non-inferiority. But Stan, how about the E-test issue and over representation of OXA enzymes in this trial?
One cannot run away from POET in "What's-Hot-in-ID" session, cause it is hot and relevant. How relevant, well... that will be up to interpretation and target groups that physicians would like to use this data for in treating patients with infective endocarditis.
Repeat TB vaccination
Would you do this?
Apparently there is this new trial that looks into such efficacy in high endemic countries and they used surrogate marker for such effect. The surrogate was quantiferon conversion rate and based on this it worked.
In the last week of October 2018, we got the chance of gathering together to listen to renown local and international speakers who shared with us, many new and exciting updates and science related to infectious disease field.
Here are some of these updates.
Many of us like them new (antibiotics) and shiny.
Professor George Karam presented to us a new array of "toys" that can be used to fight against Gram-negative bacteria and these include 2 truly broad spectrum antibiotics;
To know more head to THISnew review published in IJAA.
Increase antibiotic consumption in both MIC and LIC but not HIC.
Low and middle income countries are using more and more antibiotics and this is not showing any sign of abatement. To read further please click HERE
Australia has a great database for AMR called AURA
There is this great resource of AMR and antibiotic consumption from Australia and if you are interested to know more, please click HERE.
Malaysia is still using colistin for systemic infection
Perhaps is about time that we use polymyxin B for systemic infection and find out further on which companies that has this listed in for use in Malaysia.
India tapped into their private lab network
A few of Indian private labs pooled data together and reported the rate of resistance of major pathogens detected from blood culture. To read further on this please clickHERE.
A free online and phone based apps for optimizing antibiotic use and dosing
Yup this is free and it covers many major antibiotics including carbapenems and pip tazo as well as vancomycin. For vancomycin, they even have Bayesian to help one with dosing and TDM. Please clickHEREto know more.
The data on this new antibiotic was presented by one of the speakers during the event. It has a great potency against Pseudomonas aeruginosa including those with resistant phenotype.
Interestingly, Merck is seeking for FDA approval now following the success of this in treating both hospital and ventilator assc. pneumonia when pitted against meropenem
(doubled the dose of this drug was used in this trial, based on data from epithelial lining fluid and lung penetration PK study)
Two in one as the review was of 2018 ID week and meant for non-ID physicians. It also links one to another rapid review by Paul Sax (one of a prominent ID/HIV researchers from the States).
I believe this was written by Milana Bogorodskaya, an ID fellow who created FOAMid.com (FOAM stands for free open access medicine in ID). Do check this site out. It is packed with many goodies related to ID field.
The review covers an array of relevant 2018 ID week sessions that would benefit both the ID and non-ID physicians too. The lower half of the review may seem less relevant with topics like CMV preemptive therapy as well as diagnosis of PCP, but these I believe would benefit physicians who are involved in transplant medicine as well as cancer management.
One that piqued my interest is the highlight of an abstract that looked into the efficacy of high dose influenza vaccination in elderly. There was no benefit seen in protecting influenza-associated hospitalizations.
Why it piqued my interest?
A similar study was carried out recently in Singapore. The difference was, biannual flu vaccination with normal dosages was used instead and this was tested against annual one (SOC).
Tropic countries like ours would have year-long circulation of flu viruses with bi-annual peaks and thus this study would be relevant to us too.
What were seen?
Amongst other things, one that merits a highlight would be the reduced rate of influenza-like illness in the arm that received bi-annual vaccination.
Ceftriaxone - should we dose it 1 gm or 2 gm OD in CAP?
Based on this poster at #IDWeek2018: 1 gram would do just as good.
The data was from a large Japanese cohort of 3,817 possible candidates.
As the data was observational in nature, the authors tried to minimize bias by performing this.
(NB. Bias might lead to inaccurate measure of variable effects including treatment in this scenario on the outcome and population studied).
From the above, they managed to match 175 subjects in both the arms and what they found was; the cure rate was similar.
The mortality rate was similar too (with low rate of mortality perhaps reflecting the non-severe CAP amongst studied subjects?).
Few things worth mentioning.
- No clear definition/details were given for cure rate assessment.
- No severity score was given/shared.
However, basing on the median age (with corresponding upper and lower quartiles), respiratory rate, blood urea, as well as blood pressure; recruited subjects may belong to CURB 2 at the very least (moderate CAP).
Thus extrapolating this to severe CAP may be a bit difficult.
the colistin dose was NOT the problem as the high dose was pitted against the lower dose and higher dose did not improve outcome and in fact increases risk for AKI.
Based on a paper published in 2016 which pooled subjects from 2 big cohorts (total of 529 subjects) and 27.2% of them received the dose we would use today (9MU per day).
The propensity adjusted odd for mortality showed possible increase in chance of death (1.07; CI-95%, 0.63-1.83 - yup it crosses one thus it should read non-significant)but the risk for AKI is significant when subjects received high colistin dose by more than 2-fold (OR; 2.12; CI-95%, 1.29-3.48).
In my opinion (Helmi Sulaiman), this may be explained by;
1) erratic behavior of colistin precursor in vivo which is colistimethate sodium -CMS that disintegrates slowly to colistin.
2) Companion drug that may not help colistin at all, when the MICs of the companion against offending organisms were way higher than their MIC breakpoints as well as the possible target attainment, thus leaving the poor colistin to battle against the bugs alone in these 2 cohorts, Same fate was seen in AIDA study published HERE.
Is there any correlation between AKI and colistin level in one's body
According to Vidya Menon et. al,; NOT really.
At least based on the dose-exposure response data sourced from 12 subjects.
(presented at #IDWeek2018)
Thus they argue that we need to do TDM for colistin.
Wait a minute, TDM for colistin???
And this is not really poly B, meaning one needs to ensure conversion from colistimethate sodium -CMS to colistin must be kept at minimum (ex vivo) during TDM.
Add the issue of colistin (as well as poly B) predilection to stick to plastic (polymyxins are highly polar so they readily form many weird bondings with surrounding plastic), then one would have major headache to translate this from bench to clinical practice.
By the way what we saw on the left is a graph with 12 points of colistin Css, avg (average steady state level) and one could see that almost all the points (except one) did not even achieve the target of 2 mg/L (which corresponds to its optimal fAUC/MIC ~ 25) and increment of above 50% of serum creatinine was not predicted or associated with Css, avg at all.
Thus the recommendation/conclusion of TDM for colistin
The image is grainy and the outlook for colistin is grim (and grainy too) on this slide presented in #IDWeek2018
Let's talk about the paper where this was sourced from.
The slide was based on a paper published this year in JAC 2018. We know that there is no MIC breakpoint for Enterobacteriacea when come to colistin and CLSI guideline. It is extrapolated from breakpoints meant for Acinetobacter and Pseudomonas.
Colistin concentration at steady state (average) of 2 mg/L has been used as surrogate to get us to its "ideal" pharmacodynamic target of AUC/MIC of about 25 (anything higher you risk losing your kidneys/hearing and suffer from other neurological complications).
Using the usual dose of 9 MU per day, we can only reach a good coverage (aka PTA/probability of target attainment) when the MIC is less than 0.5 mg/L.
Anything higher, who knows what would happen and even at 1 mg/L of MIC, the range is so wide reflecting a very high degree of uncertainty (aka BSV; between subject variability).
Conclusion: colistin efficacy is suspect when MIC is above 0.5 mg/L.
(BTW even when authors said "best described", look at that R2 values. These were not good to begin with)
Mother of all candida. She can resist all your antifungals.
Her name is; Candida auris. Her ability is not limited to antifungal resistance only. Worryingly, she even has an ability to trick mycologists into thinking that they belong to other group of candida or fungi all together.
They could be misidentified as;
C. haemulonii complex, Rhodotorula glutinis, C. lusitaniae, C. famata, and C. guilliermondii
World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO), and World Organization for Animal Health (OIE) evaluated countries' responses to a self-assessment survey on their efforts to address AMR in humans, animals, and the environment.
While there has been sustained progress on developing national action plans to address antimicrobial resistance (AMR),, MAJOR GAPS REMAIN .
In almost all domains—surveillance, education, monitoring, and regulating consumption and use—more activity can be seen in the human sector.
The animal, agriculture, and environment sectors must be further engaged in AMR prevention efforts to ensure that a One Health approach can be pursued and so that the world can meet its AMR goals.
WANNA DISH OUT CIPROFLOXACIN AND THE LIKES TO YOUR PATIENTS?
You may want to consider these new warnings by FDA USA before using this class of antibiotics for your patient. On July 10, 2018, FDA strengthen the warnings about the risks of mental health side effects and serious blood sugar disturbances.
These warnings apply to both IV and oral forms. Clinicians are advised to weight the risks and benefits of fluoroquinolones and both clinicians and patients/clients should make an informed decision before their use.
PK-PD in support of accelerated programmes for antimicrobial development
HOW MUCH IS ENOUGH?
Date: Wed, Jun 27, 2018 1230 AM (Local Malaysian time)
A webinar by The Global Antibiotic Research & Development Partnership (GARDP)
This webinar featured Prof William Hope from University of Liverpool. He is one of the top experts in PKPD field. In this, he talked about the role of pharmacokinetics and pharmacodynamics for antimicrobial drug development.
He discussed the EMA guideline on the use of PK/PD and basic studies to inform dose finding strategies. There was also an interesting discussion on dose fractionation studies in PKPD field.
If you missed it, the copy of the talk in PDF form is as attached
Conference on antimicrobial resistance from bench to practice
This year, ESCMID is offering 10 grants to cover the cost of registration for deserving applicants. To apply, please write 100 words or less describing why it would be beneficial for you to attend the conference with the support of the ESCMID grant.
After the selection process has been completed, Applicants showing the ability to be in Havana at the time of the conference will have their registration fee paid for by ESCMID.
Following a long tradition of paper reading and review in ICAAC/Microbe, this year Dr Tamma from John Hopkins presented a list of papers as well as blockbuster RCTs that had the ID world talking in term of results (MERINO and AIDA)
Congratulation to 3 Malaysian projects -shortlisted for International Antibiotic Guardian 2018 Awards!
We are proud to have 3 Malaysian projects shortlisted for the award. They are;
1. Ms Lyna Irawati, a PhD student from the School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM). Her work entitled " Impact of an educational Intervention on Community Residents' Knowledge, Attitudes and Perceptions towards Antibiotics and Antibiotic Resistance in the state of penang, Malaysia", is under catergory of " Best Student of the Year"
2. Mdm Farizan Abdul Ghaffar and the team of pharmacists from Hospital Serdang. The work entitled " Promoting rational antimicrobial prescribing at Cardiology Centre Serdang Hospital, Malaysia" is under category "Prescribing & Stewardship"
3. Datin Mariani Ahmad Nizaruddin representating Malaysia Pharmaceutical Society with the work entitled " Antibiotic Resistance Awareness Campaign" under category " Public Engagement"
7 or 14 days of antibiotic treatment for Gram-negative bacteremia?
An RCT result was released recently in ECCMID 2018 to answer the above. Click HERE for the slides.
The study showed 7 days did just fine when compared to 14 days when dealing with GNB bacteremia. This was a multicenter, open-label, noninferiority randomized controlled trial, whereby 684 subjects were recruited in total.
This is a chance to highlight your good works being an Antibiotic Guardian on international platform. There are 10 awards categoriesincluding diagnostic, prescribing public engagement, etc... What you have to do is simply fill up your details on the link down there and you may be one of the winner!