No marker for making sure that the patient has VAP

Unfortunately there is no marker for making sure that the patient has VAP.

One of the marker which is coming up now a days is CPIS scoring. But this too has less sensitivity and specificity issues. A good surrogate marker for VAP , will be need of the hour in upcoming research topics. Why do we need a marker? Only when we can say for sure that the patient has VAP,then only we can treat him fully. Otherwise we may end up treating patients, who do not require the treatment.

It's confusing about loposomal Amphotericin B

When are administering  Liposomal amphotericin B, should we need to cover it from light or not. Is it photo degradable or not???

My opinion:

There is  actually no where in literature with regards to liposomal amphotericin B, they have actually mentioned that you need to cover and protect from light but at the same time they have not mentioned that  there is no  need to cover also. So as for now for liposomal  amphotericin B, there is no need to cover . Whereas  for conventional  amphotericin B there is an absolute requirement to cover it and prevent excess exposure from light. Even you have to protect the IV line tubing from the excessive light exposure

BELSOMRA- a new drug for insomnia

S NO	BELSOMRA
1.	NAME	BELSOMRA
2.	CATEGORY	Medical Neurology
3.	COMPANY	Merck’s
4.	INDICATION DEVELOPED FOR	Insomnia
5.	MECHANISM OF ACTION	Orexin antagonist
6.	MORE DETAILED M.O.A	Induces sleep by blocking binding of two wakefulness neuropeptide Orexin A and Orexin B to their receptor OX1R and OX2R
7.	NOVEL	yes/no
8.	STAGE OF DEVELOPMENT	Phase 3 completed and entering Phase 4
9.	US FDA APPROVAL	yes/no
10.	DATE OF APPROVAL BY FDA	August 13 2014
11.	INDICATION APPROVED FOR BY FDA	-
12.	INDIAN SCIENARIO	-
13.	ANYTHING SPECIAL WITH THIS DRUG	Instead of traditional way of inducing sleepiness, it fight against wakefulness
14.	BACKGROUND KNOWLEDGE REQUIRED	Orexin-A and B are excitatory neuropeptide hormones that promote wakefulness by sending inhibitory signals to the ventrolateral preoptic nucleus, an area of the hypothalamus with a high concentration of GABA-producing neurons.
15.	ISSUES WITH THE DRUG	·       To be cautious on next day driving ·       Sleep pattern does not resemble to that of normal physiological sleep, it favours REM sleep over NREM sleep ·       People who took this drug experienced somnolence
16.

YOU HAVE FOUND A NEW DRUG.HOW TO MOVE ABOUT NOW. DOSE AND DURATION OF TREATMENT FOR THE NEW DRUG.

FIRST SELECT THE BEST ANIMAL MODEL FOR THE DISEASE  IN WHICH YOU HAVE DECIDED TO WORK.

YOU HAVE A NEW DRUG IN YOUR HAND AND IS CONFUSED WHAT IS THE DOSE IN WHICH THE DESIRED EFFECT WILL COME

Lowest dose which show maximum protection or effect is the rule

How to find the best dose/standardization of doses for a new drug in an animal model??

You take multiple criteria for evaluating the disease progress or severity  and then administer the different  probable doses among which you are confused . Your aim is to find what will be your best suitable dose which will have a significant effect in decreasing the disease severity or produce maximum protection effect. 

The thing to note is that you will have the data of effect of the different doses on the same parameter which you wish to check.

This dose at which maximum benefit is seen is the best dose to give for the indication we intend to give.

How to find the duration of the treatment for a new drug in an animal model???

In the dose selected above now your aim is to find the duration of the therapy.You give treatment and then analyze the model at different time interval to find the best time duration in which the drug maximum effect has been obtained. The thing to  note is if you administer the drug more than this time ,some may argue that there will be no detrimental effect. Yes, of course but administering more than this time wont add to any beneficial effect too.

DIFFERENCE BETWEEN PUBMED AND MEDLINE

As early as 1879, US National Library of Medicine started maintaining a bibliography of all the articles in various journals, the name of the compilation was Index Medicus MEDLINE is the electronic version of original raw data that is Index Medicus with the US National Library of Medicine. The database is updated very frequently by them and is robust. The electronic version was initially only with the librarians and the computers used by the librarians was known as MEDLARS.

The MEDLINE was open for public in 1996 through which the public can search it from different location around the world. This is essential  as the super computer database is in USA. The public interface for MEDLINE is known as PUBMED.

You should also know that there are other interfaces by which you can operate the raw data of National Library of Medicine , they are EBSCO and ISI

That is the same source of information “MEDLINE” can be read via Pubmed , EBCSO and ISI

ANAEROBIC ACTIVITY OF CEFOPERAZONE SULBACTAM

ANAEROBIC ACTIVITY OF CEFOPERAZONE SULBACTAM

Sulbactam is added with Cefoperazone in order to increase the anaerobic activity of Cefoperazone. Individually sulbactam has shown activity against anaerobic bacteria including those producing beta lactamases

Antagonistic activity between the Cefoperazone and sulbactam has not been noted.(1)
In a study done for assessing the anaerobic activity of sulbactam in combination with Cefoperazone against Bacteroides fragilis it was found that out of 42 % of Bacteroides fragilis which was found initially resistant to Cefoperazone alone, 94% among them were converted to susceptible on the addition of sulbactam.(1) Out of all the strains of Bacteroides fragilis studied 67% was susceptible to Cefoperazone sulbactam and 27%was moderately susceptible.(1)

One more invitro study where the activity of the Cefoprazone alone and in combination with sulbactam was compared , it was shown that Cefoprazone sulbactam has anaerobic activity and inhibited 90-100% of all bacteria but Cefoperazone has activity of 63%. The percent susceptible against Bacteroides fragilis group is 99 to 100% for cefoperazone-sulbactam and for Cefoperazone, 49%.(2)

In one more study where 374 selected beta-lactamase-producing gram-negative anaerobes (including 22 cefoxitin-resistant strains and 36 strains refractory to the enhancing effect of beta-lactamase inhibitors) and 20 beta-lactamase-negative strains were tested against antimicrobials. The organisms included in the study consists of 217 Bacteroides fragilis group strains, 137 non-B. fragilis group Bacteroides spp., and 40 fusobacteria. (3)

The study showed that in Bacteroides fragilis group 95% were susceptible to cefoperazone-sulbactam. For the beta-lactamase-positive non-B. fragilis group Bacteroides spp., greater than or equal to 94% were susceptible cefoperazone-sulbactam. . For the beta-lactamase-positive fusobacteria, greater than or equal to 97% were susceptible cefoperazone-sulbactam.(3)

DRAWBACK:
Cefoperazone-sulbactam lacked activity against some cefoxitin-resistant B. fragilis group strains but had excellent activity against other organisms.

CONCLUSION:
Adddition of Metronidazole to Cefoperazone -sulbactam routinely is not needed. As Cefoperazone -sulbactam itself will cover most of anaerobe, addition of Metronidazole will add to unnecessary cost of treatment to the patient without any increase in benefit and also will lead to development of resistance to the Cefoperazone-sulbactam.

REFERENCES
1. D'Amato RF, Hochstein L, Frankel H. In vitro activity of cefoperazone/sulbactam and other antimicrobials against anaerobic bacteria. Diagnostic microbiology and infectious disease. 1990 Jan-Feb;13(1):51-5. PubMed PMID: 2331850. Epub 1990/01/01. eng.
2. Wexler HM, Finegold SM. In vitro activity of cefoperazone plus sulbactam compared with that of other antimicrobial agents against anaerobic bacteria. Antimicrobial agents and chemotherapy. 1988 Mar;32(3):403-6. PubMed PMID: 3364960. Pubmed Central PMCID: PMC172186. Epub 1988/03/01. eng.
3. Appelbaum PC, Spangler SK, Jacobs MR. Susceptibilities of 394 Bacteroides fragilis, non-B. fragilis group Bacteroides species, and Fusobacterium species to newer antimicrobial agents. Antimicrobial agents and chemotherapy. 1991 Jun;35(6):1214-8. PubMed PMID: 1929264. Pubmed Central PMCID: PMC284313. Epub 1991/06/01. eng