Antibiotics in neonatal bacterial infections

[Khaque]

Dear Colleagues,

Most of us on suspicion of neonatal blood stream bacterial infection initiate antibiotic therapy and stop it if the blood cultures are negative and the baby is well (usually 48 hours), but what there does not seem to be a consensus is as to how long antibiotic therapy should be continued in culture proven blood stream infection (not meningitis or osteomyelitis) or culture negative but clinically suspected or surrogate marker supported blood stream infection. In our survey of 210 neonatal units in UK some years ago the range varied from 5 to 21 days!

What I would like to know from colleagues is;

1. How long do you give antibiotics in culture proven bacterial blood stream infection (no meningitis or osteomyelitis)?

2. How long do you give antibiotics in culture negative but clinically suspected or surrogate marker supported blood stream infection?

3. Do you use any laboratory markers to determine the duration of antibiotic therapy? If yes ,what markers do you rely on most?

Grateful for your views

Khalid

Professor Khalid N. Haque

FRCP(Lond), FRCP(Edin), FRCP(Ire),

FRCPCH, FPAMS(Pak), FAAP, FICP, MBA,

DCH(Lond), DTM&H(Liv)

Professor of Neonatal Medicine

[Stefan Johansson]

Our responses:

Q1. Usually 10 (-14) days, depending on what bacteria that grows in the culture.

Q2. Usually 7 (-10) days, depending on the "certainty" of the culture-neg infection*

Q3. We use CRP as a guidance, but generally stick to the courses above

*In the very common situation with a relatively well term infant and slightly elevated CRP (-50) at presentation (which then decrease to normal), we generally use a three day course. That is the time it takes to get a negative response from the microbiology department.

[Khaque]

My question Stefan really is how did you come to the decision to use 10 or 7 days in the firat place? Dogma!, Textbooks transmitting the same message from one edition to another! or through evidence?

Khalid Haque

[Stefan Johansson]

You caught me. Dogma it is!

[JACK]

I think there are more factors playing in deciding the course of antibiotics.

The obvious ones are the presence/absence of meningitis and arthritis.

Once these two are not present then the next big factor I think is .....

............cost/resources.

When resources are unlimited I think we mostly opt for 10-14 days course. On the other hand when we have pressure that the patient has a difficult financial situation we may go for a 7-10 day course.

It may sound ethically unfair to have two different stratification but that is the best we can do in an unjust world.

Also we opt to give longer courses for babies who were sicker at presentation or those that had complications secondary to their infection. We feel that those who were sicker and also with more complications may have a more virulent organism or weaker immune system necessitating a longer course.

Of course I am shooting from the hip, with no references here.

[Stefan Johansson]

My question Stefan really is how did you come to the decision to use 10 or 7 days in the firat place? Dogma!, Textbooks transmitting the same message from one edition to another! or through evidence?

Khalid Haque

You caught me. Dogma it is!

Just one more comment - we have national guidelines regarding antibiotic treatment incl length of therapy. But I suspect the documentation for length of therapy is meager, i.e. we do what we are used to do.

I also recall our (within-the-unit) controversy regarding aminoglycoside dosing(once- or twice-daily in full term infants). The literature does not really give good evidence that one regime is superior to the other. At that time I thought the general scientific guidance for ab therapy was rather weak.

[hehady]

Q1. Two weeks for BSI; longer courses for meningitis and arthritis

Q2. 10 days

Q3. We use CRP as a guidance, we rarely look at clearance of bacteria from follow up blood cultures.

[Khaque]

As suspected most of us are creatures of habit and do what either we have been taught or what is in textbooks. I am surprised at the dogmatic statements of the number of days they give antibiotics for but provide NO evidence for their practice. I do not buy the cost argument it seems un ethical and would urge none of us to decide the duration of antibiotic therapy that way.

Khalid Haque

[Khaque]

Should have quoted this earlier;

“ Beware of those who have found the truth, follow those who seek it.”

Hijikata 13th Century

[JACK]

... I do not buy the cost argument ...

Khalid Haque

I agree with you totally that it sounds unethical and politically incorrect.

But we have some patients whose parents have no insurance cover and are extremely poor and the baby was not very sick at presentation, then we do opt for a shorter course. I am not speaking in favor of this but sharing the ground realities.

May be the situation is different in the place where you practice...may be the state takes care of all medical bills or maybe all are insured. However the world is not flat. We have to accommodate even those who cannot afford two square meals a day. Neonatology is not exclusive science meant only for the rich....we may have to bend a little rules to accommodate all - even the underprivileged. I have worked in some really poor places in the world and have seen that even in resource restricted places with a little bit of planning and management, good neonatal outcomes are possible.

However the condition of the baby should be the most important deciding factor.

We always check for clearance of bacteria from Blood Stream. We also prolong the course of antibiotics when we notice that clearance is taking longer even when the correct antibiotics are being given(as per the sensitivity reports.)

We do not use CRP either for diagnosing or following progress. It is culture result and/or clinical picture.

An active crying baby who sucks well, whose blood counts are normal, whose blood cultures are negative, who is maintaining vitals and having a normal systemic examination tells me all that I need to know and I would not complicate my life by asking for a CRP.

I do agree that the rules for antibiotic therapy are not clear and that we often ape our teachers and seniors. But till something clearer is found out I am still sticking with the 10-14 day course.

[Khaque]

To Jack: For whatever reason you are compelled to give some babies a shorter course and some babies a longer one. If other things being equal have you found a difference in outcome?

As for 'some thing clearer', there are numerous references suggesting a shorter course (4-5 days) is as good if not better than a longer course of 7-10 days. It is estimated that it takes about 7-10 years for practice to change after evidence is produced. With costs and antibiotic resistance on the increase we must reflect on the evidence and our practice.

[JACK]

Honestly speaking, we find no difference in the outcome of those that receive a shorter course. We have not done any RCT to prove this but just anecdotal information.

Cost-Factor analysis has entered health care in a big way now a days, as insurance companies aim for larger profit margins and ultimately shorter hospital stays for patients. You will find talk of Cost effectiveness everywhere in the literature.

Just few days back there was a discussion going on in the NICU-NET yahoo group regarding pressure from insurance companies for early discharge of babies.

Edited October 26, 2008 by JACK

[abomran]

Dear Professor K Haque

I usually use this guideline:

1. This will depend on the organism isolatd, but generally: 7 to 10 days for gram positive organisms, and 14 days gor gram negative organism. "after tha first negative culture"

2. 7 to 10 days for culture negative, but strongly suspected sepsis.

3. I use only CBCs and blood cultures.

Abbas Moosa Al Omran

neonatologist

Hofuf, Saudi Arabia

[Stefan Johansson]

Should have quoted this earlier;

“ Beware of those who have found the truth, follow those who seek it.”

Hijikata 13th Century

I agree completely! I would need properly designed trials when it comes to antibiotic therapy. It should not be that difficult using a multicenter approach.

My personal feeling is that we "marinate" our infants with too many different antibiotics and for too long. But, we would all need better data supporting shorter courses.

[JAMA]

Dear Khalid,

Are you planing some RCT to solve this Dogma in neer future?

I hope!

If not, let us start.

Jasim Anabrees

KFMC

Riyadh, KSA

[Khaque]

Dear Stefan and Jasim,

I have done some work on this previously and have submitted a research grant application but in the current 'ecnomic crunch' I suspect funding for research is even tighter.

[Guest xemoni]

Dear Colleagues,

What I would like to know from colleagues is;

1. How long do you give antibiotics in culture proven bacterial blood stream infection (no meningitis or osteomyelitis)?

2. How long do you give antibiotics in culture negative but clinically suspected or surrogate marker supported blood stream infection?

3. Do you use any laboratory markers to determine the duration of antibiotic therapy? If yes ,what markers do you rely on most?

1. Duration of antibiotics treatment in culture proven bacterial blood stream infection (no meningitis or osteomyelitis) is 10 days.

2. In culture negative but clinically suspected or surrogate marker supported blood stream infection, the administration of antibiotics lasts for 7 days.

3. The main laboratory markers in the asessment of the infection (although not exactly to determine the duration of antibiotic therapy) are the c-reactive protein, the number and type neutrophils and the number of platelets.

Konstantinos Mitsakis

Consultant in Paediatrics-Neonates

1st NICU

Aristotle University

Ippokrateion Hospital

Thessaloniki

Hellas (Greece)

[JAMA]

Dear Dr. Khalid,

We are willing to participate with you and if there is problem in funding, we can try it here in saudi arabia.

[JACK]

My personal feeling is that we "marinate" our infants with too many different antibiotics

"Marinate".........

That is a nice way of telling what happens in all the NICUU. Good choice of word.

[Khaque]

Dear Jasim,

If you can give me your e-mail address we can certainly discuss the feaseability of doing this work at King Faisal

Khalid Haque

[Bernhard Bungert]

Dear Prof. Haque

Im sorry that i cant add superior insight to your question.

In my own expierence i found that to determine whether a baby is infectet CRP (like a lot of other markers) is a mess:

On one side it comes late, on the other side I see about 20 newborns who are susceptible to infection (because of apnea, Temp 38 °C, maternal history) which develop a CRP over 50 g/l, and if you have the nerves and wait: crp is normal after a few days, and the babies are doing well. From my teachers i have learnt to treat this babies, but we changed practice whithout RCT.

Bernhard Bungert

[AMIRA]

pls can you tell me how much you can trust CRP as sign of infection?

also I want to know the best prophylactic antimicrobial therapy for NICU admission in general

[Khaque]

Dear Bungert and Amira,

Thanks for your interest in this thread. Indeed CRP is neither highly specific or sensitive but it is a marker most frequently available. It should be used with caution and recognising its limitations.

I am not sure that I would use CRP as a 'sign of infection' nor would I support 'prophylactic antibiotics, for NICU admissions in general.

[iliyahpius]

Dear Professor KN Haque'

i have been following your contribution to the development of neonatal medicine with keen interest, but Sir with respect the questions you asked vis-a-vis the responses by other colleagues are good enough, my only worry is that they did not consider the spectrum of the causative organisms implicated in the neonatal infection, the constitution and the vehicle in which these antibiotics are delivered.

I am senior specialist registrar in the department of paediatrics at University maiduguri Teaching Hospital Maiduguri, NIGERIA.

i Qoute your articles in my write ups, Sir i will be grateful if you can assist me with your E-mail Address so that i can henceforth communicate with you on one on one basis. Sir this is my request if you so wish.

Thank You

Yours sincerely

DR SIMON PIUS

Maiduguri,NIGERIA

[iliyahpius]

Thank tou all i look foreword to intereting responses

[Khaque]

Whilst the causative organism is an important factor in determing the duration of antibiotic therapy; for example some treat Gram neg organisms for longer than Gram pos organism. There is supportive animal/laboratory evidence for this but I am not aware of any human studies directly comparing duration of therapy according to pathogenic organisms. Indeed the vehicle in which antibiotic is delivered is important as the pH may affect the antibiotic efficacy and concentration equally the constitution of the antibiotic solution is important therefore we should follow the manufacturers guidelines

[iliyahpius]

Good Evening Sir i thank you for putting me more enlightened ,

I still look foreward to recieving your E-mail address.

Thank You Remain Blessed

DR SIMON PIUS E-mail Address ;simonpius2000@yahoo.co.uk