This document discusses new insights into treatment strategies for critically ill patients, including optimal antibiotic dosing and the potential benefits of extended infusion of antibiotics. It also reviews evidence on the use of aerosolized colistin, inhalation antibiotics, statins, probiotics, and prophylactic antibiotics in preventing infections like ventilator-associated pneumonia in ICU patients. While some studies found decreased infection rates, ICU stay, or ventilation time with these approaches, larger trials are still needed to determine clear effects on mortality or define best practices. The document emphasizes individualizing care based on pharmacokinetic factors and calls for more research on optimization of antibiotic use in critical illness.

1. NEW CRITICAL CARE ISSUES
2015 - 17
SAMIR EL ANSARY

2. Global Critical Care
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9555/
Wellcome in our new group ..... Dr.SAMIR EL ANSARY

3. New insights
into treatment strategies

4. Antibiotic dosing in critically ill patients is
challenging due to deranged drug metabolism and
elimination that can lead to suboptimal dosing.
Extended infusion of antibiotics with a time-
dependent killing mechanism, such as beta-lactams,
has been proposed as a means to overcome the
pharmacokinetic/pharmacodynamic (PK/PD)
alterations in severely ill patients in order to
optimize the time that drug concentration exceeds
the minimum inhibitory concentration (MIC) of the
target organism.

5. Patients received a loading dose
(1 g for meropenem and 4.5 g
for Pip/Tazo) followed by
extended infusion usually over
3 hours every 6 hours for
Pip/Tazo and 8 hours for
meropenem.

6. Dulhunty and colleagues , in a double-blind
randomized controlled trial, compared
continuous versus intermittent bolus
dosing of Pip/Tazo, meropenem, and
ticarcillin-clavulanate in patients with
severe sepsis.
Patients in the intervention arm received
active infusion and placebo boluses and
controls received placebo infusion and
active boluses.

7. The concentration exceeded the MIC
more often in the intervention group
than in controls most with meropenem
and least with ticarcillin-claculanate) and
the patients in the intervention group
had a higher clinical cure rate
but there was no difference in ICU or
hospital LOS or mortality.

8. The study reinforces the dosing options
available for critically ill patients based
on PK characteristics, but did not have
the statistical power to determine a
mortality benefit, although there was a
trend towards better survival in the
intervention arm.

9. With the growing development of resistance
to beta-lactams
Aminoglycosides are advocated for patients
with severe sepsis as part of combination
therapy, especially with PA infection and the
bactericidal activity of aminoglycosides is
dependent on peak concentration (Cpeak)
relative to MIC.
As noted above, the concentration of aminoglycoside can
change in critically ill patients due to variations in drug
clearance.

10. Microbiological eradication and clinical cure were
higher in patients who achieved initial optimal
Cpeak/MIC and were proportionately higher with
higher target concentration.
Patients who achieved the target concentration
after 3 days had a worse clinical cure and
microbiological eradication than those who
Achieved this goal on the first day.
Renal failure was seen in 24% of patients and was
more likely in those with impaired clearance and
higher minimum concentration.

11. Inhalation antibiotics have the potential
advantage of achieving high alveolar
concentrations with minimal systemic side
effects.
Aerosolized colistin (given via jet nebulizer
or ultrasonic nebulizer) as an adjunctive
treatment to intravenous therapy in VAP
patients with positive cultures for Gram-
negative MDR pathogens susceptible only to
colistin.

12. Patients receiving aerosolized therapy in
conjunction with intravenous colistin had
a higher clinical cure rate compared with
controls and fewer days on the ventilator
after onset of VAP but no difference in
overall mortality or ICU LOS.
Also, there was no difference in the rate
of new-onset kidney failure between
the two groups.

13. Factors influencing antibiotic de-
escalation in patients admitted to
ICU with sepsis
However, there was no difference in
mortality rate, ICU LOS or duration of
MV between patients who had de-
escalation compared with those with
no de-escalation.

14. Duration of antibiotic treatment for
nosocomial pneumonia is not clearly
defined
And a short duration may be as clinically
effective as a longer duration (>14 days)
and more cost-effective.
There was a trend towards more relapses due to non-
fermenting Gram-negative bacilli in the shorter
duration antibiotic cohort.

15. Interestingly, patients with early discontinuation
developed less frequent superinfections compared
with late discontinuation patients
These results add credence to the value of
de-escalation for VAP patients and to the
possibility that longer antibiotic courses
may cause microbial persistence and
selection pressure
leading to the development of microbial
resistance.

16. Patients with early discontinuation
developed less frequent
superinfections
compared with
late discontinuation patients

17. Prevention

18. Prophylactic systemic antibiotics have a role in
preventing early-onset VAP in closed head
injury patients.
Single-dose antibiotics within 4 hours of
intubation (ceftriaxone 2 g intravenously; 1 g
ertapenem in those with hypersensitivity to
beta-lactam
500 mg levofloxacin in those with anaphylaxis
to beta-lactam) in the prevention of early-onset
VAP or ventilator-associated tracheobronchitis
in comatose patients.

19. The patients who received prophylaxis had fewer
microbiologically confirmed cases of VAP
Less MV days, and shorter ICU LOS.
However, there was no difference in mortality or
hospital LOS between the two groups.
Although there was no increased incidence of MDR
pathogens in the prophylaxis group with late-onset
VAP
Prophylactic antibiotic at the time of intubation in high-risk patients at risk
for VAP is an interesting concept and further prospective randomized
controlled studies are required prior to generalization of the results.

20. Prophylactic antibiotic at
the time of intubation in
high-risk patients at risk for
VAP
is an interesting concept

21. Statinshave possible anti-
inflammatory and
immunomodulatory effects
and their use in patients with pneumonia had
previously been reported to lead to beneficial
outcomes.

22. There was no significant difference in 28-day
mortality or other secondary outcomes,
including duration of MV, coronary events,
ARDS, or adverse side effects between the two
groups
{With simvastatin and without }
Papazian and associates
in a double-blind, parallel-group study,
randomized VAP patients
(defined as having a Clinical Pulmonary
Infection Score >5) to receive
Simvastatin (60 mg)

23. However another recent trial
exploring the role of statins in
sepsis that also did not find any
difference in levels of
interleukin-6
But possible beneficial effects in
continuing chronic statin
therapy.

24. Probiotics
(most with Lactobacillus sp.)
may restore non-pathogenic gut flora and the
value of their use in critically ill patients has
been inconclusive.
Probiotic use in icu did not have a significant
impact on mortality or the duration of MV.

25. However, probiotic use resulted in a significant
decrease in
nosocomial pneumonia
and also led to a shorter ICU LOS.
Use of probiotics could potentially prevent
gastric colonization by pathogenic bacteria and
might explain the beneficial effects seen with
ICU-acquired pneumonia.
Whether this should be added to VAP prevention measures is still to be
determined and will need further large trials, with VAP as the primary end
point.

26. Global Critical Care
https://www.facebook.com/groups/1451610115129555/#!/groups/145161011512
9555/
Wellcome in our new group ..... Dr.SAMIR EL ANSARY

27. GOOD LUCK
SAMIR EL ANSARY
ICU PROFESSOR
AIN SHAMS
CAIRO
elansarysamir@yahoo.com