Should Antimicrobial Prophylaxis be
Given before/After BMT?
Rodrigo Martino. Department of Hematology
Hospital de la Santa Creu i Sant Pau. Barcelona
Assigned to Defend: YES………….
but……….
YES…………. but……….
 I defend restricted antimicrobial prophylaxis,
dynamically adjusted/changed over time to target periods
of high-risk for potentially-preventable infections.......
 ......while not giving prophylaxis at other time periods or
to non-high risk patients.
 Objective: Reduce the time exposed to antimicrobials of
our entire patient population.
YES…. but….Eventually
 Unlike tumors, microorganisms are independent living
beings.
 Exposure to a “highly effective” antimicrobial (a lethal
aggression from an evolutionary point of view) can kill >
99.99999% of the individuals, but prolonged/recurrent
exposure will always lead to selection of resistant strains
(individuals).
Earth’s Geological Timeline
Era/Period/Epoch
Time, Myr ago
Archaeozoic (Archean) era
5000-1500
Proterozoic era
1500-545
Bacteria: 3500 Myr
Paleozoic era
Cambrian period
545-505
Ordovician period
505-438
Silurian period
438-410
Devonian period
410-355
Protozoa: 750 Myr
Carboniferous (Mississipian/Pennsylvanian) period
355-290
Permian period
290-250
Triassic period
250-205
Jurassic period
205-135
Cretaceous period
135-65
Mesozoic era
Fungi: 560 Myr
Tertiary period
Cenozoic era
"Recent Life"
Paleocene epoch
65-55
Eocene epoch
55-38
Oligocene epoch
38-26
Miocene epoch
26-6
Pliocene epoch
6-1.8
Pleistocene epoch
1.8-0.01
Current Opportunistic
Pathogens
Current humans:
0.2have
Myrsurvived extreme agressions
over 100s of millions of years. Does this tell you anything?
Quarternary period
(Lower Paleolithic)
0.50-0.25
(Middle Paleolithic)
0.25-0.06
(Upper Paleolithic)
0.06-0.01
Holocene epoch
0.01-0
2012: Are we Headed Towards a Second
Pre-Antibiotic Era? (PC Appelbaum, JAC 2012)
Blood
or Marrow
Transplant
Risk Factors
Bacteremia
Over justin 80
years,
bacteria
(andPatients:
fungi)Clinical
have developed
for Infection and Emerging Antibiotic Resistance
resistance
to the
ATBsAvailable
discovered
byAugust
Man.2012
In
Press, Accepted
Manuscript,
online 29
Allison M. Bock, Qing Cao, Patricia Ferrieri, Jo-Anne H. Young, Daniel J.
Weisdorf
Since the late 1980’s, rapid emergence of resistance to >
ATB groups is developing: staphylococci, enterococci,
BMT
patients, compared
to the contemporaneous
hospital
streptococci,
enterobacteria,
pseudomonas,
other
population, developed infections with more frequent resistance to
NGFGNB.
antibiotics
used in the treatment against commonly isolated bacterial
organisms. These findings have important clinical implications
regarding
No trulythe
novel
ATBs
are of
inboth
the prophylactic
pipeline. and empiric
use and
selection
antibiotic regimens.
3
Guidelines on Prophylaxis in HSCT
Antibiotic Prophylaxis I
Overall B-I
IDSA (2011), ECIL 1-4 (2005-2011)
Antibiotic Prophylaxis II
Antibiotic Prophylaxis III
(AII):
from infections “favored” by prophylaxis:
•viridans type streptococci
•inherently resistant species
•candidemia
Antibiotic Prophylaxis IV
Anti-encapsulated prophylaxis for AlloHSCT
with cGVHD and/or hyposplenism and/or
hypogammaglobulinemia (AIII) [+IVIG in the
latter)
Cotrimoxazole recommended during periods of
risk: PCP, toxoplasmosis, listeriosis,
nocardiosis, other (AII)
Antifungal Prophylaxis I
AI
IDSA (2011), ECIL 1-4 (Maertens et al. BMT 2011)
Antifungal Prophylaxis II
Issues with long-term Posaconazole/Voriconazole
 Toxicity
 Intolerance
 Cost
 Resistance
Monitor discontinuation rate
(also with ATBs, TMP/SMX)
(Secondary) Antifungal Prophylaxis III
ECIL 3 (Maertens et al. BMT 2011)
Antiviral Prophylaxis
Early Post-HSCT: Low-dose Acyclovir to
prevent early HSV-I severe infections (in HSV-I
seropositive) [AI]
Post-engraftment: Low-dose Acyclovir for 1
year post-AlloHSCT recommended by some
(AII or BII).
Alternatives: Valacyclovir, famciclovir (CIII)
IDSA (2011), ECIL 1-4 (2005-2011)
Often Overlooked Factors in Choosing a
Prophylactic Regimen
-- Aspergillus spp. or other moulds
Often Overlooked Non-Pharmacologic Measures
“AAA-I”
(SOPs)
Final Comments
• I strongly oppose prophylaxis in HSCT with
carbapenems, 3/4th generation cephalosporins or
“last resource” ATBs (colistin, linezolid,
daptomycin)
• Using a restricted antimicrobial prophylaxis,
dynamically adjusted/changed over time requires:
– Knowledge (and, preferably, institutional SOPs)
– Time to think on a case by case basis