Transcript The Deleterious Role of Viruses on the Lung Allograft

How I Manage Pulmonary Infection in the
Post-Transplant Patient
Joanna Schaenman, M.D., Ph.D.
David Geffen School of Medicine at UCLA
Los Angeles, CA
October 13, 2015
Pulmonary infection : Learning objectives
1.Know the frequent causative agents of
pulmonary infection after transplantation.
2.Understand effective strategies for prophylaxis
and diagnosis of pulmonary infections
3.Know how to select antibiotic therapy to treat
common causes of pulmonary infection
Pulmonary infection: the most common infection,
highest mortality after solid organ transplantation
Person-toperson:
Influenza
Environmental:
Fungi
Reactivation:
CMV
Increased risk with augmentation of immune suppression, patient
comorbidities including advanced age
Time course of risk for pulmonary infection
Induction
Maintenance immunosuppression
Prophylaxis
• Nosocomial
infection
Transplant
Phase 1
First month
• Reactivation
• Opportunistic
• Communityacquired
• Opportunistic
Phase 2
Months 1-6
Kupeli, Curr Opin Pulm Medicine 2004
Phase 3
>6 months
Common etiologies of pulmonary infection
BACTERIA
• Community or
hospital acquired
pneumonia
• Mycobacteria
VIRUSES
• Community
acquired
respiratory
viruses
• CMV
FUNGI
• Endemic fungi
• Molds (Aspergillus)
Case 1: Fever and sepsis physiology 10 years
post kidney transplant
• 47 yo woman with
DM, s/p DDRT
• February developed
URI symptoms, rash
over thighs
• Progressive
respiratory failure,
fever, altered mental
status, required
intubation
Clinical and radiographic presentation of pneumonia is often not specific
for a particular pathogen
Diagnostic approach to lung infection
Direct testing:
• Sputum or tracheal aspirate for
Gram stain and bacterial, AFB,
and fungal cultures
• Blood cultures
• Consider bronchoscopy for
bronchoalveolar lavage
• Respiratory virus testing by PCR
Indirect testing:
• Consider blood or urine testing
for surrogate markers including
• Coccidioides Ab
• Cryptococcus ag
• Histoplasma ag
• Aspergillus galactomannan
• Legionella urine antigen
• CMV PCR
Low threshold for ordering Chest CT
Case 1: Fever and sepsis physiology 10 years
post kidney transplant
• Empiric therapy:
vancomycin,
pipercillin/tazobacta
m, levaquin
• Outside hospital
sputum culture
positive for
Streptococcus
pyogenes
• Clindamycin added
• Patient ultimately did
well, complete
Chest CT gives more information than CXR,
resolution of
but is still nonspecific for cause of infection
symptoms
Yield of bronchoscopy in SOT
• Review of 47 kidney and 14 liver transplant
recipients in Turkey
• 39% bronchial wash cultures were positive
(47% in patients off antibiotics)
• Higher yield with transbronchial biopsy (58%)
• Positive cultures included MTB,
Staphylococcus aureus, Moraxella, Klebsiella
pneumoniae, E coli, Streptococcus
pneumoniae, Pseudomonas, Aspergillus
Kupeli et al, Transplant Proceedings 2011; Kupeli et al., Curr Op Pulm Med 2012
Empiric treatment based on risk profile
• Community acquired pneumonia
Haemophilus influenzae, Streptococcus
pneumoniae, Mycoplasma, Legionella, viruses
• Fluoroquionolone,
or ceftriaxone plus
azithromycin
• Hospital acquired pneumonia
Staphylococcus aureus, Enterobacteraciae,
Acinetobacter, Pseudomonas; aspiration
• Vancomycin plus
pipercillin
tazobactam,
levaquin
• Concern for multidrug resistant
organisms
ESBL, CRE, MDR Pseudomonas, fungi
• Empiric broad spectrum
therapy
(penem, aminoglycoside,
colistin, etc)
Mycobacteria
MTB
MAC (MAI)
• Pre-transplant
screening
recommended
• Incidence of MTB 14%
in developing countries,
0.5-6% in low endemic
areas
• Often high mortality
Rapid growers (e.g.
M. abscessus)
Caution for drug-drug interactions with rifampin or rifabutin use
Case 2: Fever and sepsis physiology 3 mo.
post kidney transplant
• 74 yo man with DM,
s/p DDRT, ATG
induction
• February developed
URI symptoms,
cough, seen in clinic
but CXR showed only
atelectasis
• Admitted with
progressive cough,
malaise
Chest x-ray is often unrevealing in transplant
• Progressive
respiratory failure, recipients
required intubation
Case 2: Fever and sepsis physiology 3 mo.
post kidney transplant
• Empiric therapy:
vancomycin,
pipercillin/tazobacta
m, levaquin,
oseltamivir
• Nasopharyngeal
swab pos for RSV by
respiratory viral PCR
• Ribavirin added
• Progressive
Low threshold for further evaluation in
respiratory failure,
vulnerable patients
ARDS
Community acquired respiratory viruses (CARV)
•
•
•
•
•
•
Influenza
Respiratory syncytial virus (RSV)
Human metapneumovirus
Parainfluenza
Adenovirus
Rhinovirus
• Diagnosis via PCR
testing of
nasopharyngeal
swab or
respiratory source
• Rx Influenza with
oseltamivir or
zanamivir
• Consider ribavirin
for RSV, especially
in lung transplant
CMV pneumonitis
• Donor positive/Recipient
negative is highest risk
• Risk decreased with Valcyte
prophylaxis
• Lung>heart>liver>kidney
• Diagnosis via PCR testing, viral
culture, or histopathology
• Treat with IV ganciclovir
Kotloff et al., 2004; Kotton, 2010
Case 3: Fever 1 year post kidney transplant
• 52 yo woman with
DM, s/p DDRT
• H/o TB peritonitis
• November
developed fever,
chills, myalgias,
fatigue, no
improvement with
course of levaquin
• No neurologic
complaints or
findings
Broad diagnostic differential
for lobar pneumonia
Case 3: Fever 1 year post kidney transplant
• Empiric therapy:
vancomycin,
meropenem,
levaquin
• Sputum culture
positive for
Cryptococcus gattii,
Aspergillus flavus
• BAL positive for
Cryptococcus and
CMV; LP negative
“Bad news comes in threes” (the Transplant
• Started on
ID motto), not “Occam’s Razor”
Voriconazole
Clinically Important Fungi
Yeast
Endemic Fungi
Candida Cryptococcus
PCP
PCP is less common with
routine TMP/SMX prophylaxis
Molds
Coccidioides
Histoplasma
Blastomycosis
Aspergillus
Scedosporium
, others
Agents of
Mucormycos
is
Distribution of fungal infections by
transplant type
TRANSNET Surveillance cohort
Pappas et al., CID 2010
McPherson: Henry's Clinical Diagnosis and
Management by Laboratory Methods, 2011
Distribution of dimorphic
endemic fungi
Histoplasmosis distribution in
the Americas
Coccidioidomycosis.
• Environment is main source
for exposure, but can also
be donor-derived
• Reports suggest that
number of infections are
increasing
• Sensitivity of serologic
testing is lower in
immunosuppressed
patients
Proia, et al. AJT 2009
Diagnosis of invasive fungal infections is challenging
• Clinical and radiographic presentation is not specific for fungal
infection
• Need culture for identification and sensitivity testing
• Noninvasive testing can be helpful: Aspergillus GM, antigen testing,
future PCR or breath testing
Empiric antifungal treatment
• Endemic fungi (non-severe)
• Fluconazole,
itraconaozle
• Aspergillosis
• Voriconazole*
• Agents of mucormycosis
• Liposomal Amphotericin B
• Severe invasive fungal infection
• Liposomal Amphotericin B,
possibly combination Rx
*Watch for drug-drug interactions with tacrolimus
And last but not least…parasites
• Strongyloides:
Donor derived or
reactivation
Think about the etiology of pulmonary
infections:
Person-toperson
BACTERIA
Environmental
VIRUSE
S
Reactivation
FUNGI
To devise strategies for prevention:
Vaccination, Antibiotic prophylaxis (TMP/SMX,
Valcyte, azoles), Patient education
Pulmonary infection : Learning objectives
• Causative agents of pulmonary infection after
transplantation include bacteria, viruses, and fungi
• Prophylaxis for PCP and CMV has decreased
pneumonia incidence
• Diagnosis is important and should include sputum
testing, BAL or FNA when appropriate, and noninvasive
tests
• Antibiotic therapy should be based on culture-based
diagnosis when possible, and on suggested clinical
syndrome when unable to make clear diagnosis
References
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Kupeli E, Akcay S, Ulubay G, et al. Diagnostic Utility of Flexible Bronchoscopy in Recipients of Solid Organ
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