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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5212_Библиотеки_им_академика_М_И_Перельмана.pdf
Pre-transplant Screening and Post-transplant Infection Prevention in Heart Transplant Recipients
Jillian Oft and Phillip Zakowski
15
Abstract
In addition to advances in surgical techniques,
recipient/donor selection, and immunosuppression, progress in preventing and managing
infections after heart transplant (HTx) has dramatically improved patient outcomes. While
preventing rejection is crucial for long-term
allograft survival, immunosuppressive regimens compromise the recipient's immune system and confer an increased risk of infection.
HTx candidates and recipients are at risk for
a multitude of infections, including community and hospital-acquired infections, opportunistic infections, and reactivation of latent
infections. In this chapter, we will provide an
overview of the prevention of infections after
HTx, which begins with donor and recipient
pre-transplant screening and includes targeted
prophylaxis and infection prevention.
Keywords
Heart transplantation · Prophylaxis · Bacterial
infections · Viral infections · Protozoa
P. Zakowski (*) · J. Oft
Division of Infectious Diseases, Cedars-Sinai
Medical Center, Los Angeles, CA, USA
e-mail: phillip.zakowski@cshs.org
J. Oft
e-mail: jillian.oft@cshs.org
Clinical Pearls
• Pre-transplant screening of donors and can-
didates for bacterial/fungal/viral/protozoal infections is used to risk-stratify and
guide targeted post-transplant infection
prophylaxis.
• With careful selection, hearts from donors
with positive blood cultures can be utilized
and achieve favorable clinical outcomes
• Hearts from anti-HBc-positive donors carry
a negligible risk of transmission in recipients
immune to HBV and can be transplanted successfully with monitoring post-transplant
• Hearts from hepatitis C viremic donors may
be used with HCV-specific informed consent,
treatment, and monitoring.
• The combination of donor and recipient
CMV status enables risk stratification and
guide prophylaxis and monitoring
• With careful organ selection, it may be safe
and effective to transplant organs from
COVID-19 PCR-positive donors
• The vaccination history of the transplant can-
didate should be reviewed and updated as
much as possible prior to transplant.
• Transplant recipients should continue to
receive vaccinations post-transplant (after
6 months to reduce activating a rejection
episode) with the exception of live virus
vaccines.
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2025
J. Kobashigawa (ed.), Clinical Guide to Heart Transplantation, https://doi.org/10.1007/978-3-031-88290-6_15
181
182
J. Oft and P. Zakowski
• Additional preventive measures against infection include handwashing, remaining physically active, and being aware of potential
pathogens in and out of the hospital, including animal-borne, food, and travel-related
exposures.
Pre-transplant Screening of the Donor and Recipient
Organ donors represent a potential vector of disease transmission to the recipient. Appropriate
donor serologic screening prior to transplantation is crucial to identify infections that would
prohibit transplant or require directed treatment
or prophylaxis. The goal of pre- heart transplant
(HTx) screening is to reduce the risk of infectious exposure to the recipient without prohibitively limiting the number of available organ
donors. Infectious disease screening includes
serologic testing, nucleic acid amplification testing (NAAT,) and donor microbiology cultures.
When a donor heart becomes available, the
medical and social history available in the Organ
Procurement and Transplant Network (OPTN)
database should include relevant information on
risk factors for infection, including prior hospitalizations, blood transfusions, and intravenous
drug use, if known. Additionally, the Organ
Procurement Organization (OPO) provides
results from donor microbiology cultures, serum
serologies, and NAAT. NAAT is performed
within 96 h of donation, as close as possible but
with sufficient time so that the results are available at the time of transplant. In the following
section, we will cover donor screening for each
group of micro-organisms in greater detail.
or transport. Most commonly, the source is
a donor bacterial infection with bloodstream
involvement, such as line sepsis, pneumonia,
intra-abdominal sepsis, genitourinary sepsis, or
even post-traumatic skin/soft tissue infection.
Blood cultures should, therefore, be routinely
performed as part of the evaluation for a potential donor heart. While isolated cases report
transmission of bacteria such as Staphylococcus,
Pseudomonas, and Escherichia coli from donor
to recipient causing serious infective complications and death, more recent and comprehensive data suggests that donors who die of severe
community-acquired bacterial infections (e.g.,
bacterial meningitis, pneumonia, septic shock)
should not be arbitrarily excluded [1] and that
with careful selection, donors with positive
blood cultures can be used and maintain quality clinical outcomes [2]. With this in mind,
the International Society for Heart and Lung
Transplantation (ISHLT) specifies that heart
from donors with bacteremia can be used, provided that the following criteria are met: donor
has received a minimum of 24 h of targeted antimicrobial therapy, ideally with clearance of cultures, donor myocardial function is normal, and
there is no evidence of endocarditis on inspection of the heart [3]. Additionally, in cases where
such hearts are used for transplantation, the
recipient should undergo surveillance blood cultures on the first post-operative day. Recipients
of hearts from bacteremia donors should receive
an appropriate course of therapy targeting the
donor isolate. A similar recommendation exists
for cases in which the donor has a known history of untreated or incompletely treated
latent tuberculosis infection (LTBI): recipients
should be treated for LTBI. Patients with active
Mycobacterium tuberculosis infection are not
recommended for organ donation [4–6].
Donor Screening
Bacterial Transmission
Bacterial infections may be transmitted as a
result of active infection in the door or through
contamination of the heart during procurement
Fungal Transmission
Active fungal infection in a donor is a contraindication to transplantation. Transmission
of Histoplasma and Coccidioides via organ
transplant have been reported, although more
18315 Pre-transplant Screening and Post-transplant Infection …
commonly, infection is the result of reactivation in a previously infected recipient. Universal
donor screening for endemic mycoses is
not required, but explanted organs that contain granulomas should be tested for fungal histopathology and culture. In such cases, antigen
and serology screening for Histoplasma and
Coccidioides should be performed on blood and
any stored body fluid samples [7].
Viral Transmission
Hepatitis B
Hepatitis B (HBV) remains ubiquitous in the
global population, with over 300 million people affected. Prevalence and endemicity vary
significantly across different regions. In recent
years, the prevalence of past or present hepatitis B infection in the United States was estimated at approximately 4% [8]. The incidence
of chronic hepatitis has decreased with infection control practices and the availability of
effective vaccination. HBV vaccine provides
significant protection against HBV infection
and should be given prior to transplantation
when possible since post-transplant response
rates are decreased owing to immunosuppression. Serologic testing for anti-HBs 4–8 weeks
after completion of the vaccine series is recommended to confirm immunity.
Donor screening for HBV is performed by
surface antigen testing (HBsAg), serologic
testing for antibodies against Hepatitis B surface antigen (anti-HBs), as well as antibodies
against core antigen (anti-HBc) and universal
HBV NAAT [9]. Many transplant centers will
not accept a donor organ that is HBV NAAT
positive due to the risk of reactivation, fulminant hepatitis, hepatocellular carcinoma, and cirrhosis. In contrast, hearts from anti-HBc donors
carry a negligible risk of transmission in recipients immune to HBV [10]. No antiviral prophylaxis is required if the recipient has evidence of
natural (anti-HBc, anti-HBs) or vaccine induced
(anti-HBs only) immunity when an isolated antiHBc donor is used. However, for non-immune
recipients of anti-HBc donor organs, antiviral
prophylaxis should be provided with tenofovir or entecavir, particularly during the first
12 months. Hearts from HBsAg donors do carry
a risk of transmission but may be considered
on an individual case basis with informed consent and use of antiviral prophylaxis, potentially
indefinitely [11].
Hepatitis C
Hepatitis C (HCV) is an enveloped, singlestranded blood-borne RNA virus with tissue reservoirs in the body. Donor screening for HCV
is performed by serology and universal HCV
NAAT. Transplant centers historically excluded
donors who were infected with HCV due to the
high rate of transmission of HCV, accelerated
cardiac allograft vasculopathy, cirrhotic liver
disease, and increased mortality in those receiving HCV-infected hearts [12]. However, the
widespread availability of NAAT and substantial advances in treatment have allowed for the
expansion of the donor pool, with many centers now utilizing hearts from HCV seropositive
and viremic donors to HCV-negative recipients.
HTx using organs from HCV viremic donors has
been associated with excellent short-term outcomes. Current ISHLT recommendations state
that hearts from hepatitis C viremic donors may
be used with HCV-specific informed consent
and treatment and monitoring in accordance
with guidelines [3, 13].
Cytomegalovirus
Cytomegalovirus (CMV) is a ubiquitous b-herpesvirus and a common opportunistic infection in HTx recipients. The seroprevalence of
CMV in US adults is approximately 50% and
varies with age, geography, and socioeconomic
status. Higher seroprevalence rates have been
reported in the organ donor population. Donor
screening for CMV is performed using CMVIgG [14]. Ideally, blood should be drawn from
the donor prior to any blood transfusions, but
this may not be possible, particularly in cases of
trauma. There is no role for CMV IgM or polymerase chain reaction (PCR) in donors unless
acute CMV infection is suspected. It is generally
accepted that CMV-IgG-positive donor hearts
184
J. Oft and P. Zakowski
can be transplanted into CMV-negative recipients due to the demonstrated success of prophylaxis and treatment. Nevertheless, it is vital that
all donors have CMV serological status determined, as the combination of donor and recipient CMV status enables risk stratification for
prophylaxis and monitoring.
Human Immunodeciency Virus
There are several documented cases of Human
Immunodeficiency Virus (HIV) transmission
from donor to recipient in cardiac transplantation [15], most of which occurred prior to the
introduction of routine screening in 1985. All
potential transplant donors should be tested for
HIV. Donor screening is performed using current fourth-generation HIV antibody / p24 antigen tests, as well as universal NAAT screening.
Just as for HBV and HCV, NAAT testing for
HIV is performed within 96 h pre-transplant
to yield the most current result possible. HIVpositive hearts are not eligible for transplant to
HIV-negative recipients. However, the 2013 HIV
Organ Policy Equity Act allowed HIV-positive
donor organs to be used in HIV-positive recipients, thus expanding the donor pool for this
particular subset of patients. Such transplants
are currently conducted in the context of multicenter clinical trials and are an area of evolving
developments in the field [16].
Human T-Lymphotropic Virus
Human T-Lymphotropic Virus I (HTLV-1) is
endemic in parts of the world, including the
Caribbean, Japan, and parts of Africa. Infection
is more common in individuals from these areas
and is often asymptomatic. HTLV-2 is more
widespread but not clearly associated with
any disease. Due to low seroprevalence in the
United States and the poor predictive value of
available screening assays, routine screening of
donors for HTLV-1/2 is not recommended [7].
Individual OPOs may elect to perform testing
on certain high-risk individuals. If serologic status is known, current OPTN policy recommends
against the use of donors with HTLV-1 seropositivity due to the risk of transmission and subsequent development of adult T-cell leukemia and
spastic paraparesis, with reports of myelopathy
after solid organ transplantation [17].
West Nile Virus
West Nile Virus (WNV) is a flavivirus which can
cause neuroinvasive disease with meningoencephalitis and polio-like myelitis. It is transmissible by blood transfusion and organ transplantation,
with reports of transmission and death in solid
organ transplant recipients [18]. Serology and
PCR for WNV are available but limited by cost,
logistics, risk of false positive testing, and widely
varying risk depending on geographic distribution and time of year. Thus, although living organ
donors are screened for WNV, HTx donors are
not uniformly tested for WNV. However, donors
with known WNV should be avoided, as well as
donors with unexplained meningoencephalitis,
as this scenario could pose a risk of transmission of other central nervous system viral infections. Select OPOs may elect to perform testing
in regions of high virus circulation, particularly
during the summer months. However, WNV illustrates one of the many challenges of managing
infections in this population, as not every infection
can be definitively ruled out or treated pre-emptively. Transplant clinicians should remain vigilant
in their awareness of possible infectious risks and
counsel transplant candidates and their families
about the possibility of infectious diseases being
transmitted during HTx [18].
SARS-CoV2
The COVID-19 pandemic resulting from the
SARS-CoV-2 virus was disruptive to many areas
of the medical system, including organ transplantation, and exacerbated an already significant
national shortage of thoracic organs. Donors are
screened via PCR from nasopharyngeal swabs.
There was initial uncertainty about the risks of
using organs from COVID-19-positive donors.
However, increasing evidence suggests that with
careful organ selection, it may be safe and effective
to transplant organs from COVID-19 PCR-positive
donors. There is no evidence that a transmissible
virus exists in cardiac allografts, and there have
been no reports of donor-derived infection outside
of the lung [19]. Further discussion of COVID-19,
18515 Pre-transplant Screening and Post-transplant Infection …
including management of active COVID-19
acquired after transplant, is covered separately.
Protozoal Transmission
Toxoplasma Gondii, Trypanosoma Cruzi (Chagas Disease)
Toxoplasma gondii is a protozoan parasite
prevalent in humans and food animals, causing worldwide zoonosis and may be transmitted by organ transplant or blood transfusion.
Donors are screened via serologic testing for
Toxoplasma IgG. T.gondii donor seropositivity is not a contraindication to transplant but is
important for the purposes of risk stratification and subsequent prophylaxis and treatment.
Data from the literature are mixed regarding
outcomes from T.gondii donor-recipient mismatched cardiac transplants [20, 21]. HTx
is a safe and effective treatment for patients
with advanced heart failure caused by the
Trypanosoma cruzi parasite better known as
Chagas disease. Because the immunosuppression required for a HTx can reactivate the disease, it was once considered a contraindication
for the procedure. However, HTx is now the
preferred treatment for patients with end-stage
Chagas disease in countries where it's available. Endemic areas are in the Southwest U.S.
[22]. To prevent negative outcomes, it's important to carefully screen patients for Chagas disease before a transplant. Reactivation of Chagas
disease can lead to serious complications,
including: myocarditis, allograft dysfunction,
congestive heart failure, graft failure, and sepsis. Two drugs, benznidazole and nifurtimox, are
effective for treating Chagas disease [23].
Recipient Screening
HTx candidates undergo mirrored evaluation
for the same diseases as the donor via serologic
screening. In addition to evaluation for exposure
to prior infections, evaluation of the potential
transplant candidate’s infection risk should also
include a thorough history of antibiotic allergies
(with the nature of the reaction), a dental examination, and a routine assessment for active infection.
Bacterial/Fungal/Viral Infections
Recipients with active or uncontrolled bacterial
or fungal infections should generally delay transplant until the infection is controlled. Table 15.1
summarizes the routine infection screening recommended for a transplant candidate [7]. All candidates should be evaluated for latent tuberculosis
infection with a tuberculin skin test (TST) or interferon-gamma release assay (IGRA). Candidates or
recipients with latent TB infection (LTBI) should
be treated prophylactically to avoid progression
to active tuberculosis. Isoniazid is the mainstay
of treatment. Shorter regimens using Rifampin, or
Isoniazid and Rifapentine are alternative regimens
which may confer an advantage for compliance
and completion rates in the pre-transplant setting.
These regimens are not preferred post-transplant
due to drug-drug interactions and may not be ideal
if the patient is likely to undergo transplantation
while receiving treatment for LTBI. Treatment
LTBI should be started prior to transplantation
unless there is a contraindication. If isoniazid is
started pre-transplant, it can be held in the early
peri-transplant period and resumed when the
patient is stable and tolerating oral medications.
The presence of a pre-existing infection such as
HIV or Hepatitis B/C is not an absolute contraindication to transplant, but these patients should
be treated appropriately prior to transplant. In the
case of active or acute viral infection in a candidate, the transplant should be delayed, if possible, until the infection resolves or is controlled.
Timing of transplant of candidates with acute
community-acquired viral infections depends on
urgency of transplant, severity of infection, and
available treatment options. Vaccine-preventable
infections are a common source of morbidity postcardiac transplantation. The vaccination history
and serostatus of the transplant candidate should
be reviewed and updated prior to transplant,
including those for diphtheria, tetanus, varicella
zoster virus (VZV), hepatitis A/B, influenza A/B,
Hemophilus influenza B, polio, meningococcus,
186
Table 15.1 Recommended pathogenic screening in transplant candidates
• Antibiotic/medication allergies, adverse reactions
• Chest radiograph (to look for infiltrates, granulomas, scarring)
• Dental assessment
• Social/sexual history; high-risk behaviors, intravenous drug use, communicable diseases
• IGRA, history of tuberculosis risk factors
• Serologies for tetanus, diphtheria, measles, mumps and pneumococcal titers are recommended and may
guide pretransplant immunization recommendations
• Routine serologic testing
- HIV Ab/Ag (4th generation HIV screening test)
- CMV IgG
- Hepatitis B screening: HBsAg, anti-HBc, anti-HBs
- HCV IgG
- EBV antibody panel (EBV VCA IgG, IgM)
- HSV IgG antibody
- VZV IgG antibody
- Syphilis screening- RPR, FTA-ABS, TP-EIA, TPPA, or VDRL
- Toxoplasma IgG
• Special serologic testing based on epidemiologic risk factors or exposure history
- Coccidioides IgM and IgG antibody
- Histoplasma immunodiffusion antibody or urine antigen
- HTLV-I/II antibody
- Strongyloides IgG
- Trypanosoma cruzi IgG
Abbreviations IGRA: interferon-gamma release assay; HIV: human immunodeficiency virus; CMV: cytomegalovirus;
Hepatitis B surface antigen; anti-HBc: hepatitis B core antibody; anti-HBs: hepatitis B surface antibody; HCV: hepatitis C; EBV: Epstein-Barr Virus; HSV: Herpes Simplex Virus; VZV: Varicella Zoster Virus; HTLV: Human T-Cell
Lymphotropic Virus
J. Oft and P. Zakowski
SARS-CoV2, measles, mumps and rubella
(MMR). VZV and MMR screening are of particular importance, so that seronegative candidates can
be vaccinated if possible. Vaccination should be
administered prior to any desensitization protocol
to preserve the antibody response. Live vaccines
like MMR can only be given before transplant and
are contraindicated after transplant [7].
Preventive Measures
In addition to antimicrobial prophylaxis and
appropriate vaccination prior to transplantation,
the usual infection control measures should be
enacted after transplant. During hospitalization, hand-washing procedures by both staff
and visitors are mandatory. Healthcare providers with air-transmissible diseases should also
refrain from direct contact with the patient.
As outpatients, caution should be exercised to
minimize the risk of environmental or occupational exposures to potential pathogens, as well
as pet-related exposures (birds, certain reptiles,
livestock, stray animals), certain types of food
should be avoided (raw or undercooked meat,
unpasteurized dairy products), and the patient
should be aware of possible travel-related exposures (including endemic or communicable
diseases if traveling to a new area, as well as
exposures related to exposure to natural bodies of
water or caves, for instance). There is disagreement about the need for antibiotic prophylaxis,
but there is a strong agreement that maintenance
of good dental health is important. Despite diligent efforts at prevention, infections remain
common after transplant. The next chapter will
discuss the management of infections after HTx.
References
1. Kubak BM, Gregson AL, Pegues DA, Leibowitz
MR, Carlson M, Marelli D, et al. Use of hearts
transplanted from donors with severe sepsis
and infectious deaths. J Heart Lung Transplant.
2009;28(3):260–5.
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2. Siddiqi U, Blitzer D, Lirette S, Patel A, Hoang R,
Mohammed A, et al. Positive donor blood cultures
are not associated with worse heart transplant survival. Clin Transplant. 2023.
3. Velleca A, Shullo MA, Dhital K, Azeka E, Colvin
M, DePasquale E, et al. The International Society
for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients. J
Heart Lung Transplant. 2023;42(5):e1-141.
4. Morris MI, Daly JS, Blumberg E, Kumar D, Sester
M, Schluger N, et al. Diagnosis and management of
tuberculosis in transplant donors: a donor-derived
infections consensus conference report. Am J
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5. Malinis M, LaHoz RM, Vece G, Annambhotla P,
Aslam S, Basavaraju SV, et al. Donor-derived tuberculosis among solid organ transplant recipients in
the United States—2008 to 2018. Transplant Infect
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6. Subramanian AK, Theodoropoulos NM.
Mycobacterium tuberculosis infections in solid
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7. Malinis M, Boucher HW. Practice ASTIDC of
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8. Kruszon-Moran D, Paulose-Ram R, Martin CB,
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transplantation: an ISHLT expert consensus statement. J Heart Lung Transplant. 2020;39(5):418–32.
14. Razonable RR, Humar A. Cytomegalovirus in
solid organ transplant recipients—guidelines of the
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Balfour HH. Human immunodeficiency virus
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deceased HIV-infected donors to HIV-infected
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I, Razonable RR. Donor-transmitted HTLV-1associated myelopathy in a kidney transplant
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Managing Infections After Heart Transplantation
Jillian Oft and Phillip Zakowski
16
Abstract
Heart Transplant (HTx) recipients are at risk
for a multitude of infections, including community and hospital-acquired infections,
opportunistic infections, and reactivation
of latent infections. In this chapter, we will
provide an overview of the management of
infections after HTx. We will discuss common pathogens, unique challenges, and
general clinical approaches to managing
infections in HTx recipients.
Keywords
Heart transplantation · Prophylaxis · Bacterial
infections · Viral infections · Protozoa
Clinical Pearls
• Bacterial organisms of importance that
may cause infection post-transplant include
Staphylococci, Enterococci, Streptococci,
J. Oft · P. Zakowski (*)
Division of Infectious Diseases, Cedars-Sinai
Medical Center, Los Angeles, CA, USA
e-mail: phillip.zakowski@cshs.org
J. Oft
e-mail: jillian.oft@cshs.org
Listeria, Nocardia, C. difficile, Pseudomonas,
H. influenzae and Legionella.
•
Prophylaxis against CMV and/or HSV should
be provided for all recipients using valganciclovir or acyclovir post-transplant. Selection
and duration of prophylaxis depend on donor
and recipient’s history of infection.
• Viral infections are common in transplant
recipients, including reactivation or newly
acquired CMV, HSV, and VZV, as well as community respiratory and gastrointestinal viruses.
• Post-transplant prophylaxis against
Pneumocystis includes trimethoprim-sulfamethoxazole as first-line treatment (typically for 1 year after transplant).
• Candida and Aspergillus are common fungal
infections post-transplant.
• Transplant recipients are less likely to present
with typical features of infection, including
fever and leukocytosis, and more likely to
present with organ dysfunction.
•
The clinical approach to management of a
suspected infection in a transplant recipient
should take into account the time elapsed
since transplant, donor/recipient infectious
history, recent exposures, history of rejection and current immunosuppression regimen
including induction or recently augmented
immunosuppression.
• Generally speaking, for the assessment of
pulmonary infiltrates, bacterial and viral
infections tend to present acutely, whereas
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2025
J. Kobashigawa (ed.), Clinical Guide to Heart Transplantation, https://doi.org/10.1007/978-3-031-88290-6_16
189
190 J. Oft and P. Zakowski
fungal and parasitic infections are more
insidious in onset. Judicious use of microbial cell-free DNA testing may aid in noninvasive diagnosis. A definitive diagnosis can
often be obtained via histology from BAL
and/or transbronchial lung biopsy.
Bacterial Infections
Bacterial infections remain the most common
cause of infectious morbidity in patients at all
stages following HTx. Bacterial infections rise in
the early post-transplantation period as recipients
undergo induction of immunosuppression, presenting as wound infections, pneumonia, urinary
tract infections (UTIs), bacteremia from catheter-associated infections, and, rarely, infective
endocarditis [1]. Broadly speaking, pathogens
in the early post-transplant period are similar to
those causing infections in non-transplant surgical patients, including Staphylococci, as well as
gram-negative bacilli and Candida spp.
Peri-Operative Prophylaxis
Perioperative bacterial prophylaxis should
include activity against skin flora with a cephalosporin, with or without vancomycin. If a
chronically infected device (i.e., left ventricular
assist device infection or infected ECMO circuit) is present at the time of transplant, perioperative antibiotics are directed to the involved
pathogens. Duration depends on the extent of
infection and whether source control is established [2].
Gram-Positive Organisms
Staphylococci
Staphylococcus species are the most common Gram-positive organisms causing infections after HTx, especially early post-transplant
[3, 4]. S. aureus is the most common of these.
Common manifestations include surgical site
infections, line infections, pneumonia, or UTI.
Rarely, S. aureus has been associated with endo-
carditis shortly after transplant. Methicillinsensitive S. aureus (MSSA) may be treated
with oxacillin or cefazolin. For methicillinresistant S. aureus (MRSA), vancomycin is the
first-line drug, although other antibiotics with
MRSA activity may be preferred depending on
allergy, intolerance, or the source and severity of the infection. In severe staphylococcal
infections, combination therapy may be necessary. Coagulase-negative staphylococci (CoNS)
are another group that commonly cause infection after HTx. Nearly all cases are nosocomial.
Because these bacteria reside on human skin and
mucous membranes, they are commonly found
in the cultures of wound environments and may
represent surface colonizers with or without
involvement in a deeper infection. CoNS may
also cause line-associated bloodstream infections in patients after HTx, like other surgical
patients. Because of their potential as colonizers,
attribution of infection requires consideration of
the overall clinical picture. There is a high rate
of methicillin resistance among the coagulasenegative staphylococci, making Vancomycin
the recommended first-line drug pending
susceptibilities.
Enterococci
Enterococci are part of the normal gut flora but
take on increased significance in the immunocompromised host. Like staphylococci, enterococcal infections commonly occur early after
cardiac transplantation and manifest as wound
or line infections, gastrointestinal, biliary, and
urinary tract infections. Enterococci engage in
synergistic relationships with other gut flora
and are often involved in polymicrobial infections, although they may be the sole cause of
line-associated bloodstream infections or urinary tract infections. For sensitive enterococci,
the treatment of choice is ampicillin or vancomycin. However, in recent years, the emergence
of vancomycin-resistant enterococci (VRE)
has been a major source of morbidity and mortality [5]. VRE are a rising cause of resistant
19116 Managing Infections After Heart Transplantation
gram-positive infections in transplant recipients,
exceeding MRSA in some patient cohorts [6].
Immunosuppressive agents may also contribute
to alterations in the gut microbiome over time
and influence risk of enterococcal infections
[7]. Linezolid and daptomycin are preferred
treatment options for ampicillin-resistant VRE.
Infected lines or devices should be removed,
and any urinary or biliary obstruction should be
addressed.
Streptococcus Pneumoniae
HTx recipients are at increased risk of
Streptococcus pneumoniae infection compared
to non-transplanted individuals [8], presenting with pneumonia, bacteremia, or meningitis.
Pneumococcal infection is often communityacquired and tends to present later after transplantation (beyond one year). HTx recipients
and close contacts should maintain current pneumococcal vaccines, which protect against many
but not all serotypes. The treatment of choice is
penicillin when sensitive. In cases of pneumococcal sepsis, vancomycin should be administered empirically while sensitivities are pending.
Listeria Monocytogenes
Listeria monocytogenes is an important pathogen in the immunocompromised host. Risk correlates with the degree of immunosuppression,
typically presenting early after transplantation
or during treatment of rejection when boluses of
immunosuppression are required. In the immunocompetent host, Listeria generally causes
mild gastroenteritis, but transplant recipients
commonly present with more invasive diseases,
including bacteremia and meningitis [9]. HTx
recipients with neurologic symptoms should
undergo prompt lumbar puncture for cerebrospinal fluid (CSF) analysis and should be treated
empirically with broad-spectrum antibiotics,
including ampicillin, the treatment of choice
for listeriosis. L. monocytogenes is known to be
associated with unpasteurized meat and dairy
products, and patients are advised to avoid them.
Nocardia
Nocardia spp. are ubiquitous gram-positive rods
that cause infections in immunocompromised
individuals and are particularly associated with
defective cell-mediated immunity. Despite the
implementation of trimethoprim-sulfamethoxazole prophylaxis, Nocardia infections have
been on the rise over the past two decades,
likely due to increased detection as well as a
growing immunocompromised population,
with more recipients living longer. Nocardiosis
may present at any time post-transplant, particularly when presenting with pulmonary or
central nervous system (CNS) symptoms soon
after intensified immunosuppression. Antilymphocyte globulin, high calcineurin inhibitor
or cyclosporine levels, or high-dose corticosteroids are associated with increased risk, as well
as cytomegalovirus disease in the preceding
six months [10]. In HTx recipients, nocardiosis
typically presents as subacute pneumonia with
pulmonary nodular lesions. Up to 50% of pulmonary cases may be complicated by extrapulmonary spread [10] with brain abscess, skin and
subcutaneous tissue infections, and bone and
eye involvement reported [11]. The diagnosis
of Nocardia pulmonary infection should prompt
consideration of disseminated disease, with MRI
to evaluate for brain abscess. Initial treatment
should include antibiotic therapy with trimethoprim-sulfamethoxazole, and combination therapy with imipenem should be used for severe
or CNS disease. Alternatives include imipenem,
linezolid, or ceftriaxone. Immunosuppression
should be reduced if possible. Definitive treatment may require surgical debridement, and
the duration of antibiotics is generally at least
6–12 months [10].
Rhodococcus Equi
A Gram-positive coccobacillus, R. equi, typically causes infection in animals but can also
affect immunocompromised humans, causing
pulmonary infection later after transplantation [12, 13]. It typically presents with nodular