Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5258_Библиотеки_им_академика_М_И_Перельмана.pdf
207
Those with persistent or progressive dyspnea, worsening hypoxemia, should be
evaluated in person and may benet from hospitalization.
For those managed as outpatients, although 2024 guidelines for the general pop-
ulation favor the use of ritonavir-boosted nirmatrelvir (Paxlovid), this is a strong
cytochrome P450 3A4 inhibitor and P-glycoprotein inhibitor. It has signicant
drug–drug interactions with calcineurin inhibitors and mammalian target of rapamy-
cin inhibitors. While there is a recent report from 2022 describing the safe use of
ritonavir-boosted niramatrelvir in 25 adult SOT recipients receiving tacrolimus
(n=21), cyclosporine (n=4), everolimus (n=3), and sirolimus (n=1) with a stan-
dardized dosing protocol for adjustment of immunosuppression (see Chap. 3), we
would recommend discussion with the patient’s transplant team [38].
The preferred therapy in many centers, therefore, is remdesivir, which requires
IV administration [39]. During the omicron BA.2 wave, a prospective study of SOT
recipients who developed breakthrough COVID-19 infection after vaccination dem-
onstrated that early outpatient treatment with IV remdesivir is associated with
decreased rate of hospitalization [40], with adjusted hazard ratio 0.12 and adjusted
number needed to prevent one hospitalization of 15.2 (95% CI: 13.6–31.4).
Molnupiravir is an orally administered antiviral drug that acts as a substrate for
SARS-CoV-2 RNA polymerase and impairs SARS-CoV-2 replication. It has the
additional advantage of not requiring renal or hepatic dose adjustment and does not
exhibit pharmacological interactions with immunosuppressive treatment. However,
in a pivotal clinical trial from 2021 evaluating effectiveness versus placebo in unvac-
cinated outpatients with mild SARS-CoV-2 infection [41] (dominant variants
B.1.617.2, B.1.621, and P.1), it demonstrated a relative risk reduction of hospitaliza-
tion or death at day 28 of 30% versus 89% for nirmatrelvir/ritonavir [42], and 87%
for remdesivir [39]. There is some limited experience in using molnupiravir for SOT
recipients as of 2024 [43, 44].
Prevention
Vaccination of the SOT recipient and their household contacts remains the most
effective way to prevent morbidity and mortality from SARS-CoV-2 infection. In
general, the U.S.National Institutes of Health (NIH) recommends that vaccination
should be completed at least 2weeks prior to solid organ transplantation or started
1month after transplant. Optimal timing is not well established.
In those who are anticipated to have suboptimal response to vaccination, mono-
clonal antibodies have been used as adjunctive pre-exposure prophylaxis. The ef-
cacy of this approach varies based on the dominant circulating strain. As of April
2024, pemivibart is available under Emergency Use Authorization (EUA) for pre-
exposure prophylaxis in persons aged ≥12years weighing ≥40kg with moderate to
severe-immunosuppression and likelihood of insufcient response to SARS-CoV2-
vaccination. This is a human monoclonal antibody targeting the SARS-CoV-2
receptor binding domain with a half-life of 44.8days; notably, data supporting the
EUA relied on serum titers achieved after administration against the JN.1 variant
8 Infections intheAdult Solid Organ Transplant Recipient
208
(dominant at time of approval), rather than evidence of effectiveness from a ran-
domized controlled trial [45].
Other preventive measures are similar to those dened for the general popula-
tion, including masking, distancing, and avoiding crowds when possible (see
Chap. 14).
8.3.2.2 Inuenza
Clinical Presentation
Inuenza is an acute, febrile illness that typically manifests with respiratory symp-
toms or may be asymptomatic. While inuenza infection is usually self-limited in
immunocompetent individuals, SOT recipients may have variable presentations,
ranging from atypical, non-respiratory symptoms to severe respiratory compromise
[26]. Common non-respiratory symptoms of inuenza infection in SOT recipients
include gastrointestinal distress, sore throat, low-grade fever or even lack of fever.
SOT recipients are also more likely to shed the inuenza virus for a longer period
than immunocompetent hosts due to inability to clear the virus, prolonging their risk
of complications and possible transmission to others [26, 46].
Progression from upper to lower respiratory tract involvement has been docu-
mented in 16–40% of SOT recipients [47]. Risk factors for development of severe
disease include older age, hypogammaglobulinema, use of antilymphocyte globu-
lins, early infection after transplantation (<3months), and presence of two or more
comorbid conditions [48, 49]. Rates of severe inuenza infection are reported
between 16% and 20% in lung transplant recipients. Mortality is higher among SOT
recipients during inuenza outbreaks and was reported at 21% for lung transplant
recipients in an Australian study during the 2009 H1N1 outbreak [50]. Severe cases
of inuenza have been associated with allograft dysfunction [51, 52] and even acute
rejection [53].
Diagnosis
While it is often appropriate to treat immunocompetent hosts for inuenza empiri-
cally, the Centers for Disease Control and Prevention (CDC) recommends that pro-
viders should attempt to diagnose inuenza infection in SOT recipients to target
therapy. While rapid inuenza antigen tests are specic for inuenza infection, they
lack appropriate sensitivity in immunocompromised hosts [54, 55]. More sensitive
tests, including the viral respiratory PCR panels, are considered the gold standard in
many institutions, and can identify the inuenza subtype, which may be important
in epidemic years or in cases of treatment failure. Because inuenza testing varies
by institution, primary care providers will need to know which tests (e.g., rapid
antigen, nucleic acid amplication, PCR) are available in their location, their per-
formance characteristics, and how quickly results will be known [56, 57].
J. Hu et al.
209
Treatment
Treatment options for inuenza infection are given in Table8.5. While inuenza
treatment initiation is generally limited to beginning within 48–72h after symp-
tom onset in the general population, most experts recommend treating symptom-
atic inuenza infection in SOT recipients, regardless of duration of symptoms at the
time of treatment consideration [58]. Treatment for ambulatory and hospitalized
Table 8.5 Treatment and chemoprophylaxis options for inuenza infection
Drug Mechanism Strain Treatment notes Prophylaxis
Oseltamivir Neuraminidase
inhibitor
A/B
• Standard course is 5days in
adults; some experts extend
course to 10days
• Requires renal dose adjustment
• Preferred in pregnancy
• Resistance in inuenza A(H3N2)
and A(H1N1) pdm 09 can
develop during treatment [59, 60]
• Decreases rates of hospitalization
due to inuenza in high-risk
individuals from 3.2% to 1.6%
(relative risk reduction, 50%)
[61]
Y
Inhaled
zanamivir
Neuraminidase
inhibitor
A/B
• Risk of bronchospasm; avoid in
patients with underlying
respiratory disease
• Some inuenza viruses [most
often inuenza A(H1N1)pdm09]
can become resistant to
oseltamivir and peramivir during
treatment but remain susceptible
to zanamivir
Y
Baxlovir Cap-dependent
endonuclease
inhibitor
A/B
• CDC does not recommend as
monotherapy in
immunocompromised hosts due
to paucity of available efcacy,
safety, or resistance data in these
patients
• Concern for emergence of
resistance during treatment due
to prolonged inuenza viral
replication [62]
• Animal studies support
combination therapy but not in
human trials [63]
Y, approved for
persons >5years
of age within
48h of contact
IV
peramivir
Neuraminidase
inhibitor
A/B
• Efcacy based on clinical trials
versus placebo in which
predominant strain was inuenza
A [64]
N
8 Infections intheAdult Solid Organ Transplant Recipient
210
SOT recipients without critical illness is generally limited to use of oseltamivir;
the other agents may be considered in certain circumstances after discussion with
an infectious disease specialist. Post-exposure prophylaxis of SOT recipients is
strongly encouraged regardless of if testing has been obtained due to the high risk
of inuenza progression after acquisition. Post-exposure prophylaxis should
therefore be performed at the time of reported close exposure and treatment initi-
ated at the time of testing prior to receipt of results to improve the effectiveness of
therapy.
If the patient develops worsening lower respiratory symptoms including produc-
tive cough or pleuritic chest pain while on oseltamivir therapy, one should obtain
chest imaging to evaluate for bacterial co-infection or even consider treating empiri-
cally for a concomitant bacterial pneumonia. In a lung transplant recipient, one
should consult early with the transplant pulmonologist, preferably before starting
antibiotics (see Chap. 7).
Prevention
The cornerstone of prevention of inuenza is vaccination of SOT recipients and
their close contacts with the seasonal inactivated inuenza vaccine. Live attenu-
ated inuenza vaccine is contraindicated in SOT recipients due to theoretical risk
of dissemination of vaccine strain. Studies have demonstrated that inuenza vac-
cination is associated with reduced risk of admission for pneumonia (of any type)
and all- cause mortality, during the same season [65]. In lung transplant recipients,
inuenza vaccination decreased the incidence of subsequent infection during the
2009 H1N1 pandemic (1.3% vs. 25%) [66]. In kidney transplant recipients, inu-
enza vaccination was associated with lower risk of graft loss and death [67].
Even if vaccinated patients develop inuenza, there has been evidence of reduc-
tion of severity of disease [65] as determined by the presence of pneumonia (OR
0.34, 95% CI 0.21–0.55, P<0.001) and ICU admission (OR 0.49, 95% CI 0.26–0.90,
P=0.023) [49]. As of 2024, the American Society of Transplantation (AST) guide-
lines recommend vaccinating with inactivated inuenza as soon as 1-month post-
transplant, acknowledging that immunogenicity may be poor up to 6months and
depends on type of organ, immunosuppressive regimen, and composition of the
vaccine [48]. Vaccination strategies have included the use of high-dose inuenza
vaccine or a booster strategy 5weeks after standard inuenza vaccination. These
approaches have demonstrated improved immunogenicity in SOT recipients com-
pared to standard dose vaccination [68, 69] (See Chap. 14).
In cases of contraindication or expected diminished response to vaccination,
antiviral prophylaxis with oseltamivir may be considered. A randomized controlled
trial of liver, kidney, liver-kidney transplant or allogenic hematopoietic stem cell
transplant recipients demonstrated 80% protective efcacy from laboratory con-
rmed inuenza in the group receiving 12weeks of oseltamivir compared to pla-
cebo, with similar incidence of adverse events [70].
J. Hu et al.
211
8.3.2.3 Other Respiratory Viral Infections
In addition to SARS-CoV-2 and inuenza, infection with other viral respiratory
pathogens, including respiratory syncytial virus (RSV), parainuenza virus, human
metapneumovirus, rhinovirus, and adenovirus, is common in SOT recipients [26,
71]. Similar to inuenza, these respiratory viruses are spread by direct contact with
aerosolized droplets [26]. The clinical syndrome is similar to infection with inu-
enza and includes fever, cough, rhinorrhea, and myalgias, though the development
of lower respiratory tract symptoms with bronchiolitis and pneumonia is more com-
mon in SOT recipients than in immunocompetent individuals [72]. Nasopharyngeal
swab or wash should be collected in the clinic and sent for PCR-based assays, which
remain the gold standard for diagnosing respiratory viral infections in SOT recipi-
ents [2]. Supportive care is the mainstay of treatment for non-SARS-CoV-2 and
non-inuenza respiratory infections. If the patient develops hypoxia, they should be
promptly admitted to the hospital. In all severe cases, the transplant team should be
informed; in some circumstances the transplant team may consider whether a reduc-
tion in immunosuppression is warranted. Antiviral drug therapy for certain viral
pathogens in SOT recipients, including RSV and adenovirus [73, 74], is under
investigation.
RSV
There are currently no accepted guidelines for the use of ribavirin in the treatment
of RSV; practices vary by institution and it is typically only used in hospitalized
patients with lower respiratory tract disease, a signicantly depressed absolute lym-
phocyte count, and in lung transplant recipients [75].
As of September 2024, there are three U.S. Food and Drug Administration
(FDA)-approved vaccines to prevent RSV lower respiratory tract disease in older
adults: Arexvy (GSK plc, London, United Kingdom), Abrysvo (Pzer, NewYork,
NY, USA), and mRESvia (Moderna, Cambridge, MA, USA) [76]. While immuno-
compromised patients were not included in initial trials, CDC Advisory Committee
on Immunization Practices (ACIP) recommendations suggest offering RSV vaccine
to adult patients ≥60years of age who are at highest risk for severe RSV infection,
including those with moderate or severe immunocompromise [77
]. No head-to-
head comparison of the three vaccines is available.
Herpes Viruses
Infection with cytomegalovirus (CMV) can cause signicant respiratory illness in
SOT recipients. While infection with CMV can occur as a primary or secondary
infection, most adult cases in this patient population represent reactivation of a
latent reservoir. CMV disease can manifest as either CMV syndrome, characterized
by fever, malaise, and myelosuppression, or as CMV tissue-invasive disease, which
8 Infections intheAdult Solid Organ Transplant Recipient
212
can be isolated to the allograft or involve multiple organs simultaneously [7, 78].
Symptoms of CMV pneumonia are non-specic and are typically characterized by
subacute onset of fevers, cough, and hypoxemia, accompanied by a range of radio-
graphic ndings including bilateral inltrates, nodules, and areas of consolidation.
Lung transplant recipients are at particularly elevated risk for CMV pneumonia;
diagnosis requires the presence of signs or symptoms of pulmonary disease com-
bined with the detection of CMV cytotoxic viral inclusions in bronchoalveolar
lavage or lung tissue samples [79]. Because of the non-specic presentation, pri-
mary care providers should maintain a high index of suspicion for CMV pneumonia
in lung transplant recipients and closely collaborate with the patient’s transplant
physicians to expedite evaluation and coordinate care.
VZV and HSV establish lifelong latency in neural ganglia after initial primary
infection; in the SOT population, manifestations of VZV or HSV may be seen in up
to 70% of recipients if no prophylaxis is used [80]. Reactivation can present with
visceral involvement including pneumonitis/pneumonia. HSV pneumonia can also
occur as a result of introducing colonized oropharyngeal secretions into the lower
respiratory tract during intubation [81].
8.3.2.4 Bacterial Pneumonia
CAP is common in SOT recipients, although evidence is mixed as to whether CAP
occurs more frequently in these patients compared to the general population [82,
83]. While SOT recipients are at risk for CAP from typical organisms including
Streptococcus pneumoniae, Legionella pneumophila, and Haemophilus inuenza,
they are also at increased risk of infection with Nocardia spp., Staphylococcus
aureus, Pseudomonas aeruginosa, and other gram-negative rods (GNRs) [27].
Abrupt onset of fever accompanied by cough productive of sputum should raise
concern for CAP.A focal inltrate on chest X-ray may be useful in conrming sus-
picion for CAP but should not be used to rule in or rule out disease.
Infectious Disease Society of America (IDSA) guidelines (2019) include recom-
mendations for the treatment of CAP in patients with co-morbidities (which include
chronic heart, lung, liver, and kidney disease, as well as asplenia). For SOT recipi-
ents, CAP treatment options include monotherapy with a respiratory uoroquino-
lone or combination therapy with a beta-lactam (amoxicillin- clavulanate) or a
cephalosporin plus either doxycycline or a macrolide [27, 84]. This treatment regi-
men should only be used for stable outpatients. Drug interactions are common with
antibiotics and immunosuppressant medications—if starting a new antibiotic, espe-
cially a macrolide, the transplant team should be notied (See Chap. 3). The typical
treatment duration is 5days though providers may treat longer if symptoms are not
improving. However, if symptoms persist without response to antibiotic therapy,
consultation with a pulmonologist and/or infectious disease specialist should be
obtained to consider additional diagnostic testing and alternate diagnoses.
Hospital admission should be expedited for any patient with CAP and unstable
vital signs, and considered for certain SOT recipients who, although stable, are at
J. Hu et al.
213
high risk of decompensation. Validated clinical prediction scores to stratify the need
for hospitalization may be used, but only in combination with clinical judgment in
this population.
As discussed above, the primary care provider who is treating a lung transplant
recipient with suspected CAP should contact the patient’s lung transplant specialist.
Lung transplant recipients are at risk for opportunistic infections and resistant bac-
teria, may already be receiving macrolides chronically for anti-inammatory ther-
apy, and may need an expedited evaluation for rejection.
8.3.2.5 Mycobacterial Infections
Infection with mycobacterium, including Mycobacterium tuberculosis,
Mycobacterium avium complex (MAC), and other non-tuberculous mycobacterial
(NTM) species, is an important diagnostic consideration in the SOT recipient who
presents with subacute to chronic onset of respiratory symptoms. The incidence of
pulmonary tuberculosis (TB) in SOT recipients depends on the incidence in the
local population, epidemiologic risk factors, and new or ongoing TB exposures
[85]. The frequency of active TB among SOT patients is estimated to be 20–74
times higher than the general population, with higher prevalence rates in endemic
areas [86]. Rates of active TB are highest in lung transplant patients compared to
other SOT recipients. Approximately, 2/3 of active TB infections occur within the
rst post-transplant year, with the majority reecting reactivation of prior disease
[87]. All SOT recipients should undergo TB testing prior to transplantation to iden-
tify cases of latent tuberculosis infection (LTBI); however not all LTBI may be
identied due to anergy with end stage organ failure [88]. One-third to one-half of
all cases of active TB in SOT recipients are disseminated or occur at non-pulmonary
sites—thus primary care providers must maintain a high index of suspicion for pul-
monary as well as disseminated disease. Active pulmonary TB in SOT recipients
may manifest with non-specic symptoms such as fevers, weight loss, and fatigue,
as well as productive cough, hemoptysis, and dyspnea. If the physician suspects
pulmonary TB, standard TB evaluation should be pursued with a chest X-ray and
sputum samples sent for acid-fast bacilli (AFB) staining and culture. Primary care
providers should communicate with an infectious disease specialist and pulmonolo-
gist to determine if more invasive diagnostic testing is warranted and to determine a
treatment course if pulmonary TB is identied. Importantly, treating pulmonary TB
in SOT recipients requires medication adjustment to avoid interactions between
rifamycins and calcineurin inhibitors (See Chap. 3) [89].
In comparison to pulmonary TB, NTM infections in SOT recipients typically
occur later in the post-transplant course. However, it is important to note that these
infections have been described in the early post-transplant period as well [90]. NTM
infections involve the lung in more than 50% of cases, with lung and heart trans-
plant recipients being more susceptible than kidney and liver transplant recipients
[91]. Manifestations of respiratory NTM infections include pulmonary inltrates,
solitary pulmonary nodules, abscesses, and cavitary lesions. Symptoms of
8 Infections intheAdult Solid Organ Transplant Recipient
214
pulmonary NTM infections are non-specic and may include chronic cough, spu-
tum production, and less often, hemoptysis. Importantly, systemic symptoms, such
as fever and night sweats, may not be present [92]. In SOT recipients with suspected
NTM infection, a pulmonologist should be involved early to help direct the evalua-
tion, which may include bronchoscopy and requests for special staining, culture,
and histopathology. While these pathogens are less common than other bacterial
and viral causes of respiratory infection in SOT patients, they are important diag-
nostic considerations. Input from pulmonary and infectious diseases specialists is
essential due to difculty in making the diagnosis, the questionable benets of treat-
ment in certain situations, the need for long-term, multi-drug antibiotic regimens,
and potential interaction of these antibiotics with drugs used for immunosuppres-
sion [93].
8.3.2.6 Fungal Pneumonia
Invasive fungal pneumonia, particularly with Aspergillus species, is of concern in
SOT recipients and disproportionately affects up to 19% of lung transplant recipi-
ents [94, 95]. As opposed to the rapid symptom onset characteristic of viral or bacte-
rial pneumonia, respiratory illness due to fungal infection usually develops over
weeks or even months, with the exception being that of infection with Mucorales
spp., which is classically rapidly progressive. Mucormycosis accounts for 2% of
invasive fungal infections in recent cohorts of SOT recipients [96], with overall case
fatality rates of 40–50% [97, 98]. Additionally, the incidence of invasive fungal
infections is higher 6–12months after transplant and mold infections, such as inva-
sive aspergillosis, often occur >1 year after transplant, although donor-derived
infections are possible and may present early post-SOT [99]. Finally, invasive can-
didiasis is an important cause of infection in the SOT recipients. Diagnosis and
treatment of invasive fungal pneumonia requires the assistance of an infectious dis-
ease specialist or pulmonologist; thus early recognition by the primary care pro-
vider (through clinical and radiological manifestations) and coordinating early with
specialty care is critical.
Pneumonia due to Pneumocystis jirovecii peaks during the rst 6months
after transplantation when immunosuppression is highest [10]. Additional risk
factors include increased intensity of immunosuppression (as occurs with treat-
ment of rejection episodes), adherence to prophylaxis, a history of CMV vire-
mia, and lung transplantation which confers a sustained increase in risk
compared to other organ transplants, leading to lifelong prophylaxis for most
lung transplant recipients [10, 100, 101]. In a SOT recipient, the time course of
disease presentation is typically more rapid compared to patients with HIV
infection, with symptoms developing over days to 1–2weeks [102]. Clinicians
should have a high index of suspicion for Pneumocystis jirovecii infection in
SOT recipients who present with hypoxemia out of proportion to radiologic
ndings, particularly in patients who are no longer taking or who are not adher-
ent to Pneumocystis jirovecii prophylaxis.
J. Hu et al.
215
PJP may be diagnosed either by performing immunouorescence on sputum
samples or lower respiratory secretions. Compared to HIV-infected individuals,
SOT recipients may have lower burden of organisms thus reducing the sensitivity of
microscopy. PCR may be used as an alternative means to make a diagnosis of
Pneumocystis pneumonia if the index of suspicion is high, though it does not reli-
ably exclude airway colonization in the SOT population [103, 104]. Although the
serum beta-D-glucan (BDG) has high negative predictive values in patients with
HIV [105], in a recent meta-analysis, negative BDG was only associated with low
post-test probability of PJP (≤5%) when pre-test probability was low to intermedi-
ate (≤20%) in patients without HIV [106].
While evaluation for Pneumocystis pneumonia can be performed as an outpatient
if the patient is stable and resources are readily available, often the patient will
require admission for an expedited workup, including evaluation for other causes of
respiratory illness. Treatment with trimethoprim-sulfamethoxazole (TMP-SMX) is
the preferred course of therapy, with consideration of adjunctive glucocorticoids if
there is signicant hypoxemia. Low-dose daily prophylaxis with TMP-SMX, if tol-
erated, has the additional benet of helping to prevent infection with Toxoplasma
and Nocardia species, as well as other common causes of urinary and respiratory
tract infections [31].
Key Considerations in Respiratory Infections
• Remember atypical causes of pneumonia in immunocompromised hosts,
including viral reactivation, fungal etiologies, and mycobacterial infec-
tions. While radiographs are helpful, diagnosis may require invasive
sampling.
• SOT recipients may shed respiratory virus for longer and infections may
be more protracted with higher risk for progression to lower respiratory
tract disease.
• Vaccination of the SOT recipient and their household contacts (vaccine
cocooning) remains the most effective way to prevent morbidity and mor-
tality from SARS-CoV-2, RSV and inuenza; cocooning is also the pre-
ferred strategy for pertussis prevention (Tdap/DTaP for pediatric contacts)
• Ritonavir-boosted nirmatrelvir (Paxlovid) is a strong cytochrome P450
3A4 inhibitor and P-glycoprotein inhibitor and interacts with immunosup-
pressants such as tacrolimus, everolimus, and sirolimus.
• Reduction of immunosuppression in consultation with the transplant team
is often essential to overcome serious infections.
8 Infections intheAdult Solid Organ Transplant Recipient
216
8.4 Gastrointestinal Infections
In SOT recipients, the most common presentation of gastrointestinal infections is
diarrhea, which affects 20–50% of patients at some point after transplant. The Infectious
Disease Society of America (IDSA) denes diarrhea as >3 soft or loose stools per day.
Acute diarrhea is present for <14days, persistent diarrhea for 14–29days, and chronic
diarrhea for >30days. Risk factors for diarrhea in SOT recipients include being female
and using tacrolimus or tacrolimus plus mycophenolate [107].
The Belgian DIDACT study attempted to identify the etiology of post-transplant
diarrhea in renal transplant recipients. Treatment of infections led to diarrhea remission
in 35 patients (33% overall), with the majority of identied infections bacterial, includ-
ing C. jejuni, Salmonella spp., and C. difcile. In this cohort, 7% of patients were diag-
nosed with CMV infection [108]. In the USA, a single center, retrospective analysis of
hospitalized SOT recipients with diarrhea over a 18-month period noted that a majority
of the community-onset diarrheal episodes were self-limited without identiable cause
Case
A 54-year-old woman with a history of kidney transplantation presents with
3weeks of diarrhea and decreased appetite. She has 3–5 loose stools daily
without hematochezia, melena, or change in frequency or severity. Her immu-
nosuppression medication dosing and adherence have not changed. She has
no recent travel or change in diet or water sources. Her CMV serostatus is D+/
R−. On exam, she has normal vital signs, is not orthostatic, and has a normal
abdomen exam. What is the next appropriate step in her care?
Comment: This patient appears to be clinically stable, and it may be feasible
to continue her evaluation as an outpatient. Initial testing should include kidney
function, complete blood counts, a serum CMV PCR, and stool testing for enteric
pathogens. Modern stool “multiplex” panels often include bacterial, viral, and
parasitic testing in a single specimen and may be sent initially, if available.
If multiplex panels are not available, initial stool testing at a minimum
should include common bacterial enteric pathogens and Clostridioides dif-
cile PCR. Depending on a patient’s known exposures and clinical course,
testing for norovirus and parasitic infections such as Cryptosporidium and
Giardia may be tested up front; alternatively, they may be deferred and
ordered if initial testing results return negative and the patient continues to
have symptoms. Non-infectious causes of diarrhea should also be considered.
(See below as well as Chap. 9). If the above infectious testing is negative,
consultation with an infectious disease or gastroenterology specialist familiar
with SOT recipients should be sought, as additional tests, including endos-
copy, should be considered. If she develops new or worsening symptoms, she
will likely require an emergency department evaluation and consideration for
admission for expedited workup.
J. Hu et al.