Jurnal PD 3
Jurnal PD 3
Jurnal PD 3
Treatment of Community-Acquired
Pneumonia in Immunocompromised
Adults
A Consensus Statement Regarding Initial Strategies
Julio A. Ramirez, MD; Daniel M. Musher, MD; Scott E. Evans, MD; Charles Dela Cruz, MD; Kristina A. Crothers, MD;
Chadi A. Hage, MD; Stefano Aliberti, MD; Antonio Anzueto, MD; Francisco Arancibia, MD; Forest Arnold, DO;
Elie Azoulay, MD; Francesco Blasi, MD; Jose Bordon, MD; Steven Burdette, MD; Bin Cao, MD; Rodrigo Cavallazzi, MD;
James Chalmers, MD; Patrick Charles, MD; Jean Chastre, MD; Yann-Erick Claessens, MD; Nathan Dean, MD;
Xavier Duval, MD; Muriel Fartoukh, MD; Charles Feldman, MD; Thomas File, MD; Filipe Froes, MD;
Stephen Furmanek, MPH; Martin Gnoni, MD; Gustavo Lopardo, MD; Carlos Luna, MD; Takaya Maruyama, MD;
Rosario Menendez, MD; Mark Metersky, MD; Donna Mildvan, MD; Eric Mortensen, MD; Michael S. Niederman, MD;
Mathias Pletz, MD; Jordi Rello, MD; Marcos I. Restrepo, MD; Yuichiro Shindo, MD; Antoni Torres, MD;
Grant Waterer, MD; Brandon Webb, MD; Tobias Welte, MD; Martin Witzenrath, MD; and Richard Wunderink, MD
ABBREVIATIONS: CAP = community-acquired pneumonia; CMV = Veterans Puget Sound Health Care System (Dr Crothers), University of
cytomegalovirus; MDR = multiple drug resistant; MRSA = methicillin- Washington, Seattle WA; the Thoracic Transplant Program (Dr Hage),
resistant Staphylococcus aureus; NTM = nontuberculous mycobacteria; Indiana University, Indianapolis, IN; the Department of Pathophysi-
PCP = Pneumocystis jirovecii pneumonia; TMP-SMX = trimethoprim- ology and Transplantation (Drs Aliberti and Blasi), University of
sulfamethoxazole; TNF = tumor necrosis factor Milan, and Fondazione IRCCS Cà Granda Ospedale Maggiore Poli-
AFFILIATIONS: From the Division of Infectious Diseases (Drs Ram- clinico, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy;
irez, Arnold, and Gnoni, and Mr Furmanek), University of Louisville, the South Texas Veterans Health Care System (Drs Anzueto and
Louisville, KY; the Baylor College of Medicine and Michael E. DeBakey Restrepo), Audie L. Murphy Memorial Veterans Hospital, and Uni-
VA Medical Center (Dr Musher), Houston, TX; the Department of versity of Texas Health, San Antonio, TX; the Pneumology Service (Dr
Pulmonary Medicine (Dr Evans), University of Texas MD Anderson Arancibia), Instituto Nacional del Tórax and Clínica Santa María,
Cancer Center, Houston, TX; Pulmonary, Critical Care and Sleep Santiago de Chile, Chile; the Medical ICU (Dr Azoulay), Saint-Louis
Medicine (Dr Dela Cruz), Yale University, New Haven, CT; the Teaching Hospital, Assistance Publique-Hôpitaux de Paris
chestjournal.org 1897
for patients in whom the pathogen causing CAP has the immune system that are affected by the underlying
been identified. No large, prospective clinical studies disease and/or medical therapy. In this document we
comparing different empirical therapies in attempt to develop a unifying approach to simplify a
immunocompromised patients exist. very complex topic, involving a heterogeneous
Susceptibility to specific infections varies widely in population. The objective of this document is to suggest
immunocompromised patients and depends both on the an approach to the initial treatment of
degree of immune suppression and the components of immunocompromised patients with suspected CAP.
In each round of the Delphi survey, questions regarding the treatment Statistical Analysis
of CAP in the immunocompromised patient were submitted to all 45 At each round of the survey, the mean and SD of agreement based on
participants in the consensus process. To anonymously record the Likert scale for each question were calculated. To evaluate the level
participant responses and comments, a survey was developed using of agreement or disagreement for each question in a manner that
Research Electronic Data Capture (REDCap), which allowed incorporated both the mean and SD, a t-statistic for each question
participants to answer with their level of agreement with the was calculated. The t-statistic was used to identify which questions
suggestion, and to write specific comments regarding the had the least amount of agreement or the most controversy.
management suggested by the group. After each round, all responses Agreement was visualized by bar charts, and final agreement was
were summarized and an anonymized summary of all the comments reported as the percentage of participants who responded as Agree
was produced and sent to each participant. Participants had the or Strongly Agree.
to infection. From this perspective, patients with patients with this degree of immune dysfunction are
common comorbid conditions such as diabetes, typically infected with the same spectrum of
chronic lung disease, liver disease, kidney disease, or organisms that cause CAP in younger or healthier
even those who are elderly and frail, can be adults, and their treatment is covered in the current
considered relatively immunocompromised. However, CAP guidelines.
chestjournal.org 1899
TABLE 2 ] Patient Conditions Qualifying Patients as Immunocompromised
Patient Condition References
Primary immune deficiency diseases .
Active malignancy or malignancy within 1 y of CAP, excluding patients with localized skin cancers or early-stage .
cancers (eg, stage 1 lung cancer)
Receiving cancer chemotherapy .
HIV infection with a CD4 T-lymphocyte count < 200 cells/mL or percentage < 14% a
8
Solid organ transplantation .
Hematopoietic stem cell transplantation .
Receiving corticosteroid therapy with a dose $ 20 mg prednisone or equivalent daily for $ 14 d or a cumulative 9, 10
dose > 600 mg of prednisoneb
Receiving biological immune modulatorsc 11, 12
Receiving disease-modifying antirheumatic drugs or other immunosuppressive drugs (eg, cyclosporin, 13
cyclophosphamide, hydroxychloroquine, methotrexate)
TABLE 3 ] Core Respiratory Pathogens That May Cause Community-Acquired Pneumonia in the Immunocom-
promised Patient
Gram-Positive Bacteria Gram-Negative Bacteria “Atypical” Bacteria Respiratory Viruses
Streptococcus Haemophilus influenzae Legionella Influenza virus
pneumoniae pneumophila
Staphylococcus aureus Moraxella catarrhalis Chlamydophila Parainfluenza virus
(MSSA) pneumoniae
Streptococcus Enterobacteriaceae (eg, Klebsiella species, Mycoplasma Coronavirus
pyogenes Escherichia coli) pneumoniae
Other streptococci Coxiella burnetii Respiratory
syncytial virus
Rhinovirus
Adenovirus
Human
metapneumovirus
chestjournal.org 1901
TABLE 4 ] Common Respiratory Pathogens in Addition to Core Respiratory Pathogensa That Can Cause
Community-Acquired Pneumonia in the Immunocompromised Patient and for Which Antimicrobial
Therapy Is Available
Bacteria Mycobacteria Viruses Fungi Parasites
Enterobacteriaceae (including those Mycobacterium Cytomegalovirus Pneumocystis Toxoplasma
producing ESBL, and also CRE) TB jirovecii gondii
Nonfermenting gram-negative bacilli (eg, Nontuberculous Herpes simplex Aspergillus Strongyloides
Pseudomonas or Acinetobacter) mycobacteria virus species stercoralis
MRSA Varicella-zoster Mucorales
virus species
Nocardia species Histoplasma
species
Rhodococcus equi Cryptococcus
species
Blastomyces
species
Coccidioides
species
CRE ¼ carbapenemase-producing Enterobacteriaceae; ESBL ¼ extended-spectrum b-lactamase. See Table 1 legend for expansion of other abbreviation.
a
As described in Table 3.
important. Another reason to perform broad Preferably, bronchoscopy with BAL should be done
microbiologic studies is that treatment of opportunistic early so that initial empirical therapy does not alter the
pathogens is complex and often complicated by culture results. If the bronchoscopy can be done
toxicities and drug-drug interactions. promptly, a short delay before initiating antibiotic
therapy may be acceptable, given improved culture yield.
The extent of the microbiologic workup should be
In general, the more immunocompromised the host, the
individualized, considering the presence of risk factors
greater the potential benefit of performing
and likely organisms, as well as local capabilities. The
bronchoscopy with BAL.
field of diagnostic microbiologic techniques has
experienced significant progress. The development of If the etiology of CAP may be defined on the basis of
rapid diagnostic tests using new molecular techniques initial radiography and point-of-care diagnostic
and sophisticated new laboratory methods, such as testing, the small, but nevertheless clear risk associated
matrix-assisted laser desorption ionization-time of flight with bronchoscopy with BAL may outweigh the
(MALDI-TOF) mass spectrometry, is reshaping the benefit.30
clinical microbiology laboratory as well as our ability to
Question 7: What microbiologic studies can be done with
identify etiologic agents of CAP in
BAL fluid from hospitalized patients with CAP who are
immunocompromised patients.19 A list of common
immunocompromised?
microbiologic studies with relevant clinical
considerations is depicted in Table 6.20-29 We suggest that microbiological studies in
bronchoalveolar lavage should be ordered according to
Question 6: When should bronchoscopy with
the presence of risk factors for particular pathogens.
bronchoalveolar lavage be performed in hospitalized
patients with CAP who are immunocompromised? In some institutions a fixed panel of tests is routinely
performed on BAL from immunocompromised patients
We suggest that the decision to perform a bronchoscopy
with CAP. In other institutions, the tests are ordered
or bronchoalveolar lavage should be individualized.
considering the presence of clinical, radiographic, and
Bronchoscopy with BAL will be useful even in a immunologic risk factors for specific organisms.
clinically unstable patient if the patient is at risk for Table 731-35 lists microbiologic studies that can be done
infection with multiple opportunistic pathogens and an on BAL or tissue from a transbronchial lung biopsy
experienced team is available to perform the procedure. together with relevant clinical considerations.
6-MP ¼ 6-mercaptopurine.
chestjournal.org 1903
TABLE 6 ] Microbiologic Studies That Can Be Done in Immunocompromised Patients Hospitalized With
Community-Acquired Pneumonia
Studies References
Sputum samples for bacterial, mycobacterial, and fungal stains and cultures 20, 21
Comments: Sputum can be induced with inhaled isotonic or preferably hypertonic saline for certain pathogens
(eg, MTB, PCP) to avoid invasive procedures. Sputum samples can be tested by PCR for detection of MTB or
PCP
Nasopharyngeal swab with multiplex PCR for respiratory viruses 22, 23
Comments: A negative nasopharyngeal PCR result does not rule out viral pneumonia. If the suspicion is high,
perform the PCR on bronchoscopic samples. The finding of a virus by PCR does not rule out bacterial
infection
Nasopharyngeal swab with multiplex PCR for atypical bacteria .
Comments: Atypical pathogens such as Legionella, Chlamydophila, or Mycoplasma can also be identified in
oropharyngeal samples
Nasal PCR for MRSA .
Comments: Use in conjunction with a respiratory sample. A negative MRSA nasal PCR result, the absence of
gram-positive cocci in clusters on Gram stain, and a negative MRSA respiratory culture make MRSA
pneumonia extremely unlikely
Blood cultures times two (at least), 30 min apart 24, 25
Comments: If there is a port or central line or PICC line, to define the presence of line infection, perform blood
cultures from a peripheral vein and from the catheter lumens at the same time to calculate “time to
positivity.” The separation of samples over time improves bacterial detection in the case of intermittent
bacteremia
Urinary antigen for Streptococcus pneumoniae .
Comments: The recent administration of pneumococcal vaccine (within days) will produce a positive urinary
antigen result for Streptococcus pneumoniae
Urinary antigen for Legionella 26
Comments: Detects only Legionella pneumophila serotype 1. Other gram-negative bacteria may generate a
false positive test result. Obtain respiratory samples for culture and PCR to detect other species of
Legionella or serotypes if clinically indicated
Urinary antigen for Histoplasma capsulatum .
Comments: Very useful for disseminated disease. Cross-reaction with blastomycosis
Serum antigen for Cryptococcus neoformans .
Comments: A serum cryptococcal antigen test may produce a negative result for a patient with documented
cryptococcal pneumonia
Serum galactomannan antigen 27
Comments: Aspergillus cell wall contains the polysaccharide galactomannan. Also elevated in Fusarium,
Penicillium, blastomycosis, and histoplasmosis. False positive results may occur with IVIG, transfusions,
and some b-lactam antibiotics
Serum 1,3-b-D-glucan 27
Comments: b-D-Glucan is a cell wall component of several fungi. It screens for Aspergillus species, Candida
species, PCP, and other fungi. It does not detect mucormycosis. False positive results may occur with IVIG,
hemodialysis with cellulose, albumin, infections with Pseudomonas, and some b-lactam antibiotics
Swabs of vesicular or ulcerated skin lesions for viral PCR and cultures .
Comments: A positive PCR result for HSV or VZV from skin lesions is highly correlated with herpes or varicella-
zoster pneumonia
Biopsy of skin lesion for microbiology and pathology .
Comments: Sample must be sent to microbiology and pathology for stains and cultures for viruses, bacteria,
mycobacteria, fungi, and parasites
Viral load for CMV (PCR) 28
Comments: Obtain only if clinical suspicion is high. CMV reactivation is common in acute illness, and the
presence of copies of CMV in plasma does not necessarily indicate invasive disease. On the other hand, the
absence of viremia makes CMV pneumonitis less likely
(Continued)
CMV ¼ cytomegalovirus; HSV ¼ herpes simplex virus; IVIG ¼ IV immunoglobulin; MTB ¼ Mycobacterium TB; PCP ¼ Pneumocystis jirovecii pneumonia;
PCR ¼ polymerase chain reaction; PICC ¼ peripherally inserted central line catheter; VZV ¼ varicella-zoster virus. See Table 1 legend for expansion of other
abbreviation.
Although immunocompromised hosts may have unique availability of point-of-care tests, severity of disease at
immunologic risk and often more frequent nosocomial presentation, and use of prophylactic therapy for a
contact and antibiotic exposure, many particular opportunistic pathogen.
immunocompromised patients admitted with CAP do
The need for empirical therapy of opportunistic
not have any additional risk factors for drug-resistant
pathogens will continue to evolve as more point-of-care
bacteria (eg, methicillin-resistant Staphylococcus aureus
tests are developed for rapid diagnosis. Empirical
[MRSA], Pseudomonas). For these patients, we suggest
therapy beyond core respiratory pathogens may not be
initial empirical antimicrobial therapy targeting the core
necessary if the patient is clinically stable and the local
respiratory pathogens described in Table 3. In this group
setting allows for rapid microbiologic diagnostic tests.
of patients, the initial empirical antibacterial therapy
would be the same as the initial empirical therapy for Question 10: What role does the severity of pneumonia
hospitalized patients with CAP who are not play in the selection of initial empirical therapy?
immunocompromised.1 Additional empirical treatment
We suggest that the presence of severe pneumonia can be
beyond the core respiratory pathogens should be
used as an indication to start empirical therapy for
considered according to the presence of risk factors for
resistant gram-positive and gram-negative organisms,
drug-resistant or opportunistic pathogens and is
followed by rapid deescalation if no multidrug-resistant
discussed in the sections below.
pathogen is identified.
Question 9: In which patients with CAP who are
Severity of illness is not by itself an accurate predictor of
immunocompromised should empirical therapy be
drug resistance or opportunistic infection in pneumonia.
extended beyond the core respiratory pathogens?
For example, Streptococcus pneumoniae is capable of
We suggest to extend empirical therapy beyond core causing life-threatening septic shock, whereas invasive
respiratory pathogens when (1) risk factors for drug- pulmonary aspergillosis may present with an indolent,
resistant organisms or opportunistic pathogens are progressive course.
present and (2) the delay in empirical antimicrobial
The impact of severe pneumonia on empirical therapy is
therapy will place the patient at increased risk of
the critical need to start early with an appropriate
mortality.
antimicrobial therapy, because an initial inadequate
In addition to initial empirical treatment for core antibiotic spectrum has been identified as an
respiratory pathogens, we suggest broader initial independent risk factor for mortality in CAP. Given this
coverage when the following factors are met: (1) A circumstance, the presence of severe pneumonia or
resistant bacterium or an opportunistic pathogen is pneumonia requiring ICU care can be used as a
suspected on the basis of the presence of risk factors threshold to start empirical therapy for resistant gram-
from findings on history or physical examination, positive organisms (eg, MRSA) and resistant gram-
laboratory results, and/or imaging patterns; and (2) negative organisms (eg, Pseudomonas).
waiting for microbiologic identification of the suspected
pathogen will significantly delay initiation of F. Empirical Therapy: Specific Pathogens
antimicrobial therapy and may increase the risk of Question 11: In which immunocompromised patients
mortality. Other considerations for extending initial should the initial empirical therapy be extended to cover
empirical therapy beyond core pathogens include the possibility of CAP due to MRSA?
chestjournal.org 1905
We suggest that initial empirical therapy to cover for activity against P aeruginosa, such as piperacillin-
MRSA should be started in patients with a history of tazobactam or a carbapenem, should be used as core
colonization or infection with MRSA in the previous therapy. However, ceftazidime, which has no reliable
12 months. activity against S pneumoniae, should not be used as
monotherapy.43
In patients with a history of colonization or infection
with MRSA in the previous 12 months, initial empirical Question 13: In which immunocompromised patients
therapy should cover the possibility of infection due to should the initial empirical therapy be extended to cover
MRSA. There are other risk factors reported in the the possibility of CAP due to multidrug-resistant (MDR)
literature for MRSA infection such as prior antibiotic gram-negative bacilli?
use, recent hospitalization, hemodialysis, or wound care,
but if the local prevalence of MRSA is low these risk We suggest that in patients with a recent history of
factors will each have a low positive predictive value and colonization or infection with MDR gram-negative
should not be used to trigger empirical anti-MRSA bacilli, the initial empirical therapy should cover the
therapy.36-40 On the other hand, a single patient who possibility of infection due to the colonizing MDR gram-
accumulates many of these risk factors may have a high negative bacilli.
likelihood of CAP due to MRSA. Vancomycin or In patients with a recent history of colonization or
linezolid are the first line for initial empirical therapy. In infection with MDR gram-negative bacilli such as
regions with a high prevalence of MRSA, some members extended-spectrum b-lactamase-producing
of the panel will start empirical anti-MRSA therapy in Enterobacteriaceae, carbapenemase-producing
patients requiring ICU admission. A negative MRSA Enterobacteriaceae, MDR Pseudomonas, or MDR
result by nasal polymerase chain reaction (PCR), Acinetobacter, the initial empirical therapy should
absence of gram-positive cocci in clusters on Gram’s cover the possibility of infection with the colonizing
staining, and a negative MRSA respiratory culture can MDR gram-negative bacilli. A knowledge of the local
be used to deescalate anti-MRSA therapy. susceptibility profile for gram-negative bacilli and the
Question 12: In which immunocompromised patients most recent susceptibility profile of the colonizing
should the initial empirical therapy be extended to cover MDR gram-negative bacilli will help in the selection
the possibility of CAP due to drug-resistant gram- of empirical therapy for these organisms with difficult-
negative bacilli, including Pseudomonas aeruginosa? to-treat resistance. For empirical therapy of MDR
gram-negative bacilli, b-lactam antibiotics such as
We suggest that initial empirical therapy for piperacillin-tazobactam or imipenem may have to be
immunocompromised patients should cover resistant changed to newer b-lactam antibiotics that have better
gram-negative bacilli, including Pseudomonas activity against some of the MDR bacteria. In these
aeruginosa, if there is a history of colonization or patients, consideration should be given to the addition
infection with a resistant gram-negative bacilli in the of ceftazidime-avibactam, ceftolozane-tazobactam, or
prior 12 months, previous hospitalization with exposure meropenem-vaborbactam. Adding a polymyxin such
to broad-spectrum antibiotics, the presence of a as colistin to a traditional b-lactam is a possibility
tracheostomy, neutropenia, or a history of pulmonary when other agents are not available. In patients
comorbidity. treated empirically with these broad-spectrum agents,
History of colonization or infection with a drug-resistant we strongly emphasize an extended microbiologic
gram-negative bacillus in the previous 12 months, workup and prompt deescalation of therapy if
previous hospitalization with exposure to broad- appropriate.
spectrum antibiotics, the presence of a tracheostomy, Question 14: In which immunocompromised patients
neutropenia, a history of pulmonary comorbidity (eg, should the initial empirical therapy be extended to cover
cystic fibrosis, bronchiectasis, or recurrent exacerbations the possibility of CAP due to Pneumocystis jirovecii
of COPD requiring glucocorticoid and antibiotic use) pneumonia (PCP)?
have been reported in the literature to increase the risk
of resistant gram-negative bacilli.37-42 Patients with any We suggest initial empirical therapy should be extended
of these risk factors should be considered for initial to cover the possibility of PCP in patients with diffuse,
empirical therapy against resistant gram-negative bacilli bilateral, interstitial infiltrates or alveolar opacities and
including P aeruginosa. b-Lactam antibiotics with who are not receiving PCP prophylaxis, and those who
are either (1) HIV hosts who is newly diagnosed, or not In these patients we suggest the addition of
on antiretroviral therapy, or with CD4 counts less than trimethoprim-sulfamethoxazole (TMP-SMX) to the
200 cells/mL (or a percentage lower than 14%) or (2) non- initial regimen. The recommended dosage for TMP-
HIV hosts with severely impaired cell-mediated immunity SMX is 15 to 20 mg/kg/d of the trimethoprim
(eg, taking glucocorticoids with cytotoxic agents). component orally or IV, given in three or four divided
chestjournal.org 1907
doses.44 The dose of TMP-SMX is the same for PCP in voriconazole antifungal prophylaxis. In these patients we
the HIV-infected patient and PCP in the suggest liposomal amphotericin as part of the initial
immunocompromised non-HIV-infected patient. empirical regimen at dosages of 5 to 7.5 mg/kg daily.48
Adjunctive glucocorticoids are recommended for HIV- In patients intolerant to amphotericin, empirical therapy
infected patients with room air PaO2 < 70 mm Hg and/ with isavuconazole at an initial dosage of 200 mg every
or an alveolar-arterial (A-a) oxygen gradient $ 8 h can be used as an alternative.47 Voriconazole does
35 mm Hg.44 Corticosteroids are not beneficial in HIV- not cover mucormycosis, and therefore it is not
negative patients with PCP.45 suggested as initial empirical therapy.
Question 15: In which immunocompromised patients Question 17: In which immunocompromised patients
should the initial empirical therapy be extended to cover should the initial empirical therapy be extended to cover
the possibility of CAP due to Aspergillus? the possibility of CAP due to Nocardia?
We suggest that empirical therapy should cover the We suggest that empirical therapy should include the
possibility of pneumonia due to filamentous fungi such as possibility of Nocardia infection in patients with heart,
Aspergillus in patients with cancer and chemotherapy lung, liver, or hematopoietic stem cell transplant with
with severe and prolonged neutropenia and a pneumonia and evidence for a lung or brain abscess,
radiographic nodular pattern surrounded by a halo of and who have not been receiving prophylaxis with
ground-glass attenuation and/or cavitation. TMP-SMX.
Voriconazole is considered the first-line treatment for
In these patients we suggest the addition of TMP-SMX
patients with documented invasive aspergillosis, but we
to the initial empirical therapy at a dosage of 15 mg/kg/
do not suggest empirical voriconazole because these
d of the trimethoprim component IV in three or four
patients are also at risk for other filamentous fungi
divided doses.49 Resistance of Nocardia species to TMP-
resistant to voriconazole (eg, those causing
SMX is a rare event.50 If TMP-SMX is contraindicated,
mucormycosis).46 In these patients we suggest empirical
linezolid also has excellent activity and can be
therapy with liposomal amphotericin at dosages of 5 to
considered for empirical therapy until susceptibilities are
7.5 mg/kg daily. In patients intolerant to amphotericin,
known.50 If initial treatment already contains a drug
empirical therapy with isavuconazole at an initial dosage
with activity against Nocardia species (eg, linezolid or
of 200 mg every 8 h can be used as an alternative.47
imipenem), empirical addition of TMP-SMX is not
Patients treated with tumor necrosis factor (TNF) requested. However, TMP-SMX is the drug of choice for
inhibitors, such as etanercept, infliximab, or definite treatment.
adalimumab, are also at risk of fungal pneumonia.11,12
Question 18: In which immunocompromised patients
In these patients we suggest an aggressive diagnostic
should the initial empirical therapy be extended to cover
workup, and treat if a fungus is identified. In the
the possibility of CAP due to varicella-zoster virus?
treatment of these patients it is important to discontinue
the use of the anti-TNF drug at the time of diagnosis of We suggest that empirical therapy be extended to cover
pneumonia to improve the level of immunity of the the possibility of CAP due to varicella-zoster virus in
patient. patients with bilateral reticulonodular infiltrates who also
have a vesicular rash.
Question 16: In which immunocompromised patients
should the initial empirical therapy be extended to cover In these patients we suggest the addition of IV acyclovir,
the possibility of CAP due to Mucorales? 10 to 15 mg/kg IV every 8 h, to the initial empirical
regimen.51
We suggest that empirical therapy should cover the
possibility of pneumonia due to filamentous fungi such as Question 19: In which immunocompromised patients
Mucorales in patients with cancer and chemotherapy should the initial empirical therapy be extended to cover
with severe and prolonged neutropenia and a the possibility of CAP due to cytomegalovirus?
radiographic nodular pattern, or a reverse halo sign, or
We suggest that empirical therapy be extended to cover
pleural effusion.
the possibility of CAP due to cytomegalovirus in patients
Empirical therapy for Mucorales is especially important with bilateral interstitial pneumonia after a recent lung
when fungal infection is suspected in a patient receiving transplant or hematopoietic stem cell transplant.
chestjournal.org 1909
that appropriately support several of our suggestions; 12. Baddley JW, Cantini F, Goletti D, et al. ESCMID Study Group for
Infections in Compromised Hosts (ESGICH) consensus document
hence we need to emphasize that the suggestions offered on the safety of targeted and biological therapies: an infectious
in this consensus are based primarily on expert opinion. diseases perspective (soluble immune effector molecules [I]: anti-
tumor necrosis factor-a agents). Clin Microbiol Infect. 2018;24(suppl
2):S10-S20.
In conclusion, we have developed general suggestions
13. Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid
for the initial treatment of immunocompromised arthritis and the risk of hospitalization for pneumonia:
patients hospitalized with pneumonia. When possible, associations with prednisone, disease-modifying antirheumatic
drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum.
the care of these patients should be carried out by a 2006;54(2):628-634.
multidisciplinary group of specialists. Because 14. Sanders KM, Marras TK, Chan CK. Pneumonia severity index in the
immunocompromised patients have been excluded from immunocompromised. Can Respir J. 2006;13(2):89-93.
prospective randomized studies of CAP treatment, there 15. Carrabba M, Zarantonello M, Bonara P, et al. Severity assessment of
healthcare-associated pneumonia and pneumonia in
is an urgent need to generate scientific evidence in this immunosuppression. Eur Respir J. 2012;40(5):1201-1210.
field. 16. Gonzalez C, Johnson T, Rolston K, Merriman K, Warneke C,
Evans S. Predicting pneumonia mortality using CURB-65, PSI, and
patient characteristics in patients presenting to the emergency
Acknowledgments department of a comprehensive cancer center. Cancer Med.
Author contributions: Development of first round of Delphi 2014;3(4):962-970.
questions and draft of the initial manuscript: J. A. R., D. M. M, S. E. E.,
17. Majumdar SR, Eurich DT, Gamble JM, Senthilselvan A, Marrie TJ.
C. D. C., K. A. C., and C. A. H. Development of all other rounds of Oxygen saturations less than 92% are associated with major adverse
Delphi questions and subsequent versions of the manuscript: all events in outpatients with pneumonia: a population-based cohort
authors. Final version of the manuscript: J. A. R. and approved by all study. Clin Infect Dis. 2011;52(3):325-331.
authors.
18. Serra MC, Cervera C, Pumarola T, et al. Virological diagnosis in
Financial/nonfinancial disclosures: None declared. community-acquired pneumonia in immunocompromised patients.
Eur Respir J. 2008;31(3):618-624.
Role of sponsors: The sponsor had no role in the design of the study,
the collection and analysis of the data, or the preparation of the 19. Buchan BW, Ledeboer NA. Emerging technologies for the clinical
manuscript. microbiology laboratory. Clin Microbiol Rev. 2014;27(4):783-822.
Additional information: The e-Appendix can be found in the 20. Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American
Supplemental Materials section of the online article. Thoracic Society/Infectious Diseases Society of America/Centers for
Disease Control and Prevention clinical practice guidelines:
diagnosis of tuberculosis in adults and children. Clin Infect Dis.
References 2017;64(2):111-115.
1. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of 21. Fujisawa T, Suda T, Matsuda H, et al. Real-time PCR is more specific
adults with community-acquired pneumonia: an official clinical than conventional PCR for induced sputum diagnosis of
practice guideline of the American Thoracic Society and Infectious Pneumocystis pneumonia in immunocompromised patients without
Diseases Society of America. Am J Respir Crit Care Med. HIV infection. Respirology. 2009;14(2):203-209.
2019;200(7):e45-e67.
22. Choi SH, Hong SB, Ko GB, et al. Viral infection in patients with
2. Woodhead M, Blasi F, Ewig S, et al. Guidelines for the management severe pneumonia requiring intensive care unit admission. Am J
of adult lower respiratory tract infections: full version. Clin Microbiol Respir Crit Care Med. 2012;186(4):325-332.
Infect. 2011;17(suppl 6):E1-E59.
23. Lachant DJ, Croft DP, McGrane Minton H, Prasad P,
3. Lim WS, Baudouin SV, George RC, et al. BTS guidelines for the Kottmann RM. Nasopharyngeal viral PCR in immunosuppressed
management of community acquired pneumonia in adults: update patients and its association with virus detection in bronchoalveolar
2009. Thorax. 2009;64(suppl 3):iii1-iii55. lavage by PCR. Respirology. 2017;22(6):1205-1211.
4. Harpaz R, Dahl RM, Dooling KL. Prevalence of immunosuppression 24. Raad I, Hanna HA, Alakech B, Chatzinikolaou I, Johnson MM,
among US adults, 2013. JAMA. 2016;316(23):2547-2548. Tarrand J. Differential time to positivity: a useful method for
5. Di Pasquale MF, Sotgiu G, Gramegna A, et al. Prevalence and diagnosing catheter-related bloodstream infections. Ann Intern Med.
etiology of community-acquired pneumonia in 2004;140(1):18-25.
immunocompromised patients. Clin Infect Dis. 2019;68(9):1482-
25. Lamy B, Dargère S, Arendrup MC, Parienti JJ, Tattevin P. How to
1493.
optimize the use of blood cultures for the diagnosis of bloodstream
6. Sousa D, Justo I, Domínguez A, et al. Community-acquired pneumonia infections? A state-of-the-art. Front Microbiol. 2016;7:697.
in immunocompromised older patients: incidence, causative organisms
and outcome. Clin Microbiol Infect. 2013;19(2):187-192. 26. Como J, Moffa MA, Bhanot N, et al. Potential false-positive urine
Legionella enzyme immunoassay test results. Eur J Clin Microbiol
7. Jain S, Self WH, Wunderink RG, et al. Community-acquired Infect Dis. 2019;38(7):1377-1382.
pneumonia requiring hospitalization among U.S. adults. N Engl J
Med. 2015;373(5):415-427. 27. Hage CA, Carmona EM, Epelbaum O, et al. Microbiological
laboratory testing in the diagnosis of fungal infections in pulmonary
8. Huang L, Crothers K. HIV-associated opportunistic pneumonias. and critical care practice: an official American Thoracic Society
Respirology. 2009;14(4):474-485. clinical practice guideline. Am J Respir Crit Care Med. 2019;200(5):
9. Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in 535-550.
patients taking glucocorticosteroids. Rev Infect Dis. 1989;11(6):954- 28. Kraft CS, Armstrong WS, Caliendo AM. Interpreting quantitative
963. cytomegalovirus DNA testing: understanding the laboratory
10. Sepkowitz KA, Brown AE, Armstrong D. Pneumocystis carinii perspective. Clin Infect Dis. 2012;54(12):1793-1797.
pneumonia without acquired immunodeficiency syndrome: more 29. Matthes-Martin S, Feuchtinger T, Shaw PJ, et al. Fourth European
patients, same risk. Arch Intern Med. 1995;155(11):1125-1128. Conference on Infections in Leukemia. European guidelines for
11. Davis BP, Ballas ZK. Biologic response modifiers: indications, diagnosis and treatment of adenovirus infection in leukemia and
implications, and insights. J Allergy Clin Immunol. 2017;139(5): stem cell transplantation: summary of ECIL-4 (2011). Transpl Infect
1445-1456. Dis. 2012;14(6):555-563.
39. Aliberti S, Cilloniz C, Chalmers JD, et al. Multidrug-resistant 52. Machado CM, Dulley FL, Boas LS, et al. CMV pneumonia in
pathogens in hospitalised patients coming from the community with allogeneic BMT recipients undergoing early treatment of pre-
pneumonia: a European perspective. Thorax. 2013;68(11):997-999. emptive ganciclovir therapy. Bone Marrow Transplant. 2000;26(4):
413-417.
40. Shindo Y, Ito R, Kobayashi D, et al. Risk factors for drug-resistant
pathogens in community-acquired and healthcare-associated 53. Travi G, Pergam SA. Cytomegalovirus pneumonia in hematopoietic
pneumonia. Am J Respir Crit Care Med. 2013;188(8):985-995. stem cell recipients. J Intensive Care Med. 2014;29(4):200-212.
41. Villafuerte D, Aliberti S, Soni NJ, et al. GLIMP Investigators. 54. Lodding IP, Schultz HH, Jensen JU, et al. Cytomegalovirus viral load
Prevalence and risk factors for Enterobacteriaceae in patients in bronchoalveolar lavage to diagnose lung transplant associated
hospitalized with community-acquired pneumonia. Respirology. CMV pneumonia. Transplantation. 2018;102(2):326-332.
2020;25(5):543-551. 55. Keiser PB, Nutman TB. Strongyloides stercoralis in the
42. Restrepo MI, Babu BL, Reyes LF, et al. Burden and risk factors for immunocompromised population. Clin Microbiol Rev. 2004;17(1):
Pseudomonas aeruginosa community-acquired pneumonia: a 208-217.
multinational point prevalence study of hospitalised patients. Eur 56. Patrat-Delon S, Gangneux JP, Lavoué S, et al. Correlation of parasite
Respir J. 2018;52(2):1701190. load determined by quantitative PCR to clinical outcome in a heart
43. Barry AL, Brown SD, Novic WJ. In vitro activities of cefotaxime, transplant patient with disseminated toxoplasmosis. J Clin Microbiol.
ceftriaxone, ceftazidime, cefpirome and penicillin against 2010;48(7):2541-2545.
chestjournal.org 1911