Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Infectious Disease Reports
Published in: Current Infectious Disease Reports 6/2015

01-06-2015 | Transplant and Oncology (M Ison and N Theodoropoulos, Section Editors)

Sepsis in the Severely Immunocompromised Patient

Authors: Andre C. Kalil, Steven M. Opal

Published in: Current Infectious Disease Reports | Issue 6/2015

Login to get access

Abstract

The prevention and treatment of sepsis in the immunocompromised host present a challenging array of diagnostic and management issues. The neutropenic patient has a primary defect in innate immune responses and is susceptible to conventional and opportunistic pathogens. The solid organ transplant patient has a primary defect in adaptive immunity and is susceptible to a myriad of pathogens that require an effective cellular immune response. Risk for infections in organ transplant recipients is further complicated by mechanical, vascular, and rejection of the transplanted organ itself. The immune suppressed state can modify the cardinal signs of inflammation, making accurate and rapid diagnosis of infection and sepsis difficult. Empiric antimicrobial agents can be lifesaving in these patients, but managing therapy in an era of progressive antibiotic resistance has become a real issue. This review discusses the challenges faced when treating severe infections in these high-risk patients.
Literature
1.
Angus DC, van der Poll T. Severe sepsis and septic shock. 2013; 369: 840-852.
2.
Legrand M, Max A, Peigne V, et al. Survival in neutropenic patients with severe sepsis or septic shock. Crit Care Med. 2012;40(1):43–9.CrossRefPubMed
3.
Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America. Clin Infect Dis. 2011;52(4):e56–93.CrossRefPubMed
4.
Kern WV. Risk assessment and treatment of low-risk patients with febrile neutropenia. Clin Infect Dis. 2006;42(2):533–40.CrossRefPubMed
5.
Jeddi R, Achour M, Amor RB, et al. Factors associated with severe sepsis: prospective study of 94 neutropenic febrile episodes. Hematology. 2010;15(1):23–32.CrossRef
6.•
Kalil AC, Syed A, Rupp ME, et al. Is bacteremic sepsis associated with higher mortality in transplant recipients than in nontransplant patients? A matched case-control propensity-adjusted study. Clin Infect Dis. 2015;60(2):216–22. This study compared patients who had a solid organ transplant and sepsis to patients who did not have organ transplant but had sepsis. They were matched by age, gender, and hospital unit location at the time of blood culture collection. The results showed a statistically significant higher survival rates for septic patients who had organ transplantation than that those without transplantation, after accounting for disease severity and co-morbidities.CrossRefPubMed
7.•
Penack O, Becker C, Buchheidt M, et al. Management of sepsis in neutropenic patients: 2014 updated guidelines from the Infectious Diseases working party of the German Society of Hematology and Medical Oncology. Ann Hematol. 2014;93(7):1083–95. This evidence-based review is the most recent national set of guidelines established as a set of recommendations to manage the febrile neutropenic patient. The guideline favors early antibiotic therapy directed towards the most likely pathogens with appropriate therapy guided by local susceptibilty patterns of common bacterial pathogens.
8.
Masaoka T. Evidence-based recommendations for antimicrobial use in febrile neutropenia in Japan. Clin Infect Dis. 2004;39 Suppl 1:S49.CrossRefPubMed
9.
Viscoli C on behalf of the EORTC international antimicrobial therapy group. Management of infection in cancer patients. Euro J Cancer. 2002;38 suppl 4:82–7.
10.
Legrand M, Max A, Schlemmer B, Azoulay E, Gachot B. The strategy of antibiotic use in critically ill neutropenic cancer patients. Ann Intensive Care. 2011;1:1–22.CrossRef
11.
Hanberger H, Giske CG, Giamarello H. When and how to cover for resistant gram-negative bacilli in severe sepsis and septic shock. Curr Infect Dis Rep. 2011;31(5):416–25.CrossRef
12.•
Pop-Vicas A, Opal SM. The clinical impact of multidrug resistant gram-negative bacilli in the management of septic shock. Virulence. 2014;5(1):1–7. This review paper discusses the problem of multidrug resistant bacterial pathogens and provides some recommendations on how to treat these infections in criticall ill patients.CrossRef
13.
Dellinger RP, Levy MM, Rhodes A, et al. The surviving sepsis guidelines: 2012. Crit Care Med. 2013;41:580–637.CrossRefPubMed
14.
Klastersky J, Paesmans M, Rubenstein EB, et al. The multinational association of supportive care in cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol. 2000;18:3038–51.PubMed
15.
Sickles EA, Greene WH, Wiernik PH. Clinical presentation of infection in granulocytopenic patients. Arch Intern Med. 1975;135:715–9.CrossRefPubMed
16.
Sepkowitz KA. Treatment of patients with hematologic neoplasm, fever, neutropenia. Clin Infect Dis. 2005;40 suppl 4:S253–256.CrossRefPubMed
17.
Rolston KV. Challenges in the treatment of gram-positive and gram-negative bacteria in patients with cancer and neutropenia. Clin Infect Dis. 2005;40 suppl 4:S246–252.CrossRefPubMed
18.
Pizzo PA, Hathorn JW, Hiemenz J, et al. A randomized trial comparing ceftazidime alone with combination antibiotic therapy in cancer patients with fever and neutropenia. N Engl J Med. 1986;315:552–8.CrossRefPubMed
19.
Paul M, Soares-Weiser K, Grozinsky S, Leibovici L. Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropaenia. Cochrane Database Syst Rev. 2003;(3):CD003038.
20.
Vardakas KZ, Samonis G, Chrysanthopoulou SA, et al. Role of glycopeptides as part of initial empirical treatment of febrile neutropenic patients: a meta-analysis of randomized controlled trials. Lancet Infect Dis. 2005;5(7):431–9.CrossRefPubMed
21.•
Paul M, Dickstein Y, Borok S, et al. Empirical antibiotics targeting gram-positive bacteria for the treatment of febrile neutropenic with cancer. Cochrane Database Syst Rev. 2014;1:CD003914. This systematic review finds that the addition of empiric antibiotics that target gram-positive bacterial pathogens does not result in improved survival rates in febrile neutropenic patients when compared to antibacterial regimens that initiate coverage of these pathogens only after their presence are documented by bacterial cultures.PubMed
22.
Bow EJ. Neutropenic fever syndromes in patients undergoing cytotoxic therapy for acute leukemia and myelodysplastic syndromes. Semin Hematol. 2009;46:259–68.CrossRefPubMed
23.
Kuderer NM, Dale DC, Crawford J, et al. Mortality, morbidity and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106:2258–226.CrossRefPubMed
24.
25.•
Opal SM, van der Poll T. Endothelial barrier dysfunction in septic shock. J Intern Med. 2014. doi:10.​1111.​/​joim.​12331. This basic review details the nature of the endothelial barrier in the microcirculation and the factors that disupt the barrier function in septic shock. New molecular targets have been recently identified that might offer new treatment options for immunocompromised patients with septic shock.
26.
Skvarc M, Stubjar D, Rogina P, Kaasch AJ. Non-culture-based methods to diagnose bloodstream infections: does it work? Eur J Microbiol Immunol. 2013;3(2):97–104.CrossRef
27.
Yahav D, Paul M, Fraser A, et al. Efficacy and safety of cefepime: a systematic review and meta-analysis. Lancet Infect Dis. 2007;7:338–48.CrossRefPubMed
28.
Kim PM, Wu YT, Cooper C, et al. Meta-analysis of a possible signal of increased mortality associated with cefepime use. Clin Infect Dis. 2010;51:381–9.CrossRefPubMed
29.
Kalil AC. Is cefepime safe for clinical use? A Bayesian viewpoint. J Antimicrob Chemother. 2011;66:1207–9.CrossRefPubMed
30.
Carlet J, Cohen J, Calandra T, Opal SM, Masur H. Sepsis, time to reconsider the concept. Crit Care Med. 2008;36(3):964–7.CrossRefPubMed
31.
Vincent J-L, Opal SM, Marshall JC, Tracey KJ. Sepsis definitions: time for change. Lancet. 2013;381:774–5.CrossRefPubMed
32.•
Opal SM, Dellinger RP, Vincent J-L, Masur H, Angus DC. The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C? Crit Care Med. 2014;42:1714–21. This clinical review discusses the difficulties encountered in the study of new anti-sepsis drugs in clinical trials and offers some suggestions on how to improve future clinical trials.CrossRefPubMed
33.••
Deutchman CS, Tracey KJ. Sepsis: current dogma and new perspectives. Immunity. 2014;40:463–75. This is an excellent review of the current understanding of the molecular mechanisms that result in septic shock and offers some new ways to address the problem from a mechanistic perspective.CrossRef
34.•
Gomez H, Ince C, DeBacker D, Pickkers P, Payen D, Hotchkiss J, et al. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock. 2014;41(1):3–11. This basic review argues that the problem of sepsis at the cellular level is that cells functionallly loose their ability to maintain their specialized functions in tissues and retreat into a de-differentiated state for individual cell survival.CrossRefPubMedCentralPubMed
35.•
Mehta D, Ravindran K, Kuebler W. Novel regulators of endothelial barrier function. Am J Physiol Lung Cell Mol Physiol. 2014;307:L924–35. This paper reviews the structure and function of intercellular gap junctions between endothelial cells in health and disease.CrossRefPubMed
36.
Kumar A, Paladugu B, Haery C, et al. Timing of antibiotic administration in relation to duration of shock is a critical determinant of survival in a murine model of E. coli sepsis: association with serum lactate and inflammatory cytokines. J Infect Dis. 2006;193:251–8.CrossRefPubMed
37.
38.•
Chahin A, Opal S, Zorzopulos J, et al. The novel immunotherapeutic oligodeoxynucleotide IMT504 protects neutropenic animals from fatal Pseudomonas aeruginosa bacteremia and sepsis. Antimicrob Agents Chemother. 2015;59(2):1225–9. This experimental study demonstrates that specific short sequences of oligonucleotides can function as immunostimulants and improve the prognosis of experimental animals with febrile neutropenic systemic infections. Whether this strategy will work in neutropenic sepsis remains to be tested in clinical trials.CrossRefPubMed
39.
Kalil AC, Dakroub H, Freifeld AG. Sepsis and solid organ transplantation. Curr Drug Targets. 2007;8(4):533–41.CrossRefPubMed
40.
Trzeciak S, Sharer R, Piper D, et al. Infections and severe sepsis in solid-organ transplant patients admitted from a university-based ED. The Am J Emergency Med. 2004;22(7):530–3.CrossRef
41.
Hsu RB, Chang CI, Fang CT, Chang SC, Wang SS, Chu SH. Bloodstream infection in heart transplant recipients: 12-year experience at a university hospital in Taiwan. Euro J Cardio-Thoracic Surg. 2011;40(6):1362–7.
42.
Candel FJ, Grima E, Matesanz M, et al. Bacteremia and septic shock after solid-organ transplantation. Transplantation Proc. 2005;37(9):4097–9.CrossRef
43.
Wan Q, Ye Q, Zhou J. Mortality predictors of bloodstream infections in solid-organ transplant recipients. Exp Clin Trans. 2013;11(3):211–4.CrossRef
44.
Bodro M, Sabe N, Tubau F, et al. Risk factors and outcomes of bacteremia caused by drug-resistant ESKAPE pathogens in solid-organ transplant recipients. Transplantation. 2013;96(9):843–9. This study analyzed a cohort of solid organ transplant patients who developed bacteremia with ESKAPE organisms and concluded that the following factors were independently associated with ESKAPE infection: prior transplantation, septic shock, and prior antibiotic therapy.CrossRefPubMed
45.
Linares L, Garcia-Goez JF, Cervera C, Almela M, Sanclemente G, Cofan F, et al. Early bacteremia after solid organ transplantation. Trans Proc. 2009;41(6):2262–4.CrossRef
46.
Malinis MF, Mawhorter SD, Jain A, Shrestha NK, Avery RK, van Duin D. Staphylococcus aureus bacteremia in solid organ transplant recipients: evidence for improved survival when compared with nontransplant patients. Transplantation. 2012;93(10):1045–50.CrossRefPubMed
47.
48.
van Hal SJ, Marriott DJ, Chen SC, Nguyen Q, Sorrell TC, Ellis DH, et al. Candidemia following solid organ transplantation in the era of antifungal prophylaxis: the Australian experience. Trans Infect Dis. 2009;11(2):122–7.CrossRef
49.
Kalil AC, Levitsky J, Lyden E, Stoner J, Freifeld AG. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med. 2005;143(12):870–80.CrossRefPubMed
50.
Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers. Clin Trans. 2005;19(2):230–5.CrossRef
51.
Schmaldienst S, Dittrich E, Horl WH. Urinary tract infections after renal transplantation. Curr Opin Urol. 2002;12(2):125–30.CrossRefPubMed
52.
Wagener MM, Yu VL. Bacteremia in transplant recipients: a prospective study of demographics, etiologic agents, risk factors, and outcomes. Am J Infect Control. 1992;20(5):239–47.CrossRefPubMed
53.
Warren JW, Platt R, Thomas RJ, Rosner B, Kass EH. Antibiotic irrigation and catheter-associated urinary-tract infections. N Engl J Med. 1978;299(11):570–3.CrossRefPubMed
54.
Koneru B, Selby R, O’Hair DP, Tzakis AG, Hakala TR, Starzl TE. Nonobstructing colonic dilatation and colon perforations following renal transplantation. Arch Surg. 1990;125(5):610–3.CrossRefPubMedCentralPubMed
55.
Andreoni KA, Pelletier RP, Elkhammas EA, et al. Increased incidence of gastrointestinal surgical complications in renal transplant recipients with polycystic kidney disease. Transplantation. 1999;67(2):262–6.CrossRefPubMed
56.
Dominguez Fernandez E, Albrecht KH, et al. Prevalence of diverticulosis and incidence of bowel perforation after kidney transplantation in patients with polycystic kidney disease. Transpl Int. 1998;11(1):28–31.CrossRefPubMed
57.
Abbott KC, Oliver 3rd JD, Hypolite I, et al. Hospitalizations for bacterial septicemia after renal transplantation in the United States. Am J Nephrol. 2001;21(2):120–7.CrossRefPubMed
58.
59.
George DL, Arnow PM, Fox AS, et al. Bacterial infection as a complication of liver transplantation: epidemiology and risk factors. Rev Infect Dis. 1991;13(3):387–96.CrossRefPubMed
60.
Koivusalo A, Isoniemi H, Salmela K, Hockerstedt K. Biliary complications in 100 adult liver transplantations: a retrospective clinical study. Transpl Int. 1994;7 Suppl 1:S119–20.CrossRefPubMed
61.
Collins LA, Samore MH, Roberts MS, Luzzati R, Jenkins RL, Lewis WD, et al. Risk factors for invasive fungal infections complicating orthotopic liver transplantation. J Infect Dis. 1994;170(3):644–52.CrossRefPubMed
62.
Paya CV, Hermans PE, Washington 2nd JA, et al. Incidence, distribution, and outcome of episodes of infection in 100 orthotopic liver transplantations. Mayo Clinic Proc. 1989;64(5):555–64.CrossRef
63.
64.
Newell KA, Millis JM, Arnow PM, et al. Incidence and outcome of infection by vancomycin-resistant Enterococcus following orthotopic liver transplantation. Transplantation. 1998;65(3):439–42.CrossRefPubMed
65.
Tachopoulou OA, Vogt DP, Henderson JM, Baker M, Keys TF. Hepatic abscess after liver transplantation: 1990-2000. Transplantation. 2003;75(1):79–83.CrossRefPubMed
66.•
Hsu JL, Enser JJ, McKown T, et al. Outcomes of Clostridium difficile infection in recipients of solid abdominal organ transplants. Clin Trans. 2014;28(2):267–73. This study evaluated solid organ transplant patients who developed Clostridium difficile infection and found that the risk factors for clinical failure at 14 days were vasopressor support, previous Clostridium difficile infection, and treatment with vancomycin. Three-quarters of all transplant patients were clinically cured at 14 days.CrossRef
67.
Tsapepas DS, Martin ST, Miao J, et al. Clostridium difficile infection, a descriptive analysis of solid organ transplant recipients at a single center. Diagn Microbiol Infect Dis. 2014;80(4):239–344
68.
Corensek MJ, Stewart RW, Keys TF, Mehta AC, McHenry MC, Goormastic M. A multivariate analysis of risk factors for pneumonia following cardiac transplantation. Transplantation. 1988;46(6):860–5.CrossRefPubMed
69.
Cisneros JM, Munoz P, Torre-Cisneros J, et al. Pneumonia after heart transplantation: a multi-institutional study. Spanish Transplantation Infection Study Group. Clin Infect Dis. 1998;27(2):324–31.CrossRefPubMed
70.
Myers TJ, Khan T, Frazier OH. Infectious complications associated with ventricular assist systems. ASAIO J. 2000;46(6):S28–36.CrossRefPubMed
71.
Montoya JG, Giraldo LF, Efron B, et al. Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center. Clin Infect Dis. 2001;33(5):629–40.CrossRefPubMed
72.
Hofflin JM, Potasman I, Baldwin JC, Oyer PE, Stinson EB, Remington JS. Infectious complications in heart transplant recipients receiving cyclosporine and corticosteroids. Ann Intern Med. 1987;106(2):209–16.CrossRefPubMed
73.
Horvath J, Dummer S, Loyd J, Walker B, Merrill WH, Frist WH. Infection in the transplanted and native lung after single lung transplantation. Chest. 1993;104(3):681–5.CrossRefPubMed
74.
Kramer MR, Marshall SE, Starnes VA, Gamberg P, Amitai Z, Theodore J. Infectious complications in heart-lung transplantation. Analysis of 200 episodes. Arch Intern Med. 1993;153(17):2010–6.CrossRefPubMed
75.
Maurer JR, Tullis DE, Grossman RF, Vellend H, Winton TL, Patterson GA. Infectious complications following isolated lung transplantation. Chest. 1992;101(4):1056–9.CrossRefPubMed
76.
Hadjiliadis D, Sporn TA, Perfect JR, Tapson VF, Davis RD, Palmer SM. Outcome of lung transplantation in patients with mycetomas. Chest. 2002;121(1):128–34.CrossRefPubMed
77.
Smith PC, Slaughter MS, Petty MG, Shumway SJ, Kshettry VR, Bolman RM, 3rd. Abdominal complications after lung transplantation. J Heart Lung Transplantation 1995;14:44–51
78.
Venuta F, Boehler A, Rendina EA, et al. Complications in the native lung after single lung transplantation. Euro J Cardio-Thoracic Surg. 1999;16(1):54–8.CrossRef
79.
Stewart S, McNeil K, Nashef SA, Wells FC, Higenbottam TW, Wallwork J. Audit of referral and explant diagnoses in lung transplantation: a pathologic study of lungs removed for parenchymal disease. J Heart Lung Trans. 1995;14(6 Pt 1):1173–86.
Metadata
Title
Sepsis in the Severely Immunocompromised Patient
Authors
Andre C. Kalil
Steven M. Opal
Publication date
01-06-2015
Publisher
Springer US
Published in
Current Infectious Disease Reports / Issue 6/2015
Print ISSN: 1523-3847
Electronic ISSN: 1534-3146
DOI
https://doi.org/10.1007/s11908-015-0487-4

Other articles of this Issue 6/2015

Current Infectious Disease Reports 6/2015 Go to the issue

Genitourinary Infections (J Sobel, Section Editor)

Vulvovaginal Candidiasis in Pregnancy

Intra-abdominal Infections, Hepatitis, and Gastroenteritis (T Steiner, Section Editor)

Epidemiology and Treatment of Trichomoniasis

Transplant and Oncology (M Ison and N Theodoropoulos, Section Editors)

The Swiss Transplant Cohort Study: Lessons from the First 6 Years

Genitourinary Infections (J Sobel, Section Editor)

The Role of PCR in the Diagnosis of Candida Vulvovaginitis—a New Gold Standard?

Healthcare Associated Infections (G Bearman and D Morgan, Section Editors)

The Pros, Cons, and Unknowns of Search and Destroy for Carbapenem-Resistant Enterobacteriaceae

Central Nervous System Infections (J Lyons, Section Editor)

HIV-associated Neurocognitive Disorders and Antiretroviral Therapy: Current Concepts and Controversies
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits