Slideshow presentation of the causes of sepsis in the immunocompromised patient, its diagnosis and treatment by the multi disciplinary team

1. Immunocompromised PatientImmunocompromised Patient
with Sepsiswith Sepsis

2. What is ImmunodeficiencyWhat is Immunodeficiency
Immunodeficiency is a state in which the hosts immuneImmunodeficiency is a state in which the hosts immune
system is compromised to various degrees of severitysystem is compromised to various degrees of severity
A primary immunodeficiency is a congenital immuneA primary immunodeficiency is a congenital immune
system malfunctionsystem malfunction
AA secondary immunodeficiency is acquired viasecondary immunodeficiency is acquired via
-medications (immunosuppressants, glucocorticoids)-medications (immunosuppressants, glucocorticoids)
-malnutrition-malnutrition
-aging-aging
-malignancy-malignancy
-and/or chronic infection such as HIV-and/or chronic infection such as HIV

3. TreatmentTreatment
Knowledge of the spectrum of potential pathogensKnowledge of the spectrum of potential pathogens
patients has grown as a result of amplifiedpatients has grown as a result of amplified
immunosupppression, extended lifetime survival andimmunosupppression, extended lifetime survival and
enhanced diagnostic assaysenhanced diagnostic assays
The immunocompromised state may not alter theThe immunocompromised state may not alter the
management of the physiologic and hemodynamicmanagement of the physiologic and hemodynamic
derangements of severe sepsis or septic shock (i.e. fluidderangements of severe sepsis or septic shock (i.e. fluid
resuscitation, vasopressors, mechanical ventilation),resuscitation, vasopressors, mechanical ventilation),

4. Non-obvious causesNon-obvious causes
Immunocompromised patients requireImmunocompromised patients require
consideration in regard to antibacterial,consideration in regard to antibacterial,
antiviral and antifungal therapyantiviral and antifungal therapy
They have increased susceptibility toThey have increased susceptibility to
infections with organisms of little nativeinfections with organisms of little native
virulence in normal individualsvirulence in normal individuals

5. Differential diagnosis of potentialDifferential diagnosis of potential
infectionsinfections
Potential infections in the immunocompromised host is broad and may includePotential infections in the immunocompromised host is broad and may include
1.1. Encapsulated bacteria (i.e.Encapsulated bacteria (i.e. Strep. pneumoniaStrep. pneumonia,, Klebsiella pneumonia,)Klebsiella pneumonia,) areare
of great concern with underlying induced humoral immunodeficiency withof great concern with underlying induced humoral immunodeficiency with
accompanying diminished opsonizing capacityaccompanying diminished opsonizing capacity (molecule that enhances(molecule that enhances
phagocytosis by marking an antigen for an immune response)phagocytosis by marking an antigen for an immune response)
2.2. NocardiaNocardia andand StaphylococcusStaphylococcus infections are more common in patientsinfections are more common in patients
with neutrophil dysfunctions and neutropeniawith neutrophil dysfunctions and neutropenia
3.3. Intracellular bacteria- MycobacteriaIntracellular bacteria- Mycobacteria LegionellaLegionella
4.4. Yeast – CryptococcusYeast – Cryptococcus
5.5. Mold –Mold – AspergillusAspergillus
6.6. Viral – Cytomegalovirus (CMV), InfluenzaViral – Cytomegalovirus (CMV), Influenza
7.7. Parasitic –Parasitic – ToxoplasmaToxoplasma

6. Infectious Work-up In All SepticInfectious Work-up In All Septic
PatientsPatients
The Sepsis Six are:The Sepsis Six are:
– Administer high flow oxygen.Administer high flow oxygen.
– Take blood culturesTake blood cultures
– Give broad spectrum antibioticsGive broad spectrum antibiotics
– Give intravenous fluid challengesGive intravenous fluid challenges
– Measure serum lactate and haemoglobinMeasure serum lactate and haemoglobin
– Measure accurate hourly urine outputMeasure accurate hourly urine output
Aggressive and timely efforts to identify and control ofAggressive and timely efforts to identify and control of
the source of infectionthe source of infection
Therapy should be implemented without delayTherapy should be implemented without delay
At least two sets of aerobic and anaerobic blood culturesAt least two sets of aerobic and anaerobic blood cultures
should be obtainedshould be obtained

7. Infectious Work-up InInfectious Work-up In
Immunocompromised SepticImmunocompromised Septic
PatientsPatientsShould have additional diagnostic tests consideredShould have additional diagnostic tests considered
Keep in mind that multiple simultaneous infectious processes mayKeep in mind that multiple simultaneous infectious processes may
occur concurrentlyoccur concurrently
Bronchoscopy with biopsy are often necessary to establish aBronchoscopy with biopsy are often necessary to establish a
microbiologic diagnosismicrobiologic diagnosis
Blood cultures may also be sent for fungus and acid-fast bacilliBlood cultures may also be sent for fungus and acid-fast bacilli
Immunohistology and quantitative molecular assays, are oftenImmunohistology and quantitative molecular assays, are often
needed to establish a diagnosisneeded to establish a diagnosis
Serologic testing may demonstrate immunoglobulin-G antibodiesSerologic testing may demonstrate immunoglobulin-G antibodies
consistent with prior exposure (i.e. Strongyloides, Toxoplasma)consistent with prior exposure (i.e. Strongyloides, Toxoplasma)
A tuberculin skin test response greater than 5 mm is consideredA tuberculin skin test response greater than 5 mm is considered
positive in immunocompromised patientspositive in immunocompromised patients
Opportunistic infections should be suspected in patients notOpportunistic infections should be suspected in patients not
receiving prophylaxis (i.e.receiving prophylaxis (i.e. Pneumocystis, Mycobacterium, CMVPneumocystis, Mycobacterium, CMV))

8. Antimicrobial Therapy inAntimicrobial Therapy in
Immunocompromised PatientsImmunocompromised Patients
Typically require longer duration of therapyTypically require longer duration of therapy
Daily reassessment of antimicrobial therapy in order to de-escalateDaily reassessment of antimicrobial therapy in order to de-escalate
to the most appropriate therapyto the most appropriate therapy
Antiviral therapy should be initiated as early as possible in patientsAntiviral therapy should be initiated as early as possible in patients
with suspected viral originwith suspected viral origin
If getting chemotherapy via access port, the intravascular deviceIf getting chemotherapy via access port, the intravascular device
should be removed promptly if no other possible source isshould be removed promptly if no other possible source is
suspectedsuspected
Use of intravenous immunoglobulin (IVIg), while theoreticallyUse of intravenous immunoglobulin (IVIg), while theoretically
appealing, has not yet been proven to be clinically effectiveappealing, has not yet been proven to be clinically effective
IVIg possesses potent antimicrobial activity, immunomodulatoryIVIg possesses potent antimicrobial activity, immunomodulatory
effects and a well-documented safety profile, but its benefit,effects and a well-documented safety profile, but its benefit,
restricted supply, cost and limited experience in septic shockrestricted supply, cost and limited experience in septic shock
patients has limited its routine use in clinical practicepatients has limited its routine use in clinical practice

9. Neutropaenic PatientNeutropaenic Patient
Patients with haematological malignancies arePatients with haematological malignancies are
immunocompromised because of both theimmunocompromised because of both the
underlying malignancy and the therapyunderlying malignancy and the therapy
employed to manage itemployed to manage it
Neutrophils are thought to be essential for theNeutrophils are thought to be essential for the
eradication of pathogens, but can cause tissueeradication of pathogens, but can cause tissue
injury due to the excessive release of oxidantsinjury due to the excessive release of oxidants
and proteasesand proteases
Neutropenia acts as a common risk factor forNeutropenia acts as a common risk factor for
severe bacterial infectionssevere bacterial infections
This enables the infection to progress in a moreThis enables the infection to progress in a more
insidious and aggressive wayinsidious and aggressive way

10. Neutropaenic PatientNeutropaenic Patient
Neutropenia alters the host’s inflammatory response andNeutropenia alters the host’s inflammatory response and
makes the infection difficult to detect because the classicmakes the infection difficult to detect because the classic
signs and symptoms of infection are often missingsigns and symptoms of infection are often missing
Fever is the principal sign of infection, and it is often theFever is the principal sign of infection, and it is often the
only evidence of infection in neutropenic patientsonly evidence of infection in neutropenic patients
The prompt initiation of antibiotics has been the mostThe prompt initiation of antibiotics has been the most
important advance in the treatment of febrile neutropenicimportant advance in the treatment of febrile neutropenic
patients – prior to this the mortality from gram-vepatients – prior to this the mortality from gram-ve
infections was as high as 80%infections was as high as 80%
Today the overall survival rate for febrile neutropenicToday the overall survival rate for febrile neutropenic
patients is over 90%patients is over 90%

11. Acute Myeloid LeukaemiaAcute Myeloid Leukaemia
The treatment protocol of AML induces longThe treatment protocol of AML induces long
lasting periods of neutropenia, whichlasting periods of neutropenia, which
predisposes patients to recurring infectionspredisposes patients to recurring infections
Infections are the major cause of morbidity andInfections are the major cause of morbidity and
mortality in patients with AMLmortality in patients with AML
The infectious mortality during AML treatmentThe infectious mortality during AML treatment
ranges between 5.5 -13%ranges between 5.5 -13%
Initial source of infection often remains unknownInitial source of infection often remains unknown
Therapy is directed primarily against gram -veTherapy is directed primarily against gram -ve
microbes.microbes.

12. HIVHIV
Acute respiratory failure accounts for about 50% ofAcute respiratory failure accounts for about 50% of
patient sepsispatient sepsis
Given the improvement in immunity as a result of highlyGiven the improvement in immunity as a result of highly
retroactive antiretroviral therapy (HAART), the outcomeretroactive antiretroviral therapy (HAART), the outcome
of critical illness in HIV patients is shifting and becomingof critical illness in HIV patients is shifting and becoming
increasingly similar to those seen in immunocompetentincreasingly similar to those seen in immunocompetent
hostshosts
Pneumocystic jeroveciPneumocystic jeroveci pneumonia (PCP), although stillpneumonia (PCP), although still
the most common pathogen responsible for acutethe most common pathogen responsible for acute
respiratory failure, has been less prevalent due to therespiratory failure, has been less prevalent due to the
effect of HAARTeffect of HAART
HIV increases the risk of mortality to approximately 25-HIV increases the risk of mortality to approximately 25-
68%, the majority secondary to respiratory failure from68%, the majority secondary to respiratory failure from
PCP.PCP.

13. HIVHIV
Special consideration should be given to:-Special consideration should be given to:-
Patients CD4 countPatients CD4 count
Prophylactic antibiotics (potential for drug-Prophylactic antibiotics (potential for drug-
resistance)resistance)
Lifestyle risk factors (i.e. intravenous drug useLifestyle risk factors (i.e. intravenous drug use
resulting in endemic fungal or mycobacterialresulting in endemic fungal or mycobacterial
infection)infection)
Possible drug-interactions with HAART (i.e. non-Possible drug-interactions with HAART (i.e. non-
nucleoside reverse transcriptase inhibitorsnucleoside reverse transcriptase inhibitors
interacting with azoles and macrolides)interacting with azoles and macrolides)

14. Stem Cell TransplantStem Cell Transplant
Secondary immunodeficiency can cause aSecondary immunodeficiency can cause a
variety of infectious and non-infectiousvariety of infectious and non-infectious
complications that may require ICU carecomplications that may require ICU care
The post-transplant period is divided into threeThe post-transplant period is divided into three
phases, each of which can cause uniquephases, each of which can cause unique
complications much different from othercomplications much different from other
immuno-deficiencies:immuno-deficiencies:
1.1. Pre-engraftment (onset of conditioning therapyPre-engraftment (onset of conditioning therapy
to 30 days),to 30 days),
2.2. Early post-engraftment (30-100 days)Early post-engraftment (30-100 days)
3.3. Late post-engraftment (>100 days)Late post-engraftment (>100 days)

15. Pre-engraftment PeriodPre-engraftment Period
Includes neutropenia and mucositis, leading to dehydration fromIncludes neutropenia and mucositis, leading to dehydration from
poor oral intake, airway compromise and gastrointestinal bleedingpoor oral intake, airway compromise and gastrointestinal bleeding
Bacterial infections are common during this time of profoundBacterial infections are common during this time of profound
neutropenia and lymphopenianeutropenia and lymphopenia
Despite prophylactic therapy, 5-55% of HSCT recipients still requireDespite prophylactic therapy, 5-55% of HSCT recipients still require
intensive careintensive care
Opportunistic infections includeOpportunistic infections include
Gram +ve bacteremia (20-30%),Gram +ve bacteremia (20-30%),
Facultative gram -ve bacteria (5-10%),Facultative gram -ve bacteria (5-10%),
HerpesHerpes simplex virus (5-9%),simplex virus (5-9%),
Candida sppCandida spp. (<5%) and. (<5%) and Aspergillus sppAspergillus spp. (<5%). (<5%)
Hemodynamic instability is also complicated by multi-organ failure inHemodynamic instability is also complicated by multi-organ failure in
22-81% and death in 65% of HSCT recipients in ICU care22-81% and death in 65% of HSCT recipients in ICU care

16. Solid Organ TransplantSolid Organ Transplant
Infections are most common and most diverse during the first 6-9 months ofInfections are most common and most diverse during the first 6-9 months of
transplantation due to graft rejection, nosocomial infections and/ortransplantation due to graft rejection, nosocomial infections and/or
immunosuppressive drugsimmunosuppressive drugs
Factors that contribute to infection after SOT includeFactors that contribute to infection after SOT include
-pre-transplantation host factors-pre-transplantation host factors
(co-morbidities, medications, lack of immunity,(co-morbidities, medications, lack of immunity,
prior colonization, effective pre-transplantation screening),prior colonization, effective pre-transplantation screening),
-transplantation factors-transplantation factors
(type of SOT, time spent in surgery, surgical complications),(type of SOT, time spent in surgery, surgical complications),
-immunosuppression and allograft reactions-immunosuppression and allograft reactions
(graft-versus-host or host-versus-graft reaction)(graft-versus-host or host-versus-graft reaction)
Immunosuppressive agents may need to be reduced or discontinuedImmunosuppressive agents may need to be reduced or discontinued
depending on the active infection, drug-interaction(s) and possible drugdepending on the active infection, drug-interaction(s) and possible drug
adversitiesadversities

17. ConclusionConclusion
Regardless of the immune status, sepsis isRegardless of the immune status, sepsis is
associated with increased morbidity andassociated with increased morbidity and
mortalitymortality
Surviving Sepsis Campaign does not addressSurviving Sepsis Campaign does not address
several additional conditions faced in patientsseveral additional conditions faced in patients
with immunocompromised stateswith immunocompromised states
Keep in mind the likelihood of infection withKeep in mind the likelihood of infection with
ordinarily less virulent organisms when dealingordinarily less virulent organisms when dealing
with patients of immunocompromised stateswith patients of immunocompromised states