Infection Sherrill Brown MD Assistant Clinical Professor Division of Infectious Diseases UC Davis Medical Center 9818 Disclosures None Goals for Discussion Discuss the mechanisms that make Sickle Cell patients more susceptible to infections ID: 931965
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Slide1
Sickle Cell Disease and Infection
Sherrill Brown, M.D.
Assistant Clinical Professor
Division of Infectious Diseases
UC Davis Medical Center
9/8/18
Slide2Disclosures
None
Slide3Goals for Discussion
Discuss the mechanisms that make Sickle Cell patients more susceptible to infections.
Review Common Infectious Complications in Sickle Cell Anemia
Diagnostic and Management Guidance for these Infections
Discuss Preventative Strategies
Slide4Infection is a major cause of morbidity and mortality for sickle cell patients. Worldwide, infections are the leading cause of death in sickle cell patients.
In developed nations, such as the US, measures to prevent and effectively treat sickle cell disease and infection have led to a longer and better quality of life for our patients.
Sickling of cells can be precipitated by many factors including dehydration, hypoxia, cold, dehydration as well as adhesion molecules and cytokines associated with infections.
Slide5Why are sickle cell patients more susceptible to infection?
Sickle Gene
causing abnormal red blood cells causes
an increased susceptibility to infection
Splenic Dysfunction
Acute and Chronic Inflammation and Ischemia Causing Organ Damage
Higher Risk for Healthcare
R
elated Infections
Slide6Normal Splenic Function
Functions as a filter for damaged cells and micro-organisms in the blood.
Produces antibodies to fight infection.
Participates
in complement activation.
Encapsulated bacteria are poorly opsonized by complement proteins and can only be effectively cleared by the spleen.
Streptococcus pneumoniae,
Haemophilus
influenzae, Neisseria meningitidis and Salmonella species
Slide7Splenic Dysfunction- 6mo to 3 yrs of age
The sluggish circulation through the spleen, high rates of O2 extraction and local acidosis promotes sickling which leads to blockage and diversion of blood through shunts.
Bypassing the normal filtering mechanisms.
Macrophages responsible for engulfing abnormal cells and microorganisms get blocked with sickled cells and cannot function properly.
Repeated episodes of this over time, leads to infarcts/death of spleen tissue.
Auto-splenectomy
Lack of IgM memory B cells
Cannot mount a rapid response to encapsulated organisms.
Overwhelming sepsis can develop quickly, especially in younger individuals.
Slide8Chronic end organ damage.Bone marrow is expanded to create more RBCs, high O2 demand and blood flow is sluggish.
Sickling
Vaso-occlusion
and Infarction of
BoneDamaged
bone at high risk of
infectionOsteomyelitis
Patchy ischemia and infarction in bowel can lead to chronic intermittent translocation of gut bacteria.
Chronic microvascular disease is associated with increased risk for severe respiratory infection>Acute Chest Syndrome
Slide9Healthcare Associated Infections
Frequent transfusions with unsafe blood products in less regulated countries leads to increased risk of blood borne infection.
HIV,
Hep
B,
Hep
C, CMV, Parvovirus B19
Frequent use of prolonged central catheters leads to increased risk of Central Line Associated Bloodstream Infection
Increased pain medication requirements
respiratory depression and inactivitypneumonia, bed sores and ulcers, decreased cardiac stamina
Slide10Infections may also precipitate Vaso-occlusion.
Increased neutrophil counts correlate with the severity of SCD.
Patients with severe SCD have increased expression of leukocyte adhesion molecules suggesting a role for leukocytes in the
vaso
-occlusive process.
Slide11Slide12Encapsulated BacteriaStreptococcus pneumoniae
Haemophilus
influenzae
Neisseria
meningitidis
Salmonella species
Dysfunctions in splenic sequestration of these bacteria lead to severe infections
Meningitis, Bacteremia, Pneumonia, Osteomyelitis
Slide13OsteomyelitisNecrotic and damaged bone is at risk of infection especially from Salmonella species.
Slide14Encapsulated Bacteria Diagnosis/TreatmentDiagnosis
Blood culture prior to antimicrobials
CSF studies and culture if suspicious for meningitis
Strep pneumoniae urine antigen
MRI and Bone biopsy with path and culture if evidence of osteomyelitis
Prompt Anti-
bacterials
directed at common pathogens
Slide15Encapsulated Bacteria Prevention
Routine childhood immunizations including additional scheduled Streptococcus pneumoniae, Neisseria
meningitidis
vaccines
Annual Flu shot
Oral Penicillin prophylaxis twice daily for children 3months-5yrs
Frequent handwashing
Washing fruits/vegetables including lettuce thoroughly, avoid cross contamination of meats with food especially chicken and eggs.
Cook meats thoroughly.
Slide16https://www.cdc.gov/vaccines/schedules
/
Haemophilus
influenzae
Pneumococcal conjugate and polysaccharide
Meningococcal ACWY, B Vaccine
Important to protect from encapsulated bacteria.
Additional vaccine doses recommended for Pneumococcal and Meningococcal vaccines.
Vaccines
Slide17PROPS Trial 1986
Slide18Parvovirus B19Infectious Prior to Rash and usually transmitted through Respiratory Droplet route.
Usually mild and self-limiting infection.
Erythema
infectiosum
“Fifth disease”, “slapped cheeks”
Non-specific viral illness
Post infectious
arthropathy
More severe infections.
Infects erythroid progenitor cells->temporary cessation of erythropoiesis->Pure red cell aplasiaIn pregnancy, novel infection hydrops
fetalis
, stillbirth, and spontaneous abortion.
Slide19Parvovirus B19 and Sickle CellSickle patients with chronic anemia due to decreased RBC lifespan depending on increased erythropoiesis to maintain baseline Hemoglobin.
Infection leads to cessation of erythropoiesis for 7-10 days
Leads to aplastic crisis, severe anemia and vascular collapse in severe infection
.
Requires prompt identification, droplet isolation, blood transfusion until erythropoiesis can resume again.
Transient aplastic crisis in 65-80% of infections in Sickle cell disease.
Slide20Parvovirus Diagnosis/TreatmentDiagnosis: Parvovirus B19 IgM or Parvovirus PCR with clinical correlation
Treatment: supportive care, blood transfusions in Aplastic crisis
Slide21Parvovirus PreventionNo vaccine at this time.
Infection leads to lifelong protection, and infection uncommon after age 15.
Isolate infected or exposed individuals from other at risk populations (immune compromised, sickle cell patients) DROPLET precautions
Wash hands frequently and avoid people with respiratory illnesses or rash
Slide22Acute Chest Syndrome (ACS)Chest pain, SOB, fever, pulmonary infiltrates on CXR
Looks like a pneumonia
Precipitants include: pulmonary infection, fat embolism from bone infarcts, decreased respiration.
Sickling and
vaso
-occlusion in the lung lead to local ischemia and infarction.
Slide23ACS Diagnosis/TreatmentAttempt to identify underlying cause
Chest CT with contrast to
eval
for fat embolism
Respiratory viral panel, Flu testing, Streptococcus pneumoniae antigen, sputum culture if productive cough, MRSA nares screening
Supportive care and antimicrobials directed at possible infectious etiology
De-escalate antimicrobial therapy if alternative cause is identified.
Slide24ACS PreventionOptimize sickle cell treatment to avoid sickling episodes and end organ damage.
Decrease respiratory depressant medications and encourage deep breathing with incentive spirometry.
Get good ventilation and avoid sick contacts.
Wash hands frequently.
Get all routine vaccinations including annual flu shot, Strep pneumonia vaccines,
Hemophilus
influenzae
vaccine.
Slide25Yersinia enterocolitica
Gram negative coccobacilli
Transmitted by Fecal Oral route through contaminated hands, food, water
Causes diarrhea and can cause abdominal lymph node swelling and blood stream infection.
“pseudo-appendicitis”, RLQ abdominal pain, rectal bleeding,
ileal
perforation.
Can also cause pharyngitis and erythema
nodosum
. Disease more common in iron overload syndromes such as in Sickle Cell Disease. HLA-B27 a risk factor for reactive arthritis
Slide26Y. enterocolitica Diagnosis/Treatment
Blood Culture
Stool Culture
Pharyngeal Culture
Lymph node biopsy
Treatment indicated in those that are severely ill.
Ciprofloxacin, TMP/SMX, or Doxycycline for about 5 days
Ceftriaxone +
Genamicin
in severe sepsis
Slide27Y. enterocolitica Prevention
Eat food that has been prepared using hygienic precautions.
Avoid raw or undercooked meat and seafood (tripe, chitterlings)
Wash fruits and vegetables carefully.
Drink purified water.
Wash hands with soap and water.
Screen blood bank donors for acute symptoms of infection.
Slide28Healthcare Associated Infections (HAIs)Hospital Acquired Pneumonia
Central Line Associated Blood Stream Infections
Catheter Associated Urinary Tract Infections
Clostridium difficile Colitis
Antibiotic Resistant Bacterial Infections
Spread of Infections from Healthcare Workers or Patients to other Patients.
Slide29Hospital Acquired PneumoniaPneumonia acquired and diagnosed 2 or more days after admission to a hospital.
Higher risk of antibiotic resistant organisms as cause including MRSA or Pseudomonas.
Necessitates broader spectrum
antibiotics to start.
Prolongs hospitalizations and increases risk of needing additional procedures.
Slide30Central Line Associated Bloodstream Infections
Central lines often needed due to poor venous access, exchange transfusions,
and long
term IV therapy in sickle cell patients.
Central lines include: ports, tunneled catheters, dialysis catheters and PICC lines
The longer a central line is in
place, the higher
the
risk
of bloodstream infection developing.Can lead to repeat line procedures, endocarditis and seeding infection to additional organs in the body (brain, lungs, kidneys, bones)
Requires initiation of broad spectrum antibiotics to treat.
Slide31Catheter Associated Urinary Tract InfectionUrinary Tract Infection in the setting of Indwelling
Urinary catheter
The longer
the catheter
is used, the higher the risk of developing infection.
May be caused by drug resistant bacteria.
Can lead to pyelonephritis, blood stream
infections
and more severe illness.
Slide32Clostridium difficile ColitisInfectious Diarrhea infecting the colon caused by Clostridium difficile
Usually acquired after antibiotics use and spread from person to person on hands and surfaces.
Sickle cell patients at higher risk given increased risk for admission and antibiotics use.
Slide33Prevention of Infection at Home
Avoid
sick
contacts
.
Clean and prepare food carefully to avoid contamination.
Cook meats fully.
Stay hydrated with water and low sugar low caffeine beverages.
Get plenty of rest, avoid stress and eat healthy nutritious meals.
Caretakers, families and patients must wash their hands frequently with soap and water.Take all prescribed medications regularly. Seek care quickly if patients develop fever >38.5 or respiratory symptoms.
Slide34Prevention of Infection in the Clinic
Optimize Sickle Cell therapy to avoid pain crisis requiring
hospitalization.
Get recommended vaccines to avoid infection leading to hospitalization
.
Annual flu shot
Prescribe and take Penicillin
prophylaxis to avoid Invasive Pneumococcal Disease
.
Consider vitamin including Zinc supplementation. Counsel patients on compliance with prevention strategies.Healthcare workers wash hands
frequently
with soap and water or alcohol solution.
Patients and families wash hands frequently while at clinic.
Slide35Prevention of Infection at the Hospital
Avoid
the use of central lines and indwelling Foley catheters to avoid infection.
Minimize broad spectrum antibiotics use to avoid development of resistance.
Healthcare
workers, caretakers
and patients wash hands frequently.
Frequently utilize incentive spirometry to expand lungs and limit hypoventilation.
Slide36Barriers to Prevention of Infection
Decreased understanding from families, caretakers, patients and healthcare providers about the importance of prevention including:
Hand hygiene
Meticulous preparation of foods
Avoiding sick contacts
Compliance with taking prescribed medications and vaccinations.
Many families with sickle cell disease are from socioeconomic groups with decreased access to resources such as stable housing, nutritious food, and appropriate medical care including prescriptions.
Slide37Future directions in infection prevention, diagnosis and treatment.
Further research for prevention strategies in developing countries that are cost effective and directed at endemic pathogens. (ex. malaria, parasitic infections)
Validate biomarkers that can help determine if a bacterial infection is complicating an ACS picture or febrile syndrome. (ex.
Procalcitonin
)
Curative treatments that eliminate the damage from sickle cell in the beginning.
Slide38References
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Fonebi
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Haematol
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doi
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Servey
JT,
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Booth C,
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https://
ghr.nlm.nih.gov/condition/sickle-cell-disease
https://www.cdc.gov/vaccines/schedules/