PID ANTIBIOTIC PROPHYLAXIS - PowerPoint Presentation

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PIDANTIBIOTIC PROPHYLAXIS

Dr. Anne Pita Lomole

MBCHB, MMED Pediatrics and Child health,

MSc Infectious Disease, DTMH- EA, Asthma Cert NAEP. SA

OUTLINEIntroduction

Epidemiology

Susceptible

infections per

PID

Antibiotic prophylaxis

Conclusion

Questions

General Information for patients and family

INTRODUCTIONPrimary

immuno-deficiencies

(PIDs) expose carriers to infectious risks

that

vary in their severity and presentation as a function of the underlying

pathology

Infections are a major cause of morbidity and mortality In these patients

Prevention of infections include antimicrobials, immunotherapy and immunization

EPIDEMIOLOGY

ROLE OF ANTIBIOTIC PROHYLAXISP

rimary or adjunctive therapy in PID

Evidence lacking for antibiotic use in PID’s

Most of the evidence for use has been extrapolated from what has been seen on CF, HIV and immunosuppression after transplant

From these conditions seen to decrease number of infections and decrease morbidity and mortality

Antibiotic prophylaxis is guided by common antimicrobial pathogens seen in the specific disorders

CHART FOR SUSCEPTIBLE INFECTIONS ACCORDING TO PID

TABLE 1 CONTINUED

CHRONIC GRANULOMATOUS DISEASE

Problem: Defective phagocytosis

Bacterial abscess most frequent infection

1/3 fungal,

A

spergillus

fumigatus

/

nidulans

All patients prophylaxis with CMX 25mg/kg SMX/ 5mg/kg TMP per day

Systemically

p.o

Itraconazole

100mg children, adults 200mg/day

IF gamma has been used, side effects frequent, not recommended as first line but role in treatment

SEVERE CONGENITAL NEUTROPENIAS

PROBLEM: Neutropenia <500/

ul

for months or years

Risk of bacterial infection high in congenital neutropenia less in cyclic, low in autoimmune

Mucosal infections frequent

Invasive fungal in less than 10%

Cotrimoxazole

treatment of choice/ penicillin

G-CSF efficacy demonstrated, risk of

myelodysplasia

and acute leukemia with long term use at high doses

G-CSF should be prescribed for severe infection/extensive mucosal manifestations

Also second line –moderate relapsing infection or severe infection under antibiotic prophylaxis

Antifungals (

I

traconazole

) only justified in persistent profound neutropenia despite G-CSF

COMPLEMENT FACTOR DEFICINECIESPROBLEM: Complement factors Deficient

e.g

C1,2,4

Predisposed to invasive Strep Pneumoniae and

Hib

- C3 more marked for S.

Pnuemoniae

Properdin

deficiency -fulminating infections with N

Mengitidis

, terminal complement, carrier infections with the same

Antibiotic prophylaxis with penicillin 50.000 IU/kg/day divided in 2, adults 1 million units twice daily

Only exception- terminal complement factor deficits (infections rare and of moderate severity)

Compliance an issue

Alternative IM Penicillin 2.4 million units 2-3 weekly

ASPLENIAPROBLEM: Spleen absent, congenital or acquired

Marked susceptibility to encapsulated bacteria, susceptibility to

Ehrlichia

Species,

Capnocytophaga

canimorsus

- transmitted by dog bites

Susceptible to intracellular parasites –plasmodium,

babesia

Penicillin V most frequently used, for travel antimalarials

Optimal duration after

splenectomy

debatable- mean of 2 years in adults, 5 years for children

For those with underlying PID life long prophylaxis recommended

If adherence poor- regular,

IM injections of Penicillin G

Cotrimoxazole

alternative if allergic to penicillin

AGAMMAGLOBULINEMIA

PROBLEM: Mutation in

Btk

gene coding for protein

involved in intramedullary differentiation of B-lymphocyte precursors. B cells are absent, and the antibody production is

null

URTIS and LRTIs

due to encapsulated

bacteria common, GI infections frequent

Immunoglobulin replacement therapy intravenously or

subcutaneously started at diagnosis

S

tarting

at a dose of 400 mg/kg every 3 weeks, with the aim of achieving a residual IgG level of at least 8 g

/dL

Antibiotic prophylaxis can be proposed when infections persist despite well-conducted replacement

therapy with CMX

An alternative option could be to prescribe long-term

macrolides (AZITHROMYCIN)

in case of

bronchiectasis

COMMON VARIABLE IMMUNODEFICIENCY

PROBLEM:

hypogammaglobulinemia

associated with a <5 g/L IgG deficit and

IgA

deficit,

IgM

concentration can be normal or low, and a diminished

vaccinal

response

Infections mainly ENT

area, the bronchi, and the lungs

, large majority

caused by encapsulated bacteria

Immediate IG therapy for patients with severe infections or >3 infections in the previous year

Proposed

immunoglobulin replacement if the IgG titer is <3.5 g/

L ,IV 400-600

mg/kg/

month/SC 100-150mg/kg/

wk

Antibiotic chemoprophylaxis

complementary

role in patients with persistent infections despite “optimal” immunoglobulin

replacement (levels >8g/dl IG g)- CMX

HYPER IGM SYNDROMESProblem:

P

rofoundly

decreased plasma levels of IgG and IgA coexist with a normal-to-increased

IgM

plasma

level

Mutations in gene encoding CD40L or CD40 involved in isotype switching, cellular immunity also affected

Those with cellular defect

Pneumocystosis

and cryptosporidium common

URTIS and LRTIs due to encapsulated bacteria common, GI infections

frequent

Immunoglobulin replacement therapy intravenously or subcutaneously started at diagnosis

CMX prophylaxis for

pneumocystosis

in those with cellular defect, azithromycin role in CD40/CD40L deficiency

SCIDs AND CIDsProblem:

P

rofound

deficit of T-cell immunity, always associated with a humoral immunity

deficiency

Most frequent infections pneumocystis, however wide spectrum of infections possible

Constant risk of infection with encapsulated bacteria, viral and fungal infections also

EMERGENCY! Isolate patient

in sterile

room, urgent need for allogeneic

hematopoietic stem cell transplant [HSCT

]- curative,

gene therapy, enzyme replacement

therapy

Prior to that and after need for CMX prophylaxis as soon as cellular immunodeficiency identified

Antifungals fluconazole before 1 month of age and

itraconazole

after, Antiviral for HSV acyclovir daily

IG therapy initiated and maintained until humoral deficit corrected

STAT 3 DEFICIENCY

Problem:

caused by a signal transducer and activator of transcription 3 (STAT3)

deficiency

Hyper–immunoglobulin E is constant and

hypereosinophilia

is

frequent, B cell memory deficiency – defective T helper 17 response important for immune response in skin and lungs

Infections lack general or local inflammatory signs

Most common recurrent cold abscess due to Staph.

Aureus

, ENT and pulmonary infections frequent, pulmonary

A

spergillosis

in 25%, recurrent pneumonias

Chronic cutaneous and mucosal candidiasis is frequent

STAT- 3 DEFICIENCY CONTDCMX first line, for relapsing MSSA infections oral

cloxacillin

2-4g/day

Oral azithromycin 3x a week for chronic symptomatic bronchial colonization for bronchiectasis and

Inhaled tobramycin/

colimycin

to treat chronic 

P.

aeruginosa

 colonization with frequent exacerbations

.

If pulmonary lesions present anti –

A

spergillus

prophylaxis with antifungal justified to prevent invasive infections

Itraconazole

most frequently prescribed

Due to the B cell deficiency, immunoglobulin

replacement therapy should be prescribed for recurrent bacterial infections despite well-conducted antibiotic prophylaxis

CONCLUSION

IN SUMMARY

A

ntibiotic

and antifungal prophylaxis for innate immune

deficiencies

C

otrimoxazole

for cellular immune deficiencies;

P

olyvalent

immunoglobulin replacement therapy for humoral immune

deficiencies

V

accinations

and antibiotic prophylaxis for patients with

asplenia

or complement factor

deficiencies

LITTLE IS KNOWN ABOUT DEVELOPMENT OF ANTIBIOTIC RESISTANCE –STUDIES NEEDED

THANK YOU! QUESTIONS

REFERENCESPrevention of Infections During Primary

Immunodeficiency, David

R.

Snydman

et al

Autosomal Dominant STAT3 Deficiency and Hyper-

IgE

Syndrome, Molecular

, Cellular, and Clinical Features From a French National

Survey,

Chandesris

, Marie-Olivia

MD et al

Primary Immunodeficiency, Christine

McCusker

Immunopedia.org.za

Antibiotic Prophylaxis in Primary Immune Deficiency Disorders,

Merin

Kuruvilla

et al

General Recommendations for Patients and Families

As soon as primary immunodeficiency (PID) is diagnosed, prophylactic measures must begin.

Observance to prophylactic treatments is essential but can be difficult because of lifelong treatment.

Some treatments need specific times for administration (

ie

,

itraconazole

capsules during meals or

itraconazole

liquid suspension at distance of meal intake).

Patients and their family must be aware of their diagnosis of PID, their susceptibility to infections, and the signs that indicate a consultation is needed.

Patients with PID should consult an infectious disease expert before traveling.

Patients with innate immune defects should avoid exposure to molds (

eg

, construction/renovation areas and gardening).

Patients with combined deficiencies should drink bottled water in countries where cryptosporidiosis is particularly present.

All healthcare professionals consulted must be informed of the diagnosis (

eg

, to avoid intramuscular injections in patients with PID).

Almost all patients with PID should be vaccinated against influenza, but immunogenicity of the vaccine remains uncertain in the context of PID. Vaccination of the entourage is recommended.

Live vaccines are contraindicated in persons with PID with cellular immune deficiencies.