Infections in Immunocompromised Host A focus on Febrile Neutropenia

Infections in Immunocompromised

HostA focus on Febrile Neutropenia

Historical Background First description around 1900 Rare until development of chemotherapy In the 1960s: mainly in acute leukemia with profoundneutropenia G-ve sepsis most common with mortality = 90% Empirical therapy with synergistic combinations of antibioticsreduced mortality to + 10 % In the1980s: development of chemotherapy for solid tumorsleading to less severe and less protracted neutropenias For multiple reasons, replacement of G-ve infections by G+ve

→severity of infections decreases FN becomes a heterogeneous syndrome Risk-stratification models allow for identification of low risk

patients with additional treatment options Increase of fungal sepsis in specific groups of neutropenic patients

leads to widespread use of empirical antifungal agents

Introduction Immunocompromised Host:

Patient with intrinsic or acquired defects in host

defenses

Increased risk of infection

Incidence is increasing – HIV/AIDS, organ transplant, and cancer pts

Infection remains the leading cause of autopsy-

determined death in neutropenic cancer patients

Introduction Infectious complications are a major cause of

morbidity and mortality in cancer patients due

to advances in therapeutics of the malignancy.

Cytotoxic chemotherapeutic agents,

immunotherapy, and bone marrow transplant

almost invariably affect bone marrow function.

Introduction The normal kinetics of blood cell turnover influence

the sequence and sensitivity of each of the formed

elements.

Polymorphonuclear leukocytes (PMNs; T1/2 = 6 to 8

h)

platelets (T1/2 = 5 to 7 days)

red blood cells (RBC; T1/2 ~ 120 days)

have most, less, and least susceptibility to usually

administered cytotoxic agents, respectively.

The Causes and Consequences of Neutropenic Complications

Adapted from Lyman GH. Oncology. 2003:17(suppl):8-13.

Chemotherapy

Neutropenia

FEBRILE NEUTROPENIA

Complicated Infections

Prolonged Hospitalization

DEATH

Radiation Disease Process

Introduction

Infections are the most common complication

of neutropenia

Febrile neutropenia is a MEDICAL

EMERGENCY!!!

Typically occurs 7-10d post chemo

Timely/Thorough assessment and antibiotics

are life saving

Introduction

Risk of infection is proportional to severity

and duration of neutropenia

Recovery of ANC is the most important factor

determining the outcome of infectious

complications

DefinitionsANC = (% segs or PMNS + % Bands) x WBC/100

• Neutropenia

– ANC <1000

– ANC <500 – what most treatment guidelines consider

critical

– ANC <100 – risk of infection and death is greatest

• Fever

– Single oral temp > 38.3° C (101° F)

– Temp > 38.0° for > 1 hour (100.4° F)

NCCN Definitions of Neutropenia and Febrile Neutropenia

Neutropenia Fever

ANC <500/μLor

ANC <1000/μL and

a predicted decline to

≤500/μL

over the next 48 h

Oral temperature >38.3°C (single

reading) or

>38.0°C (>1 h)

fever + neutropenia = febrile neutropenia

ANC example

Example 1

– WBC = 3.6

– 45% Segs

– 10% Bands

ANC = 55% (3600)/100

OR = 0.55 (3600)

= 1980

Example 2

– WBC 3.0

– 38% Neutrophils

ANC = 0.38 (3000)

= 1140

Risk Factors for FN Patient-related

Age (>65 y) Female gender Poor performance status Poor nutritional status Decreased immune

function Conditions associated with

risk of serious infection Open wounds Active tissue infection

Comorbidities Chronic obstructive

pulmonary disease Cardiovascular disease Liver disease Kidney disease Diabetes mellitus Low baseline serum

hemoglobin level

NCCN. Myeloid Growth Factors in Cancer Treatment. V2.2005.

Risk Factors for FN Treatment-related

Type of chemotherapy (high-dose cyclophosphamides, anthracyclines)

History of severe neutropenia with similar chemotherapy

Preexisting neutropenia or lymphocytopenia

Extensive prior chemotherapy Concurrent or prior radiation

therapy to marrow-containing bone

Cancer-related Hematologic

malignancies Bone marrow

involvement with tumor Advanced or

uncontrolled cancer Elevated serum LDH

(lymphoma)

LDH = lactate dehydrogenase; RDI = relative dose-intensity.NCCN. Myeloid Growth Factors in Cancer Treatment. V2.2005.

Risk Factors for FN Altered skin defenses / foreign body

CVC Urinary / Foley catheter Radiation induced skin damage / cellulitis Surgery Mechanical ventilation Mucositis / Stomatitis

Colonization Recovery of an organism without clinical signs of infection Most infection are from bacteria that colonized the GIT,

URT, and Skin

Incidence of Neutropenia and FN per Tumor Type and Regimen

Neutropenia RiskRegimen FN Other

Breast

Docetaxel, doxorubicin

33% Grade 3 or 4 neutropenia: 97%

Docetaxel, doxorubicin, cyclophosphamide

25% Grade 4 neutropenia: 88%

Doxorubicin, paclitaxel

32% Grade 4 neutropenia: 89%

Bladder

MVAC 26% Grade 3 or 4 leukopenia: 62%

Paclitaxel, carboplatin

21% Grade 3 or 4 neutropenia: 39%

Neutropenia Risk

Regimen FN OtherSmall Cell Lung

Etoposide, cisplatin Fever: 18% Grade 3 or 4 neutropenia: 85%

Topotecan, paclitaxel 21% Grade 4 neutropenia: 96%

Non–Small Cell Lung

Carboplatin, paclitaxel 4% Grade 3 or 4 neutropenia: 63%

Cisplatin, paclitaxel 16% Grade 3 or 4 neutropenia: 75%

Colorectal

Irinotecan 14% Grade 3 or 4 neutropenia: 47%-48%

Non-Hodgkin’s Lymphoma

CHOP Hospitalization:

<age 65: 7.9%≥age 65: 13.8%5

Grade 3 or 4 leukopenia:34%-72%

Other immune system defects

T-lymphocyte and macrophage function (cell-

mediated immunity) Transplant patients receiving immunosuppressive

drugs, HD, HIV

B-cell function (humoral immunity) Underlying disease such as multiple myeloma or

CLL

Etiology of Infection

Primary site often includes alimentary tract and

where there has been damage to integument

– Site of infection can be documented in only 30% to

40% of febrile episodes Bacterial infections most common (fungal infections

increasing) Gram - replaced by Gram + organisms (often

methicillin resistant)


Check for other causes of feverReaction to blood products

chemotherapy

cell lyses and the underlying malignancy


Timeline helps narrow the differential

Early: Bacterial

Gram Positives (staph, strep …)

Gram Negatives (e.coli, klebsiella, Pseudomonas..)

Mixed in 25%

Infrequently anerobes


Late Candida

Aspergillosis

PCP (if on steroids)

Varied Viral

Herpes family( HSV, EBV, CMV,

RSV, Paraflu etc…

Most Common Organisms Gram-Positive Cocci and Bacilli

Most likely if infected catheter

60-70% of documented infections, WHY? Staphylococcus species

Streptococcus species

Enterococcus faecalis / faecium

Corynebacterium species

Most Common Organisms

Gram-negative Bacilli and CocciE. coli

Klebsiella sp.

Pseudomonas aeruginosa

Fungal infections: usually super infections Candida sp or other fungi can cause primary

infections

In BMT patients and prolonged N > 7 days

Most Common Organisms

ViralMostly a reactivation of latent infections

Herpes Simplex, Varicella Zoster

CMV in Stem Cell Transplant

Clinical Presentation Fever is the most important presenting symptom

in a neutropenic patient 60% of neutropenic patients who become febrile

have an established / occult infection 40% of patients based on a documented microbiological

origin

20% of patients based on clinical findings alone

Clinical Presentation Many normal signs and symptoms of infection may

be absent, WHY? Inflammation may be minimal

⇓ or absent indurations, erythema, and postulation

normally seen in bacterial skin infections

Pneumonia without infiltrate, infiltrates may not develop

until ANC > 500

Meningitis without WBCs in CSF

UTI without pyuria

Clinical Presentation

Most common sites of infection

lung→only fever and dry cough

Skin cellulitis → no pain, heat , erythema,

swelling

Clinical Presentation Search should be undertaken for subtle signs and

symptoms PAIN at most commonly infected sites

Periodontium

Pharynx

Lower esophagus

Lung

Perineum

Skin

Bone marrow aspiration site

Catheter access sites

Evaluation

Thorough Physical Exam

Cultures> 2 sets of blood cultures; 1 set from a central

venous access site and a peripheral vein

Any lesions suspected of being infected

Urine if any S&S of UTI, presence of catheter, or

abnormal U/A

Stool cultures if diarrhea present

Evaluation

CXR if s/s of respiratory tract infection or if

outpatient therapy is planned

CBCWhat would you expect?

SrCr, BUN, and transaminases

Determine high and low risk patients (see

algorithm)

Evaluation: Low/High risk neutropenia algorithm

Scores >= 21

considered low

risk

Other algorithms

available

Factors that favor low risk ANC > 100

Duration of neutropenia < 7 days

Resolution of neutropenia expected in < 10 days

Normal CXR

No IV catheter site infection

Normal hepatic and renal function

No appearance of illness

Treatment Algorithm

Outpatient Inpatient

Treatment Empiric antibiotic therapy should be administered

promptly if afebrile, but signs and symptoms of infection present

If febrile with ANC< 500 or > 500 and predicted to < 500

Gm –ve infections have a 91% mortality in the 1st 24-48 hrs

Remove any sources of infection if possible

Treatment

Initial antibioticsMust consider site of infection/ likely pathogen

Frequency of isolation

Antibiogram of hospital

Allergies

Concomitant treatments

Organ dysfunction

Must have bactericidal activity

Treatment

Optimal antibacterial spectrumCover gm-ve bacilli : E.coli, K.pneumonia,

P.aeruginosa + staphylococci, streptococci

Optimal regimen remains controversial

Proposed Classification/Management for FN Patients High Risk: Prolonged Neutropenia ( > 14 d),

Heme CA or allo BMT, substantial

comorbidity, unstable Admit, IV therapy (usually combination Rx) for duration of

neutropenia; Ampho B empiric Rx for continued fever

Proposed Classification/Management for FN Patients

Moderate Risk: Neutropenia 7-14 d, auto BMT,

stable, minimal comorbidity Initial IV Rx (monotherapy OK), early discharge with po if

response; Ampho B for cont’d fever (especially if azole prophy)

Low Risk: < 7d neutropenia, solid tumor, stable Outpatient IV or po therapy; azole Rx ok for cont’d fever

Candidates for Outpatient Therapy Appears stable

< 60 years

ANC > 100

No source identified

Responsive tumor

No comorbidity bleeding, BP, CA++, respiratory failure, altered MS

Suspected duration of neutropenia is not a determining

factor (can’t predict at time of febrile presentation)

Oral antibiotics As initial therapy or as follow up therapy

Oral ciprofloxacin + amoxicillin-clavulanate

May use clindamycin in allergic patients

Monotherapy

Monotherapy does not cover Coagulase-negative staphylococci

MRSA

Enterococcus (except imipenem covers faecalis)

Monotherapy

Ceftazidime3rd generation cephalosporin/ antipseudomonal

covers only some gram + organisms

May improve staphylococcal cover with

vancomycin

Increasing resistance ( K.pneumonia produce β-

lactamases

Monotherapy

Cefepime4th generation cephalosporin

FDA approved as monotherpay for FN

Low affinity for β-lactamases

more potent than Ceftazidime against gram +

organisms ( ↓ need for vancomycin)

Above advantage is lost when high rate of MRSA

Monotherapy

CarbapenemsImipenem+ Cilastatin or meropenem

Broad spectrum against gm+ve and gm-ve +

anerobes

Evidence support efficacy

Higher incidence of N/V

More expensive

Monotherapy- Summary Monotherapy is appropriate as initial empiric TX

No evidence to support superiority of one agent

Carbapenems are usually not used due to cost and

potential of resistance of Acinetobacter

Carbapenems reserved who failed initial empiric TX

or have Hx of infection with resistant organisms

Monotherapy- Summary

Ineffective monotherapyMonobactams→lacks gm+ve activity

Fluoroquinolones →variable gm+ve activity, used

for prophylaxis

B-lactam/b-lactamase inhibitor combinations

Two Drug Therapy

Advantages

Broad spectrum

activity

Potential synergy

Minimal emergence

of drug-resistant

strains

Disadvantages

Lack of G + activity

when AG + ceftaz is

used

Additive toxicities

when AGs are added

Empiric Combinations

Anti-Pseudomonal PCN or 3rd G Cephalosporin +

aminoglycosideMost established combination

response rates all around 70%,

no advantage of one b-lactam over another

Disadvantage; nephrotoxicity, TDM


Double β-lactam; Anti-Pseudomonal PCN + 3rd G

Cephalosporin or Moxalactam Similar response rates

Limited experience

Poorer response in documented P. aeruginosa

less nephrotoxic, high cost


Ciprofloxacin + AG or B-lactamAssociated with ↑ gm +ve infections

Cipro activity against P. aeruginosa has ↓ (<70%)

Empiric VancomycinRationale

Previous combinations lack activity against MRSA

Increasing gm+ve pathogens

Should be D/C after 3-5 days if G+ve infection not identified

Disadvantages

Excessive use → Vanco resistant organisms VRE/VRSA

↑ AG nephrotoxicity

Mortality from staphylococcal infections is < 4% in 1st 48 hrs →

can delay adding until pathogen is confirmed.

Indications for Vancomycin Clinically suspected catheter/Skin related infection

Known colonization with resistant G+ve organism/MRSA

Positive blood culture for G+ve bacteria

Hypotension / CV impairment

Severe mucositis in hospitals with high MRSA (HD-Ara-C)

Quinolone prophylaxis

Severe Sepsis

In institution frequently isolating viridans streptococci

Vancomycin Up Front? PRO

change in most common

isolates in F/N

? Less febrile days overall,

and perhaps less ampho B use

viridans streptococci may be

fatal; particular problem with

quinolone prophylaxis and

regimens that induce severe

mucositis

CON overall mortality from

documented gm(+)

bacteremia only 5%

vast majority of

patients with gm(+)

survive and respond to

addition of Vanco

VRE

Alternatives to Vancomycin

LinezolidOxazolidione

IV or oral

Thrombocytopenia

Quinupristin-dalfopristinIV

High side effect profile

High potential for DI

Drug Allergy

Need to assess type of allergy and determine

risk versus benefit

Know the organisms you need to cover

If unable to use β-lactam Vanc + Cipro

Vanc + Aztreonam

Modifying Initial Empiric Regimen

Reassess after 3 days to determine efficacy of

regimenFever status

Clinical condition improved or deteriorated Changes made sooner if condition deteriorates

Etiologic pathogen identified

Afebrile within 3-5 daysNo Etiology Identified

Continue empiric TX for 7 d

If ANC> 500 for 2 days→ may D/C Abs

D/C Abs after 14 days in prolonged neutropenia

without evidence of infection

ANC< 500 at 7 d with initial ANC< 100 or

mucositis or unstable → continue ABs

Afebrile within 3-5 days

Etiology Identified

Additional antimicrobial or AB dosage adjustment

based on susceptibility tests and serum conc.

If persistently neutropenic→Maintain broad-

spectrum antibacterial coverage.

If neutropenia resolved →narrow therapy against

organism for appropriate duration

Persistent Fever during 3-5 daysNo Etiology Identified Check for other causes of fever

Tumor lyses

Nonbacterial infection

Resistant bacterial infection

Inadequate serum and tissue levels of antibiotics

Slow response to therapy

Drug related fever

Emergence of a second infection/super infection

Infection at avascular site

Persistent Fever during 3-5 daysNo Etiology Identified

RE-ASSESS patient! If re-assessment reveals

no new cause: 3 options

1) Continue current therapy

2) Change or add antibiotics

3) Add anti-fungal drug with or without

antibiotic change


1.Continue current therapy

Pt remains stable, not deteriorate

Neutropenia expected to resolve within 5 d

Continue Abs 4-5d after recovery of neutropenia

Continue Abs for 14 days with continued neutropenia

and reassess.


2.Modify initial Abs

If there is evidence of disease progressionCatheter site drainage, abdominal pain, pulm. Infilt

Add or change ABs

Persistent Fever during 3-5 days

No Etiology Identified

3. Add antifungal

In pts with hematological CA, persistent fever,

neutropenia > 5d of Abs

Up to 1/3 of febrile neutropenic patients who

do not respond to a 1-week course of abx have

systemic fungal infections

Generally must cover Candida and Aspergillus

Adding Amphotericin B Reliable activity against Candida and Aspergillus

addition of AmphoB appears to improve outcome

Considered DOC for empiric antifungal Tx

Continue until resolution of neutropenia

Persistent neutropenia→ 2 wk course

Documented infection → variable depending on

diagnosis

Amphotericin B

0.7 mg/kg IV qd is the dose used in severe

infections

Rapid titration up to 0.7 mg/kg over 3 days is

used if infection is less severe

Amphotericin B - Toxicities Infusion Related

F/C, N/V, HA, thrombophlebitis, myalgias and

arthralgias

Premeditation may reduce these symptoms

(Tylenol, Benadryl)

Meperidine can be given for rigors

Amphotericin B - Toxicities

Nephrotoxicity80% of patients develop some type of impairment

Dose related

Potentiated by other nephrotoxins

Electrolyte Imbalances ⇓ K, Mg, Ca⇓ ⇓

Lipid formulations of Ampho B

Similar efficacy

Decreased side effects (infusion related and

nephrotoxicity)

Consider in patients at risk for nephrotoxicity

or with underlying renal dysfunction.

Expensive

Specific criteria for liposomal Ampho B Initial Creat > 2.0 and not on dialysis (long-term)

A doubling of serum creatinine and > 2.0 mg/dL

refractory disease after 10 days (or 500 mg) of

AmphoB

High risk patients (i.e. on CsA, tacrolimus, AG,

foscarnet, cis-platinum, ifosfamide;)

severe or persistent infusional AE to AmphoB

Other Agents Fluconazole

May be used if mold infections (aspergillus sp)

and drug resistant candida sp are uncommon

Not for suspected aspergillus or who used FLZ

prophylaxis

ItraconazoleWhen FLZ is not indicated

Lower toxicity than AmphoB

Other Agents Voriconazole

Increased activity against aspergillus and non-

albicans candida

Alternative to AmphoB

Less toxic, easier to administer

Bottom Line, Empiric Therapy

IV lipo-amphotericin and itraconazole FDA approved,

Ampho-B is a standard of care and has most clinical

experience Caspofungin likely to be approved in near future

Data suggest adding ONLY after 96 hours of antibacterials

AND either persistent or recurrent fever at that time

Bottom Line, Empiric Therapy Ampho B > Caspofungin > L-Ampho B > Itraconazole as

empiric Rx in patients previously receiving fluconazole

prophylaxis Voriconazole may have a role in high risk, long-term prophylaxis

(e.g. Allo BMT with GvHD), or as empiric therapy in high

aspergillus risk patient after initial blood Cxs (-), but not drug of

choice for empiric Rx of Fever/Neutropenia

Antivirals Empiric use not indicated without evidence of

viral disease

Indicated if clinical or laboratory evidence of

viral disease Skin lesions due to herpes simplex or varicella-

zoster

Heal the lesions to decrease potential portals of

entry for bacteria and fungi

Case 1

A 66-y.o. woman presents to her physician with fever, malaise, sore throat, and easy bruisability. She is diagnosed to have AML. Following induction chemotherapy, the patient becomes profoundly neutropenic (ANC≤ 100/mm3).

She is asymptomatic but develops a fever on the 3rd day of neutropenia. Her PE, which includes oral mucosa, indwelling vascular catheter site, heart, lungs, abdomen, and perianal region, is normal except for an oral temperature of 39°C. A CXR is normal, and blood cultures are obtained.

Case 11. Which one of the following measures is

most appropriate?A) Obtain additional tests including sputum, throat,

and urine cultures; then initiate treatment with appropriate empiric antimicrobial therapy

B) Await results of blood cultures and initiate empiric antimicrobial therapy if clinical deterioration occurs

C) Initiate empiric therapy with imipenem and vancomycin

D) Initiate empiric therapy with cefepimeE) Initiate empiric therapy with ceftazidime and

tobramycin

Case 12.Two sets of blood cultures grow gram-positive cocci

in clusters. The patient appears clinically stable except for continued fever. What is the most appropriate next step?

A) Await identification and antibiotic susceptibility of the organism before modifying antimicrobial therapy

B) Remove the indwelling intravascular catheter

C) Initiate therapy with vancomycin

D) Obtain additional blood cultures via catheter and peripheral vein

Case 13.The gm-+ve cocci in the blood are identified

as MRSA. Despite appropriate management for the next 6 days, fever persists. Again, the patient appears stable with no other symptoms or signs of infection. Repeat blood cultures and CXR are negative. Which of the following is the best next step?

A) Change the patient’s antibacterial regimenB) Continue the same antimicrobial therapyC) Test for Clostridium difficile toxin in stool and

perform urinalysis and urine cultureD) Administer empiric antifungal therapy

Duration of Therapy Neutrophil count is determinant of discontinuation

Afebrile by days 3 to 5 AND no infection identified ANC > 500 x 2 d, stop abx 48 h after afebrile AND ANC >

500

If ANC < 500 by day 7

If low risk and doing well, stop antibiotics when afebrile

x 5 to 7 days

If initially high risk, continue antibiotics

If an infection documented then titrate abx according

and continue a full course

Duration of Therapy

Persistent Fever ANC > 500: Stop 4 to 5 days after ANC > 500

and reassess (if no infection ID’d)

ANC < 500: Continue for 2 weeks, reassess. If no

disease present and patient stable, discontinue

Transfusion of granulocytes

has no role in the management of febrile neutropenia their exceedingly short half-life

mechanical fragility

clinical syndromes of pulmonary compromise with

leukostasis after their use.

Instead, colony stimulating factors (CSFs) are used to

augment bone marrow production of PMNs.

Use of CSF Can significantly shorten the duration of neutropenia

Has not consistently reduced other measures of

febrile morbidity

Not routinely recommended

May be indicated when a worsening course is

predicted and there is an expected long delay in

recovery of marrow

Mechanism Of Action

Granulocyte colony-stimulating factor (G-CSF), is

one of 5 "classic" hematopoietic growth factors that

are involved in the development and functional

activation of hematopoietic elements

These glycoproteins are produced naturally in

lymphocytes and monocytes, and have been

demonstrated to stimulate progenitor cells of different

hematopoietic cell lineages

The 4 other classes of CSFs

granulocyte-macrophage colony-stimulating

factor (GM-CSF; sargramostim)

macrophage colony-stimulating factor (M-

CSF),

interleukin-3

erythropoietin

Available Myeloid Growth Factors

Filgrastim

Recombinant methionyl

human G-CSF

175 amino acids

Half-life SC = 3.5 hours

Primarily renal clearance

Pegfilgrastim

Covalent conjugate

of recombinant methionyl

human G-CSF and

monomethoxypolyethylene

glycol

175 amino acids

Half-life SC = 15-80 hours

Limited renal clearance;

primarily neutrophil- mediated

clearance

Available Myeloid Growth Factors

Sargramostim

Recombinant yeast-expressed human GM-CSF

127 amino acids

Half-life = 60 minutes

Indicated only for use following induction chemotherapy in

older adult patients with AML, for myeloid reconstitution

after BMT, and for mobilization of peripheral blood stem

cells for harvest

Administration do not administer within 24 hrs of chemotherapy

G-CSF or GM-CSF is conventionally started 24 to 72

hrs after completion of chemotherapy and continued

until a PMN count of 1000 is achieved

CSF Prophylaxis for First and All Subsequent Cycles: NCCN Guidelines

If the patient’s risk for FN* is:

If the patient is receiving:

Treatment with curative intent oradjuvant therapy

Treatment to prolong survival or improve QOL

Palliative therapy to manage symptoms or improve QOL

>20%(high)

Use CSF Use CSF Consider CSF (discuss high-risk chemotherapy with patient)

10%-20%(intermediate)

Consider CSF Consider CSF (discuss high-risk chemotherapy with patient)

Consider CSF (discuss high-risk chemotherapy with patient)

<10%(low)

CSF is not recommended for most patients†

CSF is not recommended

CSF is not recommended

CSF Prophylaxis for FN Maintenance of Scheduled Dose Delivery Filgrastim

Daily dose of 5 µg/kg until post-nadir ANC recovery

to normal or near-normal levels Start 1-3 days after completion of chemotherapy and treat through

post-nadir recovery Pegfilgrastim

One dose of 6 mg per cycle of treatment Start 1-3 days after completion of chemotherapy There is evidence to support use for chemotherapy regimens given

every 3 weeks Phase 2 studies demonstrate efficacy in chemotherapy regimens given

every 2 weeksANC = absolute neutrophil count. NCCN. Myeloid Growth Factors in Cancer Treatment. V2.2005.

Prophylaxis against Infection Non-Pharmacologic therapy

Reverse isolation

Infection control guidelines

Avoid fresh fruits and vegetables

Personal hygiene

Prophylaxis against Infection

Antimicrobial ProphylaxisData supports efficacy of TMP-SMX, FQs,

fluconazole, and intraconazole to reduce # of

infectious episodes

Prophylaxis against Infection Antimicrobial Prophylaxis

No absorbable antibacterial Theorized to reduce GI colonization

have not showmen consistent efficacy Lack of compliance

Induce resistance


TMP-SMX showen consistent benefit in reducing bacterial infections

in FN patients

Effect on mortality less clear

Benefit must be weighed against risk of bone marrow

suppression, hypersensitivity, and emergence of resistance/

super infection

Should be strongly considered for patients at risk of PCP;

ALL receiving intensive chemo, AIDS, Allogenic BMT.


FluoroquinolonesEqual or superior to TMP-SMX in preventing gm-

ve infections in FN

Disadvantages ↑ gm +ve in patients receiving prophylaxis

Emergences of resistant gm-ve bacilli

Does not reduce mortality


Antifungal In pts receiving chemo for solid tumors antifungal

prophylaxis may not be beneficial and may ↑ risk of super

infection with resistant fungi

Pts with hematological malignancy and BMT may

benefit more due to longer duration of neutropenia

A. No absorbable antifungal Some have role in oropharayngeal candidiasis but not

invasive fungal infections

Prophylaxis against Infection Antifungals

B. Systemic antifungals Itraconazole →efficacy in reducing systemic candida

Fluconazole → ↓ superficial and systemic fungal infections in BMT only

Limited spectrum

Inferior to Itraconazole

Amphotericin Effective but more toxic

Prophylaxis against Infection Antivirals

Pts seropostive for HS and receiving BMT, Acute

leukemia, or past history of infection→acyclovir

prophylaxis during neutropenia

Pts seropostive for varicella and receiving

BMT→acyclovir prophylaxis during neutropenia

BMT→ganciclovir prophylaxis against CMV

during neutropenia.


Recommendation: Routine prophylaxis controversial

May not reduce the need for empiric antimicrobials

Concern about emerging drug-resistant bacteria and

fungi

No consistent reduction in mortality

Documents

Infections in Immunocompromised Host A focus on Febrile Neutropenia