Infection Risk and Neutropenia

Last updated: January 2025 | Medical Reviewer: Oncol.net Editorial Board

Overview

Infection is one of the most serious complications of cancer treatment. Many chemotherapy drugs, targeted therapies, and cancer itself can weaken the immune system, making it harder to fight off bacteria, viruses, and fungi. The main problem is low white blood cell counts, particularly neutrophils - the cells that fight bacterial infections.

Understanding your infection risk, taking preventive measures, and recognizing warning signs early can prevent serious complications and potentially life-threatening situations. While this information may seem frightening, remember that most infections can be successfully treated when caught early, and many can be prevented with proper precautions.

Understanding Neutropenia

What Are Neutrophils?

• Type of white blood cell that fights bacterial and fungal infections
• First responders to infection - they rush to infection sites and destroy invaders
• Make up 50-70% of total white blood cells in healthy adults
• Short-lived cells (6-8 hours in bloodstream) - constantly being produced by bone marrow

Neutropenia Defined

• Normal ANC (Absolute Neutrophil Count): 1500-8000 cells/μL
• Mild neutropenia: ANC 1000-1500
• Moderate neutropenia: ANC 500-1000
• Severe neutropenia: ANC <500 (significantly increased infection risk)
• Profound neutropenia: ANC <100 (very high infection risk)

How Cancer Treatment Causes Neutropenia

• Chemotherapy: Damages rapidly dividing cells, including bone marrow cells that produce neutrophils
• Timing (nadir):
  • Neutrophil counts typically lowest 7-14 days after chemotherapy
  • Timing varies by specific drugs used
  • Counts usually recover before next chemotherapy cycle
• Cumulative effect: Bone marrow recovery may be slower with repeated cycles
• Other causes:
  • Radiation therapy to large areas (especially pelvis, spine)
  • Cancer in bone marrow (leukemia, lymphoma, multiple myeloma, metastatic disease)
  • Certain targeted therapies

Risk Factors for Severe Neutropenia

• Type of chemotherapy (dose-intense regimens, certain drugs)
• Age >65 years
• Previous chemotherapy or radiation
• Poor nutritional status
• Pre-existing bone marrow problems
• Liver or kidney dysfunction
• Active infection at time of chemotherapy
• Low baseline neutrophil count

Signs and Symptoms of Infection

Fever - The Most Important Sign

• Definition of neutropenic fever:
  • Single temperature ≥100.4°F (38°C) OR
  • Temperature ≥100.4°F (38°C) sustained over 1 hour
  • With ANC <500 or expected to fall <500 within 48 hours
• Action required: Call your oncology team IMMEDIATELY or go to emergency room
• Why it's serious:
  • Neutropenic patients can become critically ill within hours
  • Mortality rate 5-10% even with treatment (higher if treatment delayed)
  • Source of fever often not found (fever of unknown origin)

Other Infection Symptoms

• Respiratory:
  • Cough (new or worsening)
  • Shortness of breath
  • Sore throat
  • Nasal congestion or sinus pressure
• Urinary:
  • Burning or pain with urination
  • Frequent urination
  • Urgency
  • Cloudy or foul-smelling urine
• Gastrointestinal:
  • Diarrhea (new or increased)
  • Abdominal pain or cramping
  • Rectal pain or tenderness
• Skin:
  • Redness, warmth, swelling (around wounds, IV sites, surgical sites)
  • New rash
  • Painful, red, or swollen areas
• General:
  • Chills or sweating
  • New pain anywhere
  • Unusual fatigue or weakness
  • Confusion or altered mental status

Infection Prevention Strategies

Hand Hygiene (Most Important)

• When to wash hands:
  • Before eating or preparing food
  • After using bathroom
  • After touching animals
  • After coughing, sneezing, or blowing nose
  • Before and after touching face or mouth
  • After touching anything potentially contaminated
• How to wash:
  • Soap and water for 20 seconds (preferred)
  • Alcohol-based hand sanitizer (60%+ alcohol) if soap unavailable
  • Scrub all surfaces including between fingers, under nails
• For others: Everyone in household should practice good hand hygiene

Food Safety

• Neutropenic diet (low-microbial diet):
  • Controversial - some centers recommend, others don't
  • Discuss with your oncology team about their recommendations
• General food safety (recommended for all):
  • Wash hands before food preparation and eating
  • Wash fruits and vegetables thoroughly
  • Cook meats to safe internal temperatures:
    • Poultry: 165°F
    • Ground meat: 160°F
    • Beef, pork, lamb (whole cuts): 145°F
  • Avoid raw or undercooked:
    • Eggs (no runny yolks, raw cookie dough)
    • Meat, poultry, seafood
    • Sushi, sashimi, raw oysters
  • Avoid unpasteurized:
    • Dairy products
    • Juices
    • Honey (for children, generally safe for adults)
  • Avoid moldy or expired foods
  • Store leftovers properly (refrigerate within 2 hours)
  • Use separate cutting boards for raw meat and produce

Avoiding Exposure to Illness

• Sick people:
  • Avoid close contact with anyone who is sick (fever, cold, flu, stomach bug)
  • Ask sick family members to wear masks or stay in separate rooms
  • Wait until they've been fever-free for 24 hours before close contact
• Crowds:
  • Avoid crowded places when counts are lowest (during nadir week)
  • Consider wearing mask in crowded indoor spaces
  • Movie theaters, concerts, sporting events - use judgment based on counts
• Children:
  • Young children are germ factories - be cautious
  • Avoid children with recent vaccinations (live vaccines)
  • Daycare and schools have many circulating infections

Personal Hygiene

• Oral care:
  • Brush teeth 2-3 times daily with soft toothbrush
  • Gentle flossing (avoid if platelets low or gums bleeding)
  • Rinse with salt water or baking soda solution
  • Avoid mouthwashes with alcohol
  • Report mouth sores immediately
• Skin care:
  • Keep skin clean and moisturized
  • Avoid cuts, scrapes, and irritation
  • Use electric razor rather than blade
  • Protect hands with gloves for dishes, gardening, cleaning
  • Promptly clean any cuts or scrapes with soap and water
  • Watch for signs of infection at IV sites, surgical wounds
• Bathroom hygiene:
  • Clean rectal area gently after bowel movements
  • Use soft, unscented toilet paper or wipes
  • Avoid rectal thermometers, suppositories, enemas (can cause breaks in rectal lining)
  • Report rectal pain or bleeding

Environmental Precautions

• Pets:
  • Generally okay to keep pets, but take precautions
  • Wash hands after petting or handling
  • Avoid cleaning litter boxes, bird cages, or aquariums (if must do, wear gloves and mask)
  • Don't allow pets to lick your face or any wounds
  • Avoid reptiles, amphibians, chicks/ducklings (Salmonella risk)
  • Keep pets' vaccinations current
• Activities:
  • Avoid gardening or handling soil/plants (fungal spores) - if must do, wear gloves and mask
  • Avoid construction areas, renovation dust
  • Swimming: check with team - generally avoid lakes, ponds; chlorinated pools usually okay
  • No hot tubs (bacteria thrive in warm water)

Growth Factor Support (G-CSF)

What is G-CSF?

• G-CSF (Granulocyte-Colony Stimulating Factor): Stimulates bone marrow to produce more neutrophils
• Brand names:
  • Filgrastim (Neupogen) - short-acting, daily injections
  • Pegfilgrastim (Neulasta) - long-acting, one injection per cycle
  • Biosimilars available (Zarxio, Udenyca, Fulphila, etc.)

When G-CSF is Used

• Primary prophylaxis: Prevent neutropenia before it occurs
  • High-risk chemotherapy regimens (>20% risk of febrile neutropenia)
  • Older adults, prior neutropenia, high-risk features
  • When chemotherapy dose intensity is critical (curative intent)
• Secondary prophylaxis: After experiencing neutropenic complications
  • Previous febrile neutropenia
  • Severe or prolonged neutropenia
  • Dose delays due to low counts
• Treatment: After febrile neutropenia has occurred (shortens duration)

How G-CSF is Given

• Subcutaneous injection: Under skin of abdomen, thigh, or upper arm
• Timing:
  • Filgrastim: Daily starting 24-72 hours after chemotherapy, continue until counts recover (usually 7-10 days)
  • Pegfilgrastim: Single injection 24 hours after chemotherapy (not <24 hours)
• Administration: Can be given at home (self-injection or by caregiver), in clinic, or by home health nurse

Side Effects of G-CSF

• Bone pain (most common, 20-30%):
  • Aching in bones, especially pelvis, spine, long bones
  • Caused by rapid expansion of bone marrow
  • Usually mild to moderate
  • Worse with pegfilgrastim than filgrastim
  • Management: acetaminophen, ibuprofen, naproxen; rarely requires opioids
• Headache
• Fatigue
• Injection site reactions (redness, pain)
• Rare: allergic reactions, spleen enlargement or rupture (very rare)

Neutropenic Fever Management

What Happens in the Emergency Room

• Immediate priority status: Neutropenic fever patients are seen urgently
• Initial evaluation:
  • Vital signs (temperature, blood pressure, heart rate, oxygen)
  • Blood cultures (before antibiotics if possible)
  • Complete blood count (CBC) to check neutrophil count
  • Comprehensive metabolic panel (kidney function, electrolytes)
  • Urinalysis and urine culture
  • Chest X-ray (if respiratory symptoms)
  • Other cultures based on symptoms (throat, wound, stool)
• Antibiotic administration:
  • Broad-spectrum IV antibiotics started within 1 hour (ideally within 60 minutes of arrival)
  • Common regimens: cefepime, piperacillin-tazobactam, meropenem
  • Additional antibiotics added based on:
    • Clinical presentation
    • Risk factors (indwelling catheters, mucositis)
    • Previous infections or resistant organisms
    • Local resistance patterns
• Admission decision:
  • Most patients with febrile neutropenia are hospitalized
  • Low-risk patients may be treated outpatient with oral antibiotics (select cases only)

Risk Stratification (MASCC Score)

Used to identify low-risk vs high-risk febrile neutropenia:

• Low-risk criteria (MASCC score ≥21):
  • Solid tumor or lymphoma (not leukemia)
  • No/mild symptoms
  • No hypotension
  • No COPD
  • Age <60
  • Outpatient at onset of fever
  • No dehydration
• Low-risk patients may be candidates for:
  • Outpatient treatment with oral antibiotics
  • Early hospital discharge (after 24-48 hours if stable)
• High-risk patients: Hospitalization required until fever resolves and ANC recovers

Hospital Course

• IV antibiotics: Continued until:
  • Fever resolves (afebrile for 24-48 hours) AND
  • ANC recovers to >500 (preferably >1000)
  • Any identified infection source is treated
• Typical duration: 3-7 days, sometimes longer
• Modifications: Antibiotics adjusted based on culture results, clinical response
• Antifungal therapy: Added if fever persists >4-7 days despite antibiotics
• G-CSF: Often given to shorten duration of neutropenia

Antimicrobial Prophylaxis

When Prophylactic Antibiotics/Antivirals Are Used

• Fluoroquinolone prophylaxis:
  • Levofloxacin or ciprofloxacin during expected severe neutropenia
  • Reduces risk of bacterial infections
  • Used in high-risk patients (acute leukemia, stem cell transplant)
  • Controversial - contributes to antibiotic resistance
• Antiviral prophylaxis:
  • Acyclovir or valacyclovir: Prevent herpes simplex virus (HSV) reactivation
  • Used in patients with history of HSV, stem cell transplant
• Antifungal prophylaxis:
  • Fluconazole, voriconazole, posaconazole: Prevent fungal infections
  • Used in high-risk patients (acute leukemia, prolonged neutropenia)
• Pneumocystis prophylaxis:
  • Trimethoprim-sulfamethoxazole (Bactrim): Prevent PCP pneumonia
  • Used with prolonged corticosteroid use, certain chemotherapy regimens, stem cell transplant
  • Alternative: atovaquone, dapsone, pentamidine (if sulfa allergy)

Monitoring and Communication

Know Your Numbers

• Ask for your CBC results at each appointment
• Understand your ANC (absolute neutrophil count)
• Know when your counts are expected to be lowest (nadir)
• Be extra cautious during nadir week

Have a Plan

• Know your oncology team's after-hours contact number
• Know which emergency room to go to (preferably one familiar with cancer patients)
• Keep thermometer at home and know how to use it
• Keep list of medications and recent labs accessible
• Educate family members about fever protocol

When to Call Your Healthcare Team

• Immediate/Emergency:
  • Fever ≥100.4°F (38°C)
  • Chills or shaking
  • Difficulty breathing
  • Confusion or altered mental status
  • Severe pain
• Same day:
  • New cough or cold symptoms
  • Diarrhea (>4 stools in 24 hours)
  • Painful urination
  • Redness, swelling, or pain at IV site or surgical site
  • Mouth sores making eating/drinking difficult

Frequently Asked Questions

Can I still go to work during chemotherapy?

It depends on your job, treatment schedule, how you feel, and your blood counts. Office jobs are generally safer than jobs with high public contact or physical labor. Avoid work during nadir week if possible. Talk with your employer about flexible schedules or working from home options. Some patients work throughout treatment, others take disability.

Do I need to wear a mask all the time?

Not necessarily. Mask recommendations depend on your neutrophil counts, local disease activity (flu season, COVID), and where you're going. Masks are most important in crowded indoor spaces, healthcare settings, and during your nadir week. Discuss with your team - some recommend masks anytime in public during treatment, others are more selective.

Can my family get vaccinated while I'm in treatment?

Yes, family members should get vaccinated - this protects both them and you. However, they should avoid LIVE vaccines (MMR, varicella, nasal flu vaccine, oral polio - rare in US). Inactivated vaccines (flu shot, COVID, Tdap, etc.) are safe and encouraged. There's a 2-week period after live vaccines where family members should avoid close contact with you.

Should I take my temperature every day?

Not necessarily every day, but check your temperature if you feel warm, have chills, or generally don't feel well. Some oncologists recommend daily temperature checks during nadir week. Know how to properly use your thermometer. Oral or temporal artery (forehead) thermometers are fine. Avoid rectal thermometers (can cause rectal injury).

What if I have a fever but feel fine?

Call anyway. You may feel fine initially but deteriorate rapidly. Neutropenic fever is defined by temperature, not by how you feel. Don't wait to see if the fever goes away - that delay could be dangerous. Always err on the side of caution and contact your healthcare team.

Can I take Tylenol or ibuprofen for fever?

DO NOT take fever-reducing medications before calling your oncology team or going to the ER. Fever is the warning sign we need to detect infection. Once you've been evaluated and antibiotics started, then fever reducers can be used. Ibuprofen/NSAIDs should be avoided if your platelets are low (bleeding risk).

Is it safe to be around children?

Generally yes, with precautions. Children often carry infections without obvious symptoms. Avoid children who are actively sick, recently vaccinated with live vaccines, or in daycare (frequent illnesses). Your own children at home are usually fine - teach them good hand hygiene. Newborns/infants are safer than toddlers/preschoolers who are in daycare.

Can I eat at restaurants?

Most oncologists say yes, with caution. Choose restaurants with good food safety practices. Avoid buffets, salad bars (food sitting out). Order well-cooked foods. Avoid high-risk items (raw seafood, undercooked eggs). Fast food is generally safe. Use judgment based on your counts - maybe avoid restaurants during nadir week.

Do probiotics help prevent infections?

Evidence is mixed. Some studies suggest probiotics may reduce certain infections, others show no benefit. If you want to try probiotics, choose refrigerated products from reputable manufacturers. However, there have been rare cases of serious infections from probiotics in severely immunocompromised patients. Discuss with your oncology team first.

How long does it take for neutrophils to recover after chemotherapy?

Typically 2-3 weeks. Counts usually drop to their lowest point (nadir) around days 7-14 after chemotherapy, then begin recovering. Most regimens are scheduled every 2-3 weeks to allow count recovery. With G-CSF support, recovery may be faster. Some regimens cause more prolonged neutropenia requiring longer breaks between cycles.

Sources and References

• National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines: Prevention and Treatment of Cancer-Related Infections
• National Comprehensive Cancer Network (NCCN) Guidelines: Hematopoietic Growth Factors
• Infectious Diseases Society of America (IDSA) Guidelines for Febrile Neutropenia
• American Society of Clinical Oncology (ASCO) Guidelines on Prevention and Management of Chemotherapy-Induced Neutropenia
• Multinational Association for Supportive Care in Cancer (MASCC) Risk Index
• Freifeld AG et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer. Clinical Infectious Diseases. 2011