Chemotherapy is an important treatment option for cancer patients, however it does come with potential side effects and complications. One of the most concerning potential complications of chemotherapy is infection. Chemotherapy works by killing rapidly dividing cancer cells, but it also damages healthy cells such as white blood cells that help fight infection. This can leave patients immunocompromised and susceptible to potentially life-threatening infections during treatment.
How does chemotherapy increase infection risk?
Chemotherapy targets all rapidly dividing cells, including cancer cells and certain healthy cells. One group of healthy cells that are vulnerable to chemotherapy’s effects are white blood cells, also called leukocytes. These include:
- Neutrophils – Help fight bacterial infections and inflammation
- Lymphocytes – Includes B cells and T cells that target specific pathogens
- Monocytes – Develop into macrophages that engulf and destroy pathogens
When chemotherapy damages these cells, the body is left with lower numbers of circulating white blood cells, a condition called neutropenia or leukopenia. This weakens the immune system and leaves patients prone to infections. The duration and severity of neutropenia depends on the type and dose of chemo drugs used. Higher chemo doses tend to cause more severe neutropenia.
Some statistics on infection risk with neutropenia:
- Patients with an absolute neutrophil count below 500 cells/mm3 are considered high infection risk
- Infection risk increases by up to 10% for every 500 cells/mm3 drop below 1500 cells/mm3
- Over 50% of patients undergoing chemotherapy for leukemia develop neutropenia
- Up to 80% of chemotherapy patients receive anti-infective medications to reduce infection risk
Neutropenia typically develops 7-14 days after each chemotherapy cycle and lasts up to one week until the bone marrow recovers and produces more neutrophils. The lower the neutrophil count, the higher the risk of infection during this time.
What types of infections are most common?
Neutropenic patients are prone to developing a wide range of bacterial, viral, and fungal infections. The most common infection risks include:
Bacterial Infections
- Pneumonia – Lung infection caused by Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella, Pseudomonas, and other bacteria.
- Skin infections – Includes cellulitis, abscesses, and wound infections from Staphylococcus aureus or streptococcal bacteria.
- Bloodstream infections – Can arise when bacteria enter the blood from infected catheters or penetrated intestinal walls.
- Urinary tract infections (UTIs) – Higher risk from catheter use during hospitalization.
- Gastroenteritis – Caused by salmonella, campylobacter, clostridium difficile, E. coli.
Viral Infections
- Herpes simplex virus (HSV) – Reactivation of oral or genital herpes.
- Varicella zoster virus (VZV) – Causes chickenpox and shingles.
- Cytomegalovirus (CMV) – Transmitted through body fluids, urine, or blood.
Fungal Infections
- Candidiasis – Yeast overgrowth in the mouth, throat, vagina or bloodstream.
- Aspergillosis – Mold infection in the lungs and sinuses.
Without an adequate immune response, these types of infections can quickly overwhelm the body and turn life-threatening if not treated promptly. Bacteremia, sepsis, pneumonia, and meningitis are some of the most dangerous complications.
Risk Factors
Certain factors can increase a chemotherapy patient’s vulnerability to infection:
- Advanced age
- Poor nutritional status
- Coexisting illnesses like diabetes or kidney failure
- Indwelling catheters
- Prior chemotherapy or radiation
- Prolonged neutropenia
- Bone marrow involvement by cancer
- Dose intensity of chemotherapy regimen
Higher risk groups include leukemia and lymphoma patients undergoing induction chemotherapy, as well as stem cell transplant recipients who receive high-dose chemotherapy. Up to 80% of stem cell transplant patients develop infections in the first year.
Signs and Symptoms
Neutropenic patients and their caregivers must watch closely for any signs of infection when white blood cell counts are low. However, neutropenic infections may present atypically since there are fewer white blood cells to mount an inflammatory response. Signs to watch for include:
- Fever – Temp over 38 C/100.4 F on one occasion or over 38 C/100.4 F for over an hour.
- Chills/sweating
- Sore throat, cough, shortness of breath
- Nasal congestion or discharge
- Burning/pain with urination
- Diarrhea
- Abdominal pain
- Unexplained bleeding/bruising
- Headaches, stiff neck, sensitivity to light
- Rash, lesions, or skin redness
- General weakness and fatigue
Because neutropenic patients are vulnerable to rapid spread of infection, they are advised to immediately go to the emergency room if they develop a fever of 38 C (100.4 F) or higher. Blood cultures, urinalysis, and chest x-rays may be done to determine if infection is present.
Potential Complications
Left untreated, infections in an immunocompromised chemotherapy patient can lead to sepsis, septic shock, organ failure, and even death. Potentially fatal complications include:
- Sepsis – Life-threatening condition where chemicals released to fight an infection trigger widespread inflammation.
- Septic shock – Dangerously low blood pressure and organ failure due to sepsis.
- Bacteremia – Bacteria multiplying in the bloodstream.
- Pneumonia or respiratory failure – Lung and respiratory infection can cause breathing difficulty.
- Meningitis – Infection of the membranes surrounding the brain.
- Cellulitis – Bacterial skin infection that can spread deep into tissues.
- Peritonitis – Infection of the peritoneum lining the abdomen.
Sepsis has a mortality rate as high as 50%. Timely antibiotics and intensive care are crucial for survival, but sepsis can still result in limb loss or impaired organ function.
Prevention
Preventing infections during chemotherapy involves:
- Careful handwashing and infection control
- Avoiding contact with sick people
- Good oral hygiene and dental care
- Avoiding raw/undercooked foods that may contain pathogens
- Avoiding cutting or irritating the skin to prevent entry points for germs
- Promptly treating any wounds, rashes or signs of infection
- Getting annual vaccinations like the flu shot
Medications may also be used prophylactically to reduce infection risk:
Antibiotics
- Fluoroquinolones like ciprofloxacin are commonly used.
- Often given for 7-14 days if neutropenia is expected to last over seven days.
Antifungals
- Given preventatively if high risk for fungal infections.
- Drugs include fluconazole, micafungin, voriconazole.
Antivirals
- Acyclovir can prevent HSV reactivation.
- Drugs like valacyclovir help prevent VZV infections.
G-CSF Medications
- Granulocyte colony-stimulating factors like Neupogen and Neulasta boost neutrophil production.
- Can allow higher chemo doses by limiting neutropenia duration and severity.
- Used prophylactically in high risk patients.
With preventative measures, close monitoring, and prompt treatment of fevers, patients can reduce serious complications from infection during chemotherapy.
Treatment
At the first sign of fever or infection, chemotherapy patients should be evaluated urgently. Initial treatment steps include:
- Blood, urine and other cultures to identify the infection
- CBC count to check neutrophil levels
- Chest x-ray if respiratory symptoms are present
- Administration of empiric broad-spectrum IV antibiotics
Broad antibiotics are given before culture results confirm the specific pathogen. This helps ensure rapid treatment before sepsis develops. The antibiotics may consist of:
- A broad spectrum beta-lactam like piperacillin-tazobactam, cefepime, imipenem or meropenem
- An aminoglycoside like gentamicin
- Vancomycin to cover drug-resistant bacteria
Once cultures identify the infecting organism, antibiotics can be adjusted and targeted appropriately. If fungal infection is suspected, antifungals are added. Daily blood counts monitor neutrophil recovery. G-CSF medications may be given to stimulate neutrophil production and shorten the duration of neutropenia.
Most neutropenic fever patients without complications can be treated with IV antibiotics as outpatients. However, hospital admission is warranted if patients exhibit:
- Sepsis
- Hemodynamic instability
- Severe pneumonia or respiratory compromise
- Serious comorbidities like organ dysfunction
- Rapidly progressing soft tissue infection
- Meningitis or encephalitis
- Gastrointestinal complications like perforation or bleeding
- Lack of response to empiric antibiotic regimen
In the ICU, sepsis and septic shock are treated aggressively with IV fluids, vasopressors, mechanical ventilation, and treatment of any organ failure. This comprehensive inpatient support helps maximize the chances of survival.
Outcomes
With prompt and appropriate antibiotic treatment, most neutropenic infections can be cured before causing permanent complications or death. However, outcomes depend heavily on:
- How quickly antibiotics were initiated when fever developed
- The severity of neutropenia
- How quickly neutrophil counts recover
- Whether the patient develops sepsis or hypotension
- Presence of any organ failure or comorbidities
- Whether initial empiric antibiotics covered the causative pathogens
Even with treatment, the case fatality rate of neutropenic sepsis has been estimated between 2% to 21% in cancer patients. The likelihood of death is highest in cases of:
- Profound neutropenia below 100 cells/mm3
- Pneumonia or other serious respiratory infections
- Bacteremia involving highly resistant bacteria
- Delayed initiation of broad antibiotics
- Septic shock and multiple organ failure
The development of respiratory compromise and hypotension are particularly ominous signs. Fungal infections also have higher mortality rates. However, most neutropenic patients can recover fully if infections are caught at the earliest sign of fever and treated aggressively per protocol. Preventing the progression to sepsis is key.
Conclusion
Infection is one of the most serious potential complications facing cancer patients undergoing cytotoxic chemotherapy. By destroying white blood cells in the bone marrow, chemotherapies impair the body’s ability to fight off pathogens. This leaves patients vulnerable to dangerous bacterial, viral and fungal infections. Neutropenic sepsis, pneumonia and meningitis can all quickly become life-threatening without prompt antibiotic treatment and supportive care. Preventing infections through prophylactic antibiotics, G-CSF medications, and excellent hygiene helps reduce risk. Fever should be treated as an emergency in neutropenic patients to avoid rapid sepsis progression. While infections were once the leading cause of death in chemotherapy patients, outcomes have improved considerably with modern preventative strategies, antibiotics, and ICU supportive care. With close monitoring and early intervention, most patients now recover fully from neutropenic fever episodes. However, severe infections in profoundly neutropenic patients can still become rapid and fatal. This makes infection one of the most serious potential complications that should be watched for closely during cytotoxic chemotherapy treatment.