Infections in the Cancer PatientIntroduction Goals of Therapy Investigations Therapeutic Choices Nonpharmacologic Choices Coleman Rotstein, MD, FRCPC,...
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Infections in the Cancer Patient Coleman Rotstein, MD, FRCPC, FACP, FIDSA Date of Revision: November 2014
Introduction
Infections are a significant cause of morbidity and mortality in cancer patients despite progress in their recognition, therapy and prevention. The ever expanding armamentarium of antineoplastic chemotherapeutic agents, radiation therapy and immunotherapy has improved survival in cancer patients, but simultaneously has rendered them more susceptible to infections because of prolonged immune dysfunction.
Goals of Therapy
Decrease morbidity associated with infection Minimize risk of death from infection
Enhance the supportive care and quality of life of cancer patients by using prophylactic measures to prevent infection while being cognizant of the possibility of the emergence of resistant organisms
Utilize outpatient antibiotic management appropriately to facilitate care, to prevent or reduce length of hospital stay and to enhance the quality of life for cancer patients
Investigations
Thorough history with attention to:
the nature of the malignancy and associated defects in host defenses, e.g., neutropenia, B-cell and/or T-cell dysfunction
the effects on host defenses of cytotoxic, myelosuppressive or immunosuppressive therapy to treat the patient's cancer; note day of onset of fever relative to the first day of the most recent cycle of chemotherapy neutropenia (severity and expected duration)
iatrogenic procedures performed on the patient, e.g., splenectomy, placement of venous access devices or other surgical procedures
whether the nature of the malignancy suggests obstruction of natural body passages, e.g., bronchus, bowel, ureter, biliary tree CNS dysfunction
occupational and travel history, and exposure to animals
Complete physical examination with particular attention to venous access sites, wounds, skin, mouth, pharynx, sinuses, rectum and other possible sites of infection; note any localizing signs of possible infection, e.g., weakness of an extremity indicating a CNS infection Laboratory tests:
CBC and differential to assess the total neutrophil count
biochemical profile with attention to renal and liver function
at least 2 sets of blood cultures: ensure blood cultures are done from peripheral site as well as all lumens of venous access devices culture of any other suspected site of infection, e.g., urine, skin, sputum
radiographic studies appropriate for suspected sites of infection, e.g., chest x-ray or CT scan of the chest for pneumonia, CT scan of the abdomen for an intra-abdominal focus of infection, CT scan or MRI of the head for encephalitis or cerebral abscess stool for Clostridium difficile and other potential pathogens (e.g., Salmonella spp., Shigella spp., Campylobacter spp., viruses and protozoa) if diarrhea is present serological or quantitative tests (serology, antigen or nucleic acid amplification tests for cytomegalovirus, Cryptococcus spp., Epstein-Barr virus, hepatitis and Toxoplasma spp.) if indicated when appropriate, biopsy for pathology and culture of skin lesions suspected to be infectious
Therapeutic Choices Nonpharmacologic Choices
Environmental precautions are important to prevent infection in cancer patients. Standard infection control measures, especially handwashing, are of particular importance in immunocompromised patients.
Special air handling, including high-efficiency particulate filtration rooms are mandatory for profoundly neutropenic patients at high
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risk for filamentous fungal infections.
Use specialized infection control procedures (contact precautions) for patients colonized with multi-drug resistant organisms, e.g., methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae. Use droplet or air-borne precautions as required for respiratory viral illnesses.
Neutropenic patients should avoid ingesting raw fruits and vegetables; avoid fresh flowers and plants in the patient's room.
Pharmacologic Choices
Antimicrobials (antibacterials, antifungals and antivirals) used to treat infections in cancer patients are presented in Table 1.
Antibacterial Therapy Although neoplasms can cause fevers in cancer patients, seek an infectious etiology in all cases of elevated temperature. Fever is defined as a single oral temperature ≥38.3°C or a temperature of ≥38°C for ≥1-hour period in the absence of obvious environmental causes.1 Most infections are caused by microorganisms that have colonized the patient at or near the site of infection, e.g., the skin, oropharynx, genitourinary tract, GI tract or lungs.
Bacteria are the principal pathogens causing infections in cancer patients, representing >60% of initially documented episodes of infection.
The choice of antibacterial agents in febrile cancer patients is predicated on the neutrophil count, the patient's clinical status, the site of infection and local microorganism susceptibilities, with particular attention to prevalent multi-drug resistant organisms such as MRSA, VRE, ESBL-producing organisms and carbapenem-resistant organisms (Figure 1). Neutropenia is defined as a neutrophil count ≤0.5 × 109/L. A more profound degree of neutropenia (<0.1 × 109/L) confers a much greater risk of developing more severe infection. In addition, the risk of infection is directly related to the duration of neutropenia. Lower risk of infection is present in patients with neutropenia of ≤7 days whereas higher risk patients are those with neutropenia >7 days' duration. Because of the high risk of life-threatening bacterial infection and the inability to reliably distinguish patients with bacterial infection from noninfected patients at presentation (particularly in neutropenic patients), initiate prompt empiric iv antibiotic therapy to cover the potential pathogens.1
In selecting the initial antibiotic regimen and the site of care (the inpatient or outpatient setting), consider concurrent comorbid medical illnesses (e.g., heart failure, renal disease, liver disease, bleeding disorders), the control of the cancer and presence of serious medical complications.2,3,4,5 Outpatient antibiotic therapy may be employed not only for nonneutropenic patients, but also for low-risk neutropenic patients who do not have the aforementioned medical conditions or uncontrolled cancer (Figure 2). Broad spectrum antibiotic therapy that ensures adequate coverage for both gram-positive and gram-negative organisms is necessary for febrile neutropenic patients.
Vancomycin may be incorporated into the initial therapeutic regimen for patients with suspected venous access catheter-related infection, positive blood cultures for gram-positive bacteria in groups or chains, severe mucositis, known colonization with MRSA, hypotension or other evidence of cardiovascular impairment.1 Alternatively, vancomycin may be added later to the initial broad spectrum regimen once susceptibility testing has been completed. Vancomycin should be discontinued if the infecting organism is subsequently shown to be susceptible to other antibiotics or if no vancomycin-susceptible organism is recovered. Linezolid or daptomycin may be required for MRSA or VRE infections.
Metronidazole or clindamycin may be used as part of the initial antibiotic regimen for presumed anaerobic infection related to the GI tract or skin provided that antianaerobic activity is not already included in the initially selected regimen (e.g., beta-lactam/beta-lactamase inhibitor combination or a carbapenem). In neutropenic patients with a suspected bacterial infection, continue antibacterial therapy until they are no longer neutropenic (neutrophils ≥0.5 × 109/L) and are afebrile for ≥48 hours. For patients with microbiologically or clinically documented infection, continue broad spectrum antibacterial therapy for a minimum of 10–14 days and until patients are afebrile and no longer neutropenic (neutrophils ≥0.5 × 109/L).
In nonneutropenic cancer patients with a suspected bacterial infection, continue antibiotic therapy for approximately 7 days and until the patient is afebrile for ≥48 hours. Alternatively, switch from iv antibiotic therapy to oral therapy to complete an appropriate course of therapy directed towards the site that is infected.
In patients who are persistently febrile and neutropenic after 4–7 days of appropriate antibacterial therapy reassess and consider antifungal therapy as outlined below.
Antifungal Therapy Nonneutropenic patients who develop oral and or esophageal candidiasis may be treated with a topical agent such as nystatin or systemic oral agents such as fluconazole, itraconazole, posaconazole or voriconazole. Patients with extensive lesions may require parenteral therapy with fluconazole, an amphotericin B formulation, caspofungin, micafungin or voriconazole.
Parenteral antifungal therapy should be initiated for documented invasive or disseminated fungal infection in nonneutropenic and neutropenic cancer patients.
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Treatment of a proven, probable or possible invasive fungal infection in a neutropenic patient requires parenteral antifungal therapy with amphotericin B, caspofungin or voriconazole. Caspofungin or voriconazole (for invasive aspergillosis) may be preferred in patients with renal dysfunction.1 The lipid-based preparations of amphotericin B have equivalent efficacy but produce less nephrotoxicity and infusion reactions than conventional amphotericin B. They may be used as salvage therapy for patients with fungal infections that fail to respond to amphotericin B or for patients with amphotericin B toxicity or intolerance.6 Caspofungin, micafungin or anidulafungin may effectively treat candidemia in neutropenic or nonneutropenic patients.7,8 Itraconazole, which is available only in an oral formulation, has enhanced activity against Aspergillus spp. compared to fluconazole and is an alternative for oral step-down therapy after parenteral treatment for invasive aspergillosis.
Voriconazole, available both in iv and oral formulations, conferred superior efficacy and survival compared to amphotericin B for primary therapy of invasive aspergillosis,9 and has better activity against infections caused by Scedosporium spp. and Fusarium spp.
Voriconazole (alone or in combination with anidulafungin or caspofungin) or a lipid-based formulation of amphotericin B may be used in the treatment of documented invasive aspergillosis.10,11,12 Posaconazole may be used for refractory invasive fungal infections or in patients intolerant to other medications.13
Antiviral Therapy There is no indication for the empiric use of antiviral drugs in the treatment of cancer patients without evidence of viral disease.1 Neuraminidase inhibitors, such as oseltamivir, are the mainstay of therapy for susceptible influenza virus causing respiratory tract infections in cancer patients.
Skin or mucous membrane lesions due to herpes simplex virus or varicella-zoster virus may be treated with oral or iv acyclovir. Oral famciclovir or valacyclovir are better absorbed from the GI tract than acyclovir, and are alternatives.14 IV foscarnet is available through Health Canada's Special Access Programme for acyclovir-resistant herpesvirus infections.
Cytomegalovirus infection in bone marrow transplant recipients may be treated with ganciclovir iv, or with valganciclovir when oral therapy is desirable.
Supportive Care Measures Granulocyte (G-CSF) and granulocyte-macrophage (GM-CSF) colony-stimulating factors may decrease the incidence and duration of neutropenia after chemotherapy. They are not routinely recommended as adjunctive treatment of febrile neutropenia. However, they may be considered for patients who remain profoundly neutropenic and have failed to respond to appropriate antimicrobial therapy for documented infection such as pneumonia, severe cellulitis or sinusitis.1,15 Once neutrophil counts reach ≥0.5 × 109/L, colony-stimulating factor support should be discontinued.
Prevention of Infection in Cancer Patients For cancer patients with pronounced T cell dysfunction, prophylaxis with oral sulfamethoxazole/trimethoprim is recommended to prevent Pneumocystis jirovecii pneumonia. Alternative prophylactic agents are inhaled pentamidine and dapsone. Strategies designed to prevent bacterial infection in profoundly neutropenic cancer patients, such as those with acute leukemia, focus on eliminating indigenous microflora and preventing acquisition of new potential pathogens. Potential antimicrobial regimens are fluoroquinolones, sulfamethoxazole/trimethoprim or orally nonabsorbable antibiotics (gentamicin, vancomycin and nystatin). Ciprofloxacin or levofloxacin significantly decrease febrile morbidity, bacterial infections and mortality for patients with acute leukemia and those undergoing bone marrow transplantation.16 Prophylaxis during the expected period of neutropenia in the first month of chemotherapy in patients with solid tumors or lymphoma (levofloxacin 500 mg for 7 days) also reduces the rate of febrile episodes.17 There may be a predilection for gram-positive infection when ciprofloxacin is used prophylactically. This may be overcome by adding another antibiotic with good activity against gram-positive organisms (e.g., a penicillin or a macrolide);18 however, this practice is not currently recommended in international guidelines.1 Antifungal prophylaxis with oral fluconazole prevents invasive fungal infection in allogeneic bone marrow transplant recipients and in patients with acute leukemia who are undergoing remission-induction chemotherapy.19,20 Itraconazole prophylaxis may be preferred for individuals at greater risk of developing invasive aspergillosis.
Posaconazole is as effective as fluconazole in preventing all invasive fungal infections, but is superior for prevention of invasive aspergillosis in hematopoietic stem-cell transplant recipients with graft-versus-host disease.21 In patients with acute leukemia who are undergoing chemotherapy, posaconazole is more effective than both fluconazole and itraconazole for prevention of invasive fungal infections.22,23 Micafungin is effective as prophylaxis in hematopoietic stem-cell transplant recipients.24
If fluconazole has been used prophylactically, it should not be used empirically or for documented fungal infections in neutropenic cancer patients. For these situations, a parenteral amphotericin B formulation1 or caspofungin10 are the drugs of choice.
However, voriconazole is the drug of choice for invasive aspergillosis.
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Vaccination of Cancer Patients Cancer patients are considered to be immunocompromised and as a result should not receive live vaccines during periods of immunosuppression.25,26 Live vaccines should be administered ≥4 weeks prior to immunosuppression.
The magnitude and duration of immune response to vaccinations may be diminished in immunosuppressed cancer patients.
Therapeutic Tips
Avoid aminoglycosides in patients with impaired renal function, particularly those receiving treatment with other nephrotoxic drugs such as cisplatin, cyclosporine or amphotericin B. In deciding on cost-effective empiric therapy, drug acquisition costs by themselves are of limited value. Also consider the relative effectiveness, side effect profile and overall resource consumption of the available treatments. Monotherapy with an iv broad-spectrum antipseudomonal beta-lactam (ceftazidime, imipenem/cilastatin, meropenem or piperacillin/tazobactam) is suitable for the treatment of febrile neutropenic episodes. A 2007 meta-analysis found cefepime monotherapy may be associated with higher all-cause mortality compared to other beta-lactams;27 however a subsequent meta-analysis found no association with increased mortality.28
Combination therapy for febrile neutropenia with a beta-lactam and an aminoglycoside is associated with more adverse events (e.g., a higher incidence of nephrotoxicity, ototoxicity) than monotherapy with a beta-lactam. Identification of low-risk patients appropriate for outpatient antibiotic management may enhance the patient's quality of life and reduce costs.
Algorithm
Figure 1: Approach to Fever in Cancer Patients
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Abbreviations: CBC = complete blood count; CNS = central nervous system; GI = gastrointestinal; GU = genitourinary
Figure 2: Management of Infection in Febrile Neutropenic Cancer Patients
Antipseudomonal combination therapy = a beta-lactam (piperacillin, piperacillin-tazobactam, ceftazidime, imipenem-cilastatin or meropenem) plus an aminoglycoside. b Piperacillin-tazobactam, ceftazidime, imipenem-cilastatin or meropenem. c Double beta-lactam therapy = ceftazidime plus either piperacillin or piperacillin-tazobactam. a
Abbreviations: MRSA = methicillin-resistant S. aureus
Drug Table Table 1: Drugs Used to Treat Infections in Cancer Patients Classb
Drug
Dosage
Adverse Effects
Drug Interactions
Costa
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Dosage
Adverse Effects
Drug Interactions
Aminoglycosides
amikacin generics
15–20 mg/kg once daily iv (extendedinterval regimen)c
Ototoxicity (auditory and/or vestibular), nephrotoxicity, neuromuscular paralysis (rare).
Synergistic or additive toxicity if used with vancomycin and/or platinum-derived antineoplastics, amphotericin B and/or other nephrotoxic/ototoxic drugs.
Aminoglycosides
gentamicin generics
5–7 mg/kg once daily iv (extendedinterval regimen)c
Ototoxicity (auditory and/or vestibular), nephrotoxicity, neuromuscular paralysis (rare).
Synergistic or additive toxicity if used with vancomycin and/or platinum-derived antineoplastics, amphotericin B and/or other nephrotoxic/ototoxic drugs.
$
Aminoglycosides
tobramycin generics
5–7 mg/kg once daily iv (extendedinterval regimen)c
Ototoxicity (auditory and/or vestibular), nephrotoxicity, neuromuscular paralysis (rare).
Synergistic or additive toxicity if used with vancomycin and/or platinum-derived antineoplastics, amphotericin B and/or other nephrotoxic/ototoxic drugs.
$
Carbapenems
imipenem/cilastatin Primaxin, generics
500 mg Q6H iv
Diarrhea, hypersensitivity reactions, neutropenia, hemolytic anemia, thrombocytopenia. Associated with seizures especially with high doses (1 g Q6H) and in patients with renal dysfunction.
Carbapenems may decrease valproic acid levels. Seizures have been reported with concurrent use of imipenem and ganciclovir.
$$$
Carbapenems
meropenem Merrem, generics
1 g Q8H iv
Diarrhea, nausea, hypersensitivity reactions, neutropenia, hemolytic anemia, thrombocytopenia.
Carbapenems may decrease valproic acid levels.
$$$
Cephalosporins
cefepime generics
2 g Q8H iv
Rash, diarrhea, GI upset, headache, hypersensitivity reactions, hematologic reactions.
May enhance anticoagulant effect of warfarin.
$$
Classb
Costa $$
Risk of seizures particularly in those with renal dysfunction.
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Dosage
Adverse Effects
Drug Interactions
Cephalosporins
ceftazidime Fortaz, generics
2 g Q8H iv
Rash, diarrhea, GI upset, headache, hypersensitivity reactions, hematologic reactions.
May enhance anticoagulant effect of warfarin.
Cephalosporins
ceftriaxone generics
1–2 g once daily iv
Rash, diarrhea, GI upset, headache, hypersensitivity reactions, hematologic reactions. Pseudocholelithiasis.
May enhance anticoagulant effect of warfarin. Do not reconstitute or mix with calciumcontaining solutions.
$
Classb
Costa $$$
Do not administer simultaneously with calcium-containing iv solutions via a Y-site. Administration may be done sequentially provided the infusion lines are thoroughly flushed between infusions.
Cyclic Lipopeptides
daptomycin Cubicin
4–6 mg/kg once daily iv
Headache, rash, elevated creatine kinase, constipation.
Possible increased risk of myopathy when used concurrently with HMG-CoA reductase inhibitors.
$$$$
Fluoroquinolones
ciprofloxacin Cipro, Ciprofloxacin, other generics
500 or 750 mg BID po
GI upset, rash, CNS toxicity.
Warfarin: increases INR. Binds with antacids, iron, sucralfate.
$
levofloxacin generics
500 mg once daily po/iv
Nausea, diarrhea, headache, insomnia, dizziness. Cases of severe liver injury including liver failure have been reported.
Binds with antacids, metal cations, sucralfate. Avoid in patients on Class Ia or III antiarrhythmics or with prolonged QTc interval.
$
Nausea, diarrhea, headache, insomnia, dizziness. Cases of severe liver injury including liver failure have been reported.
Binds with antacids, metal cations, sucralfate. Avoid in patients on Class Ia or III antiarrhythmics or with prolonged QTc interval.
$
Nausea, vomiting, rash, headache insomnia, dizziness.
Warfarin: increases INR. Binds with antacids, metal cations, sucralfate.
$
Fluoroquinolones
400 mg Q12H iv
QTc prolongation. Fluoroquinolones
moxifloxacin Avelox, generics
400 mg once daily po/iv
QTc prolongation. Fluoroquinolones
ofloxacin generics
400 mg BID po
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Dosage
Adverse Effects
Drug Interactions
Glycopeptides
vancomycin generics
15 mg/kg Q12H iv
Shock after rapid iv infusion (<1 h), fever, chills, phlebitis, “red-neck” syndrome, tingling and flushing of head, neck, chest, rash, transient leukopenia or eosinophilia, ototoxicity.
Nephrotoxicity may be enhanced if given with aminoglycosides or other nephrotoxins.
Lincosamides
clindamycin Dalacin C Phosphate Sterile Solution, generics
600 mg Q8H iv
Diarrhea, minor reversible increase in liver aminotransferases, reversible neutropenia, thrombocytopenia, pseudomembranous colitis.
May enhance action of neuromuscular blocking agents.
$
Macrolides
azithromycin Zithromax, generics
500 mg once daily iv
GI upset, QTc interval prolongation.
May increase bioavailability of digoxin, warfarin. Less likely than other macrolides to cause interactions.
$
Macrolides
erythromycin Erythrocin, generics
1 g Q6H iv
Abdominal pain, nausea, vomiting, diarrhea, QTc interval prolongation, thrombophlebitis, transient hearing loss with high doses.
May increase bioavailability of digoxin, warfarin. Inhibitor of CYP3A4 enzymes therefore many potential interactions (e.g., carbamazepine, cyclosporine, lovastatin, methylprednisolone, simvastatin, theophylline).
$$$
Nitroimidazoles
metronidazole generics
500 mg Q8–12H iv
GI upset, reversible neutropenia, seizures, peripheral neuropathy (rare), rash, metallic taste.
Disulfiram-like reaction with alcohol. Potentiation of warfarin effects and other oral coumarin-type anticoagulants.
$
Oxazolidinones
linezolid Zyvoxam, generics
600 mg Q12H po/iv
Thrombocytopenia, anemia, leukopenia, peripheral neuropathy.
May potentiate the pressor effect of adrenergic agents. Possible serotonin syndrome when used with SSRIs or MAOIs.
$$
Penicillins
amoxicillin/clavulanate Clavulin, generics
One 500/125 mg tablet TID po or
Diarrhea, rash, hypersensitivity reactions, interstitial nephritis, neutropenia,
May increase serum levels of methotrexate. May enhance anticoagulant effect
$
Classb
One 875/125 mg tablet BID po
Costa $$$
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Classb
Drug
Penicillins
piperacillin generics
Penicillins
Adverse Effects
Drug Interactions
hemolytic anemia; thrombocytopenia.
of warfarin.
4 g Q6H iv
Diarrhea, rash, hypersensitivity reactions, interstitial nephritis, neutropenia, hemolytic anemia; thrombocytopenia.
May increase serum levels of methotrexate. May enhance anticoagulant effect of warfarin.
$$
piperacillin/tazobactam generics
3.375–4.5 g Q6–8H iv
Diarrhea, rash, hypersensitivity reactions, interstitial nephritis, neutropenia, hemolytic anemia; thrombocytopenia.
May increase serum levels of methotrexate. May enhance anticoagulant effect of warfarin.
$$
Sulfonamide Combinations
sulfamethoxazole/trimethoprim
trimethoprim 20 mg/kg/day and sulfamethoxazole 100 mg/kg/day divided QID po/iv
Nausea, vomiting, diarrhea; hypersensitivity reactions, leukopenia, thrombocytopenia, hepatitis (rare).
May increase effect of phenytoin, warfarin. Enhances toxicity of methotrexate.
po: $ iv: $$$
Antifungals, echinocandins
anidulafungin Eraxis
200 mg loading dose iv, then 100 mg daily iv
Diarrhea, hypokalemia, elevated liver function tests, rash.
No clinically significant interactions.
$$$$
Antifungals, echinocandins
caspofungin Cancidas
70 mg loading dose iv, then 50 mg daily iv
Fever, nausea, vomiting, phlebitis at the injection site, diarrhea.
Increased liver function tests with cyclosporine. Carbamazepine, dexamethasone, efavirenz, nelfinavir, phenytoin, rifampin decrease caspofungin levels. Caspofungin decreases levels of tacrolimus.
$$$$
Antifungals, echinocandins
micafungin Mycamine
50 mg daily iv as prophylaxis
Headache, rash, nausea, vomiting, phlebitis at the injection site.
Micafungin increases serum levels of nifedipine and sirolimus.
$$$$
Antifungals, polyenes
amphotericin B Fungizone
0.3–1.5 mg/kg Q24H iv
Rigors, renal dysfunction (azotemia), headache, hypokalemia, phlebitis, thrombocytopenia, anemia, leukopenia (rare), hypotension.
Increased risk of azotemia when used with other nephrotoxic drugs.
$$
Antifungals, polyenes
amphotericin B lipid preparations
3–5 mg/kg Q24H iv
Less nephrotoxicity than with
Septra Injection, generics
Dosage
150 mg daily iv for treatment of esophageal candidiasis
Costa
$$$$$
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Classb
Drug
Dosage
Antifungals, polyenes
nystatin generics
3.6 million units Q4H po
Nausea, vomiting, diarrhea.
Antifungals, triazoles
fluconazole Diflucan, generics
100–400 mg Q24H po
Nausea, headache, skin rash, abdominal pain, vomiting, diarrhea.
May cause hepatotoxicity if used with other potentially hepatotoxic drugs. Coumarin-like drugs, cyclosporine, phenytoin, sulfonylureas may require dosage adjustment (monitor).
$
Antifungals, triazoles
itraconazole Sporanox, Sporanox Oral Solution
100–200 mg daily–BID po
Nausea, rash, headache, reversible increase in hepatic enzymes.
Coumarin-like drugs, cyclosporine, digoxin, phenytoin, sulfonylureas may require dosage adjustment (monitor). Didanosine, H2-antagonists, phenytoin, rifampin may decrease itraconazole levels; itraconazole increases levels of statins.
$
Antifungals, triazoles
posaconazole Posanol
Prophylaxis:
Nausea, vomiting, fever, diarrhea, dry mouth, abdominal pain, headache.
Cyclosporine, midazolam, sirolimus, statins, tacrolimus and vinca alkaloids require dose adjustments (monitor). Cimetidine, phenytoin, rifabutin may decrease posaconazole levels.
$$$$
Abelcet, AmBisome
Adverse Effects
Drug Interactions
amphotericin B.
100–400 mg Q24H iv
200 mg TID po Refractory invasive fungal infections:
400 mg BID po
Costa
$
Antifungals, triazoles
voriconazole Vfend, generics
200 mg BID po; 4–6 mg/kg Q12H iv
Visual disturbances, nausea, vomiting, rash, increased hepatic enzymes.
Coumarin-like drugs, cyclosporine, sulfonylureas may require dosage adjustment (monitor); barbiturates, carbamazepine, phenytoin and rifampin may decrease voriconazole levels.
po:$$ iv:$$$$$
Antivirals, guanine
acyclovir generics
5–10 mg/kg Q8H iv
Phlebitis, rash, hypotension,
Probenecid decreases renal
$$$$$
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Classb
Drug
Dosage
Adverse Effects
Drug Interactions
headache, nausea, tremors, confusion, seizures (1%), renal dysfunction.
clearance; may increase theophylline levels.
Antivirals, guanine nucleoside analogues
famciclovir Famvir, generics
500 mg TID po
Headache, nausea, pruritus.
Probenecid decreases renal clearance.
$
Antivirals, guanine nucleoside analogues
ganciclovir Cytovene
Induction: 5 mg/kg Q12H iv
Avoid use with zidovudine (increased hematologic toxicity).
$$
Maintenance: 6 mg/kg Q24H iv
Leukopenia, nausea, headache, behavioural changes.
Antivirals, guanine nucleoside analogues
valacyclovir Valtrex, generics
1 g TID po
Headache, nausea.
Probenecid decreases renal clearance.
$
Antivirals, guanine nucleoside analogues
valganciclovir Valcyte, generics
900 mg daily po
Leukopenia, nausea, headache, behavioural changes.
Prodrug of ganciclovir. Avoid use with zidovudine (increased hematologic toxicity).
$$
Antivirals, neuraminidase inhibitors
oseltamivir Tamiflu
75 mg Q12H po
Nausea, vomiting, diarrhea, abdominal pain.
nucleoside analogues
Costa
$
Cost of 1-day supply based on 50 kg body weight; includes drug cost only. In this table, antibacterial agents are presented first followed by antifungals and antivirals, each in alphabetical order. c The extended-interval regimen (high-dose, once-daily administration) is thought to be associated with less toxicity. However, for patients with uncertain or impaired renal function some clinicians prefer to use the conventional dosing method (daily dose divided Q8H) because of more experience with this regimen in this population. Whichever regimen is used, serum levels and renal function should be monitored and the dose and/or interval should be adjusted accordingly. a b
Dosage adjustment may be required in renal impairment; see Dosage Adjustment in Renal Impairment.
Legend:
$ < $25
$$ $25–75
$$$ $75–150
$$$$ $150–225
$$$$$ $225–300
Suggested Readings
Bow EJ, Evans G, Fuller J et al. Canadian clinical practice guidelines for invasive candidiasis in adults. Can J Infect Dis Med Microbiol 2010;21(4):e122-50. Freifeld AG, Bow EJ, Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011;52(4):427-31. Paul M, Dickstein Y, Schlesinger A et al. Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropenia. Cochrane Database Syst Rev 2013;6:CD003038. Rotstein C, Laverdiere M, Marciniak A et al. An economic evaluation of voriconazole versus amphotericin B for the treatment of invasive aspergillosis in Canada. Can J Infect Dis Med Microbiol 2004;15(5):277-84. Yu DT, Seger DL, Peterson JF et al. Fluconazole for empiric antifungal therapy in cancer patients with fever and neutropenia. BMC Infect Dis 2006;6:173.
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