RISK FACTORS:
For hematogenously disseminated invasive candidiasis: Neutropenia, . Antibacterial chemotherapy, Indwelling intravascular access devices, Prior hemodialysis, Mucocutaneous candidiasis, Cardiothoracic or abdominal surgery, Diabetes
GENERAL MEASURES :
β’ Fluid and electrolyte therapy is often required
β’ Hemodynamic and respiratory support may be required in seriously ill patients
β’ Removal of potentially infected intravascular access devices is imperative
DRUG(S) OF CHOICE:
. Caspofungin (Cancidas)
. Useful as preferred therapy for candidemia in patients with prior azole therapy, immune compromised,
neutropenia
. Initial therapy of choice for any patient with candidemia
. 70 mg IV load over 1 hour on day one followed by 50 mg IV daily
. Modify dose for severe hepatic insufficiency
. Fluconazole
. 400-800 mg IV daily for fi rst week, followed by additional IV or oral therapy at the same dose for at least 2 weeks after last positive blood culture or last evidence of infection. Higher doses of fluconazole may be required if non-albicans species are known or suspected.
. Has been shown to be as effective as amphotericin B therapy and less toxic for treatment of candidemia in
patients who are not neutropenic, do not have AIDS, and are not severely immunosuppressed by therapy
after organ transplantation
. Amphotericin B
. Is an initial therapy of choice for any patient with candidemia and the preferred therapy for patients with neutropenia, severe immune compromise prior azole therapy
. Administer first in a test dose of 1 mg and then in incrementally increasing doses to 0.3-0.7 mg/kg/day.
(Some authorities administer full dose after the test dose. In a critically ill patient, slow increase in dose is not warranted). Depending on host status and form of hematogenously invasive disseminated candidiasis, total dose requirement ranges from 200 mg to 2.0 gm over a therapeutic duration of 2-10 weeks.
PRECAUTIONS :
. Amphotericin B
. Toxicity is formidable. Acute reactions occur commonly during initiation of therapy, including fever, rigors, and hypotension. These can be ameliorated or eliminated by premedication with acetaminophen, ibuprofen or hydrocortisone, and tend to decline over time with continuing daily therapy. Use meperidine if needed to abort rigors.
. Azotemia is a common complication and may be an indication for reducing therapy in some patients (to reduce toxicity, not because of renal elimination of drug). Generally recommended to hold drug if BUN > 40 mg/dL (14.3 mmol/L) or creatinine > 3.0 mg/dL (266 ΖΓmol). Hold until above levels decline, then administer drug every other day. Maintenance of optimal fl uid status and prevention of dehydration help minimize risk of azotemia. Sodium loading with 77 mEq (77 mmol) sodium daily (= 1 L 1/2 normal saline) has been suggested by some authorities to decrease renal toxicity.
. Significant hypokalemia (often requires therapy) and renal tubular acidosis (rarely requires therapy) may
develop. Significant hypomagnesemia may worsen hypokalemia.
. Anemia commonly develops in patients on protracted therapy but is almost always reversible
. Headache and phlebitis are common
. Leukopenia, thrombocytopenia, and liver function abnormalities are rarely encountered
β’ Itraconazole, voriconazole and caspofungin do not enter the urinary stream in suffi cient concentrations to
treat urinary tract infections
ALTERNATIVE DRUGS :
β’ Liposomal preparations of amphotericin B appear to be less nephrotoxic
β’ Fluconazole therapy may be preferred for infections with C. lusitaniae , which may be resistant to amphotericin B
β’ Caspofungin or amphotericin B is preferred for infections with C. krusei which is likely resistant to fluconazole, as may be C. glabrata
β’ Other azole antifungals depending on activity and safety (itraconazole and voriconazole)
β’ Flucytosine may be used as adjunctive therapy with fluconazole for peritonitis
β’ Caspofungin in candidiasis. Data suggest that caspofungin is as effective as conventional amphotericin B for treatment of candidemia and is less frequently associated with adverse effects.
PATIENT MONITORING : Complete blood count, serum electrolytes, and serum creatinine should be measured at least twice weekly in patients on daily amphotericin B therapy. If blood cultures are positive,
they should be repeated until negative.
PREVENTION/AVOIDANCE : Fluconazole, liposomal amphotericin B and voriconazole reduce the incidence of candidiasis in patients undergoing induction therapy for acute leukemia or bone marrow transplantation
POSSIBLE COMPLICATIONS :
. Of hematogenously disseminated candidiasis
. Pyelonephritis
. Endophthalmitis
. Endocarditis, myocarditis, pericarditis
. Arthritis, chondritis, osteomyelitis
. Pneumonitis
. Central nervous system infection
EXPECTED COURSE/PROGNOSIS : Overall mortality for patients with hematogenously disseminated candidiasis is 40-75%, with mortality attributable to candidemia being 15-37%