Complications
Occurs early during period of candidaemia. Indistinguishable from septic shock due to bacterial causes. Characterised by hypotension, florid sepsis, and multiorgan failure. If the patient is showing signs of sepsis, they may need to be admitted to the intensive care unit and given additional care such as vigorous fluid resuscitation. Vasopressors and inotropes can be considered if hypotension persists. Requires immediate administration of broad-spectrum antifungals (not fluconazole), removal of potential source (e.g., intravascular catheter), abscess drainage, or relief of obstruction in the presence of urosepsis. Any Candida species possible. More common with neutropenia.
Reported occurrence has ranged from 0% to 45% of patients with candidaemia in published literature.[92][93]
Typically seen in association with candidaemia; can be asymptomatic. Chorioretinitis varies from asymptomatic lesions to blindness. All patients with candidaemia should undergo a thorough routine ophthalmological evaluation.
Endophthalmitis should be treated with lipid or liposomal amphotericin-B plus flucytosine for infections due to azole-resistant isolates, although fluconazole or voriconazole are preferred in azole-susceptible isolates. Echinocandins may not be useful in this context due to inadequate penetration into the vitreous space.[80] Treatment should be continued for 4-6 weeks or longer, depending on clinical response as determined by serial ophthalmological examinations. Vitrectomy should be strongly considered as well, along with intravitreal injection of amphotericin-B or voriconazole in cases of vitritis or macular involvement.[32] For cases of chorioretinitis without vitreal involvement, systemic antifungals for 4-6 weeks are recommended.
Occurs in 10% to 20% of cases of candidaemia.[86]
Additionally, blood cultures may only be positive in 20% to 70% of invasive candidiasis cases.[94]
Metastatic sites may require therapeutic drainage (e.g., joint or muscle abscess).
Central nervous system (CNS) infection is seen in association with candidaemia which may be related to neurosurgical procedures. Meningitis can occur in immunosuppressed or neurosurgery patients. Any infected CNS device should be removed. Treatment is recommended with liposomal amphotericin-B with or without flucytosine. Treatment is at least 2 weeks and should be continued until clinical, radiographical, and cerebrospinal fluid findings have all resolved. Step-down therapy to fluconazole can be done when Candida is susceptible.[20]
Osteomyelitis can be seen in association with candidaemia, as a complication following surgery, or in persons who inject drugs. May present with pain and fever and require diagnostic aspiration.
Haematogenous renal candidiasis frequently complicates candidaemia and is suggested by concomitant decrease in glomerular filtration rate and candiduria.
Antifungal selection depends upon Candida species involved as well as metastatic site. Experience with using echinocandins for disseminated sites is limited, and cerebrospinal fluid penetration is poor.
Skin infection manifests as localised or disseminated erythematous or macular/papular rash.
Hepatosplenic candidiasis (or chronic disseminated candidiasis) is usually indicated by abnormal liver function tests and computed tomography imaging.
Treatment of intra-abdominal infections is the same as treatment of candidaemia, with duration of therapy being determined by resolution of symptoms and resolution or improvement in imaging findings. Hepatosplenic candidiasis may require more prolonged treatment courses, lasting weeks to months with secondary prophylaxis usually continued through to the end of chemotherapy/period of immunosuppression. Adjunctive corticosteroid therapy may be indicated in patients who continue to have persistent fever despite antifungal therapy and negative cultures.
Rare complication of candidaemia; persons who inject drugs may be at higher risk.
For endocarditis, initial treatment should be with a high-dose echinocandin, or lipid or liposomal amphotericin-B with or without flucytosine.[32] Fluconazole can be used as step-down therapy in patients with fluconazole-susceptible Candida, after clinical improvement and clearance of candidaemia is documented. Other azoles (e.g., voriconazole) can be used for step-down therapy if isolates are resistant to fluconazole but susceptible to other azoles. Total duration of treatment is at least 6 weeks, although it can be much longer, especially if there is no surgical intervention or in cases complicated by perivalvular abscesses.[32]
Despite the lack of powered randomised studies, most literature suggests improved outcomes and decreased mortality in patients treated with surgical intervention in addition to antifungal therapy. Surgical intervention (valve replacement/repair or vegetectomy) is therefore recommended when possible.[79] Antifungals should be continued 6 weeks after surgery. In patients with native valve endocarditis not able to undergo valve replacement, long-term suppression with fluconazole may be considered after completion of 6 weeks of therapy. In patients with prosthetic valve Candida endocarditis, chronic suppressive therapy is recommended.[79]
For implantable cardiac devices, the same antifungal regimens are recommended as for endocarditis. All devices that can be removed should be removed. If devices cannot be removed such as ventricular assist devices then chronic suppressive therapy with fluconazole should be continued until the device is out.
Given the frequency of nosocomial candiduria, especially in intensive care units and accompanying bladder catheter use, ascending Candida infections are surprisingly uncommon and tend to occur in the presence of urinary obstructions and nephrostomy.
Candida pyelonephritis can be secondary to ascending infection from the urinary tract or haematogenous spread. Fluconazole is the only azole with good concentration in the urine. Pyelonephritis should be treated with fluconazole for at least 2 weeks, with amphotericin-B deoxycholate as an alternative. Another option is flucytosine in combination with amphotericin-B.[20]
Surgical intervention may be indicated for source control, especially in the setting of fungal balls. Removal or replacement of nephrostomy tubes or stents should be attempted when these are present. Longer courses of therapy may be needed if there are additional complications.
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