Candida Infections in Non Neutropenic Patients - Full Clinical Guideline Reference no.: CG-PHARM/2015/001 NOTE: For the empirical treatment of suspected fungal infections in neutropenic patients, see the separate guideline on the Trust intranet, or click here 1. Introduction Candida spp is the most prevalent cause of invasive fungal infections, with bloodstream infection being the main form. There has been a shift from Candida albicans to non-albican Candida spp which are less susceptible to azole antifungals e.g. fluconazole 2. Aim and Purpose 1. Candidaemia or suspected disseminated candidal infection 2. Candida in sputum or respiratory secretions 3. Oropharyngeal candida 4. Oesophageal candida 5. Candida in the urine (non neutropenic patients) 6. Osteoarticular candida 3. Guideline 1. Candidaemia or suspected disseminated candidal infection Positive blood culture for candida OR Suspected disseminated candida ie: patient persistently febrile with colonized sites and risk factors for invasive candidal disease, even if blood cultures are negative. Risk factors include previous exposure to broadspectrum antibiotics, diabetes, total parenteral nutrition, ICU patient, abdominal surgery, immunosuppressed, renal replacement therapy. Page 1 of 5
Empirical treatment Criteria Mild illness and no prior azole therapy Moderate to severe illness (e.g haemodynamically unstable) OR prior azole therapy Treatment Fluconazole 800 mg (or 12mg/kg) loading dose, then 400 mg (or 6mg/kg) once daily. Can be given IV or oral (excellent bioavailability) Anidulafungin IV 200mg on day one, then 100mg once daily In pts in whom an echinocandin is contraindicated Ambisome 3mg/kg IV once daily Directed therapy o o If the patient is stable, change to fluconazole after 3-5 days, only if the Candida isolate has confirmed susceptibility to this. If Candida glabrata or Candida krusei is isolated, continue anidulafungin until sensitivities have been confirmed by the reference lab. Voriconazole may be an oral option if sensitive Duration Treat for 14 days after the first negative blood culture. Extended treatment will be needed if there is evidence of disseminated disease e.g. eye involvement or deep seated infection. Non-antifungal management Daily or alternate day blood cultures to confirm clearance of candidaemia Central venous Catheter (CVC) related infection: - Remove and replace at a new site; catheter retention is associated with higher mortality - For fungal septic thrombophlebitis: catheter removal and incision and drainage and resection of the vein, as needed, are recommended. Evaluation for ophthalmic involvement: - Non-neutropenic patients: perform fundoscopic examination within first week of therapy, to exclude ophthalmic involvement (wait until candidaemia appears to be controlled and new spread to the eye is unlikely). Ocular findings, which usually resolve with systemic therapy alone, occur in ~15% of patients and endophthalmitis is uncommon (<2%). - Treatment of ocular disease depends on degree of involvement, chorioretinitis vs. endophthalmitis Echocardiography ( a recent observational study found infectious endocarditis in 8.3% of patients) Page 2 of 5
2. Candida in sputum or respiratory secretions Colonization of the airway with Candida and contamination of respiratory secretions with oropharyngeal material is very common. Candida pneumonia is very rare. The decision to initiate antifungal treatment should not be based on respiratory tract culture alone. 3. Oropharyngeal candida Nystatin oral suspension 100,000 units four times daily after food for 7 days If nystatin has failed, or in immunocompromised patients, fluconazole 50 100mg daily for 7-14 days If fluconazole and nystatin have failed, itraconazole oral liquid 100 200mg bd for 14 days, swished around the mouth and swallowed 4. Oesophageal candida Fluconazole : loading dose 200 400mg on day one then 100 200mg daily for 14 days If fluconazole has failed, itraconazole oral liquid 200mg bd for 14 days 5. Candida in the urine (non neutropenic patients) Remove or replace urinary catheter if present If the patient is asymptomatic treatment is not usually required - Confirm with a second sample. If this is also positive, look for and manage any pre-disposing factors e.g. urinary catheter, diabetes, structural abnormalities, reduced renal function, broad spectrum antibiotics - If the pre-disposing factors can be removed and the patient is asymptomatic, then candiduria should resolve in weeks to months. - If candiduria persists after removing pre-disposing factors, then consider imaging to look for a deep seated focus e.g. renal abscess, fungal ball. - If the patient is undergoing a urological manipulation, give fluconazole 200 400mg daily for several days before and after. Page 3 of 5
NOTE: If the patient is symptomatic - If suspected disseminated disease (see 1 above) treat as for candidaemia - If symptoms of cystitis, fluconazole 200 400mg daily for 14 days. - Pyelopnephritis Fluconazole 400mg daily for 14 days. - Renal fungus ball surgical removal, then treat as for pyelonephritis until symptoms resolve and urine no longer yields Candida. Fluconazole is the preferred treatment for candida urinary tract infections as it reaches high concentrations in the urine. Azoles other than fluconazole do not. If a candida species resistant to fluconazole is isolated, then amphotericin deoxycholate (Fungizone) may be preferred to liposomal amphotericin (Ambisome) as it reaches higher concentrations in the urinary tract. Note that Fungizone and Ambisome doses are not the same. There is very limited evidence for echinocandins and the urinary concentration is very poor. Both Ambisome and an echinocandin may be considered in pyelopnephritis if it is the result of candidaemia rather than retrograde spread from the bladder. Patients with urinary Candida resistant to fluconazole should be discussed with a consultant microbiologist 6. Osteoarticular Candida Osteomyelitis Surgical debridement is the mainstay of treatment. Fluconazole 400mg once daily (or 6mg/kg) for 6 12 months or Anidulafungin 200mg on day one, then 100mg once daily for two weeks, followed by oral fluconazole 400mg once daily for 6 12 months (confirm sensitivity to fluconazole before using) Septic arthritis native joint Washout and debridement of joint Treat as above for a minimum of 6 weeks Prosthetic joint infection Remove the prosthesis. Treat as above for at least 6/52. If prosthesis cannot be removed, then chronic suppressive treatment with fluconazole 400mg daily (if sensitivity to fluconazole confirmed) Page 4 of 5
4. References Cornely et al ESCMID guideline for the diagnosis and management of Candida diseases 2012: non neutropenic adult patients Clin Microbiol Infect 2012;18(suppl 7):19-37 Pappas et al Clinical Practice Guidelines for the Management of Candidiasis:2009 Update by the IDSA CID 2009:38 (1 Mar)503:35 Clancy et al (2012) The End of an Era in Defining the Optimal Treatment of Invasive Candidiasis CID 2012;54(8):1123-5 Andes et al Impact of Treatment Strategy on Outcomes in Patients with Candidaemia and Other Forms of Invasive Candidiasis;A Patient-Level Quantitative Review of Randomized Trials 5. Documentation Control Development of Guideline: Consultant microbiologist Antimicrobial Pharmacist Consultation with: Antimicrobial D+T subgroup Approved By: Drugs and therapeutics committee Antimicrobial Stewardship committee Integrated Care Division 15/2/16 Approval date: 1/11/15 Changes from previous version minor modification 2/2/16 Anidulafungin first line in place of micafungin in view of price fall with anidulafungin and statement in the SPC stating that due to the risk of liver tumours, micafungin should only be used when other agents are unsuitable. Review Date: 1/11/17 Key Contact: Consultant Microbiologist ( Dr Milind Khare) Page 5 of 5