Anti-infectives Knowledge Network

The antifungal armamentarium in 2012: Pharmacological and clinical implications – William Hope

Key points

• There are four major categories of systemic antifungal agents that are effective for the treatment of candidiasis: echinocandins, polyenes, a pyrimidine analogue and triazoles³
• When selecting the most appropriate treatment strategy, pharmacokinetics and pharmacodynamics need to be considered to optimise dosing and outcomes in specific patient groups^9,10

Invasive candidiasis in the individual patient (renal replacement therapy) – Patricia Muñoz

Key points

• Appropriate dosing of antifungal agents is essential in patients with invasive fungal infections, but relatively few studies have investigated the use of these drugs in patients with severe organ dysfunction, such as renal insufficiency¹¹
• Inappropriate dosing of antimicrobials during renal replacement therapy may result in undesired clinical outcomes, including reduced therapeutic efficacy and drug toxicities¹¹

Invasive candidiasis in the individual patient (HIV) – Vincent Jullien

Key points

• Patients with HIV usually receive numerous concomitant medications, including HAART, therapy for comorbid conditions, and prophylaxis against opportunistic infections¹²
• Cytochrome P450 enzymes are involved in the metabolism of some components of HAART and a number of antifungal agents¹²
• Awareness of drug–drug interactions between HAART and antifungal agents is important for clinicians in order to avoid virologic failure or toxicity¹²

Invasive candidiasis in the individual patient (liver transplant) – Faouzi Saliba

Key points

• Invasive candidiasis is the most common invasive fungal infection in solid organ transplant recipients¹³
• Surgical factors and technical complexity of the transplant surgery can strongly influence the incidence of invasive fungal infections (especially invasive candidiasis) after liver transplantation¹⁴
• Calcineurin inhibitors can have narrow therapeutic windows, so drug–drug interactions with these immunosuppressants can lead to toxicity or potential graft rejection¹⁵

Burning issues (haematology) – Johan Maertens

Key points

• Heavily immunosuppressed cancer patients have many inter-related risk factors for invasive candidiasis¹⁶
• The epidemiology of Candida infections in haematology patients differs from that in other settings, and appears to be affected by prior antifungal exposure¹⁷
• Ongoing research relating to Candida infections in haematology patients includes the development of new antifungal agents to address resistance issues, new diagnostic tools for early detection of infection, and new strategies for antifungal prophylaxis and early, pathogen-specific preemptive therapy¹⁶

Burning issues (neonates) – Paolo Manzoni

Key points

• Approximately three quarters of all Candida infections in the neonatal ICU occur in infants weighing <1000 g at birth¹⁸
• Randomised clinical trials in neonates have shown that fluconazole prophylaxis can reduce the rate of invasive Candida infection substantially¹⁹
• For treatment of Candida in neonates, the ideal antifungal agent would be well tolerated with activity against biofilms and against fluconazole-resistant strains²⁰

Evolution of Candida guidelines: where are we in 2012? – Andrew Ullmann

Key points

• There are an increasing number of management guidelines available for invasive fungal infections around the world⁴
• Diagnostic and management guidelines being finalised by ESCMID will provide an independent and exclusively European perspective on approaches to Candida diseases⁴

Treating candidaemia in adults – Matteo Bassetti

Key points

• Mortality rates associated with candidaemia remain high, and can be affected by a number of factors relating to the patient,^21, the pathogen (such as biofilm formation), and management strategies (particularly inadequate antifungal therapy)²²
• Treatment should be started as early as possible with the most appropriate antifungal agent to improve the chance of a successful outcome³
• Echinocandins are the most strongly recommended antifungal agents for targeted treatment of candidaemia in adults in the ESCMID guidelines⁴

Treating candidaemia in children – Emmanuel Roilides

Key points

• In relation to invasive fungal infections, children are not ‘little adults’: the epidemiology and pathophysiology of fungal infections differ with patient age, as do the pharmacological characteristics of antifungal agents²³
• Data describing the optimal use of antifungal agents in children and especially in neonates are limited, even for well-established drugs including amphotericin B and fluconazole²³

Complications of candidaemia – Patricia Muñoz

Key points

• Complications of candidaemia result from haematogenous spread and can affect a range of tissues or organs²⁴
• Candida endophthalmitis is a challenging complication to manage, as penetration into the eye is inadequate for some antifungal agents²⁴
• Despite aggressive medical and surgical interventions, mortality rates for fungal endocarditis remain unacceptably high²⁵

The impact of biofilms – Mahmoud Ghannoum

Key points

• Medical devices are responsible for many nosocomial infections, particularly in critically ill patients. Device-associated infections can cause major medical and economic sequelae²⁶
• The in vitro activity of azoles, echinocandins and polyenes against Candida biofilms has been studied in a number of models

Catheter-related Candida infections – Emilio Bouza

Key points

• Intravascular catheter-related infections are a major cause of morbidity and mortality, and are most commonly caused by coagulase-negative staphylococci, Staphylococcus aureus, aerobic Gram negative bacilli and Candida albicans²⁷
• Because the pathogenesis of catheter-related infections is complex, pathogens display variable virulence, and host factors have not been well defined, clinical judgment remains a key factor in determining optimal management strategies for individual patients²⁷

Real-world management of suspected Candida infection

Early therapy in the ICU – Johan Maertens, Jean-Francois Timsit, Cristóbal León

Key points

• The two main themes in this debate on the most appropriate treatment strategies for ICU patients with suspected Candida infection will be
• Do we need to treat all ICU patients with sepsis who are also colonised with Candida?
• Do we have suitable diagnostic tests to identify markers of candidiasis in ICU patients?

Early treatment – Matteo Bassetti

• Empirical and pre-emptive approaches allow treatment to be started before Candida is identified in blood cultures, and expose fewer patients at high risk for Candida infections to antifungal agents than prophylactic strategies²⁸
• In immunocompromised haematology patients, therapy should be initiated at the first signs and symptoms of invasive fungal infection. The antifungal agent most likely to be effective against the suspected fungal species should be selected on the basis of local epidemiology, the patient’s recent exposure to antifungal agents, and available diagnostic tests²⁹

Early treatment – Zdenĕk Ráčil

• Empirical and pre-emptive approaches allow treatment to be started before Candida is identified in blood cultures, and expose fewer patients at high risk for Candida infections to antifungal agents than prophylactic strategies²⁸
• In immunocompromised haematology patients, therapy should be initiated at the first signs and symptoms of invasive fungal infection. The antifungal agent most likely to be effective against the suspected fungal species should be selected on the basis of local epidemiology, the patient’s recent exposure to antifungal agents, and available diagnostic tests²⁹

Haematology patients – Michael von Bergwelt-Baildon

Key points

• Antifungal prophylaxis against Candida infections remains an important aspect of management strategies for specific patient groups, including stem cell transplant recipients in the haematology setting,³⁰ high-risk liver transplant recipients in the ICU³¹ and extremely low birth weight infants in the NICU¹⁹
• As with treatment of Candida infections, selection of the most appropriate antifungal agent for prophylaxis should be based on epidemiology, specific characteristics of the patient in question, and the properties of the available agents

Liver transplant recipients – Faouzi Saliba

Key points

• Antifungal prophylaxis against Candida infections remains an important aspect of management strategies for specific patient groups, including stem cell transplant recipients in the haematology setting,³⁰ high-risk liver transplant recipients in the ICU³¹ and extremely low birth weight infants in the NICU¹⁹
• As with treatment of Candida infections, selection of the most appropriate antifungal agent for prophylaxis should be based on epidemiology, specific characteristics of the patient in question, and the properties of the available agents

Neonates – Paolo Manzoni

Key points

• Antifungal prophylaxis against Candida infections remains an important aspect of management strategies for specific patient groups, including stem cell transplant recipients in the haematology setting,³⁰ high-risk liver transplant recipients in the ICU³¹ and extremely low birth weight infants in the NICU¹⁹
• As with treatment of Candida infections, selection of the most appropriate antifungal agent for prophylaxis should be based on epidemiology, specific characteristics of the patient in question, and the properties of the available agents

Summary and closing comments - Olivier Lortholary