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CT scan showing opacification indicative of early acute respiratory distress syndrome but no features of aspergillosis.
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Critically ill patients are at risk of developing both acute kidney injury (AKI) and invasive fungal infections (IFIs). Prompt and efficient treatment of the IFI is essential for the survival of the patient. This article examines three distinct clinical situations where liposomal amphotericin B, a broad-spectrum antifungal agent, was successfully u...
Context in source publication
Context 1
... sepsis screen of blood, urine and sputum samples was carried out, and blood cultures grew an unspecified fungus; subsequent plate culture and microscopy confirmed the presence of Aspergillus species. A transthoracic echocardiogram was normal, including an absence of heart valve lesions, and a CT scan of the chest did not indicate any typical changes consistent with aspergillosis, as shown in figure 1. ...
Similar publications
Objective: To systematically evaluate the efficacy, mortality, survival rate, and adverse reactions of high-dose liposomal amphotericin B (L-AMB) in disease treatment.
Methods: Reports of randomized controlled trials (RCTs; whether randomized, single-blind, or double-blind) of high-dose L-AMB treatment of diseases were retrieved from the PubMed, Em...
Citations
... 11 Nevertheless, administering LAMB in acute kidney injury necessitates highquality supporting care and close monitoring to maintain or restore the function of the kidney's distal tubular cells. 12 However, patients do not respond well to the anti-fungals in the RM case reports requiring nephrectomy or percutaneous nephrostomy drainage in over 50% of cases. 13 RM has a poor prognosis, with a high mortality rate between 44% and 85%. 5 The outcome relies on several factors, such as the severity and extent of the infection, the type of F I G U R E 1 Axial (A, B) and coronal (C) views of the multi-detector CT scan show enlargement of the left kidney mostly compatible with pyelonephritis (white arrow), the atrophic appearance of the right kidney with renal stones (yellow arrow), and a left-sided nephrostomy and left double J catheter (blue arrow) at the time the patient presented with acute kidney injury. ...
Key Clinical Message
Unilateral renal mucormycosis is a rare infection that should be suspected in patients with recurrent renal infections presenting nonspecific clinical features that do not respond to conventional therapies, especially in impaired immune systems due to related risk factors. Moreover, histopathological examinations should be performed to confirm the diagnosis. For treatment, the preference is that the patient is hospitalized, and surgical intervention and rapid administration of intravenous antifungals for 2–3 weeks are the treatment choices. After discharge, the patient should be followed up with periodic blood urea nitrogen and creatinine levels and, if needed, an imaging modality such as a CT scan or sonography.
Abstract
Renal mucormycosis (RM) is a rare form of mucormycosis infection and is more often in immunocompromised patients with risk factors. Unilateral renal involvement is infrequent in patients and is available as case reports. This condition usually presents with renal colic, fever and chills, and oliguria and has a high mortality rate. Herein, we report a case of unilateral renal mucormycosis presenting with pyelonephritis and acute kidney injury in a 32‐year‐old patient. The patient had numerous urological procedures in previous years due to nephrolithiasis state, which put him in an immunocompromised state. The histopathological examination of the pylocalyceal system revealed a collection of broad non‐septated fungal hyphae branching at 90° accompanied by numerous neutrophils and necrotic tissue in favor of mucormycosis. He was successfully treated with 5 mg/kg/day Liposomal Amphotericin B for 3 weeks, discharged with good general condition, and remained asymptomatic for 3 months after discharge. The diagnosis of RM relies on solid clinical suspicion, which can be authenticated by histopathological examination, and the combination of antifungal therapy and surgical intervention can result in a good outcome.
... Infection and Drug Resistance 2023:16 https://doi.org/10.2147/IDR.S372546treatment would consist of LAmB, for which small case series have indicated that it can be safely administered even in patients with renal compromise, justifying its use in such a desperate clinical situation where benefit outweighs the risk.95,96 Combination treatment is not generally recommended, but sometimes used in the salvage treatment setting, including combinations of isavuconazole/ posaconazole with LAmB.97,98 ...
Invasive mold diseases are devastating systemic infections which demand meticulous care in selection, dosing, and therapy monitoring of antifungal drugs. Various circumstances regarding PK/PD properties of the applied drug, resistance/tolerance of the causative pathogen or host intolerability can lead to failure of the initial antifungal therapy. This necessitates treatment adaption in the sense of switching antifungal drug class or potentially adding another drug for a combination therapy approach. In the current state of drastically limited options of antifungal drug classes adaption of therapy remains challenging. Current guidelines provide restricted recommendations only and emphasize individual approaches. However, novel antifungals, incorporating innovative mechanisms of action, show promising results in late stage clinical development. These will expand options for salvage therapy in the future potentially as monotherapy or in combination with conventional or other novel antifungals. We outline current recommendations for salvage therapy including PK/PD considerations as well as elucidate possible future treatment options for invasive aspergillosis and mucormycosis.
... Treatments include anti-inflammatory drugs and first gen steroids. Amphotericin-B deoxycholate, an antifungal medication, is the first line of treatment, and liposomal dose formulations are recommended due to less nephrotoxicity (Spellberg et al., 2009;Kassamali et al., 2013;Groll et al., 2019;Armstrong-James et al., 2020;Sandhu, 2021). Alternative therapies were used for treatment of black fungus using traditional herbal plants due to their antifungal properties according to Auyverdic guidelines (Sepahvand et al., 2018;Garcia, 2020;Mishra et al., 2020;Dineshwori, 2021). ...
... Treatments include anti-inflammatory drugs and first gen steroids. Amphotericin-B deoxycholate, an antifungal medication, is the first line of treatment, and liposomal dose formulations are recommended due to less nephrotoxicity (Spellberg et al., 2009;Kassamali et al., 2013;Groll et al., 2019;Armstrong-James et al., 2020;Sandhu, 2021). Alternative therapies were used for treatment of black fungus using traditional herbal plants due to their antifungal properties according to Auyverdic guidelines (Sepahvand et al., 2018;Garcia, 2020;Mishra et al., 2020;Dineshwori, 2021). ...
... The polyenes (targeting fungal ergosterol), such as amphotericin B and nystatin, have been available since the 1950s, and have a remarkable wide spectrum of activity against most fungal pathogens; furthermore, antifungal resistance to this class of drugs has not significantly emerged during this time, although there are some fungal species with intrinsic resistance, such as Aspergillus terreus and Candida lusitaneae. 12 There are however a number of limitations to this drug class, in that they are only currently available as intravenous formulations or as topical agents. Furthermore, there is significant toxicity associated with the polyenes, typically amphotericin B deoxycholate, when given intravenously, with nephrotoxicity being a particular issue due to drug microaggregate formation in the loop of Henle. ...
... Furthermore, there is significant toxicity associated with the polyenes, typically amphotericin B deoxycholate, when given intravenously, with nephrotoxicity being a particular issue due to drug microaggregate formation in the loop of Henle. 12 This has led to the development of a number of lipid-based formulations that hold the drug in its monomeric form, of which liposomal amphotericin B is the best-known example. ...
Human fungal pathogens cause a broad plethora of infections, spanning cutaneous dermatophytoses to invasive infections in immunocompromised hosts. As eukaryotic pathogens are capable of morphotype switching, they present unique challenges both for drug development and the immunological response. Whilst current antifungal therapies are limited to the orally available triazoles, intravenous echonocandins and polyenes, and flucytosine and terbinafine, there has been recent significant progress in the antifungal armamentorium with ibrexafungerp, a novel orally available terpanoid that inhibits 1,3-beta-D-glucan-approved by Food and Drug Administration in 2021, and fosmanogepix, an orally available pro-drug of manogepix, which targets glycosylphosphatidylinositol-anchored protein maturation entering Phase 3 studies for candidaemia. A number of further candidates are in development. There has been significant use of existing immunotherapies such as recombinant interferon-γ and G-CSF for fungal disease in immunocompromised patients, and there are emerging opportunities for monoclonal antibodies targeting TH2 inflammation. Omalizumab, an anti-IgE monoclonal antibody in asthma, is now used routinely for the treatment of allergic bronchopulmonary aspergillosis, and further agents targeting IL-4 and IL-5 are being evaluated. In addition, T-cell CAR therapy is showing early promise for fungal disease. Thus, we are likely to see rapid advances to our approach to the management of fungal disease in the near future.
... Clinical studies indicate that the use of liposomal AmB is empirically advisable, even when the fungal species causing the disease is unknown [411,412]. All cases have resulted in an improvement of the patient's clinical condition and many of them have achieved recovery. ...
This review examined a collection of studies regarding the molecular properties of some polyene antibiotic molecules as well as their properties in solution and in particular environmental conditions. We also looked into the proposed mechanism of action of polyenes, where membrane properties play a crucial role. Given the interest in polyene antibiotics as therapeutic agents, we looked into alternative ways of reducing their collateral toxicity, including semi-synthesis of derivatives and new formulations. We follow with studies on the role of membrane structure and, finally, recent developments regarding the most important clinical applications of these compounds.
... Liposomial amphotericin B is a broadly effective alternative treatment option for aspergillosis, although the nephrotoxicity that in ICU patients, often affected by renal insufficiency, complicates starting or requires discontinuation of this antifungal drug [62]. This is particularly relevant for patients infected by SARS-CoV-2 which has shown renal tropism and been described as a frequent cause of kidney injury [63]. ...
Patients with coronavirus disease 19 (COVID-19) admitted to the intensive care unit (ICU) often develop respiratory fungal infections. The most frequent diseases are the COVID-19 associated pulmonary aspergillosis (CAPA), COVID-19 associated pulmonary mucormycosis (CAPM) and the Pneumocystis jirovecii pneumonia (PCP), the latter mostly found in patients with both COVID-19 and underlying HIV infection. Furthermore, co-infections due to less common mold pathogens have been also described. Respiratory fungal infections in critically ill patients are promoted by multiple risk factors, including epithelial damage caused by COVID-19 infection, mechanical ventilation and immunosuppression, mainly induced by corticosteroids and immunomodulators. In COVID-19 patients, a correct discrimination between fungal colonization and infection is challenging, further hampered by sampling difficulties and by the low reliability of diagnostic approaches, frequently needing an integration of clinical, radiological and microbiological features. Several antifungal drugs are currently available, but the development of new molecules with reduced toxicity, less drug-interactions and potentially active on difficult to treat strains, is highly warranted. Finally, the role of prophylaxis in certain COVID-19 populations is still controversial and must be further investigated.
... KDIGO guidelines recommend that exposure to nephrotoxic drugs should be limited in patients at risk of developing AKI and that a risk/benefit assessment is carried out to with the risk of developing the AKI against the risk associated with not using the agent. 9 When there is a clinical diagnosis of a potentially life-threatening invasive fungal infection, AKI is not a contraindication to starting treatment with lipid-based-amphotericin B formulations. ...
... Interestingly, despite identifying numerous FLCR and some MDR C. parapsilosis blood isolate during the last 13 years in Turkey [17,18,22], none of these isolates were resistant against amphotericin B (AMB) [18,22]. Additionally, the lipid formulation of AMB, LAMB, proved to be efficacious in eradicating invasive fungal infections even in patients suffering from acute kidney injury [25]. Further, AMB is well tolerated among neonates [26] as the most susceptible patient groups developing candidemia due to C. parapsilosis [27]. ...
While being the third leading cause of candidemia worldwide, numerous studies have shown severe clonal outbreaks due to fluconazole-resistant (FLCR) Candida parapsilosis isolates associated with fluconazole therapeutic failure (FTF) with enhanced mortality. More recently, multidrug resistant (MDR) C. parapsilosis blood isolates have also been identified that are resistant to both azole and echinocandin drugs. Amphotericin B (AMB) resistance is rarely reported among C. parapsilosis isolates and proper management of bloodstream infections due to FLZR and MDR isolates requires prompt action at the time of outbreak. Therefore, using a well-established Galleria mellonella model, we assessed whether (a) laboratory-based findings on azole or echinocandin (micafungin) resistance in C. parapsilosis lead to therapeutic failure, (b) LAMB could serve as an efficient salvage treatment option, and (c) distinct mutations in ERG11 impact mortality. Our in vivo data confirm fluconazole inefficacy against FLCR C. parapsilosis isolates carrying Y132F, Y132F + K143R, Y132F + G307A, and G307A + G458S in Erg11p, while LAMB proved to be an efficacious accessible option against both FLCR and MDR C. parapsilosis isolates. Moreover, positive correlation of in vitro and in vivo data further highlights the utility of G. melonella as a reliable model to investigate azole and polyene drug efficacy.
... 72,73 Liposomal ampho tericin B is the primary alternative option for treatment of IPA in the ICU; 67 however, the drug is nephrotoxic and might result in a further decline of renal function, especially in patients who already have acute kidney injury. 74 The concern about renal toxicity is particularly relevant for patients who are infected by SARS-CoV-2, which has shown renal tropism and is a frequent cause of kidney injury. 75 Alternative second-line options are posaconazole or echinocandins. ...
Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
