Therapeutic Challenges of Non- Aspergillus Invasive Mold Infections in Immunosuppressed Patients

Abstract

While Aspergillus spp. remain the major cause of invasive mold infections in hematologic cancer patients and transplant recipients, other opportunistic molds, such as Mucorales, Fusarium, and Scedosporium spp. are increasingly encountered in an expanding population of patients with severe and prolonged immunosuppression. High potential for tissue invasion and dissemination, resistance to multiple antifungals and high mortality rates are hallmarks of these non-Aspergillus invasive mold infections (NAIMIs). Assessment of drug efficacy is particularly difficult in the complex treatment scenarios of NAIMIs. Specifically, correlation between in vitro susceptibility and in vivo responses to antifungals is hard to assess, in view of the multiple, frequently interrelated factors influencing outcomes, such as pharmacokinetic/pharmacodynamic parameters determining drug availability at the site of infection, the net state of immune suppression, delay in diagnosis, or surgical debulking of infectious foci. Our current therapeutic approach of NAIMIs should evolve toward a better integration of the dynamic interactions between the pathogen, the drug and the host. Innovative concepts of experimental research may consist in manipulating the host immune system to induce a specific antifungal response or targeted drug delivery. In this review, we discuss the challenges in the management of NAIMIs and provide an update about the latest advances in diagnostic and therapeutic approaches.

Clinical characteristics and outcomes of invasive Lomentospora prolificans infections: Analysis of patients in the FungiScope® registry

“…Treatment of invasive infections is challenging as L prolificans isolates are often pan‐drug resistant, with elevated minimum inhibitory concentrations (MICs) against all available antifungal agents . More than 10 years ago, two relatively large studies reported that voriconazole was associated with survival rates between 44% and 66% and voriconazole was deemed the treatment of choice for invasive L prolificans infections . This is supported by a recent review of patients published after 2000 in which overall mortality was lower in patients who received voriconazole compared to treatment with other antifungal agents .…”

Clinical Relevance and Characteristics of Aspergillus calidoustus and Other Aspergillus Species of Section Usti

“…From these observations, we can conclude that the optimal therapeutic approach of A. ustus IA would still deserve further investigations. Notably, this is another example that in vitro data do not necessarily correlate with clinical efficacy, as it has been previously shown for other difficult-to-treat mold infections [32]. Non-pharmacological parameters, such as recovery of the immune system or the initial severity of the disease with delay in diagnosis may represent the predominant predictors for outcome.…”

Misidentification of Scedosporium boydii Infection as Aspergillosis in a Patient with Chronic Renal Failure

“…Although S. boydii resembles Aspergillus on pathologic examination, it is typically resistant to amphotericin B. Voriconazole has been shown as an effective agent to treat systemic S. boydii infection, while posaconazole shows less activity, and isavuconazole and itraconazole have minimal activity [4,[11][12][13]. Echinocandins have some degree of activity albeit at 5 to 10 times higher concentration than that used to treat Aspergillus [4]. In summary, this case highlights the importance of circumspection when diagnosing aspergillosis from anatomic H&E GMS Figure 4: Active invading mycetoma is present in the occipital lobe, with 45-degree branching hyphae spreading horizontally at the peripheral and perpendicularly to the center.…”

“…Treatment of these infections is especially challenging because of the mold's resistance to many antifungal agents [ 13 ]. Although S. boydii resembles Aspergillus on pathologic examination, it is typically resistant to amphotericin B. Voriconazole has been shown as an effective agent to treat systemic S. boydii infection, while posaconazole shows less activity, and isavuconazole and itraconazole have minimal activity [ 4 , 11 – 13 ]. Echinocandins have some degree of activity albeit at 5 to 10 times higher concentration than that used to treat Aspergillus [ 4 ].…”

“…Although Aspergillus remains the most common filamentous mold, the differentiation from other emerging filamentous fungal agents is important due to different treatment regimens. For example, innate resistance or erratic susceptibility to amphotericin B is a characteristic of S. boydii [4,5]. In tissue sections, the characteristic morphologic appearance of the fungal hyphae has been used to help to differentiate Aspergillus and Mucorales.…”