Following the increased occurrence of Pneumocystis pneumonia (PCP) in non-HIV immunocompromised populations, particularly in solid-organ transplant (SOT) recipients, the possible mechanisms underlying this shift have been explored in recent studies.

A French study examining PCP in SOT patients linked a nonsynonymous mutation (A261T) in the P. jirovecii inosine monophosphate dehydrogenase (IMPDH) gene to prior therapy with mycophenolic acid (MPA). In addition, a recent international multicenter retrospective observational study evaluating P. jirovecii IMPDH gene in samples collected from 96 SOT patients (94 from nine separate outbreaks and 84 on MPA therapy) and 67 non-transplant controls (none on MPA), reported six mutations (H108Y, A261T, A261S, L285I, L285V, and Q289L) in the P. jirovecii IMPDH gene of which five (A261T, A261S, L285I, L285V, and Q289L) were strongly associated with SOT status and MPA exposure. Find more here.

 

The detection of fungal pathogens using traditional methods, such as culture, can be challenging due to their low sensitivity. However, some new studies have shown that next-generation sequencing (NGS) of bronchoalveolar lavage (BAL) fluid significantly enhances the detection of fungal pathogens compared with conventional microbiology testing (CMT). In a comparative study, Yin et al reported detection rates of 56.8%, 73.8%, 76.7%, and 70.5% for CMT, multiplex PCR-based targeted NGS, hybrid capture-based targeted NGS, and metagenomic NGS, respectively.

This was further buttressed by the significantly higher sensitivity demonstrated by mNGS, mp-tNGS, and hc-tNGS in the detection of Aspergillus fumigatus compared with the galactomannan assay, which suggests NGS is more effective in cases of probable IPA, where conventional diagnostics often fall short. Moreover, the turnaround time for NGS is significantly shorter than that for fungal cultures, offering clinicians a faster path to appropriate treatment. Find more details here.

Argente-Colàs and colleagues at the Navarra University Hospital in Pamplona, Spain, in a recent study, have demonstrated the superiority of Novaplex^TM Dermatophyte qPCR assay over conventional methods in the diagnosis of dermatomycosis. Novaplex^TM Dermatophyte qPCR was found to perform well with an overall agreement of 94.1% when compared with the EurobioPlex dermatophytes assay.  Discrepancies were detected in only 5.9% (59/998) of cases, with the majority (62.7%) ultimately confirmed as true-positives by the Novaplex^TM Dermatophyte assay, while only 10.2% were false-negative results. In contrast, the comparison between the qPCR assay and culture revealed no false-negative results for Candida albicans, which suggests a high specificity. Find more insights here.

Compared with previous studies, the highest reported candidal infection rate in patients with fungal pancreatic infections has been published in Pancreatology, 114 cases of invasive candidiasis from a recent single-centre, retrospective analysis of patients with infected pancreatic necrosis. Of these, 60.5% had candidemia with or without pancreatic fungal infection, and 39.5% had isolated pancreatic fungal infection. Mixed fungal-bacterial co-infections were identified in 43.9 % of fungal-positive specimens.

The factors linked with higher values of mortality amongst participants were septic shock and multiple organ dysfunction syndrome. In addition, compared with candidemia with or without pancreatic fungal infection (30.8%), mortality was higher in cases with isolated pancreatic fungal infection (69.2%), which is consistent with reports that deep-seated invasive candidiasis generally yields lower success rates than candidemia. However, the overall mortality rate from the study was remarkably low (11.4%). Find more here.

A study in Arizona evidently showed that a combination of diagnostic tests, particularly antibody testing, provides the best diagnostic yield for coccidioidal meningitis. In this study, which recruited 110 participants, most cases were diagnosed via CSF antibody tests (93.7%): the positivity rate of the first CSF test was 89.1% for IgG by enzyme immunoassay, 62.2% for IgG by immunodiffusion and 70.2% for IgG by complement fixation. PCR was only positive in 18.8% and Coccidioides antigen in 33%. Serum coccidioidal IgG antibody was positive in about 85% of cases, while culture was positive in only 4.4% of cases.

Ravi et al also emphasized the need to encourage repeat CSF evaluations for cases of suspected coccidioidal meningitis. Six of the 110 (5.5%) who were initially seronegative from the first CSF sample evaluation were diagnosed with proven or probable coccidioidal meningitis on CSF analysis from a subsequent lumbar puncture. Find more here.

 

 

A new study highlights that assays for biochemical parameters such as ferritin, triglycerides, and fibrinogen are critical for diagnosing haemophagocytic lymphohistiocytosis (HLH) in disseminated histoplasmosis (DH). Other findings from this study were a significant correlation between laboratory features, such as markedly elevated urine Histoplasma antigen and serum beta-D-Glucan (BDG) levels, with HLH in DH.

Besides the markedly elevated levels of ferritin observed in 100% of participants complicated with HLH, other factors listed in the HLH-2004 criteria, including bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, fever > 38.5 °C, splenomegaly, and hemophagocytosis were also assessed and present in 100%, 95.4%, 95.5%, 63.6% and 54.5% of the HLH cases, respectively. For emphasis, cytopaenias should strongly suggest the need to rule out HLH in DH, as affirmed in an earlier review, which reported a much higher HLH prevalence of 62.5% in DH with pancytopenia compared with 20% documented in the index study. Find more here

Besides previous evidence showing the advantages of isavuconazole over first-line voriconazole, such as lack of QTc interval prolongation, more predictable pharmacokinetics, a less complicated drug interaction profile, and improved tolerability, Giacobbe and colleagues have speculated on its role in reducing mortality in patients with invasive aspergillosis. Their study reported a crude mortality rate of 44.0% at 30 days and 62.2% at 90 days in patients with proven or probable invasive aspergillosis receiving isavuconazole treatment while under intensive care, which was lower than rates reported in most of the current literature. 

The seemingly favourable outcomes (lower mortality rates) in the index study were despite the significant association observed between sequential organ failure assessment score, septic shock, and concomitant bacterial pneumonia with 30-day mortality. Similarly, prior hospitalization, sequential organ failure assessment score and septic shock were significantly associated with 90-day mortality, which paradoxically did not increase the risk of unfavourable prognosis as documented in previous studies. Find more here.

 

Gupta and colleagues identified 134 patients with deep dermatophytosis, with Trichophyton rubrum as the most frequently isolated pathogen. Symptoms included nodules/papules (78.4% [105/134]), ulcers (25.4% [34/134]), and abscesses (8.2% [11/134]). Secondary complications were reported in 24.6% (33/134) of patients, including disseminated dermatophytosis and pseudomycetoma.   In these patients, the significant risk factors were primary and acquired immunodeficiencies. The conventional treatment options were terbinafine and itraconazole. The use of newer triazoles (voriconazole, posaconazole) and amphotericin B were also reported. Find more here.

 

The British Society for Medical Mycology has recently updated its 2015 best practice guidance to reflect the evolving fungal diagnostic landscape. Primarily from a UK perspective, no major changes were applied to histopathology, radiology, and direct microscopy.  Combining mycological tests is suggested for improved clinical outcomes, given that most diagnoses (>80%) of serious fungal diseases are made with non-culture tests; antigen, PCR, and antibody tests should be used for better care and often faster results. The importance of culture is also emphasized for the purpose of identification, antifungal susceptibility testing, and typing for delineation of outbreaks. Authors also mentioned the benefits of centralising mycology laboratory testing, including provision of crucial resources, laboratory expertise, and improved potential for combined diagnostic strategies, but acknowledged the attendant challenges like slowing down turnaround time, an important determinant factor for survival from life-threatening fungal infections. Find more here.