Thursday, November 30, 2023
| Characteristic | R. homothallicus | R. arrhizus |
|---|---|---|
| Macroscopic appearance | ||
| Growth rate | Fast-growing colonies and sporulation relatively slower than R. arrhizus | Fast-growing colonies and sporulation relatively faster than R. homothallicus |
| Obverse surface growth | Cottony, white colonies that turn grayish to olive brown with a variegated appearance; because of the large-sized zygospores, brownish tufts can be seen unevenly distributed throughout the mycelial growth | Cottony, white colonies that turn gray with typical salt and pepper appearance |
| Reverse macroscopic findings | Reverse surface has no pigment | Reverse surface has no pigment |
| Microscopic findings | ||
| Hyphae | Aseptate hyphae, less prominent rhizoids; smooth and thick-walled intercalary chlamydospore | Aseptate hyphae, well-developed nodal rhizoids with occasional intercalary chlamydospores |
| Sporangiophore | Erect, unbranched, or dichotomously branched (length 300 – 2000 µm, width 5–30 µm) | Single or tufts of mostly unbranched sporangiophores (length 1000–2000 µm, width 7–18 µm) |
| Sporangium | Sparsely noted in cultures; when present, appears spherical and greyish brown (20– 140 µm) with conspicuous dark apophysis and subspherical columella | Spherical sporangia (20–250 µm) with short apophysis and spherical columella occupying 50% of sporangium |
| Sporangiospores | Spherical to broadly ellipsoidal (3–5 × 4–8 µm), hyaline, and thick-walled with less prominent striations | Lemon-shaped or subspherical to ellipsoidal (6–8 × 4.5–5 µm) with striations, rough surface |
| Zygospores | Homothallic†; abundant golden brown zygospores (60–100 µm) with stellate spinous projections, attached to large globose suspensor cells that are unequal in size | Heterothallic zygospores not seen on primary culture; red-brown spherical or laterally flattened (60–140 µm) with flat projections; suspensors are unequal, spherical to conical |
Table 1. Mycologic characteristics of Rhizopus arrhizus and R. homothallicus based on macroscopic and microscopic findings of tissue samples from patients enrolled in a 10-month retrospective study, Chandigarh, India, January–October 2021*
*Key features highlighted in bold. †Differentiation from other homothallic Rhizopus species that produce abundant zygospores (e.g., R. sexualis and R. azygosporus) is done based on size of the suspensor cells of the zygospore and by molecular identification using the internal transcribed spacer and 28S sequences of rDNA.
| Parameter | R. homothallicus, n = 41 | R. arrhizus, n = 266 | p value |
|---|---|---|---|
| Mean age, y (+ SD) | 45.9 (± 12.8) | 52.5 (± 12.7) | 0.002 |
| Sex | |||
| M | 23/41 (56.1) | 182/266 (68.4) | 0.15 |
| F | 18/41 (43.9) | 84/266 (31.6) | |
| Risk factors | |||
| CAM | 23/41 (56.1) | 256/266 (96.2) | 0.0001 |
| Duration after COVID-19, d (+ SD) | 6.13 (± 13.5) | 11.9 (± 14.8) | 0.07 |
| Diabetes mellitus | 39/41 (95.1) | 223/238 (93.7) | 0.72 |
| Recently diagnosed diabetes mellitus | 9/39 (23.1) | 54/223 (24.2) | |
| Renal transplantation | 0 | 1/238 (0.4) | 1.00 |
| Intracranial involvement | 3/41 (7.3) | 13/266 (4.9) | 0.46 |
| Clinical features | |||
| Fever | 4/41 (9.8) | 3/55 (5.5) | 0.42 |
| Headache | 4/41 (9.8) | 10/55 (18.2) | 0.38 |
| Toothache | 4/41 (9.8) | 5/55 (9.1) | 0.91 |
| Eye swelling | 27/41 (65.9) | 27/55 (49.1) | 0.10 |
| Facial pain | 11/41 (26.8) | 22/55 (40) | 0.18 |
| Facial swelling | 16/41 (39) | 22/55 (40) | 0.92 |
| Proptosis | 3/41 (7.3) | 0 | 0.08 |
| Visual disturbance | 18/41 (43.9) | 7/55 (12.7) | 0.0005 |
| Oral ulcer | 3/41 (7.3) | 10/55 (18.2) | 0.12 |
| Nasal crust | 5/41 (12.2) | 5/55 (9.1) | 0.62 |
| Palatal eschar | 5/41 (12.2) | 10/55 (18.2) | 0.42 |
| Management | |||
| Amphotericin therapy | 38/41 (92.7) | 212/218 (97.2) | 0.14 |
| LAMB | 36/38 (94.7) | 196/212 (92.5) | |
| Conventional AMB | 2/38 (5.3) | 16/212 (7.5) | |
| Surgery | 24/36 (66.7) | 184/245 (75.1) | 0.31 |
| 30-day mortality | 4/41 (9.8) | 104/266 (39.1) | 0.0001 |
Table 2. Comparison of mucormycosis caused by Rhizopus homothallicus versus R. arrhizus in patients enrolled in a 10-month retrospective study, Chandigarh, India, January–October 2021*
*Values are no. patients/no. with data available (%) except as indicated. CAM, COVID-19–associated mucormycosis; LAMB, liposomal amphotericin B; AMB, amphotericin.
| Variable | Survivors | Nonsurvivors | Odds ratio (95% CI) | p value |
|---|---|---|---|---|
| Mean age, y (+ SD) | 55.8 (+ 12.4) | 49.4 (+ 12.6) | 1.06 (1.03–1.08) | 0.0001 |
| Male sex | 124/199 (62.3) | 81/108 (75) | 1.38 (0.75–2.53) | 0.31 |
| Intracranial involvement | 4/199 (2) | 12/108 (11.1) | 22.7 (4.03–128.1) | 0.0001 |
| Surgery for ROM | 144/173 (83.2) | 64/108 (59.3) | 0.22 (0.11–0.43) | 0.0001 |
| R. homothallicus infection | 37/199 (18.6) | 4/108 (3.7) | 0.08 (0.02–0.36) | 0.001 |
Table 3. Binary logistic regression analysis demonstrating the factors associated with death among patients with rhino-orbital mucormycosis enrolled in a 10-month retrospective study, Chandigarh, India, January–October 2021*
*Values are no. patients/no. with data available (%) except as indicated. ROM, rhino-orbital mucormycosis.
| Antifungal agent | Geometric mean (range), mg/L | MIC50, mg/L | MIC90, mg/L |
|---|---|---|---|
| Amphotericin B | 0.75 (0.03–16) | 2 | 4 |
| Itraconazole | 0.51 (0.03–16) | 0.5 | 8 |
| Posaconazole | 0.24 (0.03–8) | 0.12 | 2 |
| Isavuconazole | 0.32 (0.03–16) | 0.25 | 2 |
| Terbinafine | 0.34 (0.03–16) | 0.25 | 4 |
Table 4. Distribution of MICs of 34 Rhizopus homothallicus isolates from patients enrolled in a 10-month retrospective study, Chandigarh, India, January–October 2021*
*MIC50, MIC at which 50% of isolates are inhibited; MIC90, MIC at which 90% of isolates are inhibited.
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We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02–0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03–16], itraconazole [0.03–16], posaconazole [0.03–8], and isavuconazole [0.03–16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus.
Mucormycosis is an angioinvasive disease caused by the saprophytic fungi of the order Mucorales. The estimated prevalence of mucormycosis is ≈70 times higher in India than elsewhere[1]. Rhizopus arrhizus is the most common etiologic agent of mucormycosis in India and worldwide[2]. Other reported Mucorales include Apophysomyces variabilis, Cunnighamella spp., Lichtheimia spp., Mucor spp., Rhizomucor spp., Rhizopus microsporus, Rhizopus homothallicus, Saksenaea vasiformis, Syncephalastrum spp., and Thamostylum lucnowense[3–7]. R. arrhizus was the most common causative agent even during the recent outbreak of COVID-19–associated mucormycosis (CAM) in India[8]. Although infection with R. homothallicus was also reported in a few patients[9], the importance of mucormycosis caused by R. homothallicus is unclear. We report the percentage of patients with mucormycosis caused by R. homothallicus at our center (Postgraduate Institute of Medical Education and Research [PGIMER], Chandigarh, India) and describe clinical features, mycologic characteristics, antifungal susceptibility, treatment, and mortality rates. We also assess whether the mortality rate from rhino-orbital mucormycosis (ROM) caused by R. homothallicus is different from that of R. arrhizus disease.
The primary objectives of this study were to assess the proportion of patients with mucormycosis caused by R. homothallicus and 30-day mortality rate from ROM caused by R. homothallicus and to determine whether the species of Mucorales (R. homothallicus vs. R. arrhizus) was an independent predictor of death from ROM. The secondary objectives were to compare the profile of patients infected with R. homothallicus versus R. arrhizus and to ascertain the mycologic characteristics of R. homothallicus isolates by conducting antifungal-susceptibility testing (AFST) and amplified fragment length polymorphism (AFLP) analysis.
