Pulmonary Mucormycosis: The Evidence

Eric W. Robbins

Overview

Systematic Reviews, ROCM

Most systematic reviews focus on rhino-orbital-cerebral mucormycosis (1, 2)

Systematic Reviews, Transplant

Mucor in lung transplant patients (3)

  • conclusion: avoid surgery, use amphotericin + posaconazole

Evidence

Guidelines

Global guideline for the diagnosis and management of mucormycosis (4)

  • first line: surgical debridement with clean margins
  • next: liposomal amphotericin B
  • add-on: isavuconazole or posaconazole

Outcomes

  • Mortality rates have improved since 2000 (5)
    • survival: medical (31%) vs medical + surgery (69%)
Year Morality
before 2000 72.1%
2000-2009 58.3%
2010-2020 49.8%
  • Despite improvements, mortality rates remain high (5, 6)
    • 90-day morality: 41%

Outcomes, Malignancy

  • Outcomes in hematologic malignancies poor despite surgery (7)
    • Single center retrospective cohort
    • N = 20, with n = 1 (5%) pulmonary disease
      • 18 (90%) recent surgery
    • morality at 1 month: n = 11 (55%)

Treatments, Medications

  • MUCONAB trial, 2023: RCT of nebulized amphotericin B (8)
    • conclusion: no improvement in outcomes
  • RCT of topical amphotericin gel at surgical site in COVID-associated mucormycosis (9)
    • patients: nasopharyngeal mucor
    • intervention: 0.1% Liposomal Amphotericin-B gel vs 10% povidone-iodine and saline
    • outcome: need for surgical revision
    • result: fewer revisions

Treatment, Medications

COVID Associated Mucormycosis (9)

Conclusion: “Topical Amphotericin-B gel application in the postoperative cavity can decrease the need for revision surgery.”

Treatment, Medications

  • Case-control study isavuconazole (10)
    • Conclusion: “Isavuconazole showed activity against mucormycosis with efficacy similar to amphotericin B.”

Treatment, Surgery

1994: Seminal Ann Thorac Surg Review out of Duke (11)

  • N = 255
  • Morality statistics below
Group n (%)
overall 204 (80.0%)
isolated pulmonary mucor 166 (65.1%)
Medication, all comers 173 (67.8%)
Surgery, all comers 28 (11.0%)

Treatment, Surgery

Warning

  • Only 44% (92/209) of patients with pulmonary mucormycosis were diagnosed premortem!
treatment n (%)
medical only 56 (61%)
surgery only 19 (21%)
medical + surgery 17 (18%)

Treatment, Surgery Specifics

Of the surgically treated patients with pulmonary-localized disease:

treatment n (%)
lobectomy 22 (61.1%)
pneumonectomy 4 (11.1%)
wedge resection 3 (8.3%)
unspecified 7 (19.4%)

Treatment, Surgery

  • Meta-anlysis of 92 pulmonary mucor cases (12)

Correlates of Survival

Treatment OR [95% CI]
Medication vs not 53.9 [3.1-945.6]
Surgery vs not 5.983 [1.5-23.9]

Conclusions

  • Medications
    • Yes. amphotericin + azole (isavuconazole or posaconazole)
  • Surgery
    • Likely yes, preferably early.

References

1.
Bhattacharyya A, Sarma P, Sharma D, Das K, Kaur H, Prajapat M, et al. Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review. Indian J Pharmacol 2021;53:317.
2.
Chegini Z, Didehdar M, Khoshbayan A, Rajaeih S, Salehi M, Shariati A. Epidemiology, clinical features, diagnosis and treatment of cerebral mucormycosis in diabetic patients: A systematic review of case reports and case series. Mycoses 2020;63:1264–1282.
3.
Wand O, Unterman A, Izhakian S, Fridel L, Kramer MR. Mucormycosis in lung transplant recipients: A systematic review of the literature and a case series. Clinical Transplantation 2020;34:e13774.
4.
Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SCA, Dannaoui E, Hochhegger B, et al. Global guideline for the diagnosis and management of mucormycosis: An initiative of the european confederation of medical mycology in cooperation with the mycoses study group education and research consortium. The Lancet Infectious Diseases 2019;19:e405–e421.
5.
Muthu V, Agarwal R, Dhooria S, Sehgal IS, Prasad KT, Aggarwal AN, et al. Has the mortality from pulmonary mucormycosis changed over time? A systematic review and meta-analysis. Clinical Microbiology and Infection 2021;27:538–549.
6.
Jeong W, Keighley C, Wolfe R, Lee WL, Slavin MA, Chen SC-A, et al. Contemporary management and clinical outcomes of mucormycosis: A systematic review and meta-analysis of case reports. International Journal of Antimicrobial Agents 2019;53:589–597.
7.
Kara IO, Tasova Y, Uguz A, Sahin B. Mucormycosis-associated fungal infections in patients with haematologic malignancies. International Journal of Clinical Practice 2009;63:134–139.
8.
Muthu V, Gogineni RR, Agarwal R, Prasad KT, Sehgal IS, Dhooria S, et al. Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin b ( <span style="font-variant:small-caps;">MUCONAB</span> trial): Results of an open‐label randomized controlled trial. Mycoses 2023;66:688–696.
9.
Shaikh Z, Mishra A, Chadaram S, Preetam C, Biswas R, Adhikari A, et al. To evaluate the efficacy of topical anti-fungal therapy in postoperative cases of COVID associated mucormycosis (CAM): A single-blinded randomized control trial. American Journal of Otolaryngology 2023;44:103702.
10.
Marty FM, Ostrosky-Zeichner L, Cornely OA, Mullane KM, Perfect JR, Thompson GR, et al. Isavuconazole treatment for mucormycosis: A single-arm open-label trial and case-control analysis. The Lancet Infectious Diseases 2016;16:828–837.
11.
Tedder M, Spratt JA, Anstadt MP, Hegde SS, Tedder SD, Lowe JE. Pulmonary mucormycosis: Results of medical and surgical therapy. The Annals of Thoracic Surgery 1994;57:1044–1050.
12.
Feng J, Sun X. Characteristics of pulmonary mucormycosis and predictive risk factors for the outcome. Infection 2018;46:503–512.