Fungal Infections

Brain

Granuloma or cyptococcoma

When there is diagnostic doubt, either biopsy or removal of a mass may be required to establish the diagnosis. In most instances, these masses are thought to be malignant and it is a surprise when a fungal infection is found. If the mass is single, cure may achieved with surgical removal, followed by antifungal therapy. Most of these lesions are caused by Aspergillus, but other rarer fungi may be involved.

If cryptococcomas are large and causing mass effects, it may be appropriate to remove them, if possible, based on their anatomical location.

In patients who had a long periods of antifungal therapy, with lesions that are static in size, surgical removal is sometimes appropriate, as a prelude to stopping antifungal therapy. Usually cultures are negative and it may that any life organism is in a complex biofilm-like static phase, and further antifungal therapy is unable to eradicate the infection.

Cerebral abscess

In patients with cerebral abscesses due to fungi, stereotactic drainage (primarily for diagnosis) and in some cases total removal of a single abscess is possible. The literature suggests that those who undergo surgical drainage do better. However it is not clear if surgical intervention contributes to response for several reasons. The first is publication bias. The second is that confirming the aetiological diagnosis of one or more cerebral abscesses tends to promote more intensive and appropriate therapy. Third, those who undergo biopsy or resection may be fitter overall and more likely to survive. Fourth, cerebral fungal abscess is a better prognosis disease than infarction. Fifth, superficial lesions amenable to surgery and single lesions are also better prognostic features. Therefore the only clear recommendation is that every reasonable effort should be made to establish the fungal cause of the abscess to optimize therapy and if an abscess is easily drainable, it should be.

Cerebral haemorrhage in context of a mycotic aneurysm

There is little evidence that surgical evacuation of a cerebral haemorrhage is of value in the context of cerebral aspergillosis or mucormycosis.

Shunting for communicating hydrocephalus

Fungal meningitis may lead to communicating hydropcephalus, which is usually, but not always, temporary in cryptococcal meningitis and permanent in coccidioidal, and paracoccidioidal meningitis. Temporary or permanent ventricular shunts may be put in. If treatment is ongoing (as it is likely to be for coccidioidal meningitis), then insertion of a reservoir for administering amphotericin B is advisable, although often this needs to be administered elsewhere in the ventricular system for efficacy, because of abnormal CSF flow.

Eye

Endophthalmitis

Vitrectomy is advised for the treatment of all causes of fungal endophthalmitis in all but very mild or exceptional cases (ie very thin cornea, major bleeding tendency, neonatal endophthalmitis). Vitrectomy removes the bulk of inflammatory debris and microorganisms, and allows submission of samples for diagnosis and direct administration of amphotericin B into the orbit. When fungal keratitis complicates an intraocular lens (if the endophthalmitis is a sequel to cataract surgery), then usually the lens can be salvaged and left in place unless there is extensive infiltration around the lens or recurrent infection.

Keratitis

Most patients with superficial fungal keratitis respond to medical therapy but is associated with a five-to-six fold higher risk of subsequent perforation than bacterial keratitis. Surgery is advantageous in the presence of deep corneal lesions as over 50% of patients fail to respond to antifungal therapy alone. Imminent perforation or descemetocele formation are clear indications for surgery. The objectives of surgery are to augment medical therapy by removal of infected corneal tissue, increasing drug penetration when conjunctival flaps are formed, by stabilising the corneal epithelial surface itself or by providing structural support to the entire eye when its integrity is threatened by thinning or perforation of the cornea Surgical procedures range from simple removal of the corneal epithelium (debridement), through anterior lamellar keratectomy, creation of conjunctival flaps with tissue adhesives to therapeutic penetrating keratoplasty.

Debridement is usually performed under topical anaesthesia. Lamellar keratectomy or keratoplasty helps to remove fungal hyphae on the surface of the cornea facilitating visual improvement. In this procedure the superficial 50% of the corneal thickness is removed and replaced by a 50% thickness donor graft. Fashioning a conjunctival flap contributes to a stable conjunctival surface in those with persistent or recurrent epithelial defects and progressive ulceration especially in patients with peripheral fungal corneal ulcers, since the flap will not encroach onto the visual axis. Amniotic membrane transplantation promotes wound healing and reduces inflammation but experience is limited, especially in those with extensive corneal disease.

Corneal transplantation using entire thickness corneal grafts is used as a last resort to preserve or to restore useful vision in severely affected eyes or when there is a poor response to antifungal therapy. Complications include allograft rejection, especially when the donor graft is greater than 8.5 mm in diameter, refractive errors and other visual problems. Malignant glaucoma may be one of the complications of fungal keratitis and corneal transplantation with cataract extraction is one approach but sometimes a limited pars plana vitrectomy is also required.

Nose and sinuses

Chronic sinusitis, usually with nasal polyps (AFRS)

The goals of surgery are to:

  •   completely remove all allergic mucin and fungal debris,
  •   provide drainage and aeration of the affected sinuses while (crucially) preserving the integrity of underlying mucosa, including removal of obstructing nasal polyps
  •   allow post-operative access to previously diseased areas endoscopically, so any subsequent procedures can be done more easily.

For extensive disease, open surgery is often preferable, but localised disease can often be done endoscopically. The extent and location of disease on CT scan is the key guide to the best approach.  The choice of surgical approach depends in part on the experience and training of the surgeon. However, aeration and debridement of distant ethmoid sinues and the frontal sinuses endoscopically can be challenging, and if not dealt with thoroughly, a common cause of early relapse. The surgery may be challenging in some cases due to extensive nasal polyposis and bleeding on polyp removal. In addition, erosion of bone is well recognised in patients with AFRS sometimes leading to occasional inadvertent sinus perforation. The mucin and other tissue removed during surgery should be submitted to the laboratory for investigation including fungal culture and microscopy specifically for fungal elements in mucin.

Fungus ball of the sinuses

Removal of the fungal ball and aeration of the affected sinus(es) almost always cures the problem. Either endoscopic surgery or a Caldwell-Luc procedure for maxillary disease is appropriate.  The cheese-like, rubbery or friable soft tissue mass is removed and if it comes away easily then there is no need to biopsy the mucosa and establish if it is invasive, which it is extremely unlikely to be in a non-immunocompromised patient, with minimal distortion of the bony architecture on scan. The underlying mucosa is usually oedematous and may contain polyps. Creation of a large antrostomy into the nose may prevent recurrent bacterial sinusitis.  The ipsilateral ethmoid sinuses should be explored endoscopically and drained. Relapse may occur otherwise. The role of nasal packing with amphotericin B or another antifungal agent is not established. For fungal balls of the sphenoid sinus, some surgeons feel more comfortable complementing surgery with antifungal therapy, to prevent local invasion, which can be serious.

Ear

Surgical debridement of invasive Aspergillus otitis is a necessary part of diagnosis and management of this entity. Usually the middle ear is destroyed and infection has extended into the mastoid and/or petrous bone. In these cases local debridement to extend to uninfected bone and prevent CNS spread is usually necessary, often with complete loss of hearing on the affected side.

Lungs

Invasive pulmonary aspergillosis

Surgery (usually lobectomy, sometimes wedge resection or pneumonectomy) is sometimes life-saving. Those who have disease (usually aspergillosis, sometimes mucormycosis) abutting on the great vessels such as the pulmonary artery are at great risk of massive haemorrhage. Immediate surgery, even with low platelet and white cell counts, is required, if feasible from a pulmonary reserve and general status perspective. Platelet transfusions are given before and during the operation. Emergency surgery is also indicated for major haemoptysis in invasive fungal disease, but unfortunately is often so severe that it cannot be done fast enough.  

Pulmonary mucormycosis has a better outcome, if surgically excised. Sometimes this is impossible because it is bilateral and extensive, but even removal of a large single focus in this context may be desirable.

The other major indication for surgery is persisting lung shadows prior to bone marrow transplantation or more aggressive chemotherapy. The likelihood of fungal disease relapse is moderately high, even with secondary antifungal prophylaxis. In exceptional cases, where the necessary curative therapy for the underlying disease is highly immunosuppressive, bilateral lesions have been removed in separate procedures. A danger in this is delay of curative therapy, while the patient recovers from surgery, but resection offers a better overall outcome. Prevention of subsequent recurrence of invasive aspergillosis has occurred in most of those undergoing resection surgery; it is likely that some recurrences are re-infections.

Aspergilloma and chronic pulmonary aspergillosis

The best results of surgery for aspergillomas are when the lesion is single and there is little co-morbidity. In those patients with major haemoptysis and simple aspergillomas, surgery offers at least 84% five year survival (1970’s), with mortality rates in most series of under 2% now. Indications for surgery are:

  •  Aim for cure of the disease so avoiding later complications, progression and possibly antifungal therapy.
  •  Significant haemoptysis.
  •  Failure to control disease with medical therapy alone, including antifungal resistant infection.
  •  A large residual cavity at risk for infection.

Surgical removal of aspergillomas can be difficult because of the vascular, adherent pleura adjacent to the cavity. This makes removing the aspergilloma hard and sometimes the cavity is inadvertently opened spilling Aspergillus into the chest cavity. This may result in Aspergillus empyema, which can be difficult to treat. Many patients have underlying respiratory insufficiency and removal of a lobe of the lung would leave them unacceptably breathless.

Pleural infection

The management of Aspergillus empyema is often difficult. Surgical removal of pleural aspergillomas and thoracoplasty is also prone to many complications and should be avoided if possible. Drainage of an empyema with creation of a deep pleurocutaneous fistula (e.g. an Eloesser flap which can heal slowly (over months) is usually necessary, in addition to antifungal therapy.  An Eloesser flap procedure consists of a) creation of a superior skin flap, b) partial rib resection of 1 or 2 ribs and c) entering the pleural cavity and draining all the empyema and d) suturing the skin flap to the upper margin of the pleural defect. If the pleura is thick and fibrotic, a complete decortication may be necessary for cure and improvement of lung function.

Heart

Pericarditis

If pericardial tamponade or constriction occurs, which it can following histoplasmosis or invasive aspergillosis, drainage, placing a pericardial window or pericardiectomy may be required. Sometimes drainage is initially required, until the infection is better controlled, followed by definitive surgery.

Endocarditis

With very exceptions, surgical intervention offers the best chance of cure and survival from fungal endocarditis. Exceptions include neonates with Candida endocarditis and occasional patients in whom the risks of surgery are so high that antifungal therapy alone is really their only option. However, most of these patients will die, especially if they have Aspergillus endocarditis. Surgical intervention is frequently undertaken when a complication of AE has occurred, or a trial of antifungal therapy has failed. Surgical intervention should be embarked upon earlier than is usually the case, as recovery from fungal endocarditis with complications is infrequent. Optimisation of medical therapy is important [BSAC guidelines].

There are many surgical procedures described in the literature for repairing or replacing infected valves. Sometimes the aortic valve can be removed while an aortic root infection is repaired and the native valve replaced, for example. However the most common procedure is valve replacement with a homograft, which does not require subsequent lifelong anticoagulation. Occasionally very large pedunculated vegetations can be removed and the valve repaired, but this is unusual. Triscuspid valves are better repaired than replaced, if possible. In all cases, surgical repair should be undertaken under antifungal cover, and in most cases, fungal infection of the newly implanted valve does not occur. Antifungal therapy needs to be prolonged however and late relapse relatively common.

Pacemaker and cardioverter-defibrillator wire infection

There are several well established methods for pacemaker and cardioverter-defibrillator wire including laser-assisted lead extraction, electrosurgical dissection sheath extraction, mechanical extraction, femoral extraction, and open-chest extraction were performed as described previously. In the context of infection with large vegetations (as is commonly the casein fungal endocarditis), a combination of transvenous lead removal and sternotomy with cardiopulmonary bypass may be required.

Bone

Overall there appears to be an advantage of surgical therapy in the treatment of bony aspergillosis and other filamentous fungal infection, but not yeast infections such as Candida or Cryptococcus.

Sternal wound infection

Usually a localised abscess is present just to one side of the sternum or a persistent wound over the sternum with localised infection around the wires.  Rarely infection arising in the mediastinum tracks out through the sternum.  Delineation of extent of disease by CT scan is appropriate, followed by debridement, removal of wires in the area of infection and antifungal therapy.

Vertebral body infection

Simple debridement is the usual initial approach, but a radical debridement followed by bone grafting with, for example, a rib strut has been successful.  Sometimes instability is such that Harrington rods are necessary.  In previous cases, the timing of surgery has been variable, being undertaken as late as 5 months after diagnosis.  Late surgery is indicated for instability or failure on therapy.

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