Invasive and Allergic Fungal Sinusitis

Fungal sinusitis encompasses a wide range of clinical syndromes. Disease is classified into four major categories: 1) acute invasive fungal sinusitis, 2) chronic invasive fungal sinusitis, 3) mycetoma, and 4) allergic fungal sinusitis. Acute disease is most often a fulminant, life-threatening process seen in immunocompromised patients. Treatment requires prompt antifungal therapy and extensive surgical debridement. Other types of fungal sinusitis are more indolent. For chronic invasive sinusitis, a combination of surgical debridement and antifungal agents is the cornerstone of treatment. Mycetomas can usually be extirpated surgically and do not require therapy with antifungal agents. Treatment of allergic fungal sinusitis remains controversial, but most current management regimens utilize surgical debridement combined with corticosteroid therapy, rather than antifungal agents.     

Abscesses and deep space infections of the head and neck.

Abscesses and deep space infections of the head and neck continue to be encountered in clinical practice. Recognition of these processes requires careful physical examination, an adequate index of suspicion, and appropriate application of modern imaging techniques. The principles of management of abscesses are largely unchanged. Space infections must be drained. A specimen should always be submitted for bacteriologic evaluation to allow change in antimicrobial administration when patterns of resistance are identified. Fungal infection should be considered when rhinosinusitis develops in the hospitalized immunocompromised patient. Biopsy of abnormal tissue is the mainstay of diagnosis under these circumstances. Therapy frequently requires surgical debridement in addition to administration of antifungal chemotherapy.     

Paecilomyces lilacinus infection in a liver transplant patient: case report and review of the literature

Abstract: A 56-year-old male who was 12 months status post liver transplant presented with a 2-month history of painful, erythematous nodules over the right knee. Several biopsies yielded a mold initially phenotypically identified as a Penicillium species, but molecular sequence analysis ultimately determined the identity as Paecilomyces lilacinus . Several courses of oral voriconazole were required for resolution of the infection. A review of the literature revealed that Paecilomyces species are an infrequent cause of disease in transplant patients, with skin and soft tissue infections being the most common presentation. It is important to accurately identify these infections, and polymerase chain reaction assay using universal fungal primers offers a rapid and precise diagnostic approach. Treatment of Paecilomyces infections may require multiple courses of antifungal therapy, often with surgical debridement. We suggest that voriconazole may be a useful treatment alternative to the more traditional therapy with amphotericin B-based agents.     

Spontaneous candida mediastinitis diagnosed by endoscopic ultrasound-guided, fine-needle aspiration

Candida mediastinitis is a rare clinical entity associated with high mortality and morbidity. It is emerging as an important clinical entity, probably due to increased recognition of candida as a significant pathogen in mediastinitis. Candida mediastinitis is usually associated with cardiothoracic surgery, esophageal perforation, and head and neck infections. Optimal therapy for candida mediastinitis remains undefined. Aggressive, combined surgical debridement and antifungal therapy appears to be the most effective of available therapies. We report a case of spontaneous candida mediastinitis diagnosed by endoscopic ultrasound-guided, fine-needle aspiration and successfully treated with oral antifungal therapy alone.     

Chronic fungal sinusitis in apparently normal hosts

Several fungal species are capable of causing either noninvasive fungal sinusitis or invasive disease characterized by erosion into mucosa, submucosa, bone, and deeper contiguous structures. The diagnosis of invasive infection becomes firmly established only after histologic demonstration of hyphae within these areas. Computerized tomography and magnetic resonance imaging can assist in distinguishing between invasive and noninvasive disease by outlining bone and adjacent structures. The 2 forms of chronic fungal sinusitis mandate different therapeutic approaches. While patients with noninvasive infection require only surgical removal of hyphal masses and the reestablishment of sinus drainage for a successful outcome, invasive infection necessitates not only thorough surgical debridement of abnormal tissues but may also require prolonged antifungal chemotherapy. All patients require long-term follow-up. Even the combined approach has sometimes proven disappointing during long-term follow-up of disease, rendering investigational therapy appropriate in some patients.     

Primary cutaneous fungal infection after solid-organ transplantation: report of five cases and review.

Solid-organ transplant recipients who are receiving immunosuppressive therapy are at increased risk of acquiring opportunistic infections, particularly fungal infections. We present the cases of five liver transplant recipients who developed primary cutaneous opportunistic fungal infections that remained localized to the skin. These cases are compared with 27 previously reported cases of primary cutaneous fungal infections. In these previously reported cases, administration of systemic antifungal medications, including amphotericin B, ketoconazole, griseofulvin, and miconazole, resulted in a 71% survival rate. Medical and surgical therapy together resulted in an 86% survival rate, and surgical excision resulted in a 100% survival rate. Thus, regardless of the age of the patient, type of immunosuppressive therapy, clinical presentation, or organisms involved, surgical excision yielded the highest cure rate. When possible, surgical excision should be performed on solid-organ transplant recipients who acquire opportunistic fungal infections.     

Treatment options in emerging mold infections

Although Zygomycetes, Fusarium spp, and Scedosporium spp are far less frequent causes of invasive fungal disease than Aspergillus and Candida, they are emerging. These types of infections in severely immunocompromised patients have a common feature: a poor clinical response to antifungal therapy. Infection is usually airborne, although local infections in cases of skin trauma are also possible. These fungi are resistant to some common antifungal agents; therefore, surgical debridement of the necrotic tissue, when possible, should be combined with specific systemic antifungal treatment in immunocompromised patients. In the absence of randomized clinical trials, most experience in the treatment of these infections is with amphotericin B. Experience with new antifungal agents is still limited, and recovery from neutropenia remains the main predictor of a favorable outcome.     

Diagnosis and prevention of fungal infection in the immunocompromized patient

Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal infections. Mortality associated with disseminated fungal infection is high and treatment with conventional amphotericin B is complicated by renal toxicity. Candida and Aspergillus are among the major pathogens in this patient population. Many patients remaining neutropenic over a prolonged period of time will receive empirical antifungal therapy. The clinical and laboratory diagnosis of these infections are neither sensitive nor specific and are generally limited in the early detection of invasive fungal infection. However, several new approaches to diagnosis are being developed which should be translated into routine practice. These include antigen detection and PCR. It is still unclear how effective the various measures that are currently being used are in preventing serious fungal infection. Refinements in the prophylactic use of fluconazole, itraconazole and aerosolized amphoteric in B, and the introduction of new formulations of existing antifungals may reduce the incidence of systemic fungal infections in some patient groups. Patients with presumed fungal infection require more intense and accurate monitoring for signs of disseminated infection. Early diagnosis may guide appropriate treatment and prevent mortality.     

2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections

Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.     

Executive summary: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections

Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.     

Practice guideline for the treatment of coccidioidomycosis. Infectious Diseases Society of America.

Management of patients diagnosed with coccidioidomycosis involves defining the extent of infection and assessing host factors that predispose to disease severity. Patients with relatively localized acute pulmonary infections and no risk factors for complications often require only periodic reassessment to demonstrate resolution of their self-limited process. On the other hand, patients with extensive spread of infection or at high risk of complications because of immunosuppression or other preexisting factors require a variety of treatment strategies that may include antifungal therapy, surgical debridement, or both. Amphotericin B is often selected for treatment of patients with respiratory failure due to Coccidioides immitis or rapidly progressive coccidioidal infections. With other more chronic manifestations of coccidioidomycosis, treatment with fluconazole, itraconazole, or ketoconazole is common. Duration of therapy often ranges from many months to years, and, for some patients, chronic suppressive therapy is needed to prevent relapses.     

Zygomycosis over‐infection during voriconazole therapy for aspergillosis in a heart transplant patient,successfully treated with liposomal amphotericin and posaconazole

Aspergillosis and zygomycosis are life‐threatening fungal infections in immunocompromised patients. We report a heart transplant recipient with an early pulmonary invasive aspergillosis successfully treated with association of voriconazole and caspofungin. Zygomycosis sinusitis, which was diagnosed while he still was on voriconazole therapy, was successfully treated with the use of combination antifungal therapy including liposomal amphotericin plus posaconazole and conservative surgical debridement.     

Management of rare fungal infections

PURPOSE OF REVIEW: Fungal infections caused by rare fungi have increased in recent years. This may be due to the increase in the number of immunocompromised patients. Some rare fungi are geographically restricted, but with globalization and travel these infections are seen worldwide. The aim of this review is to address recent advances in the management of some uncommon fungal infections. RECENT FINDINGS: Dematiaceous fungi (Phaeohyphomycetes) have been reported in both immunocompromised and immunocompetent individuals. Cerebral involvement and disseminated disease are associated with high mortality rates. Surgical excision and broad-spectrum triazole antifungal therapy are associated with better outcomes. Mucormycosis in diabetic and immune-suppressed patients is associated with high mortality. Early radical surgical debridement and amphotericin B-based regimens are a key to success. Basidiobolomycosis has recently been reported to cause chronic granulomatous infection of the gastrointestinal tract. Treatment with itraconazole and surgical resection is associated with favourable outcomes. Invasive fusariosis in cancer patients is typically resistant to most antifungal agents, but recent data have suggested a response to voriconazole. Voriconazole also demonstrated activity against Scedosporium apiospermum, but was less active against Scedosporium prolificans. Amphotericin B and itraconazole are currently the treatments of choice for the southeast Asian fungus, Penicillium marneffie. SUMMARY: Parallel to the increased number of patients susceptible to invasive infections has been an increase in the number of broad-spectrum antifungal agents allowing for better therapeutic options. High-quality data are lacking because of the rarity of such infections. In future, new triazoles and echinocandins will probably replace amphotericin B as the first therapeutic choice for many uncommon fungal infections.     

Infections caused by Drechslera species: case report and review of the literature

Organisms belonging to Drechslera species are rare causes of human infection and are considered opportunistic pathogens. Only 10 cases of human infection with these organisms have been reported in the literature; an additional case--that of a healthy young woman with chronic pansinusitis due to Drechslera spicifera causing nasal obstruction and erosion of bone--is described herein. This case was managed successfully by means of surgical debridement and therapy with amphotericin B and ketoconazole. A review of the literature suggests that infections caused by Drechslera species can in fact occur in a healthy host. Involvement of the paranasal sinuses and the central nervous system is common and potentially life-threatening. Appropriate therapy consists of the administration of amphotericin B, either alone or in combination with other antifungal agents, and surgical debridement when indicated.     

Fungal infections in severe acute pancreatitis

Severe acute pancreatitis (SAP) is associated with significant morbidity and mortality. The majority of deaths related to SAP are the result of infectious complications. Although bacterial infections are most commonly encountered, fungal infections are increasingly being recognized. Candida is the most common fungal infection. The occurrence of fungal infection in patients with acute pancreatitis adversely affects the clinical course, leading to a higher incidence of systemic complications, and possibly mortality as well. Important risk factors for fungal infection in patients with acute pancreatitis include broad-spectrum antibiotics, prolonged hospitalization and surgical/endoscopic interventions, use of total parenteral nutrition, and mechanical ventilation. Patients with higher severity of pancreatitis are at a greater risk. The pathogenesis of fungal infection in patients with acute pancreatitis is multifactorial. Translocation of microorganisms across the gut epithelium, lymphocyte dysfunction, and the virulence of the invading microorganisms play important roles. Histological demonstration of fungi remains the gold standard of diagnosis, but a positive biopsy is rarely obtained. The role of biomarkers in the diagnosis is being investigated. As early diagnosis and treatment can lead to improved outcome, a high index of suspicion is required for prompt diagnosis. Limiting the use of broad-spectrum antibiotics, early introduction of enteral nutrition, and timely change of vascular catheters are important preventive strategies. The role of antifungal prophylaxis remains controversial. Surgical necrosectomy with antifungal therapy is the most widely used treatment approach. Clinical trials on antifungal prophylaxis are needed, and indications for surgical intervention need to be clearly defined.     

Aggressive combined modality treatment of progressive sinonasal fungal infections in immunocompromised patients

PURPOSE: Invasive fungal infections of the paranasal sinuses in immunocompromised hosts are often fatal despite therapeutic interventions. In an effort to achieve a better outcome in patients with these infections, aggressive management was combined with medical/surgical intervention. PATIENTS AND METHODS: A series of 18 immunocompromised patients with invasive sinonasal fungal infections was retrospectively analyzed. Management consisted of a combined modality clinical approach, including aggressively sought early diagnosis; early amphotericin use; extensive surgical debridement; and liberal use of granulocyte transfusion support. RESULTS: Eight of 13 patients with eventual neutrophil recovery survived with control of all local and systemic signs of fungal infection. All patients with persisting neutropenia died of progressive infection. CONCLUSION: We conclude that meticulous surveillance of patients in high-risk groups for fungal infection should be maintained due to the apparent value of rapid intervention with a combination of surgical resection and medical management (antifungal chemotherapy and white blood cell transfusions). Infection control and survival are ultimately dependent on recovery of marrow function and circulating neutrophils.     

Fungal prophylaxis in very low birth weight neonates: nystatin, fluconazole or nothing?

PURPOSE OF REVIEW: To examine recent evidence on the efficacy of antifungal prophylaxis to prevent neonatal systemic fungal infection. The review also aims to examine other relevant data, including the incidence of fungal infection, adverse effects of antifungal therapy and avoidable risk factors. RECENT FINDINGS: There is strong evidence that systemic fluconazole prophylaxis reduces the incidence of systemic fungal infections, with a trend towards reduction in mortality. However, the preprophylaxis incidence of fungal infection has been very high in the published studies. Fluconazole use is sometimes associated with cholestasis and there are theoretical concerns as well that prophylactic fluconazole will select for fluconazole-resistant organisms and nonalbicans Candida infections.There is reasonable evidence that oral nystatin is effective in preventing fungal infections and at the same time it is inexpensive and well tolerated.The reported incidence of systemic fungal infections is much lower in the UK than in the USA and Italy. SUMMARY: Oral nystatin prophylaxis is inexpensive, effective and nontoxic and should be used routinely for babies of birth weight less than 1500 g. Systemic fluconazole, which is more toxic and may select for resistant fungi, is probably only indicated when the rate of fungal infection remains high despite introducing measures targeting known risk factors for fungal infection. These measures include introducing enteral feeds early, reducing the duration of parenteral feeding, and reducing the use of broad spectrum antibiotics, particularly cephalosporins.Future studies of prophylactic fluconazole should use oral nystatin, not placebo, as the comparator.     

Phaeohyphomycotic infections in solid organ transplant patients

Phaeohyphomycoses are darkly pigmented fungi that rarely cause infection in immunocompetent persons. In the past 2 decades these fungi increasingly have been reported as pathogens that cause significant morbidity and mortality in the immunocompromised host, especially solid organ transplant recipients. Clinical manifestations range from superficial lesions to disseminated infections. Exophiala spp. and Alternaria spp. account for the great majority of these infections. Treatment should include complete surgical excision of the lesions that are accessible combined with antifungal therapy, especially when invasive or systemic infection is present. Itraconazole usually suffices if only subcutaneous lesions are present; however, if the infection is systemic or it involves the central nervous system, the addition of amphotericin B is required. New investigational azoles also should be considered in these types of infections. This is a very heterogenous group of fungi and as such the sensitivities to antifungal agents is variable. Therefore, sensitivities should be obtained on every fungal isolate.     

Fatal rhinocerebral mucormycosis and diabetic ketoacidosis

The typical features of a fulminating rhinocerebral infection by the fungus Rhizopus in a patient with diabetic ketoacidosis are described. The clinical presentation was characterized by an infection of the face, followed by rapid bilateral visual loss and massive cerebral infarction due to extensive vascular involvement. Early diagnosis is a prerequisite for successful treatment, which consists of control of the underlying disease, surgical debridement and systemic antifungal therapy.     

Fungal peritonitis in patients receiving peritoneal dialysis: experience with 11 patients and review of the literature

Despite progress in decreasing the incidence of and improving the therapy for bacterial peritonitis in patients receiving peritoneal dialysis, fungal peritonitis has emerged as a relatively common infection. Hospitalization, recent prior episodes of peritonitis, and antibacterial therapy appear to predispose patients to this infection. Clinically, fungal peritonitis cannot be differentiated from bacterial peritonitis except by gram stain and culture of the dialysate. The most commonly made serious error is the failure to initiate appropriate therapy quickly enough on the basis of these diagnostic parameters. For patients who no longer require dialysis, those for whom a change to hemodialysis is preferred, and those with concomitant life-threatening illness, the recommended therapy for fungal peritonitis is removal of the dialysis catheter and the institution of therapy with systemic antifungal agents. For patients who are hemodynamically and metabolically stable and for whom continued peritoneal dialysis is desirable, a trial of antifungal chemotherapy before removal of the catheter may be indicated.