Systemic fungal infections in neonates

Advances in neonatal management have led to considerable improvement in newborn survival. However, early (<72 hours) and late (>72 hours) onset systemic infections, both bacterial and fungal, remain a devastating complication and an important cause of morbidity and mortality in these babies. Most neonatal fungal infections are due to Candida species, particularly Candida albicans. The sources of candidiasis in NICU are often endogenous following colonization of the babies with fungi. About 10% of these babies get colonized in first week of life and up to 64% babies get colonized by 4 weeks of hospital stay. Disseminated candidiasis presents like bacterial sepsis and can involve multiple organs such as the kidneys, brain, eye, liver, spleen, bone, joints, meninges and heart. Confirming the diagnosis by laboratory tests is difficult and a high index of suspicion is required. The diagnosis of fungemia can be made definitely only by recovering the organism from blood or other sterile bodily fluid. Amphotericin B continues to be the mainstay of therapy for systemic fungal infections but its use is limited by the risks of nephrotoxicity and hypokalemia. Newer formulations of amphotericin B, namely the liposomal and the lipid complex forms, have recently become available and have been reported to have lesser toxicity. More recently Indian liposomal Amphotericin B derived from neutral lipids (L-Amp-LRC-1) has shown good response with less toxicity. A clinical trial with this preparation has shown to be safe and efficacious in neonatal fungal infections. Compared to other liposomal preparations, L-Amp-LRC-1 is effective at lower dose and is less expensive drug for the treatment of neonatal candidiasis.     

Systemic fungal infections in renal diseases

Invasive fungal infections are a major challenge in the management of immunocompromised patients and those with renal dysfunction. These challenges are due to the immense morbidity and mortality in such situations. Also the management strategies for invasive mycosis in patients with renal dysfunction have narrow safety profile and involve high-cost. In this review we will discuss the issues involved in the management of invasive mycosis in the patients with renal dysfunction in the form of acute renal failure, chronic kidney disease, dialysis dependency of renal transplant recipients. We also emphasize that the use of Intravenous Liposomal Amphoterecin appears to be an effective alternative to the conventional Amphoterecin B for the treatment of invasive fungal infections in patients with renal dysfunction due to its greatly improved tolerability profile. Commercially two true liposomal preparations (Fungisome and Ambisome) are available. Judgement about the preferred formulation should be made on the basis of disease morbidity, severity of renal dysfunction and the cost involved.     

Fusarium infections in immunocompromised patients

Fusarium species cause a broad spectrum of infections in humans, including superficial, locally invasive, and disseminated infections. The clinical form of fusariosis depends largely on the immune status of the host and the portal of entry, with superficial and localized disease occurring mostly in immunocompetent patients and invasive and disseminated disease affecting immunocompromised patients. Risk factors for severe fusariosis include prolonged neutropenia and T-cell immunodeficiency, especially in hematopoietic stem cell transplant recipients with severe graft-versus-host disease. The most frequent presentation of disseminated fusariosis is a combination of characteristic cutaneous lesions and positive blood cultures, with or without lung or sinus involvement. The prognosis is poor and is determined largely by degree of immunosuppression and extent of infection, with virtually a 100% death rate among persistently neutropenic patients with disseminated disease. These infections may be clinically suspected on the basis of a constellation of clinical and laboratory findings, which should lead to prompt therapy. Treatment options include the lipid formulations of amphotericin B, voriconazole, and posaconazole. Prevention of fusarial infection among high-risk patients should be considered.     

Fungal infections in immunocompromised patients]

The number of immunocompromised patients is increasing due to the intensive therapy being administered those with cancer, organ transplant, and HIV infection. Fungal infections are one of the important opportunistic infections in immunocompromised patients. Early diagnosis is difficult, and the prognosis of these patinas is usually poor. Several methods of diagnosis for fungal infections have been developed: detection of antigens of the infected fungi from the sera is useful for early diagnosis; polymerase chain reaction (PCR) technology may be the most valuable method for the diagnosis of fungal infection in immunocompromised patients, and antifungal agents are the drugs used to the fungal infections in those patients. However, there are only five drugs available to fungal infections in Japan. Although amphotericin B is the recommended first choice for treatment of invasive aspergillosis, its use for immunocompromised patients is limited because of its adverse effects. Novel antifungal agents (azoles, amphotericin B drug deliver system, and 1,3-beta-D-glucan synthetase inhibitors) have been developed and some of these compounds undergoing clinical trials.     

Fatal disseminated adenovirus infections in immunocompromised patients

Adenovirus has emerged as an important pathogen in immunocompromised patients, in whom disseminated disease occurs frequently and is associated with a high mortality rate. In a retrospective review of 1,847 consecutive autopsies, we identified 84 cases where adenovirus infection was suspected clinically. Adenovirus infection was confirmed at autopsy in 8 (10%) of 84 cases; all were immunocompromised patients. Six (75%) of these cases had disseminated adenovirus infection that contributed to death. Pathologic findings attributed to adenovirus infection included pneumonia with or without intra-alveolar hemorrhage, hepatic necrosis, enterocolitis with or without mucosal hemorrhage, epicardial hemorrhage, and ulcerations of the larynx, trachea, and ileum. This work shows that severe and fatal adenovirus infections are not infrequent, particularly in the immunocompromised population. Both clinicians and pathologists must become aware of the pathogenicity of adenovirus in this patient population, including its potential for causing life-threatening hemorrhage.     

Actinomyces and nocardia infections in immunocompromised and nonimmunocompromised patients

A retrospective survey of nocardia and actinomyces infections in five local hospitals was conducted over a 3-year period in El Paso, Texas, a border city, in the southwestern United States. The medical records of 42 patients with suspected nocardiosis or actinomycosis were reviewed. One patient was diagnosed with actinomyces and 12 patients with nocardia. Microbiological data included morphologic characteristics, biochemical profile, and susceptibility testing. Predisposing factors included leukemia, renal insufficiency, renal transplant, and lymphoma. No predisposing factors were found in 67% (n = 8) of patients (including the patient with actinomycosis). Twenty-three percent (n = 3) of patients had disseminated disease without evidence of underlying disease or immunosuppression. The mortality and morbidity of these infections appeared to be low.     

Oral infections and fever in immunocompromised patients with haematologic malignancies

The purpose of the study was to determine the prevalence of acute oral infections and to estimate their role as a possible cause of fever in immunocompromised patients with haematologic malignancies. Seventy-eight febrile episodes in 46 patients were analyzed prospectively and consecutively. An association between a rise in the leukocyte and platelet counts and normalization of the temperature was found. Acute infections were present in 92 % of the febrile episodes no infectious cause could be demonstrated in the remaining 8 %. Acute oral infections were present during 78% and acute extraoral infections during 73% of the febrile episodes. Acute candidiasis and infected mucosal ulcers were the most prevalent oral infections, occurring in about one-half and one-third of the episodes, respectively. Septicaemia and pneumonia were the most prevalent extraoral infections, each present in about one-fourth of the febrile episodes. Acute oral infections were a probable cause of fever in 14 % of the febrile episodes and a possible or a contributing cause of fever in a further 26 %. The results suggest that effective treatment or prevention of acute oral infections may reduce the morbidity and perhaps even the mortality in immunocompromised patients.     

Nosocomial infections in immunocompromised children

Immunocompromised children are at high risk for developing nosocomial infections which may cause significant morbidity and mortality in this population. In paediatric oncology, reported prevalence of nosocomial infections varies from 10 to 20%. Major predisposing factors are neutropenia, central venous catheter, corticosteroid therapy and hospital construction or renovation for invasive aspergillosis. The management of patients with febrile neutropenia should take into account the previous history of infection and the microbiologic environment of each department. Nowadays, Gram positives infections are predominant, but fungal infections remain a major threat. In organ transplant recipients, wound infections are the main early problems, followed by viral infections often due to the donor CMV seropositivity. In HIV-infected children, nosocomial infections are difficult to define, and can implicate unusual pathogens. In general, adapted preventive infection control strategy warrants prospective studies.     

Primary invasive cutaneous Microsporum canis infections in immunocompromised patients.

Two cases of primary invasive cutaneous infections caused by the zoophilic dermatophytic species Microsporum canis are presented. The first case occurred in a liver transplant recipient who was receiving immunosuppressive therapy. Multiple erythematous papules were seen on both legs, and a biopsy revealed invasive fungal hyphae. The second case was diagnosed in a human immunodeficiency virus-positive individual with a CD4 lymphocyte count of 81 mm3. Raised red nodules were seen on her scalp and face. Histopathology was consistent with bacillary angiomatosis, and in addition, invasive septate hyphae were observed. The two strains recovered from the biopsy specimens from both individuals had colony morphologies consistent with that of M. canis, but it was difficult to induce production of macroconidia. These cases serve to increase the awareness of this unusual infection, reinforce the need for cultures, and raise some interesting questions about the potential virulence of this dermatophyte species.     

Oral infections and septicemia in immunocompromised patients with hematologic malignancies.

To estimate the role of oral infections during septicemic episodes in immunocompromised patients with hematologic malignancies, 78 febrile episodes in 46 patients were monitored with daily clinical and microbiological investigations. The 19 septicemic episodes did not differ from the 59 other febrile episodes in the qualitative composition of the aerobic and facultatively anaerobic oral microflora or in the presence of teeth or acute oral infections on day 1. The oral prevalence rates of members of the family Enterobacteriaceae were higher on days 10, 11, and 12 in the febrile episodes with septicemia when compared with those of febrile episodes without septicemia. The prevalence of a probable oral focus in septicemia was 10.5%, and the prevalence of a probable or possible oral origin in septicemia was 31.6%. The results suggest that prevention and elimination of oral infections may reduce the morbidity and perhaps even the mortality in these patients.     

Fusarium infections in immunocompromised patients: Case reports and literature review

Five cases are reported ofFusarium infection in patients with aplasia following chemotherapy of leukemia. The clinical signs, diagnosis and course of the infection during treatment are outlined and discussed in conjunction with the characteristics of other cases already reported in the literature. Sixty-three cases ofFusarium infection have been reported in immunocompromised patients, 44 cases since 1985. These included patients with hematological malignancies (58 cases), especially acute leukemia (43 cases). The main sites of infection were the skin (46 cases), blood (28 cases) and lungs (13 cases). The infection was mostly diagnosed by means of skin biopsy but also by means of positive blood cultures. Forty-three strains were identified, 19 of which wereFusarium solani. Amphotericin B treatment was given in 55 cases, often combined with other antifungal agents, leukocyte transfusions or granulocyte-macrophage-colony stimulating factor. The outcome was fatal in 36 of the 63 cases reported, often due to resistance of the strain to antifungal agents, particularly amphotericin B (20 of 33 strains tested). The most important risk factor seems to be profound and prolonged aplasia. Deep mycoses due toFusarium species thus pose an important problem and are occurring in increasing numbers in immunocompromised patients. Treatment of these infections is difficult and the prognosis is poor.