M. R. Shivaprakash

Fungal Rhinosinusitis: A Categorization and Definitional Schema Addressing Current Controversies

Fungal (rhino‐) sinusitis encompasses a wide spectrum of immune and pathological responses, including invasive, chronic, granulomatous, and allergic disease. However, consensus on terminology, pathogenesis, and optimal management is lacking. The International Society for Human and Animal Mycology convened a working group to attempt consensus on terminology and disease classification.

The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus

Zygomycosis is an emerging infection worldwide. A study was conducted to understand its spectrum in the Indian scenario. All patients diagnosed for invasive zygomycosis at a tertiary care center in north India from 2000-2004, were retrospectively analyzed. A total of 178 cases (mean average of 35.6 cases/year) of zygomycosis were diagnosed. Rhino-orbito-cerebral type (54.5%) was the commonest presentation followed by cutaneous (14.6%), disseminated (9.0%), and gastrointestinal (8.4%) zygomycosis. Renal and pulmonary zygomycosis were seen in 6.7% patients each. Uncontrolled diabetes mellitus (in 73.6% of cases) was the significant risk factor in all types (Odds Ratio 1.5-8.0) except renal zygomycosis. Breach of skin was the risk factor in 46.2% patients with cutaneous zygomycosis. However, no risk factor could be detected in 11.8% patients. Antemortem diagnosis was possible in 83.7% cases. The commonest (61.5%) isolate was Rhizopus oryzae followed by Apophysomyces elegans in 27% patients. Combination of debridement surgery and amphotericin B therapy was significantly better in survival of the patients (P<0.005) than amphotericin B alone (79.6% vs. 51.7% survival). Thus, a rising trend of invasive zygomycosis was observed in patients with uncontrolled diabetes mellitus in India. Consistent diagnosis of renal zygomycosis in apparently healthy hosts and the emergence of A. elegans in India demand further study.

Recent experience with fungaemia: change in species distribution and azole resistance

Owing to a rise in frequency and change in pattern of cases with fungaemia at our tertiary care centre, we conducted a prospective study for 4 months to understand the epidemiology and outcome of this infection. Detailed case histories including management protocol and outcomes were noted. Records of 140 cases with fungaemia (27.1% adult and 72.9% paediatric patients) were analysed. Although C. tropicalis was the most common yeast isolated, significantly higher isolation of C. guilliermondii (30.4%) and C. pelliculosa (17.6%) was noted in paediatric patients; and C. albicans (26.3%) and C. glabrata (10.5%) in adult patients. Rare species isolated included C. ustus (0.7%) and Trichosporon asahii (2.1%). Mortality was high (56.9% and 47.4%, respectively), in both groups of patients. Resistance to azoles (fluconazole, itraconazole, voriconazole) emerged in C. albicans (12.5–18.8%) and C. tropicalis (10.2–13.6%). Antifungal susceptibility testing report modified the therapy from fluconazole to amphotericin B in 8 patients; 5 survived. In conclusion, the study highlighted the rise of non-albicans Candida species in our hospital with differential distribution in paediatric and adult wards and emergence of azole resistance.

Invasive aspergillosis in developing countries

To review invasive aspergillosis (IA) in developing countries, we included those countries, which are mentioned in the document of the International Monetary Fund (IMF), called the Emerging and Developing Economies List, 2009. A PubMed/Medline literature search was performed for studies concerning IA reported during 1970 through March 2010 from these countries. IA is an important cause of morbidity and mortality of hospitalized patients of developing countries, though the exact frequency of the disease is not known due to inadequate reporting and facilities to diagnose. Only a handful of centers from India, China, Thailand, Pakistan, Bangladesh, Sri Lanka, Malaysia, Iran, Iraq, Saudi Arabia, Egypt, Sudan, South Africa, Turkey, Hungary, Brazil, Chile, Colombia, and Argentina had reported case series of IA. As sub-optimum hospital care practice, hospital renovation work in the vicinity of immunocompromised patients, overuse or misuse of steroids and broad-spectrum antibiotics, use of contaminated infusion sets/fluid, and increase in intravenous drug abusers have been reported from those countries, it is expected to find a high rate of IA among patients with high risk, though hard data is missing in most situations. Besides classical risk factors for IA, liver failure, chronic obstructive pulmonary disease, diabetes, and tuberculosis are the newly recognized underlying diseases associated with IA. In Asia, Africa and Middle East sino-orbital or cerebral aspergillosis, and Aspergillus endophthalmitis are emerging diseases and Aspergillus flavus is the predominant species isolated from these infections. The high frequency of A. flavus isolation from these patients may be due to higher prevalence of the fungus in the environment. Cerebral aspergillosis cases are largely due to an extension of the lesion from invasive Aspergillus sinusitis. The majority of the centers rely on conventional techniques including direct microscopy, histopathology, and culture to diagnose IA. Galactomannan, β-D glucan test, and DNA detection in IA are available only in a few centers. Mortality of the patients with IA is very high due to delays in diagnosis and therapy. Antifungal use is largely restricted to amphotericin B deoxycholate and itraconazole, though other anti-Aspergillus antifungal agents are available in those countries. Clinicians are aware of good outcome after use of voriconazole/liposomal amphotericin B/caspofungin, but they are forced to use amphotericin B deoxycholate or itraconazole in public-sector hospitals due to economic reasons.

In vitro susceptibility of 188 clinical and environmental isolates of Aspergillus flavus for the new triazole isavuconazole and seven other antifungal drugs

Recently isavuconazole, an experimental triazole agent, was found to be active against Aspergillus species. As Aspergillus flavus is the second‐most common Aspergillus species isolated from human infection and the fungus has not been widely tested against the drug, we studied a large collection of clinical (n = 178) and environmental (n = 10) strains of A. flavus against isavuconazole and compared the results with seven other Aspergillus‐active antifungal agents (some of them triazoles, others echinocandins or polyene antifungals: voriconazole, posaconazole, itraconazole, caspofungin, anidulafungin, micafungin and amphotericin B) using Clinical and Laboratory Standards Institute methods. Strains with high minimal inhibitory concentrations (MICs) were tested by E‐test as well. The strains were collected from two different geographical locations (India and the Netherlands). Three isolates (1.6%) had high MIC (2 mg l−1 by microbroth dilution and 8 mg l−1 by E‐test) for amphotericin B. Isavuconazole showed good activity against A. flavus strains with MIC50 and MIC90 values of 1 mg l−1. As compared with voriconazole (the drug recommended for primary therapy of aspergillosis), isavuconazole had better activity (99.5% of strains had MIC of ≤1 mg l−1 for isavuconazole, compared to 74% of strains with same MIC for voriconazole). All strains were, following recently proposed clinical breakpoints, susceptible for the triazoles tested except three strains, which had MICs of 4 mg l−1 for voriconazole. Testing these strains with high MIC by E‐test, gave results of 0.5–2 mg l−1. Posaconazole had the lowest MIC50 and MIC90 of 0.125 mg l−1 and 0.25 mg l−1, respectively. Among echinocandins, 97% of strains had a minimum effective concentration (MEC) of ≤0.5 mg l−1 for caspofungin, and all strains had a MEC of ≤0.016 mg l−1 and ≤0.125 mg l−1 for anidulafungin and micafungin, respectively.

Colletotrichum truncatum: an unusual pathogen causing mycotic keratitis and endophthalmitis.

ABSTRACT In recent years, the well-known plant pathogens of the Colletotrichum genus were increasingly reported to cause ophthalmic infections in humans. Among 66 species in the Colletotrichum genus, only a few are known to be pathogenic for humans. We report here five cases of ophthalmic infections due to Colletotrichum truncatum, a species never reported earlier to cause human infection. The isolates were identified by morphological characteristics and the sequencing of internal spacer regions of ribosomal DNA. The progress of lesions in those patients was slow compared to that of lesions caused by Aspergillus or Fusarium infections. The surgical management included total penetrating keratoplasty in patients with keratitis and pars plana vitrectomy in endophthalmitis. Two patients were treated additionally with intravitreal amphotericin B deoxycholate, one patient with oral itraconazole, and another patient with oral and topical fluconazole therapy. The present series therefore highlights the expanding spectrum of agents causing eye infections and the inclusion of C. truncatum as a human pathogen.

Exophiala dermatitidis endocarditis on native aortic valve in a postrenal transplant patient and review of literature on E. dermatitidis infections.

Atul K. Patel, Ketan K. Patel, Prakash Darji, Rachna Singh, M. R. Shivaprakash and Arunaloke Chakrabarti Infectious Diseases Clinic, Vedanta Institute of Medical Sciences, Ahmedabad, India, Department of Nephrology and Renal Transplant, Sterling Hospital, Ahmedabad, India and Division of Mycology, Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

Serum galactomannan assay for the diagnosis of invasive aspergillosis in children with haematological malignancies

Diagnostic efficacy of Galactomannan (GM) assay for invasive aspergillosis (IA) is variably reported. Data from developing countries are scant. Children with haematological malignancies and fever were enrolled prospectively. Blood sample for GM was drawn on the day of admission; levels were measured with Platellia Aspergillus enzyme immunoassay. Diagnostic criteria were adapted from EORTC‐MSG‐2002. Proven, probable and possible episodes were considered as the disease group. One hundred febrile episodes in 78 patients were evaluated. The mean age was 6.1 years. Majority (75%) episodes were in patients with acute lymphoblastic leukaemia. One episode each was diagnosed with proven and probable IA, while 23 were diagnosed with possible IA. Best results were obtained with a cut‐off value of 1.0, with sensitivity, specificity, positive and negative predictive value of 60%, 93%, 75 and 87 respectively. The sensitivity dropped to 40%, at cut‐off value of 1.5 and specificity was 38%, at a cut‐off of 0.5. A higher value of GM correlated with pulmonary nodules (P = 0.037) and mortality (P = 0.001). GM assay is adjunctive to clinical/radiological evidence. A negative GM assay may not reassure the physician against the use of amphotericin in patients with febrile neutropenia, as it does not exclude the diagnosis of clinically relevant other fungal infections, particular mucormycosis.

Cavitary Pulmonary Zygomycosis Caused by Rhizopus homothallicus

ABSTRACT We report the first two proven cases of cavitary pulmonary zygomycosis caused by Rhizopus homothallicus. The diagnosis in each case was based on histology, culture of the causal agent, and the nucleotide sequence of the D1/D2 region of the 28S ribosomal DNA.

Candida in Acute Pancreatitis

PurposeA Candida infection of the pancreas, which previously was considered extremely unusual, has been increasingly reported in recent years. The present study was conducted with the aim of performing a cohort analysis of our patients with acute pancreatitis to find out the incidence, sites, and species of Candida involvement; and to evaluate the risk factors, severity, and course of illness of such patients.MethodsA total of 335 patients with acute pancreatitis were investigated for a possible Candida infection of the pancreas from January 2000 to May 2003. The clinical records of all those patients who were positive for Candida spp. isolation from pancreatic tissue were analyzed. The clinical records of 32 more cases, randomly selected from the patients who were investigated for candidal pancreatitis but were negative for Candida spp., were also analyzed in order to compare their findings with those patients with a true Candida infection of the pancreas.ResultsA true or possible Candida infection was observed in 41 (12.2%) of those 335 patients and Candida tropicalis was the most common isolate (43.9%). Candida spp. were isolated from pancreatic necrotic tissue in 22 (6.6%) patients (true infection). A possible Candida infection (positive drain fluid effluents at least twice, without any Candida isolation from pre/per operative samples from pancreas) was seen in 19 (5.7%) patients. Candida was also isolated exclusively from the blood in another 19 patients with a clinical diagnosis of acute pancreatitis. A risk factor analysis showed that patients with severe injury to the pancreas, on prophylactic fluconazole, and after surgical intervention were significantly more prone to develop a Candida infection. Patients with a Candida superinfection also had a significantly increased hospital stay and higher mortality.ConclusionThis study thus emphasizes the important role of Candida infection in patients with acute pancreatitis and demonstrates the need for early attention.