Invasive fungal infections in hemato-oncology.

BACKGROUND: Patients with hematologic malignancies (HM) carries a significant risk of developing invasive fungal infection (IFI) and are associated with a high risk of attributable morbidity and mortality. OBJECTIVES: This review has highlighted the importance of diagnosis and management of invasive fungal infections in highly immunocompromised Hemato-Oncology patients. CONTENT: IFI continues to be a therapeutic issue in immunocompromised HM patients despite of many advancements in the field of fungal diagnosis and therapies. Non-specific and often overlapping signs and symptoms render fungal infections clinically undifferentiated from bacterial infections. Definite diagnosis requires microbiological diagnostic procedures in addition to imaging techniques. Many international committees have formulated definitions to aid in the diagnosis of IFI in immunocompromised patients and assigned 3 levels of probability to the diagnosis "proven," "probable," and "possible" IFI. Early specific risk-based antifungal strategies such as prophylaxis, pre-emptive and empirical therapies, are common practices in HM patients. For low-risk patients, fluconazole is recommended as primary prophylaxis, while, posaconazole and voriconazole are recommended for high-risk patients. Emerging antifungal-resistant IFIs and breakthrough fungal infections are the new threat to these heavily immunosuppressed patients. Antifungal agents such as azoles have variable pharmacokinetics leading to uncertainty in the drug dose-exposure relationship, especially in the initiation phase. TDM (therapeutic drug monitoring) of voriconazole is strongly recommended.

Antimicrobial prescribing patterns of surgical speciality in a tertiary care hospital in India: Role of persuasive intervention for changing antibiotic prescription behaviour.

BACKGROUND: Inappropriate use of antibiotics globally has been linked to increase in antibiotic resistance. OBJECTIVES: This interventional study assessed the impact of antibiotic prescription feedback and focus group discussions (FGD) on hospital-based prescribers before and after the FGD. STUDY DESIGN: The present study was performed at a tertiary care centre in New Delhi, wherein 45 units from surgical specialities were included for FGD. Thirty-five units were assessed for the antibiotic usage during 12 months pre-intervention and 3 and 6 months post-intervention period. The outcome measured was a change in antibiotic prescription rates reflected as daily defined doses per 100 bed days as defined by the World Health Organisation. RESULTS: Reduction in the level of antibiotic consumption was observed in 15 of 35 units (42.85%) during the 3 months post-intervention period, which was significant (P < 0.05) in 3/35 (8.57%) surgical units. A significant reduction (P < 0.05) was observed for the units of endoscopic gynaecology, super-speciality and transplant surgery units B and C, and orthopaedic unit C during the 6 months period. Decreasing trend (P < 0.05) was observed in 2/35 (5.71%) units during the entire period. Overall reduction of antibiotic consumption (1.88%) was observed, with an increase in the use of low-end antibiotics and a decrease in the use of high-end antibiotics. CONCLUSION: The present study clearly demonstrates a weak impact of FGD in changing antibiotic prescribing behaviour. Further analysis of the sustainability of FGD and its long-term impact on antimicrobial resistance needs to be evaluated. The effect of continuous educational sessions and multifaceted interventions cannot be ignored.

Threshold of galactomannan antigenemia positivity for early diagnosis of invasive aspergillosis in neutropenic children.

PURPOSE: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in immunocompromised patients. Pediatric data on the accuracy and optimal cutoff of galactomannan antigen detection to diagnose IA is sparse and controversial. We evaluated the utility and optimal serum galactomannan assay (GA) cutoff in children. METHODS: Children with febrile neutropenia due to malignancy, hematopoietic stem cell transplant, aplastic anemia, or congenital neutropenia, were prospectively included from 2007 to 2011. All new episodes of febrile neutropenia were recorded. In case of a previous diagnosis of IA, subsequent episodes were excluded. One to four GA were tested by enzyme immunoassay during each episode. Bronchoalveolar lavage and other relevant samples for mycological diagnosis, and computed tomography of chest/sinus were performed wherever appropriate. IA was classified as "proven", "probable", and "possible" as per the 2008 European Organisation for Research and Treatment of Cancer and Mycoses Study Group Guidelines. The optimal cutoff value was determined using receiver operating characteristic curves in episode-wise analysis. RESULTS: There were 145 patients with 211 febrile episodes included: hematopoietic stem cell transplant (n = 15), oncological (n = 113), and hematological disorders (n = 17). Forty-five children (31.0%) developed IA (5 proven, 15 probable, and 25 possible). Cutoff value of single GA ≥ 0.7 for proven/probable/possible IA offered the best combination of sensitivity (82.2%)/specificity (82.5%), and 94.4% negative predictive value. Two consecutive positive GA ≥ 0.7 had a sensitivity/specificity of 75.0%/91.0%. Index GA ≥ 1.9 was associated with significantly higher mortality in children with IA and overall. CONCLUSION: Serum GA is sensitive to diagnose IA in pediatric patients with excellent negative predictive value at an optimal cutoff of ≥0.7. Considering two consecutive values ≥0.7 increases specificity to 91.0%.

Ecology of blood stream infection and antibiotic resistance in intensive care unit at a tertiary care hospital in North India

OBJECTIVE: To analyse the prevalent microorganisms and their antimicrobial resistance among intensive care unit patients in a tertiary care centre in New Delhi. METHODS: A retrospective study of all consecutive blood cultures from various intensive care unit patients in the hospital during four years (January 2008 to December 2011). Antibiotic consumption data in the intensive care units were also analysed during the same period. RESULTS: Out of the total 22,491 blood cultures processed, 2846 samples were positive and 3771 microorganisms were isolated. The blood culture positivity was estimated as 12.7% of which 67.5% were monomicrobial and 32.5% polymicrobial infections. Gram negative bacilli, Gram positive cocci, and fungi were isolated in 49%, 33%, and 18% cases, respectively. Coagulase negative staphylococcus was the commonest single isolate followed by Candida spp. A drastic shift in the distribution of Candida spp. towards nonalbicans along with high resistance to azole group of antifungals suggest echinocandins for the empiric therapy of candidemia. High penicillin resistance in Gram positive isolates suggest vancomycin, linezolid and tigecycline as the options for empiric therapy, whereas tigecycline and colistin are the only options remaining for highly resistant Gram negative isolates. Aminoglycosides were observed to have better sensitivity and reduced usage when compared with cephalosporins and ß-lactam + ß-lactam inhibitor combinations. CONCLUSIONS: High frequencies of multidrug resistant organisms were observed in intensive care units which is a warning as to use the only few effective antimicrobials wisely to reduce selective pressure on sensitive strains. .

Scopulariopsis brevicaulis infection of prosthetic valve resembling aspergilloma on histopathology.

Fungal prosthetic valve endocarditis is an infrequent but serious complication of valve replacement surgery. Approximately 75% of patients are affected with Candida species. Scopulariopsis species affecting prosthetic valve is rarely reported in the literature.