Issues in antifungal stewardship: an opportunity that should not be lost.

Many countries have observed an increase in the incidence of invasive fungal infections (IFIs) over the past two decades with emergence of new risk factors and isolation of new fungal pathogens. Early diagnosis and appropriate antifungal treatment remain the cornerstones of successful outcomes. However, due to non-specific clinical presentations and limited availability of rapid diagnostic tests, in more than half of cases antifungal treatment is inappropriate. As a result, the emergence of antifungal resistance both in yeasts and mycelial fungi is becoming increasingly common. The Delhi Chapter of the Indian Association of Medical Microbiologists (IAMM-DC) organized a 1 day workshop in collaboration with BSAC on 10 December 2015 in New Delhi to design a road map towards the development of a robust antifungal stewardship programme in the context of conditions in India. The workshop aimed at developing a road map for optimizing better outcomes in patients with IFIs while minimizing unintended consequences of antifungal use, ultimately leading to reduced healthcare costs and prevention development of resistance to antifungals. The workshop was a conclave of all stakeholders, eminent experts from India and the UK, including clinical microbiologists, critical care specialists and infectious disease physicians. Various issues in managing IFIs were discussed, including epidemiology, diagnostic and therapeutic algorithms in different healthcare settings. At the end of the deliberations, a consensus opinion and key messages were formulated, outlining a step-by-step approach to tackling the growing incidence of IFIs and antifungal resistance, particularly in the Indian scenario.

Convergence of Minds: For Better Patient Outcome in Intensive Care Unit Infections.

BACKGROUND: There is emergence of resistance to the last-line antibiotics such as carbapenems in Intensive Care Units (ICUs), leaving little effective therapeutic options. Since there are no more newer antibiotics in the armamentarium in the near future, it has become imperative that we harness the interdisciplinary knowledge for the best clinical outcome of the patient. AIMS: The aim of the conference was to utilize the synergies between the clinical microbiologists and critical care specialists for better patient care and clinical outcome. MATERIALS AND METHODS: A combined continuing medical education program (CME) under the aegis of the Indian Association of Medical Microbiologists - Delhi Chapter and the Indian Society of Critical Care Medicine, Delhi and national capital region was organized to share their expertise on the various topics covering epidemiology, diagnosis, management, and prevention of hospital-acquired infections in ICUs. RESULTS: It was agreed that synergy between the clinical microbiologists and critical care medicine is required in understanding the scope of laboratory tests, investigative pathway testing, hospital epidemiology, and optimum use of antibiotics. A consensus on the use of rapid diagnostics such as point-of-care tests, matrix-assisted laser desorption ionization-time of flight mass spectrometry, and molecular tests for the early diagnosis of infectious disease was made. It was agreed that stewardship activities along with hospital infection control practices should be further strengthened for better utilization of the antibiotics. Through this CME, we identified the barriers and actionables for appropriate antimicrobial usage in Indian ICUs. CONCLUSIONS: A close coordination between clinical microbiology and critical care medicine opens up avenues to improve antimicrobial prescription practices.

Multidrug-resistant pulmonary & extrapulmonary tuberculosis: A 13 years retrospective hospital-based analysis.

BACKGROUND & OBJECTIVES: Multidrug-resistant tuberculosis (MDR-TB) is a public health problem of great significance in India. In the present study an attempt was made to analyse the progression of MDR-TB pattern during a course of 13 years (2000-2012) among the patient population at a tertiary care centre in New Delhi, India. METHODS: Mycobacterial isolates obtained on Lowenstein-Jensen (L-J) medium/BacT/ALERT 3D were identified using AccuProbe molecular identification system, routine biochemical tests or GenoType Mycobacteria CM. Antimycobacterial susceptibility testing was performed using resistance ratio method on L-J medium (2000-2004) and one per cent proportion method on BacT/ALERT 3D system (2005-2012). RESULTS: Of the total 14,849 samples subjected to mycobacterial culture, 6569 pulmonary and 8280 extrapulmonary, 2364 were detected positive for mycobacteria. The average percentage positivity rate was 15.9 per cent (18.9 and 13.6% in case of pulmonary and extrapulmonary samples, respectively). Our study revealed a significant increase (P<0.001) in multidrug resistance by 12 per cent (4.7% in 2000 to 19.8% in 2012). MDR-TB was more in case of pulmonary (28.2%) than extrapulmonary (11.6%) TB (P<0.001). Only 6.5 per cent (154) of mycobacterial isolates were non-tuberculous mycobacteria and rapid growers represented by Mycobacterium fortuitum and M. abscessus were the most commonly isolated species. INTERPRETATION & CONCLUSIONS: Increase in prevalence of MDR-TB by 12 per cent in the past 13 years is alarming. Policy modifications may have to be done to strengthen the existing TB control programmes to encourage contact tracing and culture and drug susceptibility testing for all smear positive pulmonary cases to ensure early and appropriate therapy.

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.

Non-albicans Candida species in blood stream infections in a tertiary care hospital at New Delhi, India.

BACKGROUND & OBJECTIVES: During recent decades, there has been a change in the epidemiology of Candida infections, characterized by a progressive shift from a predominance of Candida albicans to non-albicans Candida species. This study was undertaken to analyze the change in the epidemiology of candidaemia and antifungal use at tertiary care hospital in New Delhi, India, over a period of 10 years. METHODS: A retrospective review of candidaemia between 1999 and 2008 and antifungal use from 2000 to 2008 was performed at Sir Ganga Ram Hosptial, New Delhi. Initially (1999-2005), isolates were differentiated as C. albicans and non- albicans Candida species. Between 2006-2008, these were identified to the species level and antifungal susceptibility was performed. RESULTS: The occurrence of candidaemia and total antifungal use increased significantly. Candidaemia due to non-albicans species increased and this was correlated with an increasing use of fluconazole. There was emergence and increased isolation of a novel species C. haemulonii with decreased susceptibility to both amphotericin B and azoles. Overall, sensitivities of 89.6, 90.9, 88.6, 68.8 and 54.3 per cent to amphotericin B, 5 flucytosine, voriconazole, fluconazole and itraconazole, respectively were observed. Cross-resistance or reduced susceptibility to both fluconazole (MIC >16 µg/ml) and voriconazole was observed in 11.3 per cent isolates. INTERPRETATION & CONCLUSIONS: The study demonstrates a shift to non-albicans Candida species causing fungaemia and the emergence of amphotericin B and azole resistant novel species, C. haemulonii. Decreased susceptibility to fluconazole, as well as the threat of emergence of cross-resistance to voriconazole in the background of high azole consumption may limit the use of these agents as a presumptive therapy for Candida blood stream infections (BSI).

Trend analysis of antimicrobial consumption and development of resistance in non-fermenters in a tertiary care hospital in Delhi, India.

OBJECTIVES: Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii are becoming increasingly important nosocomial pathogens worldwide. To study the evolution of non-fermenters in a tertiary care hospital, we undertook a retrospective 10 year (1999-2008) trend analysis of antimicrobial consumption and resistance in non-fermenters causing bacteraemia. METHODS: Antibiotic consumption and resistance were analysed by linear regression. The Pearson correlation coefficient was used for assessing correlation between them. RESULTS: A total of 69,010 blood cultures were performed, which grew 15,465 isolates (22% positivity rate), of which 1525 isolates (771 isolates of P. aeruginosa and 754 isolates of A. baumannii) were non-fermenters. Overall antibiotic consumption showed an increasing trend, from 158 to 319 defined daily doses (DDDs)/100 bed-days (r(2)= 0.62, P = 0.007). The largest relative increase in antibiotic consumption was seen for carbapenems (r(2)= 0.68, P = 0.022), followed by ß-lactam/inhibitor combinations (r(2 )= 0.45, P = 0.033), whereas third-generation cephalosporins, fluoroquinolones and aminoglycosides showed no significant changes. A significant increase in resistance in A. baumannii to fluoroquinolones (r(2 )= 0.63, P = 0.006), aminoglycosides (r(2 )= 0.63, P = 0.011) and carbapenems (r(2 )= 0.82, P = 0.013) and in P. aeruginosa to aminoglycosides (r(2 )= 0.59, P = 0.01) was observed. Carbapenem consumption was associated with the development of resistance in A. baumannii (r = 0.756, P = 0.049), whereas no such association was observed for other antimicrobials among non-fermenters. CONCLUSIONS: Our study highlights the growing problem of high antimicrobial consumption. The increasing prevalence of non-fermenters and the emergence of multidrug-resistant A. baumannii are associated with the consumption of carbapenems. The data cannot prove cause and effect.

An infrequent etiology of Infective Endocarditis.

Abiotrophia. defectiva is an infrequent but an important cause of infectious endocarditis (IE). IE caused by A. defectiva may actually be more common than what is reported in the literature because of its failure to grown on routine media like blood agar and MacConkey agar, besides difficulty in its identification by conventional methods. IE by A. defectiva generally have more fulminant course and is associated with higher mortality and morbidity due to frequent embolic episodes and valvular tissue destruction. Ceftriaxone or vancomycin in combination with gentamicin and surgical replacement of valve is the recommended management.

A cross-sectional study of SARS-CoV-2 seroprevalence among asymptomatic healthcare workers in a tertiary healthcare centre: Assessing the impact of PPE guidelines.

PURPOSE: The present study estimates the seroprevalence of SARS-COV-2 among asymptomatic HCWs and assess the impact of various categories of PPE. METHODS: A cross-sectional study of asymptomatic HCW using different levels of PPE as per their risk profile was undertaken between 18th and 24th September 2020. Participant demographics and other relevant details including the levels of PPE used were recorded using a customized questionnaire. IgG antibodies against SARS-COV-2 were detected by chemiluminescence method & used as a surrogate marker for incomplete protection. RESULTS: Out of 1033 HCWs tested, overall SARS-COV-2 sero-prevalence was 25.8%. Univariate and multivariate analysis both demonstrated that ancillary workers including security staff (OR 5.589, P â€‹< â€‹0.001) and sanitary workers (OR 3.946, P â€‹< â€‹0.001) were at significantly higher risk of seropositivity irrespective of the PPE used as per guidelines, whereas doctors were at significantly lower risk of seropositivity (OR 0.307, P â€‹= â€‹0.005). Staff working in office areas was associated with reduced risk of seropositivity (OR 0.21, P â€‹= â€‹0.045). CONCLUSIONS: We document high seroprevalence of SARS-COV-2 antibodies in asymptomatic HCWs. Doctors who are at the highest risk had the lowest seropositivity and seroprevalence among office staff having a risk level comparable to the general community was lower than that reported in general population, supporting the efficacy of PPE practices as per guidelines in these groups. In contrast, much higher rates of seropositivity were seen among ancillary workers despite the availability of adequate PPE. Active screening, proper PPE use as per guidelines, and regular infection control trainings including Covid appropriate behaviour are therefore essential to contain COVID-19 spread among HCW & preventing them to transfer infection to the patients.

Experience of Indian association of medical microbiology external quality assurance scheme centre, New Delhi: Challenges and quality assessment of clinical microbiology laboratories.

Introduction: EQAS program at New Delhi under IAMM was started in January 2014 across North and North east regions of India with 217 participants, which grew up to 540 by 2018. Materials and Methods: In 2014, 4 analytes per year were sent for 3 exercises, i.e. smear culture and serology. 2018 onwards PT analytes were increased from 4 to 12 and comparative performance of techniques analysed. Results: Out of the 22 smears sent for gram staining, ZN staining, Kinyoun staining and Albert staining, completely correct results ranged between 29.55% - 79.9%, 94.3% - 99.2%, 35.5% & 93.8%, respectively. Correct results for culture isolate identification & susceptibility testing and serology exercises varied between 70 & 92.4% and 73.1 & 98.59%, respectively. In the year 2018, 470 responses were received for bacterial culture identification & antibiotic susceptibility testing out of which manual and automated systems were used by 54% & 46% and 52.5% & 47.5% participants, respectively. Techniques used in BBV assays for HBsAg, HCV & HIV found all methods like ELISA, ELFA, CLIA and Card Test performing similarly. The major challenges in running the EQA program included requirement of large amount of specimens for PT item preparation, stability in hot and humid conditions and timely delivery of PT challenges in remote parts of the country. Conclusion: A large number of the participating laboratories (77%) had an overall score of >80% for all exercises, demonstrating acceptable baseline performance of EQAS registered laboratories. However, continued EQAS participation could further improve the quality of results.

Performance of three commercial assays for colistin susceptibility in clinical isolates and Mcr-1 carrying reference strain.

Objective: Commercially available antibiotic susceptibility tests (cAST) for colistin are reported to shows variable performance. The current controversy on the colistin susceptibility testing and scarce data from India has left the clinical laboratories in a dilemma on the appropriate and practical approach to tackle the colistin antimicrobial susceptibility testing (AST) issue. This study was aimed to evaluate the performance of commonly used cAST for colistin against broth microdilution (BMD) as the reference method in the clinical isolates. Materials and Methods: Colistin AST was performed on 225 nonduplicate isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii by BMD as the reference method and compared with Vitek-2, Micronaut-S and E-test. The accuracy of the various cASTs was analysed by assessing categorical and essential agreement (EA). Results: We observed an overall categorical agreement of 98.2%, 99.6% and 96.4% and EA of 92%, 92.4% and 72% for Vitek-2, Micronaut-S and E-test, respectively. Unacceptable rates of major error (10.5%) and very major error (21%) were observed for P. aeruginosa with Vitek-2 and E-test, respectively. All the categorical errors (CEs) (7.7%) with Vitek-2 were seen for minimum inhibitory concentrations ranging within two-fold dilution breakpoint of 2 mg/L. Conclusion: Micronaut-S was found to be an acceptable method for colistin AST. In contrast, E-test was unreliable in terms of EA. Vitek-2 was found to be reliable for colistin AST, although it was more prone to CE near the colistin breakpoints.

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.

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. .