Comparative Efficacies of the Three Echinocandins for Candida auris Candidemia: Real World Evidence from a Tertiary Centre in India.

Though echinocandins are the first line of therapy for C.auris candidemia, there is little clinical data to guide the choice of therapy within this class. This was the first study to compare the three echinocandins in terms of efficacy and outcomes for C.auris candidemia. This was a retrospective analysis of 82 episodes of candidemia caused by C.auris comparing outcomes across the three echinocandins. Majority patients in our study were treated with micafungin. Susceptibility rates were the lowest for caspofungin (35.36% resistance), with no resistance reported for the other two echinocandins. When a susceptible echinocandin was chosen, caspofungin resistance was not a factor significantly associated with mortality. Also when a susceptible echinocandin was used for therapy, the choice within the class did not affect clinical cure, microbiological cure or mortality (p > 0.05 for all). Failure to achieve microbiological cure (p = 0.018) and receipt of immune-modulatory therapy (p = 0.01) were significantly associated with increased mortality. Significant cost variation was noted amongst the echinocandins. Considering the significant cost variation, comparable efficacies can be reassuring for the prescribing physician.

This is the first study comparing efficacy of the three echinocandins in C.auris candidemia. The clinical efficacy of the three echinocandins was found to be comparable. Micafungin and anidulafungin had lower Minimum Inhibitory Concentrations. A significant cost variation was noted.

Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India.

Objectives: Fecal microbiota transplantation (FMT) is an emerging option for recurrent or refractory Clostridium difficile-associated diarrhea (CDAD). We describe a single-center experience of FMT in hematopoietic stem cell transplant (HSCT) recipients with CDAD in India. Methods: A prospective observational study of HSCT recipients with CDAD who received FMT in our center. Results: A total of 13 patients were included. All the patients were allogenic HSCT recipients; FMT was performed in seven patients due to refractory CDAD, in five patients due to the presence of both CDAD and graft vs host disease (GVHD), and in 1 patient due to recurrent CDAD. The approach to FMT was colonoscopic in 10 (77%) patients. Only one patient reported bacteremia and one patient had candidemia, both of which were unrelated to FMT. Of the 10 patients who had complete resolution of CDAD, only one patient presented with a recurrence of CDAD within 8 weeks post-FMT. Conclusion: This is the first study from India using FMT as a therapeutic modality for CDAD in the setting of HSCT. Here we demonstrate that FMT in India is an effective option, especially when patients have refractory CDAD, recurrent CDAD, or both GVHD and CDAD. Further studies should explore the efficacy and feasibility of FMT in India. How to cite this article: Prayag PS, Patwardhan SA, Ajapuje PS, Melinkeri S, Gadhikar H, Palnitkar S, et al. Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India. Indian J Crit Care Med 2024;28(2):106-110.

Enzyme Patterns and Factors Associated with Mortality among Patients with Carbapenem Resistant AcinetobacterBaumannii (CRAB) Bacteremia: Real World Evidence from a Tertiary Center in India.

Introduction: In the Indian setting, antimicrobial resistance in A. baumannii is a considerable problem, especially in intensive care units (ICUs). Due to the limited data, clinicians are left with very few choices except polymyxins for treating serious infections caused by A. baumannii. There is sparse data regarding the local mechanisms of resistance. Given the current therapeutic challenges, it is critical to know the local enzymatic patterns and antibiograms. Materials and methods: A retrospective analysis of 50 episodes of bacteremia caused by CRAB. We analyzed the enzyme patterns and the susceptibility rates to various antibiotics. Results: The resistance rates for amikacin, tigecycline, minocycline, and fluoroquinolones were 88, 82, 50, and 88% respectively. OXA-23 was the most commonly isolated enzyme (86% of the isolates produced OXA-23) followed by OXA-51 and NDM. The overall mortality was high (58%). On univariate analysis, pneumonia, and higher Pitt's bacteremia score were significantly associated with mortality (p = 0.04 and p = 0.001 respectively). Of the total patients who received combination therapy, a majority (58%) received polymyxin plus meropenem. Combination therapy using polymyxins as a backbone was not associated with reduced mortality (p = 0.1). Conclusion: A. baumannii is associated with significant morbidity and mortality, as shown in our study. The rates of resistance for aminoglycosides were very high, and minocycline showed better susceptibility rates in comparison with tigecycline. In our study, OXA-23 and NDM remained the most important enzymes. The routine use of the combination of polymyxin and meropenem may not offer a significant advantage over monotherapy. How to cite this article: Prayag PS, Patwardhan SA, Joshi RS, Panchakshari SP, Rane T, Prayag AP. Enzyme Patterns and Factors Associated with Mortality among Patients with Carbapenem Resistant Acinetobacter Baumannii (CRAB) Bacteremia: Real World Evidence from a Tertiary Center in India. Indian J Crit Care Med 2023;27(9):663-668.

Ceftazidime-avibactam with or without Aztreonam vs Polymyxin-based Combination Therapy for Carbapenem-resistant Enterobacteriaceae: A Retrospective Analysis.

Introduction: Gram-negative sepsis remains one of the most difficult to treat infections in intensive care units (ICUs). Carbapenems are often considered to be robust and reliable options for treating infections due to Gram-negative bacteria. The dominance of carbapenem-resistant enterobacteriaceae (CRE) has emerged as one of the greatest challenges faced by the medical community today. Carbapenem-resistant enterobacteriaceae may be resistant to all beta lactam antimicrobials including carbapenems and often, are even resistant to other classes of drugs. There are limited studies comparing polymyxin-based therapies with ceftazidime-avibactam (CAZ-AVI)-based therapies for treating infections caused by CRE. Methods: A retrospective study comparing outcomes between patients with bacteremia caused by CRE treated with polymyxin-based combination therapy and CAZ-AVI-based therapy (with or without aztreonam). Results: Of total 104 patients, 78 (75%) were in the CAZ-AVI group. There was no significant difference in the underlying comorbidities between the two groups. The incidence of nephrotoxicity was significantly higher in the polymyxin group (p = 0.017). Ceftazidime-avibactam-based therapy was 66% less likely to be associated with day 14 mortality (p = 0.048) and 67% less likely to be associated with day 28 mortality (p = 0.039) as compared with polymyxin-based therapy. Conclusion: Ceftazidime-avibactam-based therapy may be a superior option to polymyxin-based therapy for infections caused by CRE. This can have significant practical applications, in terms of optimizing therapy for the individual patient as well as sparing polymyxins and reducing the use of polymyxins in our hospitals. How to cite this article: Prayag PS, Patwardhan SA, Panchakshari S, Sambasivam R, Dhupad S, Soman RN, et al. Ceftazidime-avibactam with or without Aztreonam vs Polymyxin-based Combination Therapy for Carbapenem-resistant Enterobacteriaceae: A Retrospective Analysis. Indian J Crit Care Med 2023;27(6):444-450.

Therapeutic Drug Monitoring of Isavuconazole: Lessons Learnt from a Real-life Setting in a Tertiary Care Center in India.

Introduction: Isavuconazole is an emerging therapeutic option for invasive infections caused by molds, especially aspergillosis and mucormycosis. Isavuconazole has predictable pharmacokinetics and good bioavailability. These attributes have led to some doubts regarding the need for therapeutic drug monitoring (TDM). There are no data from India regarding TDM for isavuconazole. Methods: A retrospective analysis of 50 patients who received oral isavuconazole for therapeutic purposes. Plasma isavuconazole levels were measured using a reversed phase high-performance liquid chromatography (HPLC) and UV detector with acetonitrile (ACN) as protein precipitating solvent. Results: Of the 50 cases, 5 (10.0%) patients had subtherapeutic levels, while 45 (90.0%) had therapeutic levels. Higher body weight and solid organ transplantation (SOT) were significantly associated with subtherapeutic levels of isavuconazole (p-value < 0.05 for all). Receipt of a SOT was the only independent and statistically significant factor which was associated with subtherapeutic levels of isavuconazole (p-value < 0.05). Conclusion: Our study reemphasizes the need of TDM for isavuconazole and adds to the growing evidence for the need to obtain drug levels. Factors associated with subtherapeutic levels of isavuconazole need to be assessed in larger studies to help identify those patients who are at risk of having subtherapeutic drug levels. How to cite this article: Prayag PS, Soman RN, Panchakshari SP, Ajapuje PS, Mahale NP, Dhupad S, et al. Therapeutic Drug Monitoring of Isavuconazole: Lessons Learnt from a Real-life Setting in a Tertiary Care Center in India. Indian J Crit Care Med 2023;27(4):260-264.

The Dominance of Candida auris: A Single-center Experience of 79 Episodes of Candidemia from Western India.

Introduction: Invasive candidiasis is a serious infection seen in hospitalized or immunocompromised patients. Mortality rates for candidemia can be as high as 30-60%. Candida auris is an emerging species of Candida and is increasingly becoming a global public health problem. Methods: This was a retrospective observational study, in which we analyzed 79 episodes of candidemia. Blood cultures were done using the Bactec™ FX blood culturing instrument (Becton, Dickinson and Company Sparks, Maryland, USA). Species identification was done using VITEK® 2 YST panels (bioMérieux Inc., Durham, North Carolina, USA). Antifungal susceptibility testing was performed using VITEK® 2 AST-YSO8 panels (bioMérieux Inc., Durham, North Carolina, USA). Results: Among the 79 episodes, the most common species was found to be C. auris (43.03% of all the episodes). Candida tropicalis was found to be the second most common species in patients admitted to our hospital with candidemia. All the isolates of C. auris were resistant to fluconazole, while 32.35 % of the isolates were also resistant to amphotericin B. Crude mortality in patients with C. auris candidemia was higher than the crude mortality for the other species. Conclusion: This is the first study from India where C. auris was seen as the most predominant species among patients admitted with candidemia. This is a serious issue given the high rates of fluconazole resistance, mortality, and cost of therapy associated with C. auris bloodstream infections. Urgent attention needs to be diverted to infection control practices and antimicrobial stewardship programs. How to cite this article: Prayag PS, Patwardhan S, Panchakshari S, Rajhans PA, Prayag A. The Dominance of Candida auris: A Single-center Experience of 79 Episodes of Candidemia from Western India. Indian J Crit Care Med 2022;26(5):560-563.

The Ability of a Cytomegalovirus ELISPOT Assay to Predict Outcome of Low-Level CMV Reactivation in Hematopoietic Cell Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV) infections in hematopoietic cell transplant (HCT) recipients cause substantial morbidity and mortality. CMV cell-mediated immunity (CMV-CMI) can be determined by levels of interferon gamma (IFN-γ) production using an enzyme-linked immunospot (ELISPOT) CMV assay (T-SPOT.CMV assay). In this study, we evaluated the ability of this assay to predict the outcome of low-level CMV reactivation in HCT recipients. METHODS: We followed 55 HCT recipients with low-level CMV reactivation up to 8 weeks from enrollment. Progression to clinically significant CMV infection (CS-CMVi) was defined as a CMV load >1000 IU/mL or > 500 IU/mL in patients receiving matched related/autologous or matched unrelated transplants, respectively, and initiation of antiviral treatment. RESULTS: Progression to CS-CMVi occurred in 31 (56%) of the HCT recipients. Spot counts of CMV-specific pp65 and IE1 antigens were significantly lower in patients who had CS-CMVi than in patients who did not. On multivariate analysis, the ELISPOT CMV responses and steroids use were the only predictors of progression to CS-CMVi. CONCLUSIONS: A strong association between low CMV-CMI and progression to CS-CMVi was observed in HCT recipients. The implementation of serial monitoring of CMV-CMI may identify patients at risk of progression to CS-CMVi that require antiviral therapy.

A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital.

OBJECTIVES: To describe the demographics and evaluate the clinical outcomes of hypoxic coronavirus disease-2019 (COVID-19) patients treated with different immunomodulatory (IM) drugs in a resource-limited setting. MATERIALS AND METHODS: We conducted a retrospective cohort study of these patients admitted to our hospital between March 22 and May 31, 2020. Data were abstracted from multiple electronic data sources or patient charts to provide information on patient characteristics, clinical, laboratory variables, and outcomes. RESULTS: A total of 134 patients met the inclusion criteria and were followed up till June 7, 2020. The median age of the patients was 55.6 years (range 20-89 years) and 68% were men. At least one comorbidity was seen in 72% of the patients with diabetes (44%) and hypertension (46%) being the most common. At triage, fever (82%), shortness of breath (77%), and cough (61%) were the most common presenting symptoms. A PaO2/FiO2 ratio less than 300 was seen in 60%, and 4.5% required invasive mechanical ventilation within 72 hours of hospital admission. Five immunomodulatory agents (hydroxychloroquine, methylprednisolone, colchicine, etoricoxib, and tocilizumab) were administered in different combinations. Overall, in-hospital mortality was 26.9%, and 32% required mechanical ventilation. Around 69% of patients were discharged home. Five variables (SpO2, PaO2/FiO2 ratio, leucocytosis, lymphopenia, and creatinine) on admission were found to be significant in the patients who died. CONCLUSION: Our study provides the characteristics and outcomes of hypoxic COVID-19 patients treated with IM drugs in varied combination. Five independent variables were strong predictors of mortality. HOW TO CITE THIS ARTICLE: Mahale N, Rajhans P, Godavarthy P, Narasimhan VL, Oak G, Marreddy S, et al. A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital. Indian J Crit Care Med 2020;24(11):1020-1027.

Synergistic anticancer action of quercetin and curcumin against triple-negative breast cancer cell lines.

Women with the breast cancer type 1 susceptibility protein (BRCA1) mutation and loss of BRCA1 expression are reported to have an increased risk of triple-negative breast cancer (TNBC). Targeting BRCA1 modulation might offer a therapeutic option to treat TNBC patients. Our studies detected that BRCA1 is poorly expressed in TNBC cell lines and highly expressed in ER+ breast cancer cell lines. To modulate BRCA1 expression, we tested two different dietary components to find out if any would induce tumor suppressor genes. We detected that quercetin and curcumin dose-dependently enhanced the BRCA1 expression. Further, a synergistic action of quercetin and curcumin was observed in modulating the BRCA1 level and in inhibiting the cell survival and migration of TNBC cell lines. Quercetin and curcumin appeared to induce BRCA1 promoter histone acetylation. Furthermore, BRCA1 knockdown induced cell survival and cell migration in ER + cells were significantly decreased by the combined treatment of quercetin and curcumin. Our present study concluded that the combination treatment of quercetin and curcumin acts synergistically to induce anticancer activity against TNBC cells by modulating tumor suppressor genes.

Oral Versus Aerosolized Ribavirin for the Treatment of Respiratory Syncytial Virus Infections in Hematopoietic Cell Transplant Recipients.

BACKGROUND: The use of oral ribavirin (RBV) for respiratory syncytial virus (RSV) infections is not well studied. With the drastic increase in the cost of aerosolized RBV, we aimed to compare outcomes of hematopoietic cell transplant (HCT) recipients treated with oral or aerosolized RBV for RSV infections. METHODS: We reviewed the records of 124 HCT recipients with RSV infections treated with oral or aerosolized RBV from September 2014 through April 2017. An immunodeficiency scoring index (ISI) was used to classify patients as low, moderate, or high risk for progression to lower respiratory infection (LRI) or death. RESULTS: Seventy patients (56%) received aerosolized RBV and 54 (44%) oral RBV. Both groups had a 27% rate of progression to LRI (P = 1.00). Mortality rates did not significantly differ between groups (30-day: aerosolized 10%, oral 9%, P = 1.00; 90-day: aerosolized 23%, oral 11%, P = .10). Classification and regression tree analysis identified ISI ≥7 as an independent predictor of 30-day mortality. For patients with ISI ≥7, 30-day mortality was significantly increased overall, yet remained similar between the aerosolized and oral therapy groups (33% for both). After propensity score adjustment, Cox proportional hazards models showed similar mortality rates between oral and aerosolized therapy groups (30-day: hazard ratio [HR], 1.12 [95% confidence interval {CI}, .345-3.65, P = .845). CONCLUSIONS: HCT recipients with RSV infections had similar outcomes when treated with aerosolized or oral RBV. Oral ribavirin may be an effective alternative to aerosolized RBV, with potential significant cost savings.

Active Mycobacterium tuberculosis infection at a comprehensive cancer center, 2006-2014.

BACKGROUND: Morbidity and mortality from Mycobacterium tuberculosis (Mtb) infection remain significant in cancer patients. We evaluated clinical characteristics, management, and outcomes in patients with active Mtb infection at our institution who had cancer or suspicion of cancer. METHODS: We retrospectively examined medical records of all patients with laboratory-confirmed active Mtb infection diagnosed between 2006 and 2014. RESULTS: A total of 52 patients with laboratory-confirmed active Mtb infection were identified during the study period, resulting in an average rate of 6 new cases per year. Thirty-two (62%) patients had underlying cancer, while 20 (38%) patients did not have cancer but were referred to the institution because of suspicion of underlying malignancy. Among patients with cancer, 18 (56%) had solid tumors; 8 (25%) had active hematologic malignancies; and 6 (19%) had undergone hematopoietic-cell transplantation (HCT). Patients with and without cancer were overall similar with the exception of median age (61 years in cancer patients compared to 53 years in noncancer patients). Pulmonary disease was identified in 32 (62%) patients, extrapulmonary disease in 10 (19%) patients, and disseminated disease in 10 (19%) patients. Chemotherapy was delayed in 53% of patients who were to receive such treatment. Eleven patients (all of whom had cancer) died; 3 of these deaths were attributable to Mtb infection. CONCLUSIONS: Although not common, tuberculosis remains an important infection in patients with cancer. Approximately one-third of patients were referred to our institution for suspicion of cancer but were ultimately diagnosed with active Mtb infection rather than malignancy.

Candida auris - Comparison of sensititre YeastOne and Vitek 2 AST systems for antifungal susceptibility testing - A single centre experience.

INTRODUCTION: Candida auris is emerging as an important cause of candidemia and deep seated candidal infection. We compared the susceptibility results of bloodstream Candida auris isolates by Vitek 2 with Sensititre YeastOne (SYO) method. METHODS: Forty-seven C. auris blood stream isolates were simultaneously tested for AFST by Vitek 2 and SYO. RESULTS: All strains were resistant to Fluconazole. 25.5% isolates showed pan-azole resistance. In comparison with SYO, lower MICs for voriconazole were noted with Vitek 2 (VME rate 76.1%). All strains were sensitive to anidulafungin and micafungin by SYO. For micafungin, Vitek 2 demonstrated higher MICs and an ME rate of 23.5%. Susceptibility interpretation of caspofungin by SYO was challenged by development of 'Eagle effect' resulting in sensitivity of 28.2%. We studied the evolution of caspofungin 'Eagle effect' with SYO by serial hourly MIC readings and noted that paradoxical growth commenced at 21 hrs of incubation. Compared to SYO, Vitek 2 showed higher resistance rate to Amphotericin B with ME rate of 25.6%. CONCLUSION: Laboratories using commercial AFST systems for Candida auris need to be aware of the possibility of ME and VME for amphotericin B and voriconazole respectively with Vitek 2 and 'Eagle effect' for caspofungin with SYO.

Comparison of Efficacy of Pressure Controlled vs. Traditional Manual Mask Ventilation for Newborn Resuscitation - A Simulation-Based Pilot Randomized Control Trial.

OBJECTIVES: To determine efficacy of non-invasive positive pressure face mask ventilation using a ventilator device (NIPPmV) for achieving early effective ventilation compared to that by self-inflating bag (SIB) or T- piece resuscitator (TPR). METHODS: The authors video recorded 33 trained resuscitators using NIPPmV (provided using ventilator device), SIB [a 500 ml silicone SIB without a positive end expiratory pressure (PEEP) valve] and a TPR. Using a continuous pressure recording system and a neonatal manikin, the authors evaluated the efficacy of the ventilation to achieve early effective ventilation during 30 s of ventilation. The primary outcome was time to achieve effective chest rise. Secondary outcomes were peak inspiratory pressure (PIP), ventilation rate and the need to perform ventilation corrective steps during positive pressure ventilation (PPV) among the devices. RESULTS: Total 99 videos were recorded. The time(s) taken to achieve the first chest rise was significantly lesser in NIPPmV group compared to SIB and TPR (3.0 ± 1.7 vs. 3.7 ± 1.9 vs. 7.5 ± 5.4, respectively, p <0.001). The mean PIP delivered by NIPPmV compared to SIB & TPR (19.8 ± 1.6 vs. 35.6 ± 7.4 vs. 17.8 ± 2.0 cm H20 respectively; p <0.001) was more accurate with preset PIP. Ventilation, in terms of breath rate, was observed to be controlled more accurately with NIPPmV compared to SIB & TPR (50 vs. 42 vs. 33 per min respectively; p <0.001). CONCLUSIONS: The non-invasive positive pressure face mask ventilation using a ventilator (NIPPmV) resulted in achieving early, effective and consistent ventilation.

COVID-19 Associated Vertebral Osteomyelitis Caused by Aspergillus Species-A Case Series.

Coronavirus Disease (COVID-19) associated fungal infections including pulmonary aspergillosis, mucormycosis and other invasive fungal infections have been increasingly described in the current pandemic. Aspergillus osteomyelitis is a rare clinical form of aspergillosis. Most cases of Aspergillus osteomyelitis are reported in immunocompromised patients. We describe four cases of vertebral osteomyelitis caused by Aspergillus species in the post COVID-19 setting. To the best of our knowledge, Aspergillus vertebral osteomyelitis has not been described in the post COVID-19 setting. None of the four patients described in this series were immunocompromised and all of them had received steroids during their hospitalization for COVID-19 pneumonitis. Vertebral osteomyelitis caused by Aspergillus species is a rare clinical manifestation of Aspergillosis. It requires a high index of suspicion and prompt efforts to establish a diagnosis. For a clinician involved in assessing a patient with Spondylodiscitis, the work up must not be limited to testing for Tuberculosis. Every attempt must be made to establish the microbiological diagnosis. Combined medical and surgical management is generally needed for Aspergillus osteomyelitis.

Factors associated with subtherapeutic levels of oral posaconazole tablet: a detailed analysis from a tertiary care center in India.

OBJECTIVES: Posaconazole is a broad-spectrum triazole antifungal, with activity against various clinically important fungi. The delayed release (DR) tablet of posaconazole has been shown to have a superior pharmacokinetic profile in comparison with the oral suspension. METHODS: We retrospectively analyzed the factors associated with posaconazole levels <1.25 µg/ml in 164 patients receiving the DR tablet for therapeutic purposes. RESULTS: Of the 164 patients, 53 (32.3%) showed subtherapeutic trough levels of posaconazole. The use of proton pump inhibitors (95% CI 1.41-3.91; P-value = 0.028) and the presence of diarrhea (95% CI 1.95-6.93; P-value = 0.001) were significantly associated with subtherapeutic levels. A total of 13 of the 21 patients receiving posaconazole tablets through a nasogastric tube had therapeutic levels. CONCLUSION: This is the largest study from India that analyzed factors associated with subtherapeutic levels of the DR tablet of posaconazole. These findings reinforce the importance of therapeutic drug monitoring. Unlike in previous studies, obesity and hypoalbuminemia were not found to be significant factors in our settings. The use of proton pump inhibitors and diarrhea remained significant factors, as found in previous studies. Administering the DR tablet of posaconazole through a nasogastric tube may be a viable option.