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.

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.

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.

Prevalence of Maternal Cytomegalovirus Antibodies and Neonatal Congenital Cytomegalovirus at Less than 34 Weeks of Gestation: A Prospective Study.

OBJECTIVE: Congenital cytomegalovirus (cCMV) acquired postnatally can lead to hearing loss and adverse central nervous system (CNS) function, especially in the preterm neonate. We prospectively determined the prevalence of maternal serum CMV-immunoglobulin (IgG) and the incidence of cCMV at <34 weeks of gestation. STUDY DESIGN: Study was conducted in the United States and India. Maternal blood was collected within 5 days after delivery. CMV-IgG antibodies were quantitated by an immunoassay. Baby's urine at birth was tested for CMV-DNA by the polymerase chain reaction. RESULTS: In total, 65 women and 74 neonates were studied. In the United States, 6 out of 21 (76%), while in India, 42 out of 44 (96%) mothers were seropositive (combined 89%). In the United States, none of the neonates had CMV in the urine, while in India 4 out of 52 (7.7%) were positive (combined 5.4%) CONCLUSION: Mother's blood and baby's urine should be tested for serum CMV-IgG antibodies and CMV-DNA at delivery at <34-weeks of gestational age. Targeted screening will help in making an early diagnosis of cCMV, initiate therapy, and detect and treat early CNS problems including hearing loss. KEY POINTS: · Maternal serum CMV screening after premature delivery at less than 34 weeks of gestation.. · Neonatal urine CMV screening at less than 34 weeks of gestation.. · Prematurity: importance of CMV during premature labor and delivery at less than 34 weeks..

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.

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.

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.

Prolonged Shedding of SARS-CoV-2 in Feces of COVID-19 Positive Patients: Trends in Genomic Variation in First and Second Wave.

The main route of the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are through respiratory pathways and close contact of human-to-human. While information about other modes of transmission is comparatively less, some published literature supporting the likelihood of a fecal-oral mode of transmission has been accumulating. The diagnosis of SARS-COV-2 infected cases is based on the real-time reverse transcription-PCR (RT-PCR). The fecal excretion of SARS-COV-2 has been reported frequently, however, the role of fecal viral load with the severity of disease is not yet clear. Our study focused on the investigation of SARS-CoV-2 shedding in the fecal samples of patients with coronavirus disease 2019 (COVID-19). A total of 280 RT-PCR-positive patients were enrolled, among them 15.4% had gastrointestinal (GI) symptoms. It was shown that 62% of the patients were positive for SARS-CoV-2 RNA in fecal specimens. This positivity was not related to the presence of GI symptoms and the severity of disease. The next generation sequencing [NGS] of SARS-CoV-2 from fecal samples of patients was performed to analyze mutational variations. Findings from this study not only emphasized the potential presence of SARS-CoV-2 in feces, but also its continuing mutational changes and its possible role in fecal-oral transmission.

Rhino-Orbito-Cerebral Mycosis and COVID-19: From Bad to Worse?

Background: There has been an increase an alarming rise in invasive mycoses during COVID-19 pandemic, especially during the second wave. Aims: Compare the incidence of invasive mycoses in the last three years and study the risk factors, manifestations and outcomes of mycoses in the COVID era. Methodology: Multicentric study was conducted across 21 centres in a state of western India over 12-months. The clinico-radiological, laboratory and microbiological features, treatment and outcomes of patients were studied. We also analysed yearly incidence of rhino-orbito-cerebral mycosis. Results: There was more than five-times rise in the incidence of invasive mycoses compared to previous two-years. Of the 122 patients analysed, mucor, aspergillus and dual infection were seen in 86.9%, 4.1%, and 7.4% respectively. Fifty-nine percent had simultaneous mycosis and COVID-19 while rest had sequential infection. Common presenting features were headache (91%), facial pain (78.7%), diplopia (66.4%) and vison loss (56.6%). Rhino-orbito-sinusitis was present in 96.7%, meningitis in 6.6%, intracranial mass lesions in 15.6% and strokes in 14.8%. A total of 91.8% patients were diabetic, while 90.2% were treated with steroids during COVID-19 treatment. Mortality was 34.4%. Conclusion: Invasive fungal infections having high mortality and morbidity have increased burden on already overburdened healthcare system. Past illnesses, COVID-19 itself and its treatment and environmental factors seem responsible for the rise of fungal infection. Awareness and preventive strategies are the need of hours and larger studies are needed for better understanding of this deadly disease.

Once-a-Day Ceftriaxone-Amikacin Combination as Empiric Antibiotic Therapy to Enable Outpatient Management of Febrile Neutropenia in Children-16-Year Experience from a Single Institute.

Shailesh KanvindeBackground To enable outpatient department (OPD) management of febrile neutropenia (FN), we used once-a-day (OD) ceftriaxone-amikacin (CFT-AMK) as empiric antibiotic therapy. Our experience over 16-year period is presented. Methods This was a retrospective study conducted from January2002 to December2017. Inclusion criteria were <18 years of age, undergoing cancer chemotherapy, and having FN. Exclusion criteria were FN after palliative chemotherapy, bone marrow transplantation, or at diagnosis of malignancy. Empiric CFT-AMK was used in all, except those having respiratory distress, hypotension, altered sensorium, paralytic ileus, or clinical evidence of peritonitis. Admission criteria were age <1 year, acute myeloid leukemia (AML) chemotherapy, poor performance status, need for blood transfusions, convenience, insurance, or persistent fever >48 to 72 hours after CFT-AMK. Outcomes analyzed were response (defervescence within 48-72 hours), OPD management, antibiotic upgrade, and mortality. AML diagnosis, >7 days to absolute neutrophil count >0.5 × 10 9 /L, poor performance status, and malignancy not in remission were considered high-risk FN criteria. Results CFT-AMK was given in 877/952 (92.2%) FN episodes. Seventy-six percent had hematolymphoid malignancies. Response, antibiotic upgrade, and mortality were seen in 85.7 and 65.5% ( p < 0.0001), 15 and 45.5% ( p < 0.0001), and 0 and 2% ( p = 0.003) of low- and high-risk patients, respectively. Treatment was started in OPD in 52%, of which 21.6% required subsequent admission. Of those initially admitted, early discharge (hospital stay < 5 days) was possible in 24.6%. Forty-one percent episodes were managed entirely on OPD. Overall, 80% of low-risk and 42% of high-risk episodes received treatment wholly or partially on OPD. Conclusion Our results show empiric OD CFT-AMK allows OPD management for most of the low-risk and a proportion of high-risk FN following chemotherapy in children, without compromising clinical outcomes.

Preparedness of Acute Care Facility and a Hospital for COVID-19 Pandemic: What We Did!

BACKGROUND AND AIM: India is facing the pandemic of coronavirus disease (COVID-19) just like the whole world. The private sector is the backbone of a healthcare facility in India. Presently, only a few major hospitals in the country are actively dealing with the COVID-19 patients while others are facing troubles due to lack of manpower, management, and required experience to face the pandemic. Despite the lockdown, the cases are ever increasing and each and every hospital in the country should be prepared to face this pandemic the world has never seen before. As one of the largest multispecialty hospitals and a designated COVID center, we have developed and adopted some strategies for better preparedness to face the surge of this pandemic. We would like to share our experience and hope that the strategies laid down and adopted by us will help many other acute care facilities in many parts of India. MATERIALS AND METHODS: Different strategies are adopted to deal with the crisis situation of the COVID-19 pandemic. Our adopted strategies were directed to mitigate the challenges of administration, hospital space organization, management of staff and supplies, maintenance of standard of care, and specific COVID care and ethics during this pandemic. RESULTS: Based on strategies adopted by us, we feel more confident and prepared to deal with COVID-19 pandemic. CONCLUSION: Our approach for preparing for the COVID-19 pandemic may not be the best one but we believe that the basic managerial principles we adopted will guide many other institutions to find their path in tackling the pandemic in the best possible way. HOW TO CITE THIS ARTICLE: Jog S, Kelkar D, Bhat M, Patwardhan S, Godavarthy P, Dhundi U, et al. Preparedness of Acute Care Facility and a Hospital for COVID-19 Pandemic: What We Did! Indian J Crit Care Med 2020;24(6):385-392.

Cytomegalovirus infection as a cause of cytopenia after chemotherapy for hematological malignancies.

OBJECTIVE: Unlike hematopoietic stem cell transplantation, there is very little information on cytomegalovirus (CMV) related cytopenias occurring in patients having acute lymphoblastic leukemia (ALL) or Non Hodgkin's lymphoma (NHL) receiving standard dose chemotherapy (SDCT). We studied the role of CMV infection in cytopenias after SDCT for childhood ALL or NHL. DESIGN: Retrospective study. SETTING: Pediatric Oncology Unit. METHODS: Between January 2007 and March 2010, we screened all children having ALL/NHL having prolonged cytopenia (ANC<1,000/cmm and/or platelets <1,00,000/cmm; >10 days beyond date for next chemotherapy; not explainable on basis of previously administered chemotherapy) for CMV infection. Testing for CMV infection was done by pp65 antigen assay, qualitative or quantitative RT-PCR. CMV positive episodes were analyzed for relationship to previous chemotherapy, clinical features and response to treatment. RESULTS: As defined, 24 episodes of cytopenia were identified. CMV infection was detected in 13/24 (54%) episodes in 9 patients. Duration of cytopenia in patients having CMV infection: 14-126 days (median 28 d). Neutropenia or thrombocytopenia were seen in 11/13 and 13/13 episodes, respectively. Fever (2-20 d) and loose motions (3-60 d) in 11/13 and 9/13 episodes, respectively. Eye examination records were available in 5 children; 3 had simultaneous or delayed chorioretinitis. Gancyclovir was used in all but 1 CMV-positive episode. In treated cases, counts recovered after a median of 8 days (3-56 d). CONCLUSION: Following chemotherapy for ALL/NHL, cytopenia that is prolonged or not explainable on the basis of chemotherapy toxicity should be evaluated for CMV infection.

Our experience with pectoralis major flap for management of sternal dehiscence: A review of 25 cases.

OBJECTIVE: To report our experience of the pectoralis major flap as the treatment modality for post coronary artery bypass sternal wound dehiscence. MATERIALS AND METHODS: A retrospective study of 25 open heart surgery cases, performed between January 2006 and December 2010 at Deenanath Mangeshkar Hospital, Pune, was carried out. Unilateral or bilateral pectoralis major muscle flap by the double breasting technique using rectus extension was used in the management of these patients. The outcome was assessed on the basis of efficacy of flap surgery in achieving wound healing and post-surgery shoulder joint movements to evaluate donor site morbidity. The follow-up ranged from 5 months to 3.5 years. RESULTS: Twenty-three (92%) patients were discharged with complete wound closure. One patient (4%) had wound dehiscence after flap surgery. One patient (4%) died in the hospital in the immediate postoperative period due to mediastinitis. No recurrent sternum infection has occurred till date in 24 patients (96%). For one patient (4%) who had wound dehiscence, daily dressing was done and wound healing was achieved with secondary intension. At follow-up, shoulder joint movements were normal in all the patients. CONCLUSIONS: The double breasting technique of the pectoralis major muscle flaps with rectus sheath extension is efficient in covering the entire length of the defect and can reduce the morbidity, without affecting the function of the shoulder joint.

Clinical findings and pro-inflammatory cytokines in dengue patients in Western India: a facility-based study.

BACKGROUND: Descriptions of dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from Pune, Western India, with respect to clinical profile and pro-inflammatory cytokines. METHODOLOGY/PRINCIPAL FINDINGS: In 2005, 372 clinically suspected dengue cases were tested by MAC-ELISA and RT-PCR for dengue virus (DENV) aetiology. The clinical profile was recorded at the hospital. Circulating levels of IFN-gamma, TNF-alpha, IL-6, and IL-8 were assessed by ELISA and secondary infections were defined by IgM to IgG ratio. Statistical analysis was carried out using the SPSS 11.0 version. Of the 372 individuals, 221 were confirmed to be dengue cases. Three serotypes, DENV-1, 2 and 3 were co-circulating and one case of dual infection was identified. Of 221 cases, 159 presented with Dengue fever (DF) and 62 with Dengue hemorrhagic fever (DHF) of which six had severe DHF and one died of shock. There was a strong association of rash, abdominal pain and conjunctival congestion with DHF. Levels of IFN-gamma were higher in DF whereas IL-6 and IL-8 were higher in DHF cases (p<0.05). The mean levels of the three cytokines were higher in secondary compared to primary infections. Levels of IFN-gamma and IL-8 were higher in early samples collected 2-5 days after onset than late samples collected 6-15 days after onset. IFN-gamma showed significant decreasing time trend (p = 0.005) and IL-8 levels showed increasing trend towards significance in DHF cases (interaction p = 0.059). There was a significant association of IL-8 levels with thrombocytopenia and both IFN-gamma and IL-8 were positively associated with alanine transaminase levels. CONCLUSIONS/SIGNIFICANCE: Rash, abdominal pain and conjunctival congestion could be prognostic symptoms for DHF. High levels of IL-6 and IL-8 were shown to associate with DHF. The time trend of IFN-gamma and IL-8 levels had greater significance than absolute values in DHF pathogenesis.