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.

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.

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.

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.

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.