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Background: Safe and effective use of colistin requires robust pharmacokinetic (PK) and pharmacodynamic (PD) data to guide dosing. Aim: To evaluate the pharmacokinetics of colistimethate sodium and colistin in critically ill patients and correlate with clinical efficacy and renal function. Materials and Methods: Twenty critically ill adult patients with colistin-susceptible multidrug-resistant (MDR) infections and normal renal function treated with intravenous colistimethate sodium – at a 9 million units (270 mg CBA) loading dose followed by maintenance (MD) of 3 million units t.i.d, 24 hours later – were evaluated for clinical cure (CC) at the end of therapy. Patient characteristics and plasma colistin levels at 0, 0.5, 1, 2, 4, 8 and 12 hours after the loading dose and at 1, 2 and 8 hours after the eighth and ninth infusion of MD were evaluated. Colistimethate sodium and colistin levels were measured by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Results: Among the 20 patients who were evaluated, 60% had pneumonia. Predominant pathogens were Klebsiella pneumoniae and Acinetobacter spp. Clinical cure was 50% (10/20). Mean peak loading dose concentrations were 3 ± 1.1 mg/L (1.75–5.14) and 2.37 ± 1.2 mg/L (1.52–5.54) for ‘cure’ and ‘failure’ groups, respectively (p = 0.13), while mean steady-state (Cssavg) concentrations were 2.25 ± 1.3 mg/L and 1.78 ± 1.1 mg/L in ‘cure’ and ‘failure’ groups, respectively (p = 0.19). Nephrotoxicity was 5% on day 7 of therapy. However, bacteriological cure could not be correlated with PK/PD. Conclusions: Subtherapeutic Cssavg with clinical failure and lower efficacy without significant nephrotoxicity highlights the need for therapeutic drug monitoring to guide colistin dosing.

The study aims to characterize community-acquired sepsis patients admitted to our 1300-bedded tertiary care hospital in South India from the Surviving Sepsis Campaign (SSC) guideline-compliant e-sepsis registry stratified by focus of infection. The prospective observational study recruited 1009 adult sepsis patients presenting to the emergency department at the center based on Sepsis-2 criteria for a period of three years. Of the patients, 41% were between 61 and 80 years with a mean age of 57.37 ± 13.5%. A total of 13.5% (136) was under septic shock and in-hospital mortality for the study cohort was 25%. The 3 h and 6 h bundle compliance rates observed were 37% and 49%, respectively, without significant survival benefits. Predictors of mortality among patients with bloodstream infections were septic shock (p = 0.01, OR 2.4, 95% CI 1.23–4.79) and neutrophil-to-lymphocyte ratio (p = 0.008, OR 1.01, 95% CI 1.009–1.066). The presence of Acinetobacter (p = 0.005, OR 4.07, 95% CI 1.37–12.09), Candida non-albicans (p = 0.001, OR16.02, 95% CI 3.0–84.2) and septic shock (p = 0.071, OR 2.5, 95% CI 0.97–6.6) were significant predictors of mortality in patients with community-acquired pneumonia. The registry has proven to be a key data source detailing regional microbial etiology and clinical outcomes of adult sepsis patients, enabling comprehensive evaluation of regional community-acquired sepsis to tailor institutional sepsis treatment protocols.

Background Candida auris infections are an emerging global threat with poor clinical outcome, high mortality rate, high transmission rate and outbreak potential. The objective of this work is to describe a multidisciplinary approach towards the investigation and containment of a Candida auris outbreak and the preventive measures adopted in a resource limited setting. Methods This outbreak investigational study was conducted at a 1300-bedded tertiary care academic hospital in South India. The study included 15 adult inpatients with laboratory confirmed Candida auris isolates. The outbreak cluster was identified in adult patients admitted from September 2017 to 2019. The system response consisted of a critical alert system for laboratory confirmed Candida auris infection and multidisciplinary ‘Candida auris care team’ for patient management. The team implemented stringent Infection Prevention and Control (IPC) measures including patient cohorting, standardized therapy and decolonization, staff training, prospective surveillance and introduction of Candida auris specific care bundle. Results Two outbreak clusters were identified; first cluster occurring between October and November 2017 and the second cluster in May 2018. The cohorts consisted of 7 and 8 Candida auris positive patients in the first and second waves of the outbreak respectively with a total survival rate of 93% (14/15). Deployment of containment measures led to gradual decline in the incidence of adult Candida auris positive cases and prevented further cluster formation. Conclusions The sustained implementation of guideline and evidence-based IPC measures and training of healthcare workers for improving awareness on systematically following standardized protocols of Candida auris related IPC practices successfully contained Candida auris outbreaks at our hospital. This demonstrates the feasibility of establishing a multidisciplinary model and bundling of practices for preventing Candida auris outbreaks in a Low- and Middle-income country.

Polymyxins being last resort drugs to treat infections triggered by multidrug-resistant pathogens necessitates the implementation of antimicrobial stewardship program (ASP) initiatives to support its rational prescription across healthcare settings. Our study aims to describe the change in the epidemiology of polymyxins and patient outcomes following the implementation of ASP at our institution. The antimicrobial stewardship program initiated in February 2016 at our 1300 bed tertiary care center involved post-prescriptive audits tracking polymyxin consumption and evaluating prescription appropriateness in terms of the right indication, right frequency, right drug, right duration of therapy and administration of the right loading dose (LD) and maintenance dose (MD). Among the 2442 polymyxin prescriptions tracked over the entire study period ranging from February 2016 to January 2020, the number of prescriptions dropped from 772 prescriptions in the pre-implementation period to an average of 417 per year during the post-implementation period, recording a 45% reduction. The quarterly patient survival rates had a significant positive correlation with the quarterly prescription appropriateness rates (r = 0.4774, p = 0.02), right loading dose (r = 0.5228, p = 0.015) and right duration (r = 0.4361, p = 0.04). Our study on the epidemiology of polymyxin use demonstrated favorable effects on the appropriateness of prescriptions and mortality benefits after successful implementation of antimicrobial stewardship in a real-world setting.

In many parts of the world, including in India, pharmacist roles in antimicrobial stewardship (AMS) programmes remain unexplored. We describe the evolution and effect of the role of adding clinical pharmacists to a multidisciplinary AMS at a tertiary care teaching hospital in Kerala, India. Through effective leadership, multidisciplinary AMS (February 2016) and antitubercular therapy (ATT) stewardship programmes (June 2017) were established. Clinical pharmacists were introduced as core members of the programmes, responsible for the operational delivery of key stewardship interventions. Pharmacy-led audit and feedback monitored the appropriateness of antimicrobial prescriptions and compliance to AMS/ATT recommendations. Between February 2016 and January 2017, 56% (742/1326) of antimicrobial prescriptions were appropriate, and 54% (318/584) of recommendations showed compliance. By the third year of the AMS, appropriateness increased to 80% (1752/2190), and compliance to the AMS recommendations to 70% (227/325). The appropriateness of ATT prescriptions increased from a baseline of 61% (95/157) in the first year, to 72% (62/86, June 2018–February 2019). The compliance to ATT recommendations increased from 42% (25/60) to 58% (14/24). Such a model can be effective in implementing sustainable change in low- and middle-income countries (LMICs) such as India, where the shortage of infectious disease physicians is a major impediment to the implementation and sustainability of AMS programmes.

Background Antimicrobial resistance is a major public health threat internationally but, particularly in India. A primary contributing factor to this rise in resistance includes unregulated access to antimicrobials. Implementing antimicrobial stewardship programs (ASPs) in the acute hospital setting will help curb inappropriate antibiotic use in India. Currently, ASPs are rare in India but are gaining momentum. This study describes ASP implementation in a large, academic, private, tertiary care center in India. Methods An ASP was established in February 2016 consisting of an administrative champion, hospitalist, microbiologist, intensivist, and pharmacists. Antimicrobial stewardship program interventions included postprescriptive audit and establishment of institutional guidelines. The ASP tracked appropriate drug selection including loading dose, maintenance dose, frequency, route, duration of therapy, de-escalation, and compliance with ASP recommendations. Defined daily dose (DDD) of drugs and cost of antimicrobials were compared between the pre-implementation phase (February 2015–January 2016) and post-implementation phase (February 2016–January 2017). Results Of 48 555 patients admitted during the post-implementation phase, 1020 received 1326 prescriptions for restricted antibiotics. Antibiotic therapy was appropriate in 56% (742) of the total patient prescriptions. A total of 2776 instances of “inappropriate” antimicrobial prescriptions were intervened upon by the ASP. Duration (806, 29%) was the most common reason for inappropriate therapy. Compliance with ASP recommendations was 54% (318). For all major restricted drugs, the DDD/1000 patient days declined, and there was a significant reduction in mean monthly cost by 14.4% in the post-implementation phase. Conclusions Implementation of a multidisciplinary antibiotic stewardship program in this academic, large, Indian hospital demonstrated feasibility and economic benefits.

Background In India, Candida bloodstream infections have a reported incidence of 1–12 per 1,000 admissions and a mortality rate of up to 60%. Antimicrobial stewardship programs (ASP) can improve quality of care and clinical outcomes. This study evaluates the impact of a comprehensive candidemia ASP bundle in a hospital in southern India with an established stewardship program. Methods A single-center, pre-post quasi-experimental study was conducted at a tertiary-care center in southern India to analyze the impact of an ASP care bundle for the management of adults with candidemia. During the intervention period (October 2017–December 2018), the ASP provided recommendations to providers in accordance with the 2016 IDSA Guidelines for the Management of Candidemia, which included the following bundle: (1) appropriate selection and dosing of antifungal therapy; (2) repeat blood cultures every 48 hours until clearance; (3) removal of central venous catheters and other potential removable foci of infection; (4) echocardiogram; (5) ophthalmologic evaluation; and (6) appropriate duration of therapy. The primary outcome was initiation of appropriate antifungal therapy. Additional clinical outcomes were also compared with a historical cohort. Results One hundred and four patients with candidemia were included: 52 in the pre-intervention and 52 in the post-intervention group. Overall, baseline demographics were similar between the two groups (Table 1). Candida tropicalis (26.9%) and Candida parapsilosis (29.8%) were the most common causes of candidemia in the cohort. Following intervention, administration of appropriate antifungal therapy improved by 40.4% (28.8% pre vs. 69.2% post, P < 0.01). Average time to effective treatment initiation following culture positivity decreased from 57.6 hours to 12 hours in the post-intervention group (P < 0.01). Thirty-day all-cause mortality was similar between the two groups (34.6% 38.4%, P = 0.84). Conclusion Implementation of a comprehensive candidemia care bundle by the ASP significantly improved the use and timing of initiation of appropriate antifungal therapy. Disclosures All authors: No reported disclosures.

Background Colistin has re-emerged as last line antimicrobial to combat MDR GNB. There is need for robust pharmacokinetic (PK) and pharmacodynamics (PD) data to guide dosing. This study assessed the PK of CMS and colistin and its impact on clinical cure (CC) and acute kidney injury (AKI) in critically ill patients with normal baseline renal function. Methods Adult critically ill patients with colistin susceptible MDR/XDR infections and normal renal function who were treated with intravenous CMS (9MU CMS loading dose (LD) followed by maintenance (MD) 3MU every 8 hour starting 24 hours after LD) were recruited into this prospective observational study. For PK sampling, 3mL venous blood was drawn immediately before LD and at 0.5, 1, 2, 4, 8 and 12 hours after LD. During MD, samples were collected before and at 1, 2 and 8 hours after the eight and nineth infusion. Colistin plasma concentrations were determined by LC–MS. Results A total of 280 serum samples were analyzed from 20 patients. Sixty percent had pneumonia. Predominant pathogens were Klebsiella pneumonia (12) and Acinetobacter spp. (8). Mean creatinine clearance (CrCl) was 115 ± 24 mL/minute (72.3–208.8). All patients received combination therapy with colistin, 18(90%) received meropenem and 5(25%) received tigecycline. Clinical cure rate was 50% (10/20) and mortality rate was 25% (5/20). Mean LD colistin Cmax were 3 ± 1.1 mg/L (1.75–5.14) and 2.37 ± 1.2 mg/L (1.52–5.54) among CC and CF groups, respectively (P = 0.13). MD colistin Css avg was 2.25 ± 1.3 mg/L and 1.78 ± 1.1 mg/L in CC and CF groups, respectively. The mean AUC0–24/MIC ratio of MD colistin was 92.76 ± 65.5 and 76.59 ± 51.8 for CC and CF groups, respectively (P = 0.27). In pneumonia, AUC0–24/MIC for Acinetobacter spp. was higher in the CC (71.18 ± 10.20) than in the CF group (40.88 ± 16.28) (P = 0.05). Renal injury was 5% at 7 days and 40% at end of therapy. Ten to 20% of patients with CrCl ≥ 100 mL/minute had Css avg ≥ 2 mg/L. Majority of CF with AKI had Css avg between 1 and 1.5 mg/L Conclusion Clinical cure was low at 50%. Sub-inhibitory Css avg and increased volume of distribution following MD could have contributed to high failure. Colistin exposures were similar to those reported in other published cohorts with no consistent exposure-response relationship. Based on these results, there is an important role for therapeutic drug monitoring with Colistin. Disclosures All authors: No reported disclosures.

Background Polymyxin B(PB) and Colistin (PE) use have increased in India due to emergence of resistant Gram-negative organisms. The Indian Council of Medical Research has identified carbapenems, polymyxins (PE and PB) as key antimicrobials which require restriction in hospitals. We describe epidemiology of PB and PE use following implementation of an Antibiotic Stewardship Program (ASP) in a 1300-bed, private, tertiary-care center in Southern India. Methods An ASP was established at Amrita Hospital in Feb 2016 consisting of an administrative champion, hospitalist, microbiologist, intensivist and 5 pharmacists. Institutional guidelines for polymyxins were established and disseminated. The ASP team performed daily post-prescriptive reviews, evaluated and tracked appropriateness of PB and PE use, including administration of a loading dose (LD), maintenance dose (MD), frequency, route and duration of therapy. ASP recommendations and compliance were recorded. Results During the 12-month study period (Feb ‘16-Jan ‘17), 348 patients received 295 PE and 94 PB courses. Mean age was 50 yrs and 73% were male. Patients on Medicine and Hematology/Oncology teams accounted for 42% of all prescriptions. The most common infections were bacteremia (34%), pneumonia (29%) and UTI (23%). Pathogens were recovered in 69% (269/389) of cases, Klebsiella pneumoniae 23% (90/389) and Acinetobacter baumanii11 % (45/389) were most common. 290 (75%) of polymyxin course were judged to be inappropriate (78% of PE and 22% of PB). The most frequent reasons for inappropriate therapy included incorrect frequency of administration (64% for PB and 58% for PE), inappropriate MD (60% for PB and 48% for PE) and wrong duration of therapy (54% for PE and 48% for PB). 95% of incorrect MD for both PE and PB were too low. The reasons for inappropriateness were similar for both polymyxins.While all inappropriate LD episodes for PB (n = 22 %) were due to lack of a LD, errors for PE (n = 34%) involved either omission of LD or administration of LD that was too low.ASP recommendations were made in 190 instances with 58% provider compliance. Conclusion Review of PB and PE use in our hospital indicates a high percentage of inappropriate use and highlights stewardship opportunities for improving care of patients with resistant infections. Disclosures K. S. Kaye, Xellia: Consultant, Consulting fee; Merck: Consultant and Grant Investigator, Consulting fee and Research support; The Medicines Company: Consultant and Grant Investigator, Consulting fee and Research support