Retrospective Study of Nephrotoxicity Rate among Adult Patients Receiving Colistin Compared to ß-lactam Antibiotics.

PURPOSE: Patients receiving colistin for carbapenem-resistant gram-negative bacteria (CR-GNB) infections generally have multiple risk factors for nephrotoxicity, so it might be possible that colistin may be erroneously blamed for the nephrotoxicity. MATERIALS AND METHODS: We retrospectively analyzed case records of patients who received colistin and those who received antibiotics other than colistin [carbapenem or ß-lactam-ß-lactamases inhibitors (ßL-ßLI)] for gram-negative bacteremia. Those patients with preexisting renal failure and those who received antibiotics for <72 hours were excluded from the study. Nephrotoxicity was assessed using the risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, end-stage kidney disease (RIFLE) criteria. RESULTS: Out of the 222 patients, the colistin arm had 118 and the noncolistin arm had 104 patients. Even though the colistin arm had significantly higher number of sicker patients with neutropenia (40.7% vs 14.4%, p = 0.0001), mechanical ventilation (0.0001), having lines (0.0001), on inotropes (0.003), receiving other nephrotoxic drugs (0.0001), and higher Pitt score (p = 0.0001), there was no significant difference in the nephrotoxicity between the two arms (10.2% vs 9.6%, p = 0.89). Logistical regression showed a higher Pitt bacteremia score (p = 0.03) and a higher Charlson comorbidity index (p = 0.02), but not colistin administration (p = 0.32), were independently associated with nephrotoxicity. CONCLUSION: Administration of colistin was not associated with higher rates of nephrotoxicity than carbapenems or ßL-ßLI agents. HOW TO CITE THIS ARTICLE: Ghafur A, Bansal N, Devarajan V, Raja T, Easow J, Raja MA, et al. Retrospective Study of Nephrotoxicity Rate among Adult Patients Receiving Colistin Compared to ß-lactam Antibiotics. IJCCM 2019;23(11):518-522.

Monotherapy versus Combination Therapy against Nonbacteremic Carbapenem-resistant Gram-negative Infections: A Retrospective Observational Study.

BACKGROUND: Superiority of colistin-carbapenem combination therapy (CCCT) over colistin monotherapy (CMT) against carbapenem-resistant Gram-negative bacterial (CRGNB) infections is not conclusively proven. AIM: The aim of the current study was to analyze the effectiveness of both strategies against CRGNB nonbacteremic infections. DESIGN: This was a retrospective observational cohort study. SUBJECTS AND METHODS: Case record analysis of patients who had CRGNB nonbacteremic infections identified over a period of 4 years (January 2012-December 2015) was done by medical record review at a tertiary care center in India. STATISTICAL ANALYSIS: P < 0.05 was considered as significant. Multivariate analysis was performed using Cox regression. RESULTS: Out of 153 patients (pneumonia 115, urinary tract infection 17, complicated skin and soft-tissue infection 18, intra-abdominal infection 1, and meningitis 2), 92 patients received CCCT and 61 received CMT. Univariate analysis revealed higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, pneumonia as the diagnosis, and Klebsiella as the causative organism to be the risk factors for higher 28-day mortality (P = 0.036, 0.006, 0.016, respectively). Combination therapy had no significant impact on mortality (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.327-2.535, P = 0.857). Multivariate analysis revealed that higher APACHE II score and infection due to Klebsiella were found to be independent risk factors for higher mortality (OR = 3.16 and 4.9, 95% CI = 1.34-7.4 and 2.19-11.2, P = 0.008 and 0.0001, respectively). CONCLUSIONS: In our retrospective single-center series of CRGNB nonbacteremic infections, CCCT was not superior to CMT. Multicenter large observational studies or prospective randomized clinical trials are the need of the hour.

Colistin Nephrotoxicity in Adults: Single Centre Large Series from India.

CONTEXT: Limited Indian data are available on the rate of colistin nephrotoxicity and other risk factors contributing to the development of this important side effect. AIM: This study aims to generate data on colistin nephrotoxicity from a large cohort of Indian patients. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Case record analysis of patients who received colistin, in an oncology center in India, between January 2011 and December 2015. Nephrotoxicity was assessed using risk, injury, failure, loss, and end-stage (RIFLE) criteria. STATISTICAL ANALYSIS: P < 0.05 was considered as statistically significant. RESULTS: Out of the 229 patients, 13.1% (30/229) developed abnormal RIFLE. Abnormal RIFLE group (n = 30), in comparison to the normal renal function group (n = 199), had higher number of patients in intensive care unit (ICU) (96% vs. 79%, P = 0.02), higher Acute Physiology and Chronic Health Evaluation (APACHE II) score (23 vs. 19 P = 0.0001), Charlson score (5.9 vs. 4.3, P = 0.001), mechanical ventilation (90% vs. 67%, P = 0.016), 28 days mortality (63% vs. 25%, P = 0.0001), and abnormal baseline creatinine (36% vs. 8%, P = 0.001). Coadministration of vancomycin had higher rates of nephrotoxicity (P = 0.039). There was no significant difference in nephrotoxicity between 6 and 9 MU/day dosing pattern (8.8% vs. 13.8%, P = 0.058). CONCLUSION: Nephrotoxicity rate in our retrospective single center large series of patients receiving colistin was 13.1%. Patients with abnormal baseline creatinine, ICU stay, and higher disease severity are at higher risk of nephrotoxicity while on colistin. A daily dose of 9 million does not significantly increase nephrotoxicity compared to the 6 million. Concomitant administration of vancomycin with colistin increases the risk of nephrotoxicity.

Diving deep for the needle in the haystack: An outbreak investigation of Burkholderia cenocepacia bacteremia.

In an Indian oncology setting, between August and December 2021, 56 patients, developed Burkholderia cenocepacia bacteremia. An investigation revealed a contaminated batch of the antiemetic drug palonosetron. The outbreak was terminated by withdrawing the culprit batch and the findings were reported promptly to regulatory authorities.

Possible Ambiguity in Interpretation Between Immunoglobulin G4-Related Disease (IgG4-RD) and Sarcoidosis in a Post-COVID-19 Pandemic.

A 36-year-old lady presented with fever, cough, maculopapular rash, painless sialadenitis, episcleritis, and arthralgia of more than 10 months, occurring in episodes since she tested positive for COVID-19 in 2020. Her symptoms were well controlled with corticosteroid and immunosuppressant therapy. Her clinical presentation and findings on bronchoscopy resembled that of sarcoidosis. However, the bronchial biopsy histopathology ruled out sarcoidosis. An increased serum immunoglobulin G4 level and its possible association with COVID-19 raises the question of whether the possibility of immunoglobulin G4-related disease (IgG4-RD) could be entertained.

Beta 1,3-1,6 Glucans Produced by Two Novel Strains of Aureobasidium Pullulans Exert Immune and Metabolic Beneficial Effects in Healthy Middle-aged Japanese Men: Results of an Exploratory Randomized Control Study.

Objectives: In this pilot study, we have evaluated the specific metabolic and immune-related benefits of the AFO-202 strain and N-163 strain of black yeast Aureobasidium pullulans-produced beta 1,3-1,6 glucan in healthy human subjects. Methods: Sixteen healthy Japanese male volunteers (aged 40 to 60 years) took part in this clinical trial. They were divided into four groups (n = 4 each): Group I consumed AFO-202 beta-glucan (2 sachets of 1 g each per day), IA for 35 days and IB for 21 days; Group II consumed a combination of AFO-202 beta-glucan (2 sachets of 1 g each) and N-163 beta-glucan (1 sachet of 15 g gel each per day), IIA for 35 days and IIB for 21 days. Results: Decrease in HbA1C and glycated albumin (GA), significant increase of eosinophils and monocytes and marginal decrease in D-dimer levels, decrease in neutrophil-to-lymphocyte ratio (NLR), with an increase in the lymphocyte-to-CRP ratio (LCR) and leukocyte-to-CRP ratio (LeCR) was observed in Group I between pre- and post-treatment. Decrease in total and LDL cholesterol, a decrease of CD11b, serum ferritin, galectin-3 and fibrinogen were profound in Group II between pre- and post-treatment. However, there was no statistically significant difference between day 21 and day 35 among the groups. Conclusion: This outcome warrants larger clinical trials to explore the potentials of these safe food supplements in the prevention and prophylaxis of diseases due to dysregulated metabolism, such as fatty liver disease, and infections such as COVID-19 in which balanced immunomodulation are of utmost importance, besides their administration as an adjunct to existing therapeutic approaches of both communicable and non-communicable diseases.

Impact of COVID-19 on non-COVID intensive care unit service utilization, case mix and outcomes: A registry-based analysis from India.

Background: Coronavirus disease 2019 (COVID-19) has been responsible for over 3.4 million deaths globally and over 25 million cases in India. As part of the response, India imposed a nation-wide lockdown and prioritized COVID-19 care in hospitals and intensive care units (ICUs). Leveraging data from the Indian Registry of IntenSive care, we sought to understand the impact of the COVID-19 pandemic on critical care service utilization, case-mix, and clinical outcomes in non-COVID ICUs.  Methods: We included all consecutive patients admitted between 1 st October 2019 and 27 th September 2020. Data were extracted from the registry database and included patients admitted to the non-COVID or general ICUs at each of the sites. Outcomes included measures of resource-availability, utilisation, case-mix, acuity, and demand for ICU beds. We used a Mann-Whitney test to compare the pre-pandemic period (October 2019 - February 2020) to the pandemic period (March-September 2020). In addition, we also compared the period of intense lockdown (March-May 31 st 2020) with the pre-pandemic period. Results: There were 3424 patient encounters in the pre-pandemic period and 3524 encounters in the pandemic period. Comparing these periods, weekly admissions declined (median [Q1 Q3] 160 [145,168] to 113 [98.5,134]; p=0.00002); unit turnover declined (median [Q1 Q3] 12.1 [11.32,13] to 8.58 [7.24,10], p<0.00001), and APACHE II score increased (median [Q1 Q3] 19 [19,20] to 21 [20,22] ; p<0.00001). Unadjusted ICU mortality increased (9.3% to 11.7%, p=0.01519) and the length of ICU stay was similar (median [Q1 Q3] 2.11 [2, 2] vs. 2.24 [2, 3] days; p=0.15096). Conclusion: Our registry-based analysis of the impact of COVID-19 on non-COVID critical care demonstrates significant disruptions to healthcare utilization during the pandemic and an increase in the severity of illness.

Feasibility and Safety of Peripheral Intravenous Administration of Vasopressor Agents in Resource-limited Settings.

BACKGROUND: Vasopressors are conventionally administered through a central venous catheter (CVC) and not through a peripheral venous catheter (PVC) since the latter is believed to be associated with increased risk of extravasation. Placement of a CVC requires suitably trained personnel to be on hand, and in resource-limited settings, this requirement may delay placement. Because of this and in cases where suitably trained personnel are not immediately available, some clinicians may be prompted to utilise a PVC for infusing vasopressors. The objective of this study is to assess the feasibility and safety of vasopressors administered through a PVC. MATERIALS AND METHODS: Patients who received vasopressors through a PVC for more than one hour were included in a single centre, consecutive patient observational study. Patients with a CVC at the time of initiation of vasopressors were excluded. Data regarding the size, location of PVCs, dose, duration and number of vasopressors infused were recorded. The decision to place CVC was left to the discretion of the treating physician. Extravasation incidents, severity and management of such events were recorded. RESULTS: One hundred twenty-two patients age 55(4) years [mean (SD)] were included in the study. The commonest PVC was of 18G calibre (57%), and the most common site of placement was the external jugular vein (36.5%). Noradrenaline was the most common vasopressor used at a dose of 10.6 (7) mcg/min [mean (SD)] and the median duration of nine hours (IQR: 6-14). CVC was placed most commonly due to an increasing dose of vasopressors after 4.5(4) hours [mean (SD)]. Grade 2 Extravasation injury occurred in one patient after prolonged infusion of fifty-two hours, through a small calibre (20G) PVC, which was managed conservatively without any sequelae. CONCLUSION: Vasopressors infused through a PVC of 18G or larger calibre into the external jugular, or a forearm vein is feasible and safe. Clinicians need to balance the safety of peripheral vasopressor infusion with the additional costs and complications associated with CVC in resource-limited settings.

Implementing an intensive care registry in India: preliminary results of the case-mix program and an opportunity for quality improvement and research.

Background: The epidemiology of critical illness in India is distinct from high-income countries. However, limited data exist on resource availability, staffing patterns, case-mix and outcomes from critical illness. Critical care registries, by enabling a continual evaluation of service provision, epidemiology, resource availability and quality, can bridge these gaps in information. In January 2019, we established the Indian Registry of IntenSive care to map capacity and describe case-mix and outcomes. In this report, we describe the implementation process, preliminary results, opportunities for improvement, challenges and future directions. Methods: All adult and paediatric ICUs in India were eligible to join if they committed to entering data for ICU admissions. Data are collected by a designated representative through the electronic data collection platform of the registry. IRIS hosts data on a secure cloud-based server and access to the data is restricted to designated personnel and is protected with standard firewall and a valid secure socket layer (SSL) certificate. Each participating ICU owns and has access to its own data. All participating units have access to de-identified network-wide aggregate data which enables benchmarking and comparison. Results: The registry currently includes 14 adult and 1 paediatric ICU in the network (232 adult ICU beds and 9 paediatric ICU beds). There have been 8721 patient encounters with a mean age of 56.9 (SD 18.9); 61.4% of patients were male and admissions to participating ICUs were predominantly unplanned (87.5%). At admission, most patients (61.5%) received antibiotics, 17.3% needed vasopressors, and 23.7% were mechanically ventilated. Mortality for the entire cohort was 9%.  Data availability for demographics, clinical parameters, and indicators of admission severity was greater than 95%. Conclusions: IRIS represents a successful model for the continual evaluation of critical illness epidemiology in India and provides a framework for the deployment of multi-centre quality improvement and context-relevant clinical research.