Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

Burden and Management of Multi-Drug Resistant Organism Infections in Solid Organ Transplant Recipients Across the World: A Narrative Review.

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.

Distinct patterns of postoperative fever in paediatric neurosurgery patients.

PURPOSE: Postoperative fever is a common problem following neurosurgery but data on the causes among paediatric patients is sparse. In this report, we determined the incidence, causes, and outcomes of postoperative fever in paediatric neurosurgical patients (< 18 years), and contrasted the findings with an adult cohort published recently from our unit. METHODS: We recruited 61 patients who underwent 73 surgeries for non-traumatic neurosurgical indications over 12 months. A standard protocol was followed for the evaluation and management of postoperative fever. We prospectively collected data pertaining to operative details, daily maximal temperature, clinical features, and use of surgical drains, urinary catheters, and other adjuncts. Elevated body temperature of > 99.9 °F or 37.7 °C for > 48 h or associated with clinical deterioration or localising features was considered as "fever"; elevated temperature not meeting these criteria was classified as transient elevation in temperature (TET). RESULTS: Twenty-six patients (35.6%) had postoperative fever, more frequent than in adult patients. TET occurred in 12 patients (16.4%). The most common causes of fever were aseptic meningitis (34.6%), followed by urinary tract infections (15.4%), pyogenic meningitis, COVID-19, and wound infections. Postoperative fever was associated with significantly longer duration of hospital admission and was the commonest cause of readmission. CONCLUSION: In contrast to adults, early temperature elevations in paediatric patients may portend infectious and serious non-infectious causes of fever, including delayed presentation with aseptic meningitis, a novel association among paediatric patients. Investigation guided by clinical assessment and conservative antibiotic policy in keeping with the institutional microbiological profile provides the most appropriate strategy in managing paediatric postoperative fever.

Effectiveness of Adjunctive High-Dose Infliximab Therapy to Improve Disability-Free Survival Among Patients With Severe Central Nervous System Tuberculosis: A Matched Retrospective Cohort Study.

BACKGROUND: Few treatment options exist for patients with severe central nervous system (CNS) tuberculosis (TB) worsening due to inflammatory lesions, despite optimal antitubercular therapy (ATT) and steroids. Data regarding the efficacy and safety of infliximab in these patients are sparse. METHODS: We performed a matched retrospective cohort study based on Medical Research Council (MRC) grading system and modified Rankin Scale (mRS) scores comparing 2 groups of adults with CNS TB. Cohort A received at least 1 dose of infliximab after optimal ATT and steroids between March 2019 and July 2022. Cohort B received only ATT and steroids. Disability-free survival (mRS score ≤2) at 6 months was the primary outcome. RESULTS: Baseline MRC grades and mRS scores were similar between the cohorts. Median duration before initiation of infliximab therapy from start of ATT and steroids was 6 (IQR: 3.7-13) months and for neurological deficits was 4 (IQR: 2-6.2) months. Indications for infliximab were symptomatic tuberculomas (20/30; 66.7%), spinal cord involvement with paraparesis (8/30; 26.7%), and optochiasmatic arachnoiditis (3/30; 10%), worsening despite adequate ATT and steroids. Severe disability (5/30 [16.7%] and 21/60 [35%]) and all-cause mortality (2/30 [6.7%] and 13/60 [21.7%]) at 6 months were lower in cohort A versus cohort B, respectively. In the combined study population, only exposure to infliximab was positively associated (aRR: 6.2; 95% CI: 2.18-17.83; P = .001) with disability-free survival at 6 months. There were no clear infliximab-related side effects noted. CONCLUSIONS: Infliximab may be an effective and safe adjunctive strategy among severely disabled patients with CNS TB not improving despite optimal ATT and steroids. Adequately powered phase 3 clinical trials are required to confirm these early findings.

Determination of potential combination of non-ß-lactam, ß-lactam, and ß-lactamase inhibitors/ß-lactam enhancer against class D oxacillinases producing Acinetobacter baumannii: Evidence from in-vitro, molecular docking and dynamics simulation.

Carbapenem-resistant Acinetobacter baumannii, a predominant nosocomial pathogen in hospitals of intensive care units, is associated with bacteremia and ventilator-associated pneumonia with a high-risk mortality rate. To increase the effectiveness of the ß-lactam (BL) antibiotics, the use of ß-lactamase inhibitors (BLI) acts as a booster when given in combination with BL antibiotics. To this aspect, we selected BL antibiotics of cefiderocol, cefepime, non-BL antibiotic eravacycline, BLI of durlobactam, avibactam, and a ß-lactam enhancer (BLE) of zidebactam. To prove our hypothesis, we determined the minimum inhibitory concentration (MIC) of various BL or non-BL/BLI or BLE combinations using broth microdilution method followed by in silico analysis of molecular docking, molecular dynamics (MD) simulation, and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) identifies the potential combination. In MIC testing, eravacycline, cefepime/zidebactam, cefiderocol/zidebactam, and eravacycline in combination with zidebactam or durlobactam were found to be effective against oxacillinases (OXAs) (OXA-23/24/58 like) expressing A. baumannii isolates. The docking results of the selected ligands toward OXA-23, OXA-24, and OXA-58 had an excellent binding score ranging from -5.8 to -9.3 kcal/mol. Further, the docked complexes were subjected and evaluated using gromacs for molecular dynamics simulation of 50 ns toward selected class D OXAs. The binding energies obtained from MM-PBSA shed light on the binding efficiencies of each non-BL, BL, and BLI/BLE, thereby helping us to propose the drug combinations. Based on the MD trajectories scoring acquired, we propose using eravacycline, cefepime/zidebactam, cefiderocol/zidebactam, and eravacycline in combination with durlobactam or zidebactam would be promising for treating OXA-23, OXA-24, and OXA-58 like expressing A. baumannii infections.

A Standardized Protocol for the Safe Retrieval of Infectious Postmortem Human Brain for Studying Whole-Brain Pathology.

ABSTRACT: We describe a safe and standardized perfusion protocol for studying brain pathology in high-risk autopsies using a custom-designed low-cost infection containment chamber and high-resolution histology. The output quality was studied using the histological data from the whole cerebellum and brain stem processed using a high-resolution cryohistology pipeline at 0.5 µm per pixel, in-plane resolution with serial sections at 20-µm thickness. To understand the pathophysiology of highly infectious diseases, it is necessary to have a safe and cost-effective method of performing high-risk autopsies and a standardized perfusion protocol for preparing high-quality tissues. Using the low-cost infection containment chamber, we detail the cranial autopsy protocol and ex situ perfusion-fixation of 4 highly infectious adult human brains. The digitized high-resolution histology images of the Nissl-stained series reveal that most of the sections were free of processing artifacts, such as fixation damage, freezing artifacts, and osmotic shock, at the macrocellular and microcellular level. The quality of our protocol was also tested with the highly sensitive immunohistochemistry staining for specific protein markers. Our protocol provides a safe and effective method in high-risk autopsies that allows for the evaluation of pathogen-host interaction, the underlying pathophysiology, and the extent of the infection across the whole brain at microscopic resolutions.

Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings.

BACKGROUND: In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed. METHODS: We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort. RESULTS: In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72-0.74) and calibration (calibration slopes: 1.01-1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone. CONCLUSIONS: We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.

Efficacy of Crushed Delayed-Release Posaconazole Tablets in Rhino-Orbito-Cerebral Mucormycosis.

A significant proportion of patients with Rhino-orbito-cerebral mucormycosis (ROCM) develop oroantral fistulas. Due to the unclear efficacy of crushed delayed-release posaconazole tablets (DRPT) via nasogastric tube in this group of patients, clinicians often use inferior alternatives like posaconazole suspension. In this prospective study, we report good plasma concentrations (median, 2,639 ng/mL; interquartile range [IQR], 1,690 to 3,575 ng/mL; and range, 1,004 to 4,835ng/mL) and complete cure and survival at 3 and 6 months in 19 such patients.

The role and diagnostic accuracy of serology for COVID-19.

BACKGROUND: The role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls. METHODS: Adult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect™ IgM ELISA kit and SCoV-2 Detect™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared. RESULTS: There were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5-85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75-90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98-100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity. CONCLUSION: The serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

High susceptibility to varicella among urban and rural pregnant women in South India: a brief report.

Varicella infection during pregnancy has serious and/or difficult implications and in some cases lethal outcome. Though epidemiological studies in developing countries reveal that a significant proportion of patients may remain susceptible during pregnancy, such an estimate of susceptible women is not known in India. We designed this study to study the prevalence and factors associated with susceptibility to varicella among rural and urban pregnant women in South India. We prospectively recruited 430 pregnant women and analysed their serum varicella IgG antibodies as surrogates for protection. We estimated seroprevalence, the validity of self-reported history of chickenpox and factors associated with varicella susceptibility. We found 23 (95% CI 19.1-27.3) of women were susceptible. Nearly a quarter (22.2%) of the susceptible women had a history of exposure to chickenpox anytime in the past or during the current pregnancy. Self-reported history of varicella had a positive predictive value of 82.4%. Negative history of chickenpox (adjusted prevalence ratio (PR) 1.85, 95% CI 1.15-3.0) and receiving antenatal care from a rural secondary hospital (adjusted PR 4.08, 95% CI 2.1-7.65) were significantly associated with susceptibility. We conclude that high varicella susceptibility rates during pregnancy were noted and self-reported history of varicella may not be a reliable surrogate for protection.

Rhinofacial conidiobolomycosis: Clinical and microbiological characterisation and shift in the management of a rare disease.

BACKGROUND: Conidiobolomycosis is a rare tropical rhinofacial fungal infection which has not been well characterised. The available evidence in its management is sparse due to lack of clinical studies and the limited data on antifungal susceptibility patterns. OBJECTIVE: To analyse the clinical manifestations, antifungal treatment and outcomes of patients with conidiobolomycosis and to determine antifungal susceptibility profiles of the isolates. PATIENTS/METHODS: Retrospective analysis of data of all patients with a diagnosis of conidiobolomycosis confirmed by histopathology and culture at a tertiary care hospital from 2012 to 2019 was done. RESULTS: There were 22 patients, 21 males and one female, with a mean age of 37.1 years. Most common presenting symptom was nasal obstruction, found in 20 (90.90%) patients. Patients who presented within 12 months had a better cure rate (85%) compared to those who presented late (67%). Among the 19 patients who had a follow-up, good outcome was seen in 15 of the 17 (88.24%) patients who were on itraconazole or potassium iodide containing regimen. Of the six patients who received additional trimethoprim-sulphamethoxazole (co-trimoxazole), 67% showed good outcome with two patients showing complete cure and two patients still on treatment with significant improvement. High minimum inhibitory concentration (MIC) values were noted for azoles and amphotericin B, whereas co-trimoxazole showed lowest MIC ranges. CONCLUSION: Itraconazole and potassium iodide are reasonable first-line options for the treatment of conidiobolomycosis. Good clinical response to KI and comparatively lower MIC of co-trimoxazole are promising. Further studies are required for developing clinical breakpoints that can predict therapeutic outcomes.

Clinical management of COVID-19.

The novel coronavirus disease 2019 (COVID-19) with its early origin from Wuhan city in China has evolved into a global pandemic. Maximal precautionary measures and resources have been put forward by most nations in war footing to mitigate transmission and decrease fatality rates. This article was aimed to review the evidence on clinical management and to deal with the identification of high-risk groups, warning signs, appropriate investigations, proper sample collection for confirmation, general and specific treatment measures, strategies as well as infection control in the healthcare settings. Advanced age, cardiovascular disease, diabetes, hypertension and cancer have been found to be the risk factors for severe disease. Fever lasting for >five days with tachypnoea, tachycardia or hypotension are indications for urgent attention and hospitalization in a patient with suspected COVID-19. At present, reverse transcription-polymerase chain reaction (RT-PCR) from the upper respiratory tract samples is the diagnostic test of choice. While many drugs have shown in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are insufficient clinical data to promote or dissuade their usage. Among the currently available drugs, hydroxychloroquine and lopinavir/ritonavir may be considered for patients with severe COVID-19 infection, awaiting further clinical trials. Stringent droplet and contact precautions will protect healthcare workers against most clinical exposures to COVID-19.

Mucormycosis-A clinicoepidemiological review of cases over 10 years.

BACKGROUND: Limited data exist for epidemiology and outcomes of various agents causing mucormycosis in various clinical settings from developing countries like India. OBJECTIVES: To study the epidemiology and outcomes of various agents causing mucormycosis in different clinical settings in a tertiary care hospital from South India. PATIENTS AND METHODS: We reviewed details of 184 consecutive patients with culture-proven mucormycosis with consistent clinical syndrome and supporting features from September 2005 to September 2015. RESULTS: The mean age of patients was 50.42 years; 70.97% were male. Unlike developed countries, R microsporus (29/184; 15.7%) and Apophysomyces elegans (20/184; 10.8%) also evolved as important pathogens in addition to R arrhizus in our setting. Paranasal sinuses (136/184; 73.9%) followed by musculoskeletal system (28/184; 15.2%) were the common areas of involvement. Apophysomyces elegans typically produced skin and musculoskeletal disease in immune-competent individuals with trauma (12/20; 60%) and caused significantly lower mortality (P = 0.03). R microsporus was more common in patients with haematological conditions (25% vs 15.7%) and was less frequently a cause for sinusitis than R arrhizus (27.58% vs 10.9%). The overall mortality was 30.97%. Combination therapy with surgery and antifungals offered the best chance for cure. CONCLUSIONS: Agents causing mucormycosis may have unique clinical and epidemiological characteristics.

Risk Factors of Clinical and Immunological Failure in South Indian Cohort on Generic Antiretroviral Therapy.

Background: Since the time of NACO Antiretroviral (ART) roll-out, generic ART has been the mainstay of therapy. There are many studies documenting the efficacy of generic ART but with the passage of time, failure of therapy is on the rise. As institution of second line ART has significant financial implications both for a program and for an individual it is imperative that we determine factors which contribute towards treatment failure in a cohort of patients on generic antiretroviral therapy. Methodology: This was a nested matched case-control study assessing the predictors for treatment failure in our cohort who had been on Anti-retroviral therapy for at least a year. We identified 42 patients (Cases) with documented treatment failure out of our cohort of 823 patients and 42 sex, age and duration of therapy-matched controls. Using a structured proforma, we collected information from the out-patient and in-patient charts of the Infectious Diseases clinic Cohort in CMC, Vellore. A set of predetermined variables were studied as potential risk factors for treatment failure on ART. Results: Univariate analysis showed significant association with 1) Self-reported nonadherence<95% [OR 12.81 (95%CI 1.54-281.45)]. 2) Treatment interruptions in adherent cases (OR 9.56 (95% CI 1.11-213.35)]. 3) Past inappropriate therapies [OR 9.65 (95% CI 1.12-215.94)]. 4) Diarrhoea [OR 16.40 (95% CI 2.02-3.55.960]. 5) GI opportunistic infections (OR 11.06 (95% CI 1.31 -244.27)] and 6) Drug Toxicity [OR 3.69 (95% CI 1.15-12.35).In multiple logistic regression analysis, we found independent risk factors of treatment failure to be: Self-reported non-adherence (<95%) with OR 15.46(95%CI 1.55 - 154.08), drug toxicity - OR 4.13(95%CI 1.095 - 15.534) and history of diarrhoea - OR 23.446(95%CI 2.572 - 213.70). Conclusion: This study reveals that besides adherence to therapy, presence of diarrhoea and occurrence of drug toxicity are significant risk factors associated with failure of anti-retroviral therapy. There is a need for further prospective studies to assess their role in development of treatment failure on ART and thus help development of targeted interventions.

Posaconazole: an emerging therapeutic option for invasive rhino-orbito-cerebral mucormycosis.

Posaconazole has significant activity against the Mucormycetes. However, data are limited on the clinical efficacy of posaconazole for treating rhino-orbito-cerebral mucormycosis (ROCM). The aim of this study is to assess the efficacy and safety of posaconazole in patients with ROCM. We included 12 consecutive adult patients admitted with ROCM and treated with posaconazole between January 2010 and February 2015. The main outcome of the study was the overall success rate (i.e. either complete or partial response) at the end of treatment. We also assessed serum posaconazole concentrations in a subgroup of patients. Of the 12 patients who received posaconazole, eight patients (66.6%) had complete resolution with median follow-up of 6.5 months (range 2-24 months). Two patients (16.6%) had significant reduction of disease and two (16.6%) had marked residual disease on follow-up. Uncontrolled diabetes was the predisposing factor in all except one patient. One patient developed diarrhoea on posaconazole, which settled without discontinuation of the drug. Posaconazole appears to be a safe and effective antifungal agent in diabetic patients with ROCM, especially in those who have toxicity with polyene therapy.

Tumor necrosis factor-alpha antagonists in patients with complicated spinal tuberculosis: A case series and literature review.

INTRODUCTION: Spinal tuberculosis is often associated with poor outcomes; host-directed inflammation involving the spine contributes to this disability. METHODS: A retrospective review of patients with complicated spinal tuberculosis having received tumor necrosis factor-alpha (TNF-α) antagonists at a referral hospital in South Africa. A literature review was performed to identify all published cases of complicated spinal tuberculosis that received a TNF-α antagonist as part of their treatment. RESULTS: We describe 23 cases, of which 19 were previously reported in the literature. All patients were treated with either thalidomide (n=6) or infliximab (n=16), except for one who received both. All in all, 21 (91%) cases improved neurologically and, at the end of follow-up, 18 could walk. CONCLUSION: There is accumulating experience to confer the efficacy and safety of TNF-α antagonists in treating complicated spinal tuberculosis cases. Evidence from randomized controlled trials is urgently required to substantiate these findings.

Ceftazidime-avibactam and aztreonam combination for Carbapenem-resistant Enterobacterales bloodstream infections with presumed Metallo-ß-lactamase production: a systematic review and meta-analysis.

INTRODUCTION: Carbapenem-resistant Enterobacterales (CRE) due to Metallo-ß-lactamase (MBL) production are treated with either polymyxins or the novel combination of ceftazidime-avibactam and aztreonam (AA). This study aims to evaluate the 30-day mortality of AA in patients with BSI caused by MBL-CRE infections. METHODOLOGY: In this systematic review and meta-analysis, all articles up to June 2023 were screened using search terms like 'CRE', 'MBL', 'AA' and 'polymyxins'. The risk ratio for AA vs polymyxins was pooled using a random-effect model, and the results were represented by a point estimate with a 95% confidence interval. RESULTS: After removing the duplicates, the titles and abstracts of 455 articles were screened, followed by a full-text screening of 50 articles. A total of 24 articles were included for systematic review, and four comparative studies were included in the meta-analysis. All four studies had a moderate or serious risk of bias. The pooled risk ratio for 30-day mortality for AA vs. polymyxins was 0.51 (95%CI: 0.34-0.76), p < 0.001. There was no significant heterogeneity. CONCLUSION: The meta-analysis from studies with a high risk of bias shows that AA is associated with lesser 30-day mortality when compared to polymyxins in patients with MBL-producing CRE BSI. Registration with PROSPERO- CRD42023433608.