Knowledge, Attitude, and Practice (KAP) Survey on the Management of Multidrug-Resistant Gram-Negative Infections With Innovative Antibiotics: Focus on Ceftazidime-Avibactam.

BACKGROUND: Antimicrobial resistance (AMR) is a major public health dilemma and a chief health concern globally. The rising incidence of resistance against carbapenems, which are considered most effective against gram-negative bacteria, has added to the concern and has limited the number of available treatment options. Newer antibiotic options may be required to tackle the mounting concern of antibiotic resistance. However, only a few antimicrobials are in the pipeline for managing infections instigated by multidrug-resistant (MDR) gram-negative bacteria. This justifies the prudent application of already available antibiotics. Among newer antibiotics available to healthcare professionals (HCPs), ceftazidime-avibactam (CAZ-AVI) has shown good efficacy in the management of MDR gram-negative infections. METHOD: A cross-sectional survey on the knowledge, attitude, and practices (KAP) among HCPs was carried out using a questionnaire comprising 21 parameters related to AMR patterns on the need for innovative antibiotics to manage MDR gram-negative infections and the usage of CAZ-AVI by HCPs while managing such infections. The KAP scores were calculated to rank respondents' KAP levels. RESULT: Out of the 204 study respondents, the majority (~80%) (n=160) believed that renewed efforts should be made to seek antimicrobial agents that will add to the armamentarium of treatment options for MDR gram-negative infections. CAZ-AVI is an important treatment alternative for managing MDR gram-negative infections (n=90, 45%). Further, it can be the first choice of definitive therapy for oxacillinases (OXA)-48-producing carbapenem-resistant Enterobacterales (n=84, 42%). HCPs also believed that the use of CAZ-AVI in clinical practice will require high levels of antimicrobial stewardship (n=100, 49%). CONCLUSION: Novel and innovative antibiotics are the need of the hour in the management of MDR gram-negative infections. CAZ-AVI has established its effectiveness in treating these infections; however, the molecule must be utilized prudently while keeping stewardship principles in mind.

Early and Appropriate Use of Ceftazidime-Avibactam in the Management of Multidrug-Resistant Gram-Negative Bacterial Infections in the Indian Scenario.

The increasing prevalence of antibiotic-resistant pathogens exerts a substantial burden on the healthcare infrastructure worldwide. The World Health Organization (WHO) has declared that multidrug-resistant (MDR) Gram-negative pathogens, especially, carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii, and Pseudomonas aeruginosa as the topmost priority while developing newer antimicrobials. The increasing prevalence of infectious diseases caused by MDR Gram-negative bacteria also poses a challenge when choosing the empiric antimicrobial therapy for seriously ill hospitalized patients. The infections caused by MDR Gram-negative organisms ultimately result in increased mortality, morbidity, prolonged hospital stay, and increased cost of management. To tackle these challenges, newer antimicrobials like ceftazidime-avibactam were explored. The article also discusses the in vitro activity and therapeutic efficacy of ceftazidime-avibactam along with its pharmacokinetic properties and the role it will play in the management of MDR Gram-negative organisms in the Indian setting. Several studies have highlighted the role of early and appropriate antibiotic use in the reduction of mortality in patients with Gram-negative infections. Timely initiation of appropriate antibiotic therapy for serious infections leads to favorable clinical outcomes. Early and appropriate use of ceftazidime-avibactam while treating MDR Gram-negative infections has been associated with improved clinical outcomes. The aim of this review is to highlight the efficacy of ceftazidime-avibactam in the treatment of MDR Gram-negative infections. We have also summarized the information on outcomes achieved by early and appropriate use of ceftazidime-avibactam.

In vitro activity of Ceftazidime-Avibactam and its comparators against Carbapenem resistant Enterobacterales collected across India: results from ATLAS surveillance 2018 to 2019.

ATLAS (Antimicrobial Testing Leadership and Surveillance) detects trends in multi-drug resistance longitudinally over time. In the present study, the in vitro activity of ceftazidime-avibactam and comparators was analyzed against Escherichia coli (n = 458) and Klebsiella pneumoniae (n = 455)  isolates obtained from 9 centers across India. The overall susceptibility to ceftazidime-avibactam was observed to be 72% among K. pneumoniae isolates and 87% among E. coli isolates. Among the tested carbapenem resistant isolates, 51% of CR-K. pneumoniae and 24% of CR-E. coli were susceptible to ceftazidime- avibactam. OXA-48 like was identified in 52% of the K. pneumoniae isolates followed by co-production of NDM with OXA-48 like in 27%. NDM was predominantly identified in 68% of the E. coli isolates followed by OXA-48 like in 24% isolates. The findings suggest that ceftazidime- avibactam is a reasonable alternative to standard therapy for management of carbapenem resistant Enterobacterales infections particularly with K. pneumoniae and E. coli with the OXA-48 like genotype.

Optimum patient selection for irinotecan-containing regimens in metastatic colorectal cancer: Literature review and lessons from clinical practice.

Metastatic colorectal cancer (mCRC) accounts for over 20% of CRC cases and is associated with a poor prognosis. Irinotecan is an important first- and second-line chemotherapy option for mCRC. In this review, we summarize the clinical efficacy and safety of irinotecan-based regimens for the treatment of mCRC and discuss various tumor- and patient-related factors that affect the clinical response, survival, and toxicity associated with these regimens. Uridine diphosphate glucuronosyltransferase (UGT) gene polymorphisms such as UGT1A1*28/*6, age, performance status, serum lactate dehydrogenase levels, and bilirubin levels could be important considerations for predicting outcomes and tolerability with irinotecan-based regimens. The role of tumor location; chemotherapy backbone; and emerging evidence on the presence of microsatellite instability-high status, consensus molecular subtype 4 tumors, and signet-ring morphology in predicting response to irinotecan-based therapy have also been highlighted. Careful consideration of these factors will help guide clinicians in optimizing the selection of mCRC patients for irinotecan-based treatment.

Understanding masked depression: A Clinical scenario.

BACKGROUND: Masked depression is often misdiagnosed due to the predominance of somatic symptoms and is further complicated by lack of awareness among doctors. AIM: The present survey was conducted to gather the views of psychiatrists and nonpsychiatrists regarding presentation and management aspects of masked depression. This may help in unmasking this condition and facilitate early identification and appropriate management of patients presenting with this condition. MATERIALS AND METHODS: This questionnaire-based survey was conducted as an interview through computer-aided telephonic interview among 300 doctors (150 psychiatrists and 150 nonpsychiatrists) across India. RESULTS: Both psychiatrists and nonpsychiatrists reported a high prevalence of somatic symptoms among patients with masked depression. Nonpsychiatrists (44%) more often than psychiatrists (20%) noted chronic pain in the majority of patients with masked depression. Psychiatrists (31%) more often than nonpsychiatrists (9%) noted lack of concentration in the majority of patients with masked depression. Sexual dysfunction among young patients and noncompliance to therapy for chronic illness were considered as potential predictors of masked depression. There was a general agreement among psychiatrists and nonpsychiatrists that medical liaising is beneficial for the management of patients with masked depression. CONCLUSION: Both psychiatrists and nonpsychiatrists agree that somatic symptoms are commonly encountered in patients with masked depression. However, these somatic symptoms are often interpreted as physical illness rather than as an entity of depression which creates an unmet need in terms of managing masked depression, especially by nonpsychiatrists.