A Multicenter Evaluation of Overall Susceptibility and Antimicrobial Resistance Among Streptococcus pneumoniae Isolates.

PURPOSE: S. pneumoniae ranks as the fourth-most lethal pathogen globally in terms of fatalities associated with or attributable to resistance. In this study, the Antimicrobial Testing Leadership and Surveillance (ATLAS) analysis from India aims to study the overall antimicrobial susceptibility (AMS) among pneumococcal isolates collected between 2018 and 2021. METHODS: Non-duplicate clinically significant S. pneumoniae isolates were collected between 2018 and 2021. In vitro activity of antibiotics was assessed against S. pneumoniae. Susceptibility was confirmed at an International Health Management Associates (IHMA) laboratory using supplied broth microdilution panels (Omron Microscan Systems, Inc., Omron Corp., Kyoto, Japan), according to the Clinical and Laboratory Standards Institute (CLSI) guidelines for all antibiotics. RESULTS: Of the total 86 non-duplicate isolates of Streptococcus pneumoniae collected from the tertiary care centers, the proportion of isolates increased from 8.14% (n=7) in 2018 to 43.02% (n=37) in 2020. Most isolates (n = 18; 48.65%) were collected from the age group of 31-60 years in the year 2020. Erythromycin revealed a decrease in susceptibility from the year 2018 (71.43%) to 2020 (16.22%). A decreased susceptibility of 90% was recorded for levofloxacin in the year 2021. Meropenem revealed a decrease in susceptibility from the year 2018 (85.71%) to 2020 (35.14%). Penicillin susceptibility decreased from 37.5% in 2019 to 27.03% in the year 2020. Clindamycin indicated a 100% susceptibility in the year 2018 which then decreased to 71.88% in 2019 and 56.76% in 2020. Linezolid and vancomycin were found to have uniform susceptibility of 100% throughout the years from 2018 to 2021. CONCLUSION: An increase in resistance to penicillin and macrolides among S. pneumoniae isolates was observed in the Indian population. Addressing the elevating rates of S. pneumoniae resistance may require pneumococcal conjugate vaccines (PCVs) with expanded serotype coverage and targeted antimicrobial stewardship efforts.

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.

Evaluation of the trimeric autotransporter Ata as a vaccine candidate against Acinetobacter baumannii infections.

Acinetobacter baumannii is a multidrug-resistant (MDR) nosocomial pathogen for which immunotherapeutic alternatives are needed. We previously identified a surface autotransporter of A. baumannii, Ata, that bound to various extracellular matrix/basal membrane proteins and was required for full virulence, biofilm formation, and the adhesion of A. baumannii to collagen type IV. We show here that Ata binding to collagen type IV was inhibited by antibodies to Ata. In addition, in the presence of complement and polymorphonuclear cells (PMNs), antibodies to Ata were highly opsonic against A. baumannii ATCC 17978 and showed low to moderate killing activity against four heterologous A. baumannii strains, whereas in the absence of PMNs, antibody to Ata efficiently promoted complement-dependent bactericidal killing of all of the tested A. baumannii isolates. Using a pneumonia model of infection in both immunocompetent and immunocompromised mice, we found that, compared to normal rabbit sera, antisera to Ata significantly reduced the levels of A. baumannii ATCC 17978 and two MDR strains in the lungs of infected mice. The ability of Ata to engender anti-adhesive, bactericidal, opsonophagocytic, and protective antibodies validates its potential use as an antigenic target against MDR A. baumannii infections.