In vitro activity of cefiderocol against comparators (ceftazidime-avibactam, ceftazidime-avibactam/ aztreonam combination, and colistin) against clinical isolates of meropenem-resistant Klebsiella pneumoniae from India.

Cefiderocol (FDC), a novel siderophore drug, is active against Gram-negative bacteria producing carbapenemases, including metallo-beta-lactamases. The objective of this study is to compare the in vitro activity of FDC with ceftazidime-avibactam (CZA), CZA/aztreonam (AT) combination, and colistin (CST), in clinical isolates of meropenem-resistant (MER-R) Klebsiella pneumoniae. From the 2,052 clinical specimens submitted for culture testing, 245 K. pneumoniae isolates were recovered within a 6-month period in 2021. One hundred three non-duplicate, non-outbreak, MER-R (minimum inhibitory concentration, MIC >4 µg/mL) strains were included in the study. Identification and susceptibility were performed using VITEK-2 (bioMérieux). Meropenem-susceptible isolates (n = 10) served as controls. For FDC, broth microdilution (BMD) was performed after in-house standardization. Disk diffusion (Liofilchem, Italy) and broth microdilution (ComASP, STC, Liofilchem, Italy) were used for susceptibility testing of CZA and CST, respectively. Synergy testing for CZA and AT was performed using disk approximation method. CLSI breakpoints were used for the interpretation of the results. For FDC, MIC50 and MIC90 were 2 and 8 µg/mL, respectively. A total of 80% of isolates were susceptible to FDC, 26.2% of isolates were susceptible to CZA, synergy testing with CZA/AT was positive for 74 (72%) of the isolates, and 89.3% were intermediate to CST. Nine (8.7%) were susceptible only to FDC. FDC is active in vitro against MER-R K. pneumoniae >CZA/AT > CZA > CST, as observed in this study, applying CLSI criteria. Clinico-microbiological studies should be performed to assess the clinical efficacy of this novel drug in this region with a high prevalence of carbapenem resistance among Gram-negative organisms. IMPORTANCE Management of infections with multi-drug resistant Klebsiella pneumoniae is a major challenge in hospital settings, with few treatment options. In this study, the authors aim to assess the in vitro susceptibility of these clinical isolates to cefiderocol, a novel siderophore. Comparators are colistin, ceftazidime-avibactam, and ceftazidime-avibactam/aztreonam synergy, which are currently available options for treatment in this region. Baseline-resistance rates against cefiderocol are higher than those in the previously published studies, with MIC50 and MIC90 at 2 and 8 µg/mL, respectively.

Antibiotic Susceptibility Testing (AST) Practices in India: Need for a National AST Forum.

Background Accurate interpretation of antibiotic susceptibility testing (AST) is one of the most crucial functions of the microbiology laboratory. However, its performance depends on a number of critical factors. We conducted a status survey to understand the existing practices in Indian laboratories that have a potential to influence performance of AST. Method We developed a 22-point online survey questionnaire on information about respondent's specifications, use of AST consumables, existing quality control protocols, and matters of contention in AST practices, and sent it by Google forms to 362 clinical microbiologists (holding MD or DNB certification). Participation was voluntary. Results were analyzed using descriptive statistics. Results Among 362, a total of 103 returned the questionnaire. The first 100 responses that were complete (all 22 questions answered) were analyzed. Respondents were from medical colleges (61%), private hospitals (26%), and stand-alone laboratories (13%). Analysis revealed that the Clinical & Laboratory Standards Institute (CLSI) guidelines were followed by all. Overall, 54% used disc diffusion as the primary method for performing AST. For the internal quality control testing of media and AST, 24% and 16% had adequate testing components and frequency, respectively. For performing AST of colistin, broth microdilution was used by 19%. Also, 86% participated in external quality control programs, and 54% respondents were dissatisfied or unsure about the development of competencies in AST methodology during their postgraduate training. Conclusion This survey reveals that potential gaps exist in the performance parameters and internal quality control of AST. There is an urgent need for harmonization in AST performance and postgraduate training in clinical microbiology in India.

Impact of an Antimicrobial Stewardship Intervention on Usage of Antibiotics in Coronavirus Disease-2019 at a Tertiary Care Teaching Hospital in India.

Background: There was evidence that antibiotic usage increased in hospitalized COVID-19 patients during the early days of the pandemic. Objective: We assessed the impact of stewardship interventions on antibiotic usage in these patients. Methods: We designed a quasi-experimental study using an interrupted time series. Patients were stratified according to the severity category of the illness - mild and moderate-to-severe (O2 saturation ≥94% and <93% respectively). Baseline antibiotic usage data was collected in the pre-intervention phase. Intervention was given in the form of focus group discussion (FGD) and followed up with feedback-audit during the post-intervention phase. Primary outcome was the change in days of therapy (DOT) per 1000 patient-days. Results: 361 adult patients were recruited in both phases during July to December, 2020. In the post-intervention phase, DOT per 1000 patient-days reduced from 589 to 523 (P=0.013) and from 843 to 585 (P <0.0001) in mild and moderate-to-severe categories, respectively. De-escalations at 48 hours increased significantly from 21% to 41% (P=0.0079) and from 31% to 62% (P=0.0006), respectively. No difference in mortality was observed. Conclusion: We found high usage of empirical antibiotics in adult patients hospitalized with COVID-19. FGD and feedback audits can successfully reduce antibiotic overuse in these patients.

Not always a commensal: A case of mastitis by Corynebacterium amycolatum.

Gram positive rods seen on Gram's stain are often dismissed as skin commensal organisms. Diphtheroids (Non-diphtherial Corynebacterium species), as they are collectively called, are taken as harmless bystanders in a skin and soft tissue infection (SSTI). However, emerging evidence has established virulence factors in some of these species leading to various infections. Here, we describe a case of mastitis in a 43 year old female caused by Corynebacterium amycolatum. The organism was seen as thick Gram positive rods on Gram stain and was isolated as a pure growth on Blood agar. Identification was done on Vitek-2 and confirmed by matrix assisted laser desorption-ionization - Time-offlight (MALDI-TOF). Patient was managed successfully with surgical excision and antibiotics.

Disseminated Pyomyositis Due to Burkholderia cepacia: A Case Report.

Pyomyositis is a tropical infection affecting skeletal muscles manifesting as high-grade fever with pain in the affected limbs usually caused by Gram-positive microorganisms. Gram-negative organisms causing pyomyositis is uncommon but has been reported. Burkholderia cepacia is a Gram-negative nonfermenter causing opportunistic infections in immunocompromised patients, has been reported to cause pyomyositis only once before. We report a case of B. cepacia pyomyositis in a patient with no history of immunocompromised status, manifesting as disseminated infection with hemophagocytic syndrome presenting to our intensive care unit.