Purpose: This study was conducted to find out the occurrence of hypervirulent Klebsiella pneumoniae (hvKP) isolates from different clinical specimens in a tertiary care hospital of eastern India and investigate the distribution of virulence factors, capsular serotypes and antibiogram profile. The distribution of carbapenemase-encoding genes in convergent (hvKP and carbapenem-resistant) isolates was also studied. Materials and methods: A total of 1004 K. pneumoniae isolates were obtained from different clinical specimens from August 2019 to June 2021 and hvKP isolates were identified using the string test. Genes of capsular serotypes K1, K2, K5, K20, K54 and K57, virulence-associated genes, rmpA, rmpA2, mrkD, allS, iroN, iutA, iuc, kfuB and ybtS, and carbapenemase-encoding genes, NDM-1, OXA-48, OXA-181, and KPC, were evaluated by polymerase chain reaction. Antimicrobial susceptibility was determined primarily by the VITEK-2 Compact automated platform (bioMérieux, Marcy-l’Étoile, France) and supplemented by disc-diffusion/EzyMIC (HiMedia, Mumbai, India) wherever needed. Results: Out of 1004 isolates, 33 (3.3%) were hvKP. Most frequent capsular serotype was K2 in 11 (33.3%). Amongst virulence genes, mrkD, iutA and kfuB were detected most frequently in 93.9%, 84.8% and 63.6% isolates respectively. Classical Klebsiella pneumoniae isolates were significantly more resistant than hvKP to cephalosporins, amoxicillin-clavulanic acid, and fluoroquinolones (p < 0.05). Carbapenem resistance was seen in 10 hvKP convergent isolates with the most prevalent carbapenemase-encoding gene being OXA-48 and OXA-181 in 50% isolates. Conclusion: There is a need for continued surveillance of hvKP strains in view of the impending threat of a global spread of convergent strains.

Objective Challenges in susceptibility testing of colistin along with increase in the prevalence of colistin-resistant carbapenemase-producing Enterobacteriaceae (CRE) pathogens needs addressal. Evaluation of user-friendly methods is necessary as an alternative to broth microdilution (BMD), the reference susceptibility testing method, for routine implementation in diagnostic clinical microbiology laboratories. Genotypic detection of the plasmid-mediated colistin resistance is also needed for infection control purposes. Materials and Methods Colistin susceptibility of 200 nonduplicate clinical CRE isolates from December 2017 to June 2019 was determined by BMD, agar dilution (AD), E test, and rapid polymyxin NP test and interpreted as per the European Committee on Antimicrobial Susceptibility Testing. The results of AD, E test, and NP test were compared with that of BMD, considering minimal inhibitory concentration (MIC) ≤ 2 µg/mL as susceptible and > 2 µg/mL as resistant. Presence of any plasmid-mediated colistin resistance (mcr-1 and 2) was evaluated in 27 colistin-resistant CRE isolates by polymerase chain reaction. Statistical Analysis Performance of different phenotypic methods was analyzed by comparing MIC results of AD and E test with that of reference BMD method. Agreement between BMD and the other two methods was expressed in terms of categorical agreement and essential agreement. Errors were expressed as very major error (VME: false-susceptible) and major error (ME: false-resistance) by AD/E test. VME and ME of 3% disagreement were considered unacceptable. Results Colistin resistance was found in 27 (13.5%) isolates by BMD method. The VME rates of both AD (11%) and E test (37%) could not meet the Clinical and Laboratory Standards Institute recommendation (< 3% VME rate is acceptable) as alternative tests to the reference BMD. Colistin NP test showed sensitivity and specificity of 85% and 98%, respectively. The percentage discordant result in NP test was highest in Enterobacter spp. (17%). None of the 27 colistin resistant isolates showed presence of mcr-1 and mcr-2 genes. Conclusion High VME rate in AD and E tests precludes their use as alternatives to BMD for colistin susceptibility testing. NP test with moderate sensitivity but excellent specificity can be a good alternative for testing colistin susceptibility in CRE isolates, except in Enterobacter spp. Absence of mcr-1 and mcr-2 gene necessitates the exploration of other mechanisms of colistin resistance.

The era of multidrug-resistant (MDR) Gram-negative bacilli (GNB) has renewed interest in fosfomycin. The present study evaluated the in vitro activity of fosfomycin against MDR urinary and nonurinary GNB isolates. Fosfomycin susceptibility was carried out by agar dilution for a total of 279 (142 from urine and 137 from other samples) MDR-GNB. Disk diffusion was done for urinary isolates only. Urinary tract isolates had a high degree of susceptibility to fosfomycin (overall susceptibility, 90.8%), whereas only 42.9% of nonurinary isolates retained susceptibility to the drug. Percentage susceptibility rates for urinary and nonurinary isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. were 99%, 91.3%, 66%, 0% and 62%, 44.4%, 32%, 11%, respectively. Fosfomycin showed excellent in vitro activity for uropathogens. Large-scale evaluation of fosfomycin against MDR systemic isolates is required to evaluate its therapeutic efficacy.

Introduction: Cefiderocol (CFDC), a novel semi-synthetic siderophore cephalosporin has been developed to combat the menace of infections caused by carbapenem-resistant Gram-negative bacilli (CR-GNB) including Carbapenem-resistant Enterobacterales (CRE) and Carbapenem-resistant Nonfermenting Gram-negative bacilli (CR-NFGNB). Methods: We determined the in vitro activity of CFDC against a contemporary collection of 503 CR-GNB isolates by the reference broth microdilution method (BMD) using Iron depleted cation adjusted Mueller-Hinton broth (ID-CAMHB). Performance of CFDC disk diffusion (DD) was evaluated against the reference BMD, as an alternative convenient testing method. Molecular characterization of carbapenemase in CR-GNB was performed by PCR targeting bla_NDM-1, bla_{OXA-48like alleles}, bla_KPC, bla_IMP, and, bla_VIM. Minimum inhibitory concentration (MIC) distribution of CFDC in CR-GNB harbouring different carbapenemase enzymes was also analyzed. Results: In our study, 81.7% (411/503) of CR-GNB isolates [81.3%, (278/342) CRE and 82.6% (133/161) CR-NFGNB] were susceptible to CFDC (p> 0.05). Categorical agreement (CA) of DD ranged from 79.8% to 87.5%, Minor error (mE) ranged from 0 to 14%, Major error (ME) ranged from 0 to 3.5%, and Very Major error (VME) ranged from 0 to 12.5% with variations by species tested. Overall CFDC MIC50 and MIC90 values of CR-GNB isolates without any carbapenemase genes were higher as compared to those with the presence of carbapenemase genes (4 μg/mL and 128 μg/mL versus 2 μg/mL and 16 μg/mL respectively). Discussion: CFDC is not yet available for clinical use in India. Hence, multicentric studies are the need of the hour in India for standardization of CFDC susceptibility using disks and CAMHB from different manufacturers as well as understanding mechanisms of high MIC values.

Seriously ill patients presenting with purpura fulminans, sepsis and multi-organ failure often require extensive diagnostic workup for proper diagnosis and management. Host of common infections prevalent in the tropics, e.g. malaria, dengue; other septicemic infections e.g. meningococcemia, typhoid, leptospirosis, toxic shock syndrome, scarlet fever, viral exanthems like measles, infectious mononucleosis, collagen vascular diseases (Kawasaki disease, other vasculitis) diseases, and adverse drug reactions are often kept in mind, and the index of suspicion for rickettsial illness is quite low. We present a case of Indian tick typhus presenting with purpura fulminans (retiform purpura all over the body), sepsis and multiorgan failure without lymphadenopathy and eschar, successfully treated with doxycycline and discharged home. Hence, a high index clinical suspicion and prompt administration of a simple therapy has led to successful recovery of the patient.